document: the - and -lactam 
   scaffolds are found in various 
   biologically relevant compounds . additionally , these core structures 
   are crucial intermediates in the synthesis of various natural products 
   as well as pharmaceuticals , prompting the development of new methods 
   for the synthesis of these valuable structures . 
   our group has explored the synthesis 
   of -lactams by the reactions of aryl- , thioaryl- , and cyano - substituted anhydrides . 
   furthermore , we have demonstrated that one - pot four - component reactions 
   ( 4crs ) are possible in the case of thioaryl substitution . 
   recent computational studies of the cyanosuccinic anhydride reactions 
   demonstrate that they proceed by a mannich - like mechanism via the 
   enol tautomer of the anhydride . 
   related 
   reactions reported by castagnoli , cushman , and haimova likely proceed 
   by this mechanism as well . 
   consistent with the proposed mechanism , those 
   anhydrides are poorly enolizable and require forcing conditions . 
   two 
   decades later , cushman and haimova reported analogous reactions with 
   homophthalic anhydride , which is highly enolizable . 
   the high reactivity 
   of this anhydride at lower temperatures is consistent with the mannich - like 
   mechanism . 
   these results prompted us to 
   explore mannich - type reactions and 
   related 4crs of variously substituted anhydrides . 
   although aryl - substituted 
   succinic anhydrides showed some variation in reactivity based on the 
   substituents attached to the aromatic ring , direct attachment of an 
   electron - withdrawing group resulted in higher reactivity . 
   furthermore , in the case of cyanosuccinic anhydrides , 
   the diastereoselectivity was reversed relative to the aryl and thioaryl 
   cases and could be controlled by resident stereogenic centers . 
   we envisioned that the electron - withdrawing capability of a sulfone 
   would impart the anhydride with similar reactivity as the nitrile - substituted 
   anhydride , albeit with drastically different steric requirements ( scheme 1 ) . 
   herein we report the development of anhydride 
   mannich reactions ( amrs ) using sulfone - substituted anhydrides for 
   the synthesis of - and -lactams as well as a six - step 
   formal synthesis of ( )-isoretronecanol . 
   multigram - scale syntheses of 
   anhydrides 3a  d were achieved from 
   readily available starting materials . 
   anhydride 3a was synthesized by conjugate addition of 
   benzenesulfinic acid sodium salt ( 7 ) to maleic anhydride 
   to yield a diacid , which was cyclized 
   in one step ( scheme 2a ) . 
   the syntheses of anhydrides 3b  d were achieved by michael addition 
   of sulfone acetate 8 to various tert - butyl acrylates followed by ester cleavage and cyclization ( scheme 2b ) . 
   anhydride 3a readily 
   reacted with imines to form -lactams . 
   as with previous amrs 
   , the carboxylic acid 5 ( table 1 ) is the first - formed product . unlike all previous 
   related intermediates , these carboxylic acids were prone to facile 
   decarboxylation . 
   mild heating drove the decarboxylation to completion , 
   allowing isolation of the sulfone - substituted lactams in high yields 
   with only the anti diastereomer detectable by h nmr spectroscopy . in all cases , non - enolizable substrates 
   the lack of reactivity of ketones and enolizable 
   aldehydes in the amr probably stems from the rapid equilibration to 
   the enamine tautomer , which is unreactive in the mannich addition 
   step . 
   the stereochemical 
   configuration of the products was assigned by 
   x - ray crystallography . 
   lactam 10e has an anti configuration between the aromatic ring and the sulfonyl group . 
   the other lactams were assigned by comparison of the coupling constants 
   of the adjacent protons ( e.g. , 10f ; figure 1a ) . furthermore , acid intermediate 5f , which 
   leads to 10f by decarboxylation , was also crystalline 
   and was found to have an anti configuration between 
   the sulfone and aromatic substituents ( figure 1b ) . 
   our previous mechanistic work on the cyano - substituted anhydrides 
   suggests that the anti - configured carboxylic acids 
   are the kinetic products of the amrs . 
   subsequent 
   decarboxylation leads to the anti - sulfones , which 
   would also be expected to be thermodynamically preferred . 
   x - ray structures 
   of 5f , 10f , and 10 g and j values for 10e and 10j . 
   the stereochemical outcome of 
   the reactions of imines with 3a is adequately explained 
   by a transition state that is analogous 
   to what is operative for cyanosuccinic anhydrides 
   the iminium ion is attacked by the enolate of the anhydride , 
   and the cyclic transition state is stabilized by hydrogen bonding 
   to the sulfone . 
   after the mannich reaction , subsequent rapid transannular 
   acylation forms the lactam product.1 the carboxylic acid 
   intermediates could be trapped with trimethylsilyldiazomethane 
   ( tmschn2 ) . 
   after many esterification conditions 
   were tried , treatment of crude mixtures of 5 with a commercially 
   available solution of tmschn2 resulted in reasonable yields 
   of methyl esters 11a  c ( table 2 ) . 
   these intermediates 
   could also be smoothly desulfonylated with magnesium in methanol to 
   produce the corresponding esters 12 in good yield . 
   although 
   this reaction was successful for 11a and 11b , no ester product was observed in the attempted desulfonylation 
   of 11c . 
   unlike the analogous -lactams , these intermediates were impossible 
   to isolate , thus preventing assignment of the configuration of the 
   predominant diastereomer . 
   upon decarboxylation , sulfone lactams 13 were formed as single isomers in high yields ( table 3 ) . determined by h 
   this 
   change in diastereoselectivity upon decarboxylation suggests 
   the formation of a planar anion followed by selective protonation 
   from one face of the anion . 
   this result is in accordance with experimental 
   data and models of sulfone anions proposed by corey . similar to our results with the succinic anhydride , 
   the reaction 
   tolerated a variety of non - enolizable aldehydes and a variety of alkylamines 
   and anilines . 
   while some of our initial reactions gave low yields 
   ( 4050% ) , the use of commercially available imines or those 
   purified by distillation significantly increased the yields of the 
   lactam products . 
   methyl - substituted anhydrides 3c and 3d provided trisubstituted -lactams in high 
   yields with good 
   diastereomeric ratios ( scheme 3 ) . 
   these results 
   suggest that substitution on the anhydride provides excellent facial 
   selectivity , resulting in the formation of only two diastereomers 
   of the intermediate carboxylic acids . 
   studies are ongoing 
   in our laboratory to develop an enantioselective michael addition 
   with sulfone acetate 8 to provide the anhydrides as single 
   enantiomers , which would presumably provide enantiomerically pure 
   lactam products . 
   this new amr was applied to a formal synthesis of ( )-isoretronecanol 
   ( scheme 4 ) . 
   the reaction of imine 16 with anhydride 3a followed by ring - closing metathesis 
   provides the pyrrolizidine core of the natural product from cinnamaldehyde , 
   allylamine , and 3a in two steps . the elimination of 18 yields 21 , which has been converted to ( )-isoretronecanol 
   in two steps in low yield . 
   further 
   reduction yields lactam ester 22 , which has been converted 
   to ( )-isoretronecanol in one step . while this second route is redox - inefficient , it provides material in a much higher yield and avoids 
   the high - pressure conditions necessary to reduce pyrrole 21 . 
   this synthetic route showcases the versatility of the anhydride 
   michael reaction of the sulfone - substituted anhydride , exemplifying 
   its usefulness in the assembly of heterocyclic targets . 
   this synthesis 
   demonstrates that the amr of sulfone - substituted anhydrides will be 
   useful for the assembly of many heterocyclic targets , natural and 
   otherwise . 
   in 
   summary , we have successfully synthesized various sulfone - substituted 
   - and -lactams in good yields with high diastereoselectivities 
   ( > 95:5 ) by an anhydride mannich reaction . 
   we have previously studied 
   the reactivity of several different substituted succinic anhydrides , 
   but these are the first new results employing glutaric anhydyrides 
   since the original work of castagnoli . unlike previous 
   reactions of this type to date , the carboxylic acid products were 
   prone to decarboxylation . although the -lactam acids derived 
   from the substituted succinic anhydride could be trapped as esters , 
   the analogous -lactam products could not be intercepted . 
   another 
   important difference was observed in the diastereoselectivity of the 
   initial mannich - type reaction . 
   although the reactions of succinic 
   anhydyrides were very selective , the acid products derived from the 
   glutaric anhydrides were generally formed as diastereomeric mixtures . 
   in both cases , 
   we have shown that this methodology is highly robust and 
   have showcased it in the formal synthesis of a biologically active 
   natural product . 
   unless otherwise specified , all 
   commercially available reagents were used as received . all reactions 
   using dried solvents 
   were carried out under an atmosphere of argon 
   in flame - dried glassware with magnetic stirring . 
   dry solvent was dispensed 
   from a solvent purification system that passes solvent through two 
   columns of dry neutral alumina . 
   h nmr spectra and proton - decoupled c nmr spectra were obtained on a 400 or 600 mhz nmr spectrometer . 
   chemical shifts (  ) are reported in parts per million ( ppm ) 
   relative to residual solvent ( chcl3 , s ,  7.26 ) . 
   multiplicities are given as s ( singlet ) , d ( doublet ) , t ( triplet ) , 
   dd ( doublet of doublets ) , m ( multiplet ) , br m ( broad multiplet ) , or 
   br s ( broad singlet ) ; c nmr chemical shifts are reported 
   relative to cdcl3 ( t ,  77.23 ) unless otherwise noted . 
   high - resolution mass spectra were recorded in positive esi mode in 
   methanol or acetonitrile . 
   silica gel chromatographic purifications 
   were performed by flash chromatography with silica gel packed in glass 
   columns . 
   the eluting solvent for each purification was determined 
   by thin - layer chromatography ( tlc ) on glass plates coated with silica 
   gel and visualized by uv light or by staining with ceric ammonium 
   molybdate ( cam ) followed by gentle heating . 
   the following abbreviations 
   are used throughout : ethyl acetate ( etoac ) , hexanes ( hex ) , dichloromethane 
   ( dcm ) , triethylamine ( tea ) , diisopropylethylamine ( dipea ) . 
   benzenesulfinic acid sodium salt ( 10.0 
   g , 60.9 mmol ) was dissolved 
   in 100 ml of h2o at 0 c . 
   then 10% hcl was added , and the mixture was extracted two 
   times with etoac . 
   the combined organic layers were dried over na2so4 , and the solvent was removed in vacuo to yield 
   a white solid , which was dissolved in 50 ml of toluene . 
   ac2o ( 70 ml , 20 mmol ) was added , and the reaction mixture was heated 
   at reflux for 3 h. the solvent was evaporated in vacuo , and the resulting 
   brown solid was washed several times with cold dcm and collected in 
   a fritted funnel , yielding a white to light - brown solid ( 6.8 g , 46% 
   yield over the two steps ) . 
   mp 132.4133.1 c ( dec . ) ; h nmr ( 400 mhz , cdcl3 )  7.96 ( dd , j = 8.4 , 1.3 hz , 2h ) , 7.867.76 ( m , 1h ) , 7.727.63 
   ( m , 2h ) , 4.52 ( dd , j = 10.3 , 4.4 hz , 1h ) , 3.68 ( dd , j = 19.9 ( gem ) , 4.4 hz , 1h ) , 3.39 ( dd , j = 19.7 ( gem ) , 10.6 hz , 1h ) ; c nmr ( 100 mhz , cdcl3 )  166.0 , 162.9 , 135.8 , 135.4 , 129.9 , 129.7 , 64.4 , 
   30.1 ; ir ( neat ) 1782 , 1739 ( c = o ) , 1169 ( s = o ) cm ; hrms ( esi - tof ) 
   m / z [ m + h ] calcd for c10h9o5s 241.0171 , found 241.0165 . 
   the amine and 
   the aldehyde were 
   dissolved in thf ( 0.10 m ) , and 3 equiv of triethyl orthoformate was 
   added . 
   the anhydride was added , and then the reaction mixture was allowed 
   to stir for 3 h. water was added to the mixture ( final concentration 
   0.05 mmol ) , followed by the addition of 3 equiv of k2co3 and heating at reflux for 4 h , unless otherwise stated . 
   the 
   reaction mixture was allowed to cool to rt and then extracted two 
   times with etoac . 
   the solvent was evaporated 
   in vacuo , and the crude mixture was purified by flash chromatography 
   using an etoac/3050% gradient , unless otherwise stated . 
   general procedure a was used with sulfone 
   anhydride 3a ( 0.24 g , 0.99 mmol ) , benzylamine ( 109 l , 
   0.99 mmol ) , and benzaldehyde ( 102 l , 1.0 mmol ) to yield 10a ( 0.32 g , 83% ) as a foam ( 50:50 etoac / hex , rf = 0.59 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.687.64 ( m , 2h ) , 7.62 ( tt , j = 
   7.5 , 1.3 hz , 1h ) , 7.487.41 ( m , 2h ) , 7.327.23 ( m , 6h ) , 
   7.097.06 ( m , 2h ) , 6.836.79 ( m , 2h ) , 5.09 ( d , j = 14.9 hz , 1h ) , 4.70 ( d , j = 3.3 hz , 
   1h ) , 3.66 ( ddd , j = 9.9 , 4.4 , 3.3 hz , 1h ) , 3.44 ( d , j = 14.9 hz , 1h ) , 3.03 ( dd , j = 18.2 ( gem ) , 
   4.3 hz , 1h ) , 2.95 ( ddd , j = 18.2 ( gem ) , 9.9 , 1.2 
   hz , 1h ) ; c nmr ( 101 mhz , cdcl3 )  170.5 , 
   137.7 , 136.4 , 134.7 , 134.4 , 129.5 , 129.3 , 128.9 , 128.7 , 128.7 , 128.4 , 
   127.8 , 126.1 , 63.5 , 60.6 , 44.5 , 30.7 ; ir ( thin film ) 1692 ( c = o ) , 
   1322 ( s = o ) cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c23h21no3sna 414.1140 , found 414.1120 . 
   general procedure a was used with sulfone 
   anhydride 3a ( 0.30 g , 1.26 mmol ) and ( e)-n - methyl-1-phenylmethanimine ( 156 l , 1.26 
   mmol ) . because the commercially available imine was used in this experiment , 
   the anhydride was added immediately after the imine was dissolved 
   instead of waiting for 3 h or overnight . 
   the reaction yielded 10b ( 0.332 g , 83% ) as a foam ( 50:50 etoac / hex , rf = 0.35 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.89 ( d , j = 7.5 hz , 2h ) , 7.69 ( t , j = 7.5 hz , 1h ) , 7.58 ( t , j = 7.8 hz , 2h ) , 
   7.367.31 ( m , 3h ) , 7.067.02 ( m , 2h ) , 4.97 ( d , j = 3.5 hz , 1h ) , 3.66 ( dt , j = 9.8 , 4.1 
   hz , 1h ) , 2.90 ( dd , j = 18.1 ( gem ) , 4.7 hz , 1h ) , 2.82 
   ( dd , j = 18.1 ( gem ) , 9.8 hz , 1h ) , 2.64 ( s , 3h ) ; c nmr ( 150 mhz , cdcl3 )  170.6 , 138.2 , 136.8 , 
   134.6 , 129.7 , 129.5 , 129.0 , 128.9 , 126.1 , 64.3 , 63.6 , 31.0 , 28.4 ; 
   ir ( thin film ) 1690 ( c = o ) , 1308 ( s = o ) cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c17h17no3sna 338.0827 , 
   found 338.0818 . 
   general procedure a was used with sulfone 
   anhydride 3a ( 0.240 g , 1.00 mmol ) , prop-2-yn-1-amine 
   ( 64.0 l , 1.00 mmol ) , and benzaldehyde ( 102 l , 1.00 mmol ) 
   to yield 10c ( 0.182 g , 54% ) as a foam . the residue was 
   purified by flash column chromatography ( 50:50 etoac / hex , rf = 0.53 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.89 ( m , 2h ) , 7.68 ( t , j = 7.4 
   hz , 1h ) , 7.607.53 ( t , 2h ) , 7.357.29 ( m , 3h ) , 7.077.02 
   ( m , 2h ) , 5.23 ( d , j = 4.0 hz , 1h ) , 4.51 ( dd , j = 17.6 , 2.6 hz , 1h ) , 3.75 ( ddd , j = 9.4 , 
   5.1 , 4.0 hz , 1h ) , 3.253.20 ( m , 1h ) , 2.96 ( dd , j = 18.2 ( gem ) , 5.1 hz , 1h ) , 2.89 ( ddd , j = 18.2 
   ( gem ) , 9.8 , 1.1 hz , 1h ) , 2.25 ( t , j = 2.5 hz , 1h ) ; c nmr ( 150 mhz , cdcl3 )  169.9 , 137.3 , 136.6 , 
   134.6 , 129.6 , 129.4 , 129.0 , 128.9 , 126.4 , 76.2 , 73.3 , 63.9 , 60.9 , 
   31.1 , 30.5 ; ir ( thin film ) 1699 ( c = o ) , 1414 , 1322 ( s = o ) 
   cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c19h17no3sna 362.0827 , found 362.0831 . 
   general procedure a was used with sulfone 
   anhydride 3a ( 0.24 g , 0.99 mmol ) , propylamine ( 82 l , 
   0.99 mmol ) , and furan-2-carbaldehyde ( 83 l , 1.00 mmol ) to yield 10d ( 0.167 g , 50% ) as a foam . 
   the residue was purified by 
   flash column chromatography ( 50:50 etoac / hex , rf = 0.47 ) . 
   h nmr ( 600 mhz , cdcl3 )  
   7.907.86 ( m , 2h ) , 7.707.65 ( m , 1h ) , 7.57 ( dd , j = 8.3 , 7.2 hz , 2h ) , 7.32 ( d , j = 1.8 
   hz , 1h ) , 6.27 ( dd , j = 3.3 , 1.9 hz , 1h ) , 6.19 ( d , j = 3.3 hz , 1h ) , 5.07 ( d , j = 4.1 hz , 1h ) , 
   3.96 ( ddd , j = 8.9 , 6.1 , 4.1 hz , 1h ) , 3.40 ( ddd , j = 13.9 , 8.8 , 7.1 hz , 1h ) , 2.952.85 ( m , 2h ) , 2.65 
   ( ddd , j = 13.9 , 8.6 , 5.2 hz , 1h ) , 1.471.37 
   ( m , 1h ) , 1.331.24 ( m , 1h ) , 0.82 ( t , j = 7.4 
   hz , 3h ) ; c nmr ( 75 mhz , cdcl3 )  169.9 , 
   149.4 , 143.5 , 136.7 , 134.5 , 129.6 , 128.6 , 110.6 , 109.8 , 60.8 , 55.2 , 
   42.7 , 31.2 , 20.1 , 11.1 ; ir ( thin film ) 1690 ( c = o ) , 1416 , 1308 
   ( s = o ) cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c17h19no4sna 356.0932 , found 356.0929 . 
   general procedure a was used with sulfone 
   anhydride 3a ( 0.3 g , 1.2 mmol ) , propylamine ( 100 l , 
   1.2 mmol ) , and benzaldehyde ( 126 l , 1.2 mmol ) to yield 10e ( 0.36 g , 87% ) as a solid ( 50:50 etoac / hex , rf = 0.36 ) . 
   mp 149.8150.4 c ; h nmr ( 400 mhz , cdcl3 )  7.89 ( dt , j = 8.5 , 1.4 hz , 2h ) , 7.767.54 ( m , 3h ) , 7.437.24 ( m , 
   3h ) , 7.136.98 ( m , 2h ) , 5.09 ( d , j = 3.5 hz , 
   1h ) , 3.703.56 ( m , 2h ) , 2.972.76 ( m , 2h ) , 2.54 ( dddd , j = 13.7 , 8.4 , 5.1 , 1.1 hz , 1h ) , 1.551.31 ( m , 2h ) , 
   0.85 ( td , j = 7.3 , 1.2 hz , 3h ) ; c nmr 
   ( 100 mhz , cdcl3 )  170.6 , 138.4 , 136.7 , 134.5 , 129.6 , 
   129.3 , 128.8 , 128.7 , 126.0 , 63.8 , 61.1 , 42.6 , 30.9 , 19.9 , 11.1 ; ir 
   ( thin film ) 1688 ( c = o ) cm ; hrms ( esi - tof ) m / z [ m  h ] calcd 
   for c19h20no3s 342.1164 , found 342.1155 . 
   general procedure a ( except that the decarboxylation 
   was performed at room temperature overnight ) was used with sulfone 
   anhydride 3a ( 0.3 g , 1.2 mmol ) , propylamine ( 102 l , 
   1.2 mmol ) , and 4-cyanobenzaldehyde ( 0.164 g , 1.3 mmol ) to yield 10f ( 0.36 g , 80% ) as a foam ( 50:50 etoac / hex , rf = 0.35 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.89 ( dt , j = 8.5 , 1.8 hz , 2h ) , 7.777.54 
   ( m , 5h ) , 7.26 ( m , 2h ) , 5.20 ( d , j = 3.6 hz , 1h ) , 
   3.67 ( dt , j = 13.7 , 8.0 hz , 1h ) , 3.57 ( dt , j = 10.0 , 4.3 hz , 1h ) , 2.88 ( dd , j = 18.2 
   ( gem ) , 4.5 hz , 1h ) , 2.76 ( dd , j = 18.1 ( gem ) , 10.0 
   hz , 1h ) , 2.52 ( ddd , j = 13.8 , 8.6 , 5.0 hz , 1h ) , 1.44 
   ( m , 2h ) , 0.87 ( t , j = 7.3 hz , 3h ) ; c 
   nmr ( 600 mhz , cdcl3 )  170.7 , 144.1 , 136.6 , 134.9 , 
   133.3 , 129.9 , 128.9 , 127.2 , 118.1 , 113.1 , 63.8 , 60.6 , 43.1 , 31.3 , 
   20.1 , 11.2 ; ir ( thin film ) 1692 ( c = o ) , 1445 , 1412 ( s = o ) 
   cm ; hrms 
   ( esi - tof ) m / z [ m + na ] calcd for c20h20n2o3sna 391.1092 , found 391.1098 . 
   general procedure a was used with sulfone 
   anhydride 3a ( 88 mg , 0.36 mmol ) , propylamine ( 30 l , 
   0.36 mmol ) , and aldehyde ( 50 mg , 0.37 mmol ) to yield 10 g ( 87 mg , 65% ) as a solid ( 50:50 etoac / hex , rf = 0.17 ) . 
   mp 125.3126.1 c ; h nmr 
   ( 600 mhz , cdcl3 )  7.927.86 ( m , 2h ) , 7.697.62 
   ( m , 1h ) , 7.55 ( t , j = 7.9 hz , 2h ) , 7.28 ( m , 1h ) , 
   6.936.82 ( m , 3h ) , 5.16 ( s , 1h ) , 3.80 ( d , j = 9.8 hz , 1h ) , 3.69 ( s , 3h ) , 3.49 ( dt , j = 13.5 , 
   8.1 hz , 1h ) , 2.96 ( dd , j = 17.9 ( gem ) , 4.0 hz , 1h ) , 
   2.85 ( dd , j = 17.9 ( gem ) , 9.9 hz , 1h ) , 2.48 ( ddd , j = 13.7 , 8.5 , 5.2 hz , 1h ) , 1.461.28 ( m , 2h ) , 0.82 
   ( t , j = 7.3 hz , 3h ) ; c nmr ( 151 mhz , 
   cdcl3 )  171.2 , 157.5 , 137.7 , 134.2 , 130.5 , 129.5 
   ( 2c ) , 129.0 ( 2c ) , 125.7 , 121.1 , 111.5 , 62.8 , 55.6 , 42.8 , 31.7 , 20.3 , 
   11.3 ; ir ( thin film ) 1681 ( c = o ) cm ; hrms 
   ( esi - tof ) m / z [ m + na ] calcd for c20h23no4sna 396.1245 , 
   found 396.1252 . 
   general 
   procedure a was used with sulfone anhydride 3a ( 0.18 
   g , 0.73 mmol ) , benzylamine ( 76 l , 0.69 mmol ) , and aldehyde 
   ( 0.1 ml , 0.79 mmol ) to yield 10h ( 0.25 g , 82% ) as a foam 
   ( 50:50 etoac / hex , rf = 0.36 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.817.74 ( m , 2h ) , 
   7.657.14 ( m , 13h ) , 6.12 ( d , j = 15.8 hz , 
   1h ) , 5.74 ( dd , j = 15.6 , 8.5 hz , 1h ) , 4.93 ( d , j = 15.0 hz , 1h ) , 4.38 ( dd , j = 8.8 , 4.3 
   hz , 1h ) , 3.90 ( d , j = 15.0 hz , 1h ) , 3.65 ( dt , j = 9.9 , 5.1 hz , 1h ) , 3.01 ( dd , j = 18.0 
   ( gem ) , 5.5 hz , 1h ) , 2.86 ( dd , j = 18.1 ( gem ) , 10.0 
   hz , 1h ) ; c nmr ( 151 mhz , cdcl3 )  170.1 , 
   136.8 , 135.3 , 135.2 , 135.0 , 134.4 , 129.5 , 128.8 , 128.7 , 128.7 , 128.4 , 
   127.7 , 126.8 , 126.7 , 125.3 , 61.7 , 59.9 , 44.7 , 30.8 ; ir ( thin film ) 
   1690 ( c = o ) , 1146 ( s = o ) cm ; hrms 
   ( esi - tof ) m / z [ m + na ] calcd for c25h23no3sna 440.1296 , 
   found 440.1282 . 
   general procedure a was used with sulfone 
   anhydride 3a ( 0.3 g , 1.26 mmol ) , isopropylamine ( 100 
   l , 1.22 mmol ) , and benzaldehyde ( 128 l , 1.26 mmol ) to 
   yield 10i ( 0.297 g , 70% ) as a foam ( 50:50 etoac / hex , rf = 0.42 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.987.86 ( m , 2h ) , 7.72 ( tt , j = 7.2 , 1.5 hz , 1h ) , 7.687.56 ( m , 2h ) , 7.407.26 ( m , 
   3h ) , 7.176.97 ( m , 2h ) , 5.10 ( d , j = 2.3 hz , 
   1h ) , 4.203.98 ( m , 1h ) , 3.57 ( ddd , j = 9.6 , 
   2.6 , 2.1 hz , 1h ) , 2.93 ( ddd , j = 18.2 ( gem ) , 9.6 , 
   1.9 hz , 1h ) , 2.882.75 ( m , 1h ) , 1.21 ( dd , j = 6.8 , 2.0 hz , 3h ) , 0.85 ( dd , j = 6.9 , 1.9 hz , 
   3h ) ; c nmr ( 151 mhz , cdcl3 )  170.7 , 
   140.7 , 136.6 , 134.5 , 129.6 , 129.2 , 128.8 , 128.7 , 125.9 , 64.5 , 60.1 , 
   45.5 , 31.2 , 20.8 , 19.5 ; ir ( thin film ) 1693 ( c = o ) , 1145 ( s = o ) 
   cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c19h21no3sna 366.1140 , found 366.1147 . 
   general procedure a was used with sulfone 
   anhydride 3a ( 0.30 g , 1.26 mmol ) , allylamine ( 93 l , 
   1.24 mmol ) , and benzaldehyde ( 128 l , 1.26 mmol ) to yield 10j ( 0.33 g , 78% ) as a foam ( 50:50 etoac / hex , rf = 0.42 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.88 ( dt , j = 8.5 , 2.0 hz , 2h ) , 7.777.67 
   ( m , 1h ) , 7.59 ( m , 2h ) , 7.437.27 ( m , 3h ) , 6.99 ( m , 2h ) , 5.55 
   ( dddd , j = 17.6 , 10.0 , 7.8 , 4.3 hz , 1h ) , 5.235.15 
   ( m , 1h ) , 5.145.02 ( m , 2h ) , 4.40 ( ddt , j = 
   15.4 , 3.9 , 1.9 hz , 1h ) , 3.753.65 ( m , 1h ) , 2.95 ( m , 3h ) ; c nmr ( 151 mhz , cdcl3 )  170.42 , 138.2 , 
   136.8 , 134.5 , 131.0 , 129.7 , 129.5 , 129.4 , 128.9 , 126.2 , 119.0 , 63.9 , 
   60.7 , 43.4 , 31.0 ; ir ( thin film ) 1691 ( c = o ) , 1145 ( s = o ) 
   cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c19h19no3sna 364.0983 , found 364.0974 . 
   general procedure a was used with sulfone 
   anhydride 3a ( 0.30 g , 1.2 mmol ) , propylamine ( 100 l , 
   1.2 mmol ) , and 4-methoxybenzaldehyde ( 151 l , 1.2 mmol ) to yield 10k ( 0.38 g , 84% ) as a foam ( 50:50 etoac / hex , rf = 0.27 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.927.86 ( d , j = 7.8 hz , 2h ) , 
   7.69 ( m , 1h ) , 7.58 ( t , j = 7.8 hz , 2h ) , 6.96 ( dd , j = 9.2 , 2.5 hz , 2h ) , 6.84 ( dd , j = 9.0 , 
   2.5 hz , 2h ) , 5.04 ( d , j = 3.5 hz , 1h ) , 3.80 ( sharp 
   s , 3h ) , 3.663.53 ( m , 2h ) , 2.90 ( dd , j = 18.2 
   ( gem ) , 4.7 hz , 1h ) , 2.852.76 ( dd , j = 18.2 
   ( gem ) , 10.2 hz , 1h ) , 2.52 ( m , 1h ) , 1.511.32 ( m , 2h ) , 0.880.79 
   ( t , j = 7.8 hz , 3h ) ; c nmr ( 150 mhz , 
   cdcl3 )  170.4 , 159.9 , 136.9 , 134.4 , 130.3 , 129.6 , 
   128.8 , 127.4 , 114.7 , 64.1 , 60.7 , 55.3 , 42.5 , 31.1 , 20.0 , 11.1 ; ir 
   ( thin film ) 1687 ( c = o ) , 1354 , 1144 ( s = o ) cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c20h23no4sna 396.1245 , 
   found 396.1252 . 
   n - benzylidenebenzylamine 
   ( 0.1 ml , 0.53 mmol ) was added to a round - bottom flask containing na2so4 ( 0.37 g , 2.6 mmol ) and thf ( 6 ml ) , and then 
   sulfone anhydride 3a ( 0.13 g , 0.54 mmol ) was added . 
   the 
   reaction mixture was allowed to stir for 1.5 h , after which the na2so4 was removed by filtration and the solvent was 
   removed in vacuo . 
   the residue was redissolved in etoac , transferred 
   to a separatory funnel , and washed with hcl ( 1.2 m or 10% ) and brine . 
   the combined organic layers were dried over na2so4 , and the solvent removed in vacuo . 
   the resulting acid was redissolved 
   in a mixture of toluene and methanol ( 12 ml:7 ml ) and cooled to 0 
   c . to the cold solution , tmschn2 ( 0.53 ml , 1.1 mmol , 
   2 m solution in hexanes ) 
   after 2 h the solvent was removed in vacuo , and 
   the resulting material was purified by column chromatography ( 3060% 
   etoac : hex ) to yield 11a ( 0.157 g , 66% over the two steps ) 
   as an amorphous solid ( 50:50 etoac / hex , rf = 0.47 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.647.18 
   ( m , 15h ) , 5.21 ( d , j = 14.5 hz , 1h ) , 4.89 ( s , 1h ) , 
   3.70 ( d , j = 18.7 ( gem ) hz , 1h ) , 3.383.30 
   ( m , 2h ) , 3.13 ( s , 3h ) ; c nmr ( 150 mhz , cdcl3 )  170.0 , 164.9 , 134.9 , 134.8 , 134.8 , 134.4 , 131.1 , 129.6 , 
   129.5 , 129.5 , 129.0 , 128.9 , 128.9 , 128.2 , 76.2 , 63.9 , 52.7 , 44.9 , 
   35.0 ; ir ( thin film ) 1783 , 1784 ( c = o ) , 1124 ( s = o ) cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c25h23no5sna 472.1195 , found 472.1176 . 
   propylamine ( 68 l , 0.83 mmol ) and 
   3,5-dimethoxybenzaldehyde ( 0.14 g , 0.84 mmol ) were dissolved in thf 
   ( 8 ml ) . 
   na2so4 ( 0.59 g , 4.2 mmol ) was added , 
   and the mixture was allowed to stir for 1.5 h. sulfone anhydride 3a ( 0.20 g , 0.83 mmol ) was added , and the reaction was allowed 
   to stir for an additional 1 h. the na2so4 was 
   filtered off , and the solvent was removed in vacuo . 
   the residue was 
   redissolved in etoac , transferred to a separatory funnel , and washed 
   with hcl ( 1.2 m or 10% ) and brine . 
   the combined organic layers were 
   dried over na2so4 , and the solvent was removed 
   in vacuo . 
   the resulting crude acid was dissolved in a mixture of toluene 
   and methanol ( 13 ml:7 ml ) and cooled to 0 c . to the cold solution , 
   tmschn2 ( 0.83 ml , 
   1.7 mmol , 2 m solution in hexanes ) was 
   added dropwise over a period of 5 min , and the reaction was monitored 
   by tlc for the disappearance of starting material . 
   after 2 
   h the solvent was removed in vacuo , and the resulting material was 
   purified by column chromatography ( 3060% etoac : hex ) to yield 11b ( 0.22 g , 57% over the two steps ) as an amorphous solid 
   ( 50:50 etoac / hex , rf = 0.31 ) . 
   h nmr ( 600 mhz , cdcl3 )  8.017.83 ( m , 2h ) , 
   7.817.68 ( m , 1h ) , 7.687.52 ( m , 2h ) , 6.39 ( d , j = 2.3 hz , 1h ) , 6.22 ( s , 2h ) , 5.38 ( s , 1h ) , 3.74 ( s , 6h ) , 
   3.663.59 ( m , 1h ) , 3.55 ( d , j = 18.4 ( gem ) 
   hz , 1h ) , 3.26 ( m , 3h ) , 3.14 ( d , j = 18.5 ( gem ) hz , 
   1h ) , 2.58 ( ddd , j = 13.8 , 8.7 , 5.2 hz , 1h ) , 1.651.32 
   ( m , 2h ) , 0.92 ( t , j = 7.3 hz , 3h ) ; c 
   nmr ( 150 mhz , cdcl3 )  169.9 , 164.7 , 160.9 , 137.3 , 
   135.3 , 134.9 , 130.4 , 129.2 , 100.8 , 76.7 , 64.3 , 55.4 , 52.8 , 43.2 , 35.8 , 
   20.2 ( 2c ) , 11.3 ; ir ( thin film ) 1748 , 1702 ( c = o ) , 1144 , 1457 
   ( s = o ) cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c23h27no7sna 484.1406 , found 484.1404 . 
   n - benzylidenemethylamine 
   ( 0.1 ml , 0.81 mmol ) was added to a round - bottom flask containing na2so4 ( 0.57 g , 4.0 mmol ) and thf ( 8 ml ) , and then 
   sulfone anhydride 3a ( 0.19 g , 0.80 mmol ) was added . 
   the 
   reaction mixture was allowed to stir for 1.5 h , after which the na2so4 was removed by filtration and the solvent removed 
   in vacuo . 
   the residue was redissolved in etoac , transferred to a separatory 
   funnel , and washed with hcl ( 1.2 m or 10% ) and brine . 
   the combined 
   organic layers were dried over na2so4 , and the 
   solvent was removed in vacuo . 
   the crude acid was redissolved in a 
   mixture of toluene and methanol ( 13 ml:7 ml ) and cooled to 0 c . 
   to the cold solution , tmschn2 ( 0.81 ml , 1.6 mmol , 2 m solution 
   in hexanes ) 
   was added dropwise over a period of 5 min , and the reaction 
   was monitored by tlc for the disappearance of starting material . 
   after 
   2 h the solvent was removed in vacuo , and the resulting material 
   was purified by column chromatography ( 3060% etoac : hex ) to 
   yield 11c ( 0.20 g , 67% over the two steps ) as an amorphous 
   solid ( 50:50 etoac / hex , rf = 0.28 ) . 
   h nmr ( 400 mhz , cdcl3 )  7.88 ( dt , j = 8.6 , 2.2 hz , 2h ) , 7.727.63 ( m , 1h ) , 7.647.50 
   ( m , 2h ) , 7.367.23 ( m , 4h ) , 7.05 ( d , j = 7.2 
   hz , 2h ) , 5.31 ( s , 1h ) , 3.49 ( d , j = 18.4 ( gem ) hz , 
   1h ) , 3.15 ( d , j = 2.3 hz , 3h ) , 3.01 ( d , j = 18.5 ( gem ) hz , 1h ) , 2.58 ( s , 2h ) ; c nmr ( 100 mhz , 
   cdcl3 )  169.75 , 164.51 , 135.32 , 135.1 , 134.3 , 130.2 , 
   129.4 , 129.3 , 128.7 , 127.6 , 76.7 , 66.5 , 52.9 , 35.5 , 28.3 ; ir ( thin 
   film ) 1736 , 1690 ( c = o ) , 1177 , 1360 ( s = o ) cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c19h19no5sna 396.0882 , 
   found 396.0887 . 
   ester 11a ( 0.104 g , 0.23 
   mmol ) was dissolved in anhydrous meoh ( 12 ml ) , and magnesium turnings 
   ( 169 mg , 6.9 mmol , flame - dried under argon ) were added to the reaction 
   mixture . 
   the mixture was heated to 50 c for 15 min and then 
   to 64 c for 1.5 h , cooled to rt , poured into an erlenmeyer flask 
   containing 10% hcl ( 20 ml ) , and extracted with diethyl ether . 
   the 
   organic layer was dried over na2so4 , and the 
   solvent was removed in vacuo . 
   purification by flash chromatography 
   ( 3050% etoac / hex ) yielded 12a as an oil ( 0.54 
   g , 76% ) . 
   h nmr data for the major diastereomer ( 600 mhz , 
   cdcl3 ) :  7.417.33 ( m , 4h ) , 7.307.23 
   ( m , 3h ) , 7.187.13 ( m , 1h ) , 7.057.01 ( m , 2h ) , 5.11 
   ( d , j = 14.7 hz , 1h ) , 4.634.56 ( d , j = 5.4 hz , 1h ) , 3.64 ( s , 3h ) , 3.48 ( d , j = 14.9 hz , 1h ) , 3.07 ( m , 1h ) , 2.942.75 ( m , 2h ) . the h nmr data are in accordance with the literature . 
   ester 11b ( 75.4 mg , 0.163 
   mmol ) was dissolved in anhydrous meoh ( 12 ml ) , and magnesium turnings 
   ( 162 mg , 6.67 mmol , flame - dried under argon ) were added to the reaction 
   mixture . 
   the mixture was heated to 50 c for 15 min and then 
   to 64 c for 1.5 h , cooled to rt , poured into an erlenmeyer flask 
   containing 10% hcl ( 30 ml ) , and extracted with diethyl ether . 
   the 
   organic layer was dried over na2so4 , and the 
   solvent was removed in vacuo . 
   purification by flash chromatography 
   ( 3050% etoac / hex ) yielded 12b as an oil ( 0.35 
   g , 67% ) . 
   h nmr ( 400 mhz , cdcl3 )  6.42 
   ( t , j = 2.2 hz , 1h ) , 6.35 ( d , j = 
   2.3 hz , 2h ) , 4.83 ( d , j = 5.3 hz , 1h ) , 3.79 ( s , 6h ) , 
   3.74 ( s , 3h ) , 3.66 ( dt , j = 13.6 , 8.1 hz , 1h ) , 3.04 
   ( ddd , j = 9.6 , 7.0 , 5.2 hz , 1h ) , 2.84 ( dd , j = 17.2 , 9.8 hz , 1h ) , 2.76 ( d , j = 7.0 
   hz , 1h ) , 2.61 ( ddd , j = 13.6 , 8.3 , 5.2 hz , 1h ) , 1.541.37 
   ( m , 2h ) , 0.84 ( t , j = 7.4 hz , 3h ) ; c 
   nmr ( 100 mhz , cdcl3 )  173.1 , 172.7 , 161.5 , 142.0 , 
   104.5 , 100.1 , 64.2 , 55.5 , 52.6 , 45.9 , 42.5 , 33.8 , 20.2 , 11.3 ; hrms 
   ( esi - tof ) m / z [ m + na ] calcd for c17h23no5na 344.1474 , 
   found 344.1465 . to a 500 ml round - bottom flask were added 
   benzenesulfinic 
   acid sodium salt ( 5.1 g , 30.8 mmol ) , tert - butyl bromoacetate 
   ( 3.8 ml , 25.6 mmol ) , and 170 ml of ethanol . 
   the crude mixture 
   was suspended in et2o ( 150 ml ) and washed with water ( 2 
    150 ml ) and brine ( 150 ml ) . 
   the organic layer was dried over 
   sodium sulfate and concentrated in vacuo to yield 8 ( 6.31 
   g , 96% ) as a clear oil . 
   h nmr ( 300 mhz , cdcl3 )  7.90 ( m , 2h ) , 7.68 ( m , 1h ) , 7.55 ( m , 2h ) , 4.03 ( s , 2h ) , 
   1.33 ( s , 9h ) ; c nmr ( 75 mhz , cdcl3 )  
   161.2 , 138.8 , 134.1 , 129.1 , 128.5 , 83.6 , 62.0 , 27.6 . 
   these data are 
   in accordance with the literature . to a dry 250 ml round - bottom flask were 
   added 8 ( 6.31 g , 24.6 mmol ) , cesium carbonate ( 400 mg , 
   1.23 mmol ) , tert - butyl acrylate ( 3.6 ml , 24.6 mmol ) , 
   and 80 ml of acetonitrile . 
   the reaction mixture was heated to 50 c 
   overnight and then diluted with water and extracted with ethyl acetate 
   ( 3  100 ml ) . 
   the crude product 
   was purified on silica gel ( 20:80 etoac / hex ) to yield 3ba ( 4.91 g , 52% ) as an amorphous solid . 
   h nmr ( 300 mhz , 
   cdcl3 )  7.89 ( d , j = 7.3 hz , 2h ) , 
   7.68 ( m , 1h ) , 7.57 ( dd , j = 8.4 , 6.9 hz , 2h ) , 3.99 
   ( m , 1h ) , 2.24 ( m , 4h ) , 1.42 ( s , 9h ) , 1.35 ( s , 9h ) ; c 
   nmr ( 75 mhz , cdcl3 )  170.9 , 164.4 , 137.4 , 134.1 , 
   129.4 , 129.0 , 83.5 , 81.0 , 70.1 , 32.1 , 28.0 , 27.7 , 22.3 ; ir ( thin film ) 
   2979 , 1730 , 1309 , 1138 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c19h28o6sna 407.1504 , found 407.1502 . to a dry 250 ml round - bottom flask were 
   added 8 ( 3.00 g , 11.7 mmol ) , cesium carbonate ( 382 mg , 
   1.17 mmol ) , tert - butyl crotonate ( 1.90 ml , 11.7 mmol ) , 
   and 40 ml of acetonitrile . 
   the reaction mixture was heated to reflux 
   overnight and then diluted with water and extracted with ethyl acetate 
   ( 3  100 ml ) . 
   the crude product 
   was purified on silica gel ( 20:80 etoac / hex ) to yield 3ca ( 3.75 g , 80% ) as an amorphous solid ( mixture of diastereomers ) . 
   nmr data for one diastereomer : h nmr ( 600 mhz , cdcl3 )  7.90 ( m , 3h ) , 7.64 ( m , 2h ) , 7.53 ( m , 3h ) , 4.10 ( d , j = 8.0 hz , 1h ) , 2.71 ( m , 2h ) , 2.43 ( m , 1h ) , 1.42 ( s , 16h , 
   overlap with minor diastereomer ) , 1.27 ( s , 14h , overlap with minor 
   diastereomer ) , 1.12 ( d , j = 6.7 hz , 3h ) ; c nmr ( 150 mhz , cdcl3 )  170.7 , 164.4 , 138.4 , 134.0 , 
   129.2 , 128.9 , 83.3 , 80.8 , 73.7 , 39.9 , 29.6 , 28.1 , 27.6 , 17.1 ; ir ( thin 
   film ) 2980 , 1729 , 1325 , 1135 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c20h30o6sna 421.1661 , found 421.1653 . to a dry 250 ml round - bottom flask 
   were 
   added 8 ( 3.00 g , 11.7 mmol ) , cesium carbonate ( 382 mg , 
   1.17 mmol ) , tert - butyl methacrylate ( 1.90 ml , 11.7 
   mmol ) , and 40 ml of acetonitrile . 
   the reaction mixture was heated 
   to reflux for 48 h and then diluted with water and extracted with 
   ethyl acetate ( 3  100 ml ) . 
   the crude product was purified on silica gel ( 20:80 etoac / hex ) to 
   yield 3da ( 4.20 g , 90% ) as an amorphous solid ( mixture 
   of diastereomers ) . 
   nmr data for one diastereomer : h nmr 
   ( 400 mhz , cdcl3 )  7.89 ( m , 2h ) , 7.69 ( m , 1h ) , 7.58 
   ( m , 2h ) , 4.03 ( dd , j = 11.9 , 3.3 hz , 1h ) , 2.28 ( m , 
   2h ) , 1.99 ( m , 1h ) , 1.43 ( s , 9h ) , 1.37 ( s , 9h ) , 1.16 ( d , j = 6.6 hz , 3h ) ; c nmr ( 101 mhz , cdcl3 )  
   174.2 , 164.7 , 137.6 , 134.3 , 129.5 , 129.2 , 83.6 , 81.1 , 69.6 , 38.2 , 
   30.6 , 28.2 , 27.8 , 18.4 ; ir ( thin film ) 2978 , 2936 , 1727 , 1325 , 1138 
   cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c20h30o6sna 421.1661 , found 421.1662 . to a dry 250 ml flask 
   were added 3ba ( 4.91 g , 12.7 mmol ) , ch2cl2 ( 50 ml ) , and trifluoroacetic acid ( 50 ml ) . 
   the reaction mixture 
   was stirred for 1 h and then concentrated in vacuo and azeotropically 
   distilled with ch2cl2 ( 3  10 ml ) . 
   the 
   crude mixture was taken up in 45 ml of trifluoroacetic anhydride and 
   stirred overnight . 
   the reaction mixture was concentrated in vacuo 
   and azeotroped with toluene ( 3  10 ml ) . 
   filtering the off - white 
   solid with diethyl ether yielded 3b ( 3.01 g , 93% ) as 
   a white solid . 
   mp 122.2122.8 c ; h nmr ( 600 
   mhz , cd3cn )  7.97 ( m , 2h ) , 7.83 ( m , 1h ) , 7.70 ( m , 
   2h ) , 4.55 ( m , 1h ) , 3.06 ( m , 1h ) , 2.87 ( m , 1h ) , 2.50 ( m , 2h ) ; c nmr ( 150 mhz , cd3cn )  165.3 , 160.7 , 137.3 , 
   135.0 , 129.5 , 129.0 , 63.4 , 27.1 , 17.1 ; ir ( thin film ) 3098 , 2929 , 
   1816 , 1746 1322 , 1152 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c11h10o5sna 277.0147 , found 277.0145 . 
   to a dry 250 ml flask 
   were added 3ca ( 3.73 g , 9.30 mmol ) , ch2cl2 ( 50 ml ) , and trifluoroacetic acid ( 50 ml ) . 
   the reaction mixture 
   was stirred for 1 h and then concentrated in vacuo and azeotropically 
   distilled with ch2cl2 ( 3  10 ml ) . to the 
   crude mixture 
   was added acetic anhydride ( 33 ml ) , and the mixture 
   was taken up in 100 ml of toluene and stirred overnight . 
   the mixture 
   was concentrated in vacuo and azeotroped with benzene ( 3  10 
   ml ) . 
   trituration with diethyl ether afforded 3c ( 2.31 
   g , 92% ) as a solid ( mixture of diastereomers ) . 
   nmr data for one diastereomer : h nmr ( 600 mhz , cd3cn )  7.93 ( m , 2h ) , 7.84 
   ( m , 1h ) , 7.70 ( m , 2h ) , 4.40 ( m , 1h ) , 3.29 ( m , 1h ) , 3.03 ( m , 1h ) , 2.75 
   ( m , 1h ) , 1.18 ( m , 3h ) ; c nmr ( 151 mhz , cd3cn )  164.8 , 160.4 , 135.2 , 129.6 , 129.3 , 128.9 , 69.6 , 33.9 , 
   24.4 , 19.4 ; ir ( thin film ) 2991 , 2957 , 1814 , 1758 , 1311 , 1146 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c12h12o5sna 291.0293 , found 291.0303 . to a dry 250 ml flask 
   were added 3da ( 4.00 g , 10.0 mmol ) , ch2cl2 ( 50 ml ) , and trifluoroacetic acid ( 50 ml ) . 
   the reaction mixture 
   was stirred for 1 h and then concentrated in vacuo and azeotropically 
   distilled with ch2cl2 ( 3  10 ml ) . to the 
   crude mixture 
   were added acetic anhydride ( 33 ml ) and 100 ml of toluene , 
   and the resulting mixture was stirred overnight , concentrated in vacuo , 
   and azeotroped with benzene ( 3  10 ml ) . 
   trituration with diethyl 
   ether afforded 3d ( 2.53 g , 94% ) as a solid ( mixture of 
   diastereomers ) . 
   nmr data for one diastereomer : h nmr ( 400 
   mhz , cdcl3 )  7.90 ( m , 2h ) , 7.74 ( m , 1h ) , 7.62 ( m , 
   3h , overlap with minor diasteromer ) , 4.22 ( dd , j = 
   3.0 , 9.0 hz , 1h ) , 2.95 ( ddd , j = 2.1 , 6.1 , 15.2 hz , 
   1h ) , 2.762.58 ( m , 1h ) , 2.13 ( ddd , j = 6.2 , 
   13.2 , 15.2 hz , 1h ) , 1.44 ( s , 3h ) ; c nmr ( 100 mhz , cdcl3 )  167.8 , 160.3 , 137.1 , 135.2 , 129.8 , 129.4 , 64.8 , 
   32.6 , 25.5 , 16.4 ; ir ( thin film ) 3066 , 2970 , 1803 , 1755 , 1310 , 1154 
   cm ; hrms ( esi - tof ) m / z [ m + h2o + na ] calcd for c12h14o6sna 309.0409 , found 309.0402 . to a dry 10 ml flask 
   were added 
   2 ml of acetonitrile , triethyl orthoformate ( 0.11 ml , 0.63 mmol ) , 
   amine ( 0.39 mmol ) , and aldehyde ( 0.39 mmol ) . 
   anhydride 3b ( 0.39 mmol ) in 2 
   ml of acetonitrile was added , and the reaction mixture was stirred 
   for 30 min at room temperature and then refluxed for 4 h. the mixture 
   was cooled to room temperature and concentrated in vacuo . 
   the product 
   was purified by flash column chromatography ( conditions given for 
   each compound ) . to a dry 10 
   ml flask 
   was added 
   4 ml of acetonitrile , triethyl orthoformate ( 0.11 ml , 0.63 mmol ) , 
   the prepared imine ( 0.39 mmol ) , and anhydride 3b  d ( 0.39 mmol ) . 
   the reaction mixture was stirred for 30 min 
   at room temperature and then refluxed for 4 h. the mixture was cooled 
   to room temperature and concentrated in vacuo . 
   the residue was purified 
   by flash column chromatography ( conditions given for each compound ) . 
   general procedure c. the residue was purified 
   by flash column chromatography ( 70:30 etoac / hex , rf = 0.40 ) to yield 13a as a solid ( 105 mg , 
   80% ) . 
   mp 152.6153.1 c ; h nmr ( 300 mhz , cdcl3 )  7.91 ( m , 2h ) , 7.69 ( m , 1h ) , 7.59 ( m , 2h ) , 7.32 ( m , 
   3h ) , 7.04 ( m , 2h ) , 5.10 ( s , 1h ) , 3.36 ( ddd , j = 5.0 , 
   4.9 , 2.3 hz , 1h ) , 2.84 ( s , 3h ) , 2.73 ( m , 1h ) , 2.45 ( ddd , j = 17.9 ( gem ) , 6.6 , 4.6 hz , 1h ) , 2.08 ( m , 2h ) ; c nmr 
   ( 75 mhz , cdcl3 )  169.3 , 139.0 , 137.3 , 134.4 , 129.6 , 
   129.3 , 128.6 , 128.4 , 126.0 , 65.0 , 60.7 , 34.4 , 27.9 , 17.8 ; ir ( thin 
   film ) 3057 , 2930 , 1635 , 1302 , 1142 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c18h19no3sna 352.0983 , found 352.0973 . 
   general procedure b. the residue was purified 
   by flash column chromatography ( 60:40 etoac / hex , rf = 0.40 ) to yield 13b as a foam ( 117 mg , 
   84% ) . 
   h nmr ( 300 mhz , cdcl3 )  7.92 ( m , 
   2h ) , 7.747.64 ( m , 1h ) , 7.60 ( m , 2h ) , 7.30 ( m , 3h ) , 7.15 ( m , 
   2h ) , 5.40 ( s , 1h ) , 4.68 ( m , 1h ) , 3.28 ( m , 1h ) , 2.78 ( m , 1h ) , 2.49 
   ( ddd , j = 12.3 , 11.9 , 9.8 hz , 1h ) , 1.92 ( m , 2h ) , 
   1.31 ( d , j = 6.8 hz , 3h ) , 0.89 ( d , j = 7.0 hz , 3h ) ; c nmr ( 75 mhz , cdcl3 )  
   169.7 , 141.6 , 137.5 , 134.3 , 129.6 , 129.0 , 128.6 , 128.0 , 126.0 , 65.0 , 
   53.8 , 47.6 , 28.5 , 20.3 , 20.1 , 17.5 ; ir ( thin film ) 2967 , 2945 , 1641 , 
   1303 , 1143 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c20h23no3sna 380.1296 , found 380.1306 . 
   general procedure c. the residue was purified 
   by flash column chromatography ( 70:30 etoac / hex , rf = 0.48 ) to yield 13c as a foam ( 130 mg , 
   85% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.63 ( t , j = 7.4 hz , 1h ) , 7.39 ( m , 7h ) , 7.30 ( m , 3h ) , 7.25 ( t , j = 6.1 hz , 2h ) , 6.79 ( m , 2h ) , 5.76 ( d , j = 14.6 hz , 1h ) , 4.69 ( s , 1h ) , 3.22 ( d , j = 14.6 
   hz , 1h ) , 3.17 ( m , 1h ) , 3.07 ( m , 1h ) , 2.67 ( dd , j = 
   18.1 ( gem ) , 6.8 hz , 1h ) , 2.43 ( m , 1h ) , 2.18 ( m , 1h ) ; c nmr ( 150 mhz , cdcl3 )  169.0 , 138.8 , 137.0 , 136.1 , 
   134.0 , 129.5 , 129.4 , 129.3 , 128.6 , 128.6 , 128.5 , 127.7 , 125.9 , 63.9 , 
   57.2 , 47.6 , 28.3 , 16.1 ; ir ( thin film ) 3059 , 2936 , 1642 , 1307 , 1144 
   cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c24h23no3sna 428.1296 , found 428.1303 . 
   general procedure c. the residue was purified 
   by flash column chromatography ( 60:40 etoac / hex , rf = 0.40 ) to yield 13d as a foam ( 103 mg , 
   75% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.99 ( m , 
   2h ) , 7.69 ( m , 1h ) , 7.59 ( m , 2h ) , 7.30 ( m , 3h ) , 6.98 ( dd , j = 7.3 , 2.0 hz , 2h ) , 5.40 ( d , j = 2.4 hz , 1h ) , 4.95 
   ( dd , j = 17.5 , 2.6 hz , 1h ) , 3.38 ( td , j = 5.0 , 2.5 hz , 1h ) , 3.30 ( dd , j = 17.5 , 2.5 hz , 
   1h ) , 2.81 ( ddd , j = 17.7 , 10.5 , 6.9 hz , 1h ) , 2.52 
   ( ddd , j = 18.0 ( gem ) , 6.7 , 4.3 hz , 1h ) , 2.28 ( m , 
   1h ) , 2.12 ( m , 2h ) ; c nmr ( 150 mhz , cdcl3 ) 
    168.7 , 138.4 , 137.3 , 134.4 , 129.5 , 129.3 , 128.9 , 128.6 , 126.2 , 
   77.7 , 73.1 , 64.6 , 57.9 , 34.3 , 28.3 , 17.3 ; ir ( thin film ) 3303 , 3055 , 
   1650 , 1267 , 1148 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c20h19no3sna 376.0983 , found 376.0977 . 
   general procedure c. the residue was purified 
   by flash column chromatography ( 60:40 etoac / hex , rf = 0.40 ) to yield 13e as a foam ( 124 mg , 
   89% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.92 ( m , 
   2h ) , 7.71 ( m , 1h ) , 7.60 ( m hz , 2h ) , 7.29 ( m , 3h ) , 6.96 ( dd , j = 7.5 , 1.9 hz , 2h ) , 5.83 ( dddd , j = 17.7 , 
   10.5 , 8.2 , 4.3 hz , 1h ) , 5.21 ( m , 2h ) , 5.11 ( s , 1h ) , 4.86 ( ddd , j = 15.0 , 4.3 , 2.0 hz , 1h ) , 3.31 ( td , j = 4.7 , 1.8 hz , 1h ) , 3.002.82 ( m , 2h ) , 2.54 ( ddd , j = 18.0 ( gem ) , 6.8 , 3.7 hz , 1h ) , 2.19 ( m , 2h ) ; c nmr ( 151 mhz , cdcl3 )  169.1 , 139.1 , 137.3 , 134.4 , 
   132.4 , 129.5 , 129.3 , 128.7 , 128.4 , 126.0 , 118.8 , 64.4 , 57.2 , 47.9 , 
   28.0 , 17.1 ; ir ( thin film ) 3054 , 2988 , 1641 , 1307 , 1148 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c20h21no3sna 378.1140 , 
   found 378.1136 . 
   general procedure c. the residue was purified 
   by flash column chromatography ( 70:30 etoac / hex , rf = 0.40 ) to yield 13f as a foam ( 110 mg , 
   72% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.92 ( m , 
   2h ) , 7.67 ( t , j = 7.5 hz , 1h ) , 7.56 ( m , 2h ) , 7.32 
   ( m , 2h ) , 7.27 ( m , 3h ) , 7.19 ( m , 5h ) , 5.54 ( s , 1h ) , 3.48 ( m , 1h ) , 2.95 
   ( m , 1h ) , 2.66 ( dt , j = 18.1 ( gem ) , 6.2 hz , 1h ) , 2.20 
   ( m , 2h ) ; c nmr ( 150 mhz , cdcl3 )  169.8 , 
   142.3 , 139.7 , 137.2 , 134.4 , 129.6 , 129.2 , 129.1 , 128.6 , 128.3 , 127.3 , 
   127.0 , 126.2 , 64.9 , 62.2 , 28.8 , 18.2 ; ir ( thin film ) 3066 , 3008 , 2946 , 
   1654 , 1304 , 1143 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c23h21no3sna 414.1140 , found 414.1131 . 
   general procedure c. the residue was purified 
   by flash column chromatography ( 70:30 etoac / hex , rf = 0.46 ) to yield 13 g as a foam ( 126 mg , 
   91% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.91 ( m , 
   2h ) , 7.69 ( m , 1h ) , 7.59 ( t , j = 7.8 hz , 2h ) , 7.31 
   ( dd , j = 8.4 , 6.6 hz , 2h ) , 7.25 ( m , 1h ) , 7.05 ( d , j = 7.4 hz , 2h ) , 5.22 ( s , 1h ) , 3.95 ( dtd , j = 13.6 , 6.8 , 3.3 hz , 1h ) , 3.32 ( td , j = 5.0 , 2.0 
   hz , 1h ) , 2.81 ( m , 1h ) , 2.43 ( m , 2h ) , 1.99 ( m , 2h ) , 1.61 ( m , 2h ) , 0.87 
   ( t , j = 7.4 hz , 3h ) ; c nmr ( 150 mhz , 
   cdcl3 )  169.2 , 139.7 , 137.4 , 134.3 , 129.6 , 129.2 , 
   128.5 , 128.3 , 126.1 , 64.7 , 57.9 , 48.0 , 28.0 , 20.3 , 17.6 , 11.3 ; ir 
   ( thin film ) 2967 , 2929 , 2871 , 1639 , 1308 , 1147 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c20h23no3sna 380.1296 , 
   found 380.1290 . 
   general 
   procedure b. the residue was purified by flash column chromatography 
   ( 60:40 etoac / hex , rf = 0.50 ) to yield 13h as an orange amorphous solid ( 101 mg , 68% ) . 
   h nmr ( 300 mhz , cdcl3 )  7.93 ( dd , j = 7.2 , 1.6 hz , 2h ) , 7.70 ( m , 1h ) , 7.60 ( dd , j = 
   8.2 , 6.6 hz , 2h ) , 7.32 ( m , 5h ) , 6.37 ( dd , j = 16.0 , 
   1.2 hz , 1h ) , 6.07 ( dd , j = 15.8 , 6.4 hz , 1h ) , 4.94 
   ( dt , j = 6.6 , 1.6 hz , 1h ) , 4.66 ( m , 1h ) , 3.35 ( td , j = 6.4 , 2.0 hz , 1h ) , 2.68 ( dt , j = 17.2 , 
   7.0 hz , 1h ) , 2.40 ( dt , j = 17.2 , 7.1 hz , 1h ) , 2.09 
   ( dt , j = 14.4 , 7.2 hz , 1h ) , 1.99 ( dt , j = 14.4 , 7.2 hz , 1h ) , 1.33 ( d , j = 6.8 hz , 3h ) , 
   1.18 ( d , j = 6.9 hz , 3h ) ; c nmr ( 75 
   mhz , cdcl3 )  169.7 , 137.6 , 135.4 , 134.2 , 132.0 , 
   129.8 , 129.6 , 128.8 , 128.6 , 128.4 , 126.5 , 63.5 , 51.8 , 47.3 , 29.1 , 
   20.7 , 20.2 , 18.78 ; ir ( thin film ) 3059 , 2975 , 1639 , 1446 , 1305 , 1145 
   cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c22h25no3sna 406.1453 , found 406.1447 . 
   general procedure b. the residue was purified 
   by flash column chromatography ( 60:40 etoac / hex , rf = 0.42 ) to yield 13i as a foam ( 96 mg , 
   69% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.92 ( d , j = 8.4 hz , 2h ) , 7.69 ( t , j = 7.4 hz , 1h ) , 
   7.60 ( t , j = 7.8 hz , 2h ) , 6.97 ( d , j = 8.6 hz , 2h ) , 6.84 ( m , 2h ) , 5.18 ( m , 1h ) , 3.93 ( m , 1h ) , 3.77 ( s , 
   3h ) , 3.30 ( m , 1h ) , 2.81 ( m , 1h ) , 2.45 ( m , 2h ) , 2.01 ( m , 2h ) , 1.61 
   ( m , 2h ) , 0.88 ( t , j = 7.5 hz , 3h ) ; c 
   nmr ( 150 mhz , cdcl3 )  169.2 , 159.5 , 134.2 , 131.5 , 
   129.5 , 128.6 , 127.3 , 114.5 , 105.0 , 64.9 , 57.5 , 55.3 , 48.0 , 28.1 , 20.3 , 
   17.6 , 11.3 ; ir ( thin film ) 2964 , 2920 , 1633 , 1250 , 1144 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c21h25no4sna 410.1402 , 
   found 410.1400 . 
   general procedure c. the residue was purified 
   by flash column chromatography ( 60:40 etoac / hex , rf = 0.40 ) to yield 13j as a foam ( 133 mg , 
   87% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.89 ( m , 
   2h ) , 7.69 ( m , 1h ) , 7.59 ( m , 2h ) , 7.28 ( m , 2h ) , 7.01 ( m , 2h ) , 5.21 
   ( s , 1h ) , 3.92 ( ddd , j = 13.6 , 9.0 , 7.4 hz , 1h ) , 3.27 
   ( td , j = 5.1 , 2.2 hz , 1h ) , 2.78 ( ddd , j = 17.4 , 10.1 , 6.8 hz , 1h ) , 2.41 ( m , 2h ) , 1.96 ( m , 2h ) , 1.59 ( m , 
   2h ) , 0.86 ( t , j = 7.4 hz , 3h ) ; c nmr 
   ( 150 mhz , cdcl3 )  169.2 , 138.3 , 137.2 , 134.4 , 134.2 , 
   129.6 , 129.4 , 128.5 , 127.5 , 64.6 , 57.5 , 48.0 , 28.1 , 20.3 , 17.9 , 11.3 ; 
   ir ( thin film ) 2964 , 2937 , 1641 , 1306 , 1146 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c20h22clno3sna 
   414.0907 , found 414.0921 . 
   general procedure c. the residue was purified 
   by flash column chromatography ( 60:40 etoac / hex , rf = 0.42 ) to yield 13k as a foam ( 92 g , 61% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.95 ( d , j = 8.4 hz , 2h ) , 7.70 ( t , j = 7.4 hz , 1h ) , 
   7.61 ( t , j = 7.9 hz , 2h ) , 7.24 ( m , 1h ) , 7.17 ( m , 
   2h ) , 7.05 ( d , j = 7.8 hz , 1h ) , 5.51 ( s , 1h ) , 3.97 
   ( m , 1h ) , 3.14 ( m , 1h ) , 2.94 ( m , 1h ) , 2.53 ( dd , j = 
   18.3 ( gem ) , 7.4 hz , 1h ) , 2.42 ( m , 1h ) , 2.34 ( m , 2h ) , 2.07 ( m , 1h ) , 
   1.98 ( m , 1h ) , 1.69 ( m , 2h ) , 1.14 ( t , j = 7.5 hz , 
   3h ) , 0.92 ( t , j = 7.4 hz , 3h ) ; c nmr 
   ( 151 mhz , cdcl3 )  168.9 , 141.1 , 137.6 , 136.1 , 134.3 , 
   129.63 , 129.60 , 128.63 , 128.60 , 126.5 , 126.1 , 62.5 , 54.2 , 48.2 , 27.3 , 
   24.3 , 20.4 , 16.3 , 15.4 , 11.5 ; ir ( thin film ) 3006 , 2966 , 1639 , 1300 , 
   1144 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c22h27no3sna 408.1609 , found 408.1620 . 
   general procedure b. the residue was purified 
   by flash column chromatography ( 80:20 etoac / hex , rf = 0.50 ) to yield 13l as a foam ( 104 mg , 
   64% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.92 ( m , 
   2h ) , 7.69 ( t , j = 7.1 hz , 1h ) , 7.60 ( m , 2h ) , 6.32 
   ( s , 1h ) , 6.16 ( d , j = 2.1 hz , 2h ) , 5.14 ( d , j = 2.1 hz , 1h ) , 3.95 ( ddd , j = 13.4 , 9.6 , 
   6.5 hz , 1h ) , 3.72 ( s , 6h ) , 3.34 ( td , j = 4.8 , 1.9 
   hz , 1h ) , 2.79 ( m , 1h ) , 2.46 ( m , 2h ) , 2.03 ( m , 2h ) , 1.63 ( m , 2h ) , 0.89 
   ( t , j = 7.4 hz , 3h ) ; c nmr ( 150 mhz , 
   cdcl3 )  169.1 , 161.5 , 142.3 , 137.4 , 134.2 , 129.6 , 
   128.6 , 104.2 , 99.5 , 64.6 , 58.0 , 55.4 , 48.2 , 28.0 , 20.3 , 17.7 , 11.3 ; 
   ir ( thin film ) 2962 , 2937 , 1641 , 1594 , 1306 , 1145 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c22h27no5sna 440.1508 , 
   found 440.1517 . 
   general procedure b. the residue was purified 
   by flash column chromatography ( 70:30 etoac / hex , rf = 0.35 ) to yield 13 m as a foam ( 101 mg , 
   75% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.88 ( d , j = 7.2 hz , 2h ) , 7.65 ( m , 1h ) , 7.56 ( t , j = 7.7 hz , 2h ) , 7.27 ( dd , j = 1.9 , 1.0 hz , 1h ) , 
   6.24 ( m , 1h ) , 6.10 ( m , 1h ) , 5.16 ( d , j = 2.9 hz , 
   1h ) , 3.78 ( ddd , j = 13.6 , 9.6 , 6.4 hz , 1h ) , 3.59 
   ( td , j = 6.1 , 3.1 hz , 1h ) , 2.71 ( m , 2h ) , 2.43 ( dt , j = 17.5 , 6.6 hz , 1h ) , 2.09 ( m , 2h ) , 1.58 ( m , 1h ) , 1.49 
   ( m , 1h ) , 0.85 ( t , j = 7.4 hz , 3h ) ; c 
   nmr ( 150 mhz , cdcl3 )  169.4 , 151.3 , 143.0 , 137.3 , 
   134.2 , 129.5 , 128.5 , 110.6 , 108.4 , 61.8 , 52.9 , 47.8 , 28.5 , 20.4 , 19.0 , 
   11.3 ; ir ( thin film ) 2965 , 2933 , 2875 , 1647 , 1503 , 1306 , 1148 cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c18h21no4sna 370.1089 , found 370.1076 . 
   the residue was purified by flash column chromatography 
   ( 70:30 etoac / hex , rf = 0.35 ) to yield 14 as a solid ( 111 mg , 87% ) . 
   mp 127.4128.1 c ; h nmr ( 600 mhz , cdcl3 )  7.99 ( m , 2h ) , 7.74 
   ( m , 1h ) , 7.65 ( m , 2h ) , 7.35 ( dd , j = 8.4 , 7.1 hz , 
   2h ) , 7.28 ( m , 1h ) , 7.05 ( d , j = 6.8 hz , 2h ) , 5.21 
   ( s , 1h ) , 3.45 ( d , j = 6.9 hz , 1h ) , 2.91 ( s , 3h ) , 
   2.53 ( m , 1h ) , 2.45 ( dd , j = 15.7 , 5.3 hz , 1h ) , 2.11 
   ( dd , j = 15.8 , 11.6 hz , 1h ) , 0.91 ( d , j = 6.7 hz , 3h ) ; c nmr ( 150 mhz , cdcl3 )  
   171.1 , 139.3 , 137.0 , 134.5 , 129.6 , 129.4 , 129.1 , 127.9 , 125.3 , 73.7 , 
   60.3 , 38.1 , 34.4 , 29.1 , 22.4 ; ir ( thin film ) 2912 , 1658 , 1305 , 1130 
   cm ; hrms ( esi - tof ) m / z 
   the residue was purified by flash column chromatography 
   ( 80:20 etoac / hex , rf = 0.35 ) to yield 15 as a white solid ( 169 mg , 79% ) . 
   mp 143.7144.3 c ; h nmr ( 600 mhz , cdcl3 )  7.70 ( d , j = 7.5 hz , 2h ) , 7.50 ( t , j = 7.4 hz , 1h ) , 
   7.37 ( t , j = 7.7 hz , 2h ) , 5.89 ( s , 2h ) , 5.31 ( d , j = 9.5 hz , 1h ) , 4.22 ( ddd , j = 13.4 , 9.5 , 
   3.6 hz , 1h ) , 3.72 ( s , 3h ) , 3.71 ( s , 6h ) , 2.48 ( m , 4h , nch3 and 1 methylene h ) , 2.40 ( m , 1h ) , 1.84 ( m , 1h ) , 1.27 ( d , j = 6.9 hz , 3h ) ; c nmr ( 150 mhz , cdcl3 )  173.1 , 161.4 , 158.6 , 137.4 , 133.4 , 128.50 , 128.48 , 106.8 , 
   90.6 , 61.9 , 55.6 , 55.2 , 51.9 , 35.0 , 31.8 , 29.3 , 17.1 ; ir ( thin film ) 
   3006 , 2939 , 1614 , 1286 , 1134 cm ; hrms ( esi - tof ) m / z [ m + h ] calcd for c22h28no6s 434.1637 , found 434.1649 . 
   allylamine ( 0.29 ml , 3.8 mmol ) and trans - cinammaldehyde 
   ( 0.53 ml , 4.2 mmol ) were added to a round - bottom flask containing 
   thf ( 38 ml ) and na2so4 ( 3.3 g , 23.0 mmol ) , and 
   the mixture was allowed to stir for 1 h. the anhydride ( 0.92 g , 3.8 
   mmol ) was added , and the resulting mixture was allowed to stir for 
   2 h. the na2so4 was filtered off , and the solvent 
   was evaporated in vacuo . 
   the residue was 
   triturated with hexanes , transferred to a fritted funnel , and washed 
   in portions with hexanes five times ( 5 ml ) and two times with a 9:1 
   mixture of cold hexanes and chcl3 ( 10 ml total ) , yielding 
   1.2 g of an off - white solid , which was 85% pure by nmr . 
   a 
   portion of the resulting acid ( 0.885 g , 2.2 mmol ) was redissolved 
   in anhydrous toluene and methanol ( 60 ml:30 ml ) , and tmschn2 ( 2.2 ml , 4.4 mmol , 2 m in hexanes ) was added at 0 c dropwise 
   over a period of 5 min . 
   the mixture was allowed to stir for 1.5 h 
   and monitored by tlc for disappearance of the starting material . 
   the 
   solvent was removed in vacuo , and the crude mixture was purified by 
   flash column chromatography ( etoac / hex 3060% ) , yielding 17 ( 0.85 g , 92% ) as an amorphous solid ( 50:50 etoac / hex , rf = 0.44 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.987.89 ( m , 2h ) , 7.817.56 ( m , 3h ) , 
   7.417.24 ( m , 5h ) , 6.54 ( d , j = 15.8 hz , 1h ) , 
   5.845.72 ( m , 2h ) , 5.345.25 ( m , 2h ) , 5.02 ( d , j = 8.4 hz , 1h ) , 4.40 ( ddt , j = 15.3 , 4.7 , 
   1.7 hz , 1h ) , 3.713.42 ( m , 3h ) , 3.443.27 ( m , 2h ) , 3.13 
   ( d , j = 18.2 ( gem ) hz , 1h ) ; c nmr ( 150 
   mhz , cdcl3 )  169.4 , 165.3 , 136.7 , 135.8 , 135.2 , 
   135.0 , 131.7 , 130.6 , 129.3 , 128.9 , 128.9 , 126.8 , 121.9 , 119.4 , 76.1 , 
   62.0 , 53.4 , 43.8 , 35.6 . 
   ir ( thin film ) 1736 , 1715 , 1694 ( c = o ) , 
   1309 , 1148 ( s = o ) cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c23h23no5sna 448.1195 , found 448.1195 . 
   ester 17 ( 0.602 g , 1.41 mmol ) was dissolved in anhydrous benzene 
   ( 114 ml ) , which was degassed by bubbling with argon for approximately 
   5 min . 
   then grubbs second - generation catalyst ( 35 mg , 3 mol % ) was 
   added , and the mixture was heated to reflux for 9 h. the solvent was 
   evaporated in vacuo , and the residue was redissolved in etoac ( 30 
   ml ) . 
   saturated nh4cl ( 10 ml ) was added , and the mixture 
   was allowed to stir for 30 min . 
   the mixture was transferred to a separtory 
   funnel , and the organic layer was washed with brine , dried over na2so4 , and then purified ( etoac / hex 3060% ) , 
   yielding 18 ( 0.39 g , 86% ) as an amorphous solid ( 50:50 
   etoac / hex , rf = 0.16 ) . 
   h nmr 
   ( 600 mhz , cdcl3 )  8.027.93 ( m , 2h ) , 7.74 
   ( td , j = 7.4 , 1.3 hz , 1h ) , 7.61 ( t , j = 7.9 hz , 2h ) , 5.90 ( dq , j = 6.0 , 2.1 hz , 1h ) , 
   5.55 ( dq , j = 6.2 , 2.2 hz , 1h ) , 5.38 ( tt , j = 4.3 , 1.8 hz , 1h ) , 4.33 ( ddt , j = 15.7 , 
   4.2 , 2.1 hz , 1h ) , 3.783.67 ( m , 2h ) , 3.62 ( s , 3h ) , 3.00 ( d , j = 15.7 hz , 1h ) ; c nmr ( 150 mhz , cdcl3 )  172.8 , 165.7 , 136.9 , 134.9 , 130.6 , 130.3 , 129.3 , 
   129.2 , 79.0 , 70.1 , 53.3 , 50.7 , 39.5 ; ir ( thin film ) 1735 , 1716 , 1687 
   ( c = o ) , 1311 , 1148 ( s = o ) cm ; hrms 
   ( esi - tof ) m / z [ m + na ] calcd for c15h15no5sna 344.0569 , 
   found 344.0568 . 
   alkene 18 ( 0.25 g , 0.77 mmol ) was dissolved in anhydrous meoh ( 30 
   ml ) , and the reaction mixture was degassed by bubbling with argon 
   for 5 min . 
   then pd / c ( 45 mg ) was added and h2 was bubbled 
   into the reaction flask , and the mixture was allowed to stir for 3 
   h ( monitored by tlc ) . 
   the pd / c was filtered off and washed with etoac 
   ( 3  10 ml ) . 
   the solvent was removed in vacuo , yielding 19 ( 0.246 g , 99% ) as an amorphous solid ( 50:50 etoac / hex , rf = 0.1 ) . 
   h nmr ( 600 mhz , cdcl3 )  7.987.90 ( m , 2h ) , 7.797.70 ( m , 1h ) , 
   7.60 ( dd , j = 8.5 , 7.3 hz , 2h ) , 4.61 ( dd , j = 9.7 , 5.9 hz , 1h ) , 3.72 ( s , 3h ) , 3.623.49 ( m , 
   2h ) , 3.17 ( d , 
   j = 17.1 hz , 1h ) , 3.153.05 
   ( m , 1h ) , 2.071.93 ( m , 2h ) , 1.91 ( dtd , j = 
   12.2 , 6.0 , 3.9 hz , 1h ) , 1.25 ( dq , j = 12.6 , 9.3 hz , 
   1h ) ; c nmr ( 150 mhz , cdcl3 )  170.6 , 
   166.0 , 134.9 , 130.3 , 130.2 , 129.2 , 75.6 , 63.9 , 53.4 , 42.1 , 39.4 , 28.5 , 
   25.8 ; ir ( thin film ) 1734 , 1686 ( c = o ) , 1146 ( s = o ) cm ; hrms ( esi - tof ) m / z [ m + na ] calcd for c15h17no5sna 346.0725 , found 346.0730 . 
   to sulfone 19 ( 0.10 g , 0.31 
   mmol ) dissolved in 3 ml of chcl3 was added dbu ( 70 l , 
   0.46 mmol ) , and the reaction mixture was stirred overnight . the mixture 
   was concentrated in vacuo and purified by flash chromatography ( 70:30 
   etoac / hex , rf = 0.40 ) to yield 20 as a colorless oil ( 0.047 g , 84% ) . 
   h nmr ( 600 mhz , cdcl3 )  3.72 ( s , 3h ) , 3.58 ( t , j = 7.1 
   hz , 2h ) , 3.52 ( m , 2h ) , 2.93 ( m , 2h ) , 2.40 ( p , j = 
   7.4 hz , 2h ) ; c nmr ( 150 mhz , cdcl3 )  
   172.8 , 164.0 , 161.6 , 98.6 , 51.0 , 41.5 , 41.2 , 26.6 , 25.6 . these data 
   ester 18 ( 50 mg , 0.16 mmol ) 
   was dissolved in 2 ml of chcl3 , and dbu ( 36 l , 0.24 
   mmol ) was added . 
   after 90 min , 
   the solvent evaporated in vacuo , and the crude mixture was purified 
   by flash chromatography ( 20:80 etoac / hex , rf = 0.45 ) , yielding 21 as an oil ( 12 mg , 41% ) . 
   h nmr ( 600 mhz , cdcl3 )  7.04 ( d , j = 3.4 hz , 1h ) , 6.47 ( t , j = 3.5 hz , 1h ) , 6.17 ( d , j = 3.1 hz , 1h ) , 4.20 ( dd , j = 9 , 3 hz , 
   1h ) , 3.78 ( s , 3h ) , 3.48 ( dd , j = 19.8 ( gem ) , 3.6 
   hz , 1h ) , 3.19 ( dd , j = 18.6 ( gem ) , 9 hz , 1h ) ; c nmr ( 150 mhz , cdcl3 )  170.6 , 169.6 , 136.1 , 
   119.2 , 112.2 , 106.6 , 52.9 , 38.1 , 38.0 . 
   alkene 20 ( 47 mg , 0.25 mmol ) 
   was dissolved in 2.2 ml of methanol 
   under an atmosphere of argon , and 10% pd / c ( 14 mg ) was added to the 
   vial . 
   the flask was purged with h2 gas via a balloon , and 
   the reaction mixture was stirred under an atmosphere of h2 overnight . 
   the reaction vessel was purged with argon , and then the 
   mixture was filtered through celite and concentrated to yield 22 as an oil ( 45 mg , 99% ) . 
   h nmr ( 600 mhz , cdcl3 )  4.09 ( ddd , j = 9.7 , 9.1 , 3.8 hz , 
   1h ) , 3.69 ( s , 3h ) , 3.57 ( q , j = 9.3 hz , 1h ) , 3.38 
   ( td , j = 8.5 , 4.8 hz , 1h ) , 3.03 ( t , j = 11.7 hz , 1h ) , 2.78 ( d , j = 8.9 hz , 2h ) , 2.05 
   ( q , j = 9.5 hz , 1h ) , 1.95 ( m , 1h ) , 1.82 ( m , 1h ) , 
   1.24 ( m , 1h ) ; c nmr ( 150 mhz , cdcl3 )  
   174.0 , 172.2 , 62.7 , 51.9 , 41.8 , 39.9 , 36.0 , 27.4 , 26.0 . these data
summary: sulfone - substituted 
   - and -lactams have been prepared 
   in a single step with high diastereoselectivity . 
   sulfonylglutaric 
   anhydrides produce intermediates that readily decarboxylate to provide 
   -lactams with high diastereoselectivity . 
   substituents at the 
   3- or 4-position of the glutaric anhydride induce high levels of stereocontrol . 
   sulfonylsuccinic anhydrides produce intermediate carboxylic acids 
   that can be trapped as methyl esters or allowed to decarboxylate under 
   mild conditions . 
   this method has been applied to a short synthesis 
   of the pyrrolizidine alkaloid ( )-isoretronecanol .