the ubiquitous use of heterocycles in the pharmaceutical , agrochemical as well as in the dye and fine - chemical industries has led to the establishment of numerous strategies for their synthesis and functionalisation . stereodefined heterocycles are also significant components of numerous biologically active natural products . as a result of the widespread prevalence of heterocyclic motifs in synthetic chemistry , alongside the continued drive for efficient , selective synthetic protocols within the chemical community , there is an ongoing requirement for novel asymmetric syntheses of heterocyclic scaffolds . for example , the oxazolidin-4-one core is found in the natural products synoxazolidinone a and b which were isolated from s. pulmonaria and exhibit antibiotic and antifungal activity at low concentrations ( figure 1 ) . in addition , oxazolidin-4-ones are found in lipoxazolidinones a , b , and c isolated from a marine actinomycete strain . these naturally occurring oxazolidin-4-ones also exhibit antibacterial activity comparable with the commercial antibacterial agent linezolid ( zyvox ) that contains a structurally related oxazolidin-2-one core . therefore , the development of a synthetic strategy for the asymmetric generation of heterocyclic scaffolds of this type is a worthwhile goal . in this manuscript , we describe an isothiourea - catalysed formal [ 3 + 2 ] cycloaddition using both racemic and enantioenriched oxaziridines to form stereodefined oxazolidin-4-ones . building on birman and okamoto s introduction of isothiourea catalysts for kinetic resolutions we have recently established , alongside romo , isothiourea lewis base catalysis for the preparation of a range of synthetically relevant heterocyclic scaffolds . substituted thfs , dihydrobenzofurans and pyrrolidines have been accessed by an asymmetric intramolecular michael addition / lactonisation process . in addition , stereodefined anti--lactams and dihydropyranones were obtained by related intermolecular michael addition / cyclisation protocols . this methodology was extended using a strategic phsh elimination as part of a cascade process for the synthesis of substituted pyrones and functionalised pyridines . additionally , asymmetric formal [ 2 + 2 ] cycloadditions employing n - sulfonyl imines to form anti--lactams have been studied . however , to date , formal [ 3 + 2 ] cycloaddition processes catalysed by isothioureas have not been developed . oxaziridines have previously been reported as electrophiles for the synthesis of oxazolidin-4-ones by ye and co - workers using ketenes in the presence of either n - heterocyclic carbene ( nhc ) precatalyst 1 or cinchona alkaloids . the ,-disubstituted oxazolidin-4-ones were isolated in good yield and with high diastereo- and enantioselectivity ( scheme 1a ) , although this process is somewhat limited due to the use of synthetically challenging ketenes and their precursors . more recently , feng described chiral bisguanidinium salt 2 for the asymmetric oxyamination of azlactones with concurrent kinetic resolution of the oxaziridine ( scheme 1 b ) . building upon these precedents , herein we report our results on the isothiourea - catalysed asymmetric formal [ 3 + 2 ] cycloaddition of homoanhydrides and oxaziridines to form stereodefined oxazolidin-4-ones ( scheme 1c ) and their subsequent derivatisations . formal [ 3 + 2 ] intermolecular cycloadditions for the synthesis of oxazolidin-4-ones catalysed by a ) nhc precatalyst 1 ; b ) bisguanidinium salt 2 ; c ) hyperbtm 3 . our investigation began with the lewis base - catalysed reaction of commercially available phenylacetic acid 4 with racemic oxaziridine 5 ( table 1 , conditions a ) . treatment of the acid with pivaloyl chloride and ipr2net to form a mixed anhydride in situ followed by addition of ( 2s,3r)-hyperbtm 3 and oxaziridine 5 gave high conversion into the desired [ 3 + 2 ] oxazolidin-4-one product 6 , with a small amount of imine 14 and -lactam 15 ( derived from a previously disclosed intramolecular formal [ 2 + 2 ] cycloaddition of an ammonium enolate and imine 14 ) also observed by h nmr spectroscopy ( table 1 , entry 1 ) . however , imine 14 was difficult to remove from the desired product by column chromatography , resulting in contaminated oxazolidin-4-ones . to probe the origin of imine 14 , control experiments demonstrated that treating oxaziridine 5 in ch2cl2 with ipr2net ( 1 equiv ) led to the formation of ipr2(et)n - oxide and imine 14 . to prevent this undesired imine formation through oxidation of the base a number of alternative bases disappointingly , 2,6-lutidine and cs2co3 gave comparable amounts of imine 14 ( entries 2 and 3 ) . in the reaction with cs2co3 ( entry 3 ) , imine formation is presumably derived from reaction of oxaziridine 5 with chloride ions[7b ] generated from the reaction of phenylacetic acid 4 with pivaloyl chloride to form the  activated  mixed anhydride . to overcome this problem and remove the need for an activation step , homoanhydride 7 was used in place of phenylacetic acid and assessed under similar reaction conditions ( table 1 , conditions b ) . pleasingly , this alternative ammonium enolate precursor resulted in formation of oxazolidin-4-one 6 exclusively in high yield with excellent enantiocontrol , however lower levels of diastereoselectivity were obtained ( entry 4 ) . the oxazolidin-4-one diastereomeric mixture 6 a and 6 b was reduced using lialh4 to give diol 16 in good yield maintaining stereointegrity ( scheme 2 ) , confirming that the configuration at c(5 ) is equivalent in both the syn- and anti - diastereomers formed . the absolute configuration was determined by comparison of the specific rotation of diol 16 with literature values ( see the supporting information for details ) . to assess the effect of the oxaziridine on the stereochemical outcome of the process , alternative oxaziridines were investigated using phenylacetic anhydride 7 as the standard ammonium enolate precursor ( entries 57 ) . aromatic halogen substitution in the ortho- and para - position was examined under the optimised conditions and led to high yields of the desired [ 3 + 2 ] products 11 and 12 , both in approximately 55:45 d.r . but with slightly reduced levels of enantiocontrol for both diastereoisomers . gratifyingly , the scope of the process could be extended with regards to the n - substituent . replacing the n - tosyl group with an n - nosyl led to the formation of oxazolidin-4-one 13 in high yield , however slightly reduced ee values were obtained for the syn- and anti - products . [ c ] determined by hplc analysis . [ d ] conditions a. [ e ] conditions b. lialh4 reduction of oxazolidin-4-one 6 . these reaction conditions were next applied to a range of homoanhydrides to assess the scope of the reaction ( table 2 ) . anhydrides with both electron - withdrawing and -donating aromatic substituents were tolerated , giving a range of oxazolidin-4-ones in high yields with approximately 50:50 d.r . , but with excellent levels of enantiocontrol observed for each diastereoisomer 6 , 17 and 18 ( up to 99 % ee ) . extended aromatic systems and aromatic groups bearing substituents in the ortho- , meta- and para - position also participated well under the previously optimised reaction conditions giving oxazolidin-4-ones 1922 in good yields again with excellent levels of ee for both diastereoisomers . 3-thiophenylacetic anhydride led to isolation of oxazolidin-4-one 23 in 79 % yield but lower levels of ee were obtained for both the syn- and anti - diastereoisomer ( 87 and 81 % , respectively ) . pleasingly , the reaction was extended beyond aromatic substitution patterns to include alkenyl oxazolidin-4-one 24 , obtained in good yield and high ee ( syn- and anti - diastereoisomer ) . unexpectedly , p - trifluoromethyl substitution gave oxazolidin-4-one 25 in 49:51 d.r.anti/syn , with both diastereoisomers formed with low levels of enantioselectivity ( 43 % eeanti , 36 % eesyn ) . [ c ] determined by hplc analysis . whilst these results are synthetically relevant , their utility for the synthesis of oxazolidin-4-ones is partially limited due to the diastereomeric mixtures of heterocycles obtained . although this methodology is applicable to the synthesis of enantioenriched diols ( scheme 2 ) , further investigations sought to investigate the cause of low diastereocontrol in this process allowing selective access to either syn and anti diastereoisomers . the conversion of ( )-oxaziridine 5 into product 6 under the standard reaction conditions was monitored over time by h nmr spectroscopy and the ee of unreacted oxaziridine 5 and oxazolidin-4-one 6 was analysed by chiral hplc analysis ( table 3 ) . notably , over the early part of the reaction the d.r . of 6 remains fairly constant with the initial d.r . of 78:22 anti / syn at 1 min , reducing to 71:29 after 4 h at 78 c . the ee of both diastereoisomers of oxazolidin-4-one 6 remain consistently high throughout the duration of the reaction . interestingly , the ee of the unreacted oxaziridine 5 gradually increased with conversion up to 41 % ee at 4 h , which indicates that a partial kinetic resolution was occurring under the reaction conditions . the ee values of 5 obtained experimentally in table 3 correlate with the predicted values based upon the given conversion and d.r . significantly , high conversion was only achieved after an extended reaction time and upon warming to room temperature , which indicates that one enantiomer of the oxaziridine requires increased temperature to react efficiently with the ammonium enolate . this experiment also provided evidence that chirality transfer from ( )-oxaziridine 5 to product 6 was the cause of the low diastereocontrol in this process , which has implications with regard to the mechanism of this isothiourea - catalysed formal [ 3 + 2 ] process . investigation of enantio- and diastereoselectivity over time [ a ] determined by h nmr spectroscopic analysis . [ c ] determined by hplc analysis . to further investigate and utilise the chirality transfer in this process the use of an excess of ( )-oxaziridine 5 ( 2 equiv with respect to homoanhydride 7 ) was trialled ( scheme 3 ) . in this case , oxazolidin-4-one 6 was isolated in 71 % yield with an improved 75:25 d.r . the remaining oxaziridine 5 was isolated in 42 % ee , with the ( s , s)-enantiomer in excess . this formally represents a kinetic resolution of ( )-5 with 49 % conversion with respect to the oxaziridine ( as judged by crude h nmr spectroscopic analysis ) equating to a selectivity factor s=4 . use of excess ( )-oxaziridine 5 . in light of these results , it was reasoned that using an enantiomerically pure oxaziridine would lead to the formation of a single diastereoisomer of the corresponding oxazolidin-4-one product through complete chirality transfer . to assess this , enantioenriched oxaziridine ( r , r)-5 was accessed in 94 % ee ( following a single recrystallisation ) using a modified procedure developed by jrgensen and co - workers ( scheme 4 ) . pleasingly , using enantioenriched oxaziridine ( r , r)-5 with phenylacetic anhydride 7 and ( 2s,3r)-hyperbtm 3 ( scheme 5a ) gave anti - oxazolidin-4-one 6 a in high yield , ee and excellent d.r . this matched case arises from the ammonium enolate generated with homoanhydride 7 and ( 2s,3r)-hyperbtm 3 reacting with ( r , r)-5 with excellent stereocontrol . using enantiomeric catalyst ( 2r,3s)-hyperbtm ent-3 , low reactivity and reduced isolated yields however , performing the reaction at 0 c allowed the desired syn - oxazolidin-4-one 6 b to be isolated in 95 % yield and 80:20 d.r . ( syn / anti ) , with the major syn product formed in excellent ee ( 98 % ) ( scheme 5 b ) . this again suggests complete chirality transfer from the oxaziridine with the configuration at c(5 ) determined by the catalyst . in the mis - matched case the minor anti - oxazolidin-4-one product was isolated in reduced ee ( 67 % ) , presumably as a result of a competitive uncatalysed background reaction for this catalytically unfavoured process . investigation of a ) matched and b ) mis - matched effects between ammonium enolate and enantiomerically enriched oxaziridine . the results described in scheme 5 lead us to propose a catalytic cycle for the synthesis of oxazolidin-4-ones , shown in scheme 6 . subsequent deprotonation of 27 to give ( z)-ammonium enolate 28 , stabilised by a favourable no to *c interaction,[8h , 9d , 27 ] followed by intermolecular stereoselective -oxidation leads to acyl ammonium 29 . this mechanism provides an alternative to that proposed by ye and co - workers who suggest that for their related nhc - catalysed formal [ 3 + 2 ] process the azolium enolate generated is oxidised by an oxaziridine to form a transient epoxide species and an imine , with subsequent collapse of the epoxide and nucleophilic attack onto the imine generating an acyl azolium species that can cyclise into an oxazolidin-4-one . our observation of a matched / mis - matched effect using enantioenriched oxaziridine suggests the formation of a transient planar imine intermediate in this process is unlikely . however , the possibility of an alternative mechanistic pathway operating in the mis - matched case can not be ruled out . proposed mechanism for lewis base catalysed formal [ 3 + 2 ] cycloaddition of ammonium enolates with oxaziridines . the significance of the matched / mis - matched effect was further demonstrated through reaction of a range of homoanhydrides with ( r , r)-oxaziridine 5 ( 94 % ee ) using hyperbtm 3 ( table 4 ) . under the previously optimised conditions , electron - donating and -withdrawing aromatic substituents were easily incorporated resulting in high yields , enantioselectivities and , importantly , high d.r . of oxazolidin-4-ones 17 a and 18 a , respectively . substitution in either the ortho- or meta - positions of the aryl ring was also well tolerated , forming oxazolidin-4-ones 19 a , 21 a and 22 a as single diastereoisomers with excellent levels of enantioselectivity . alkenyl and heteroaryl homoanhydride substituents were also successfully incorporated to give 30 a and 31 a respectively , with high levels of stereocontrol . however , the introduction of a p - trifluoromethyl substituent gave oxazolidin-4-one 25 in a reduced 60:40 d.r.anti/syn , with both diastereoisomers formed in high enantioselectivity ( > 99 % ee ) . this suggests that major product anti-25 a is formed with high levels of enantioselectivity but undergoes base - mediated epimerisation at c(5 ) into syn-25 b. this result also provides a plausible explanation for the unexpected result using the p - trifluoromethyl - substituted homoanhydride with ( )-oxaziridine 5 , with epimerisation at c(5 ) in combination with the expected mixture at c(2 ) leading to the observed drop in ee of both diastereoisomers of 25 ( table 2 ) . [ c ] determined by hplc analysis . to demonstrate the synthetic utility of this [ 3 + 2 ] process , removal of the n - tosyl protecting group on oxazolidin-4-ones 6 a and 17 a18 a was achieved with smi2 at low temperature to give the parent heterocycles 3234 in high yields , with complete retention of ee . further hydrolysis of oxazolidin-4-one 32 with hcl led to formation of ( r)-mandelic acid 35 in quantitative yield . our investigation began with the lewis base - catalysed reaction of commercially available phenylacetic acid 4 with racemic oxaziridine 5 ( table 1 , conditions a ) . treatment of the acid with pivaloyl chloride and ipr2net to form a mixed anhydride in situ followed by addition of ( 2s,3r)-hyperbtm 3 and oxaziridine 5 gave high conversion into the desired [ 3 + 2 ] oxazolidin-4-one product 6 , with a small amount of imine 14 and -lactam 15 ( derived from a previously disclosed intramolecular formal [ 2 + 2 ] cycloaddition of an ammonium enolate and imine 14 ) also observed by h nmr spectroscopy ( table 1 , entry 1 ) . however , imine 14 was difficult to remove from the desired product by column chromatography , resulting in contaminated oxazolidin-4-ones . to probe the origin of imine 14 , control experiments demonstrated that treating oxaziridine 5 in ch2cl2 with ipr2net ( 1 equiv ) led to the formation of ipr2(et)n - oxide and imine 14 . to prevent this undesired imine formation through oxidation of the base a number of alternative bases disappointingly , 2,6-lutidine and cs2co3 gave comparable amounts of imine 14 ( entries 2 and 3 ) . in the reaction with cs2co3 ( entry 3 ) , imine formation is presumably derived from reaction of oxaziridine 5 with chloride ions[7b ] generated from the reaction of phenylacetic acid 4 with pivaloyl chloride to form the  activated  mixed anhydride . to overcome this problem and remove the need for an activation step , homoanhydride 7 was used in place of phenylacetic acid and assessed under similar reaction conditions ( table 1 , conditions b ) . pleasingly , this alternative ammonium enolate precursor resulted in formation of oxazolidin-4-one 6 exclusively in high yield with excellent enantiocontrol , however lower levels of diastereoselectivity were obtained ( entry 4 ) . the oxazolidin-4-one diastereomeric mixture 6 a and 6 b was reduced using lialh4 to give diol 16 in good yield maintaining stereointegrity ( scheme 2 ) , confirming that the configuration at c(5 ) is equivalent in both the syn- and anti - diastereomers formed . the absolute configuration was determined by comparison of the specific rotation of diol 16 with literature values ( see the supporting information for details ) . to assess the effect of the oxaziridine on the stereochemical outcome of the process , alternative oxaziridines were investigated using phenylacetic anhydride 7 as the standard ammonium enolate precursor ( entries 57 ) . aromatic halogen substitution in the ortho- and para - position was examined under the optimised conditions and led to high yields of the desired [ 3 + 2 ] products 11 and 12 , both in approximately 55:45 d.r . but with slightly reduced levels of enantiocontrol for both diastereoisomers . gratifyingly , the scope of the process could be extended with regards to the n - substituent . replacing the n - tosyl group with an n - nosyl led to the formation of oxazolidin-4-one 13 in high yield , however slightly reduced ee values were obtained for the syn- and anti - products . [ c ] determined by hplc analysis . [ d ] conditions a. [ e ] conditions b. lialh4 reduction of oxazolidin-4-one 6 . these reaction conditions were next applied to a range of homoanhydrides to assess the scope of the reaction ( table 2 ) . anhydrides with both electron - withdrawing and -donating aromatic substituents were tolerated , giving a range of oxazolidin-4-ones in high yields with approximately 50:50 d.r . , but with excellent levels of enantiocontrol observed for each diastereoisomer 6 , 17 and 18 ( up to 99 % ee ) . extended aromatic systems and aromatic groups bearing substituents in the ortho- , meta- and para - position also participated well under the previously optimised reaction conditions giving oxazolidin-4-ones 1922 in good yields again with excellent levels of ee for both diastereoisomers . 3-thiophenylacetic anhydride led to isolation of oxazolidin-4-one 23 in 79 % yield but lower levels of ee were obtained for both the syn- and anti - diastereoisomer ( 87 and 81 % , respectively ) . pleasingly , the reaction was extended beyond aromatic substitution patterns to include alkenyl oxazolidin-4-one 24 , obtained in good yield and high ee ( syn- and anti - diastereoisomer ) . unexpectedly , p - trifluoromethyl substitution gave oxazolidin-4-one 25 in 49:51 d.r.anti/syn , with both diastereoisomers formed with low levels of enantioselectivity ( 43 % eeanti , 36 % eesyn ) . [ c ] determined by hplc analysis . whilst these results are synthetically relevant , their utility for the synthesis of oxazolidin-4-ones is partially limited due to the diastereomeric mixtures of heterocycles obtained . although this methodology is applicable to the synthesis of enantioenriched diols ( scheme 2 ) , further investigations sought to investigate the cause of low diastereocontrol in this process allowing selective access to either syn and anti diastereoisomers . the conversion of ( )-oxaziridine 5 into product 6 under the standard reaction conditions was monitored over time by h nmr spectroscopy and the ee of unreacted oxaziridine 5 and oxazolidin-4-one 6 was analysed by chiral hplc analysis ( table 3 ) . notably , over the early part of the reaction the d.r . of 6 remains fairly constant with the initial d.r . of 78:22 anti / syn at 1 min , reducing to 71:29 after 4 h at 78 c . the ee of both diastereoisomers of oxazolidin-4-one 6 remain consistently high throughout the duration of the reaction . interestingly , the ee of the unreacted oxaziridine 5 gradually increased with conversion up to 41 % ee at 4 h , which indicates that a partial kinetic resolution was occurring under the reaction conditions . the ee values of 5 obtained experimentally in table 3 correlate with the predicted values based upon the given conversion and d.r . significantly , high conversion was only achieved after an extended reaction time and upon warming to room temperature , which indicates that one enantiomer of the oxaziridine requires increased temperature to react efficiently with the ammonium enolate . this experiment also provided evidence that chirality transfer from ( )-oxaziridine 5 to product 6 was the cause of the low diastereocontrol in this process , which has implications with regard to the mechanism of this isothiourea - catalysed formal [ 3 + 2 ] process . investigation of enantio- and diastereoselectivity over time [ a ] determined by h nmr spectroscopic analysis . [ c ] determined by hplc analysis . to further investigate and utilise the chirality transfer in this process the use of an excess of ( )-oxaziridine 5 ( 2 equiv with respect to homoanhydride 7 ) was trialled ( scheme 3 ) . in this case , oxazolidin-4-one 6 was isolated in 71 % yield with an improved 75:25 d.r . the remaining oxaziridine 5 was isolated in 42 % ee , with the ( s , s)-enantiomer in excess . this formally represents a kinetic resolution of ( )-5 with 49 % conversion with respect to the oxaziridine ( as judged by crude h nmr spectroscopic analysis ) equating to a selectivity factor s=4 . use of excess ( )-oxaziridine 5 . in light of these results , it was reasoned that using an enantiomerically pure oxaziridine would lead to the formation of a single diastereoisomer of the corresponding oxazolidin-4-one product through complete chirality transfer . to assess this , enantioenriched oxaziridine ( r , r)-5 was accessed in 94 % ee ( following a single recrystallisation ) using a modified procedure developed by jrgensen and co - workers ( scheme 4 ) . pleasingly , using enantioenriched oxaziridine ( r , r)-5 with phenylacetic anhydride 7 and ( 2s,3r)-hyperbtm 3 ( scheme 5a ) gave anti - oxazolidin-4-one 6 a in high yield , ee and excellent d.r . this matched case arises from the ammonium enolate generated with homoanhydride 7 and ( 2s,3r)-hyperbtm 3 reacting with ( r , r)-5 with excellent stereocontrol . using enantiomeric catalyst ( 2r,3s)-hyperbtm ent-3 , low reactivity and reduced isolated yields however , performing the reaction at 0 c allowed the desired syn - oxazolidin-4-one 6 b to be isolated in 95 % yield and 80:20 d.r . ( syn / anti ) , with the major syn product formed in excellent ee ( 98 % ) ( scheme 5 b ) . this again suggests complete chirality transfer from the oxaziridine with the configuration at c(5 ) determined by the catalyst . in the mis - matched case the minor anti - oxazolidin-4-one product was isolated in reduced ee ( 67 % ) , presumably as a result of a competitive uncatalysed background reaction for this catalytically unfavoured process . investigation of a ) matched and b ) mis - matched effects between ammonium enolate and enantiomerically enriched oxaziridine . the results described in scheme 5 lead us to propose a catalytic cycle for the synthesis of oxazolidin-4-ones , shown in scheme 6 . subsequent deprotonation of 27 to give ( z)-ammonium enolate 28 , stabilised by a favourable no to *c interaction,[8h , 9d , 27 ] followed by intermolecular stereoselective -oxidation leads to acyl ammonium 29 . this mechanism provides an alternative to that proposed by ye and co - workers who suggest that for their related nhc - catalysed formal [ 3 + 2 ] process the azolium enolate generated is oxidised by an oxaziridine to form a transient epoxide species and an imine , with subsequent collapse of the epoxide and nucleophilic attack onto the imine generating an acyl azolium species that can cyclise into an oxazolidin-4-one . our observation of a matched / mis - matched effect using enantioenriched oxaziridine suggests the formation of a transient planar imine intermediate in this process is unlikely . however , the possibility of an alternative mechanistic pathway operating in the mis - matched case can not be ruled out . proposed mechanism for lewis base catalysed formal [ 3 + 2 ] cycloaddition of ammonium enolates with oxaziridines . the significance of the matched / mis - matched effect was further demonstrated through reaction of a range of homoanhydrides with ( r , r)-oxaziridine 5 ( 94 % ee ) using hyperbtm 3 ( table 4 ) . under the previously optimised conditions , electron - donating and -withdrawing aromatic substituents were easily incorporated resulting in high yields , enantioselectivities and , importantly , high d.r . of oxazolidin-4-ones 17 a and 18 a , respectively . substitution in either the ortho- or meta - positions of the aryl ring was also well tolerated , forming oxazolidin-4-ones 19 a , 21 a and 22 a as single diastereoisomers with excellent levels of enantioselectivity . alkenyl and heteroaryl homoanhydride substituents were also successfully incorporated to give 30 a and 31 a respectively , with high levels of stereocontrol . however , the introduction of a p - trifluoromethyl substituent gave oxazolidin-4-one 25 in a reduced 60:40 d.r.anti/syn , with both diastereoisomers formed in high enantioselectivity ( > 99 % ee ) . this suggests that major product anti-25 a is formed with high levels of enantioselectivity but undergoes base - mediated epimerisation at c(5 ) into syn-25 b. this result also provides a plausible explanation for the unexpected result using the p - trifluoromethyl - substituted homoanhydride with ( )-oxaziridine 5 , with epimerisation at c(5 ) in combination with the expected mixture at c(2 ) leading to the observed drop in ee of both diastereoisomers of 25 ( table 2 ) . [ c ] determined by hplc analysis . to demonstrate the synthetic utility of this [ 3 + 2 ] process , removal of the n - tosyl protecting group on oxazolidin-4-ones 6 a and 17 a18 a was achieved with smi2 at low temperature to give the parent heterocycles 3234 in high yields , with complete retention of ee . further hydrolysis of oxazolidin-4-one 32 with hcl led to formation of ( r)-mandelic acid 35 in quantitative yield . the asymmetric formal [ 3 + 2 ] cycloaddition of ammonium enolates with both ( )-oxaziridines and ( r , r)-oxaziridines has been developed using a range of 2-aryl and 2-alkenylacetic anhydrides with the commercially available isothiourea catalyst hyperbtm 3 . this process allows access to stereodefined oxazolidin-4-ones that can be readily deprotected or reduced to give enantioenriched building blocks in high yield . further studies using enantioenriched oxaziridines led to the observation of a matched / mis - matched effect with isothiourea hyperbtm 3 , which has been utilised to obtain oxazolidin-4-ones in high d.r . with excellent ee . ongoing studies within this laboratory are focused upon the continued development of lewis base catalysis . for general experimental details , full characterisation data , nmr spectra , and hplc traces , see the supporting information . the appropriate oxaziridine ( 1 equiv ) and ( 2s,3r)-hyperbtm 3 ( 10 mol % ) were added to a solution of the appropriate homoanhydride ( 1.5 equiv ) and cesium carbonate ( 2 equiv ) in ch2cl2 ( 0.2 m ) at 78 c . the reaction mixture was stirred at 78 c then warmed slowly to room temperature over 16 h before being quenched with hcl ( 1.0 m ) . the reaction mixture was extracted with ch2cl2 ( 2 ) , the combined organics dried over mgso4 , filtered and concentrated in vacuo . the crude residue was purified by column chromatography on silica gel ( eluent petrol / et2o 80:20 unless otherwise stated ) to afford the desired oxazolidin-4-one . for general experimental details , full characterisation data , nmr spectra , and hplc traces , see the supporting information . the appropriate oxaziridine ( 1 equiv ) and ( 2s,3r)-hyperbtm 3 ( 10 mol % ) were added to a solution of the appropriate homoanhydride ( 1.5 equiv ) and cesium carbonate ( 2 equiv ) in ch2cl2 ( 0.2 m ) at 78 c . the reaction mixture was stirred at 78 c then warmed slowly to room temperature over 16 h before being quenched with hcl ( 1.0 m ) . the reaction mixture was extracted with ch2cl2 ( 2 ) , the combined organics dried over mgso4 , filtered and concentrated in vacuo . the crude residue was purified by column chromatography on silica gel ( eluent petrol / et2o 80:20 unless otherwise stated ) to afford the desired oxazolidin-4-one . as a service to our authors and readers , this journal provides supporting information supplied by the authors . such materials are peer reviewed and may be re - organized for online delivery , but are not copy - edited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors
a highly enantioselective lewis base - catalysed formal [ 3 + 2 ] cycloaddition of ammonium enolates and oxaziridines to give stereodefined oxazolidin-4-ones in high yield is described . employing an enantioenriched oxaziridine in this process leads to a matched / mis - matched effect with the isothiourea catalyst and allowed the synthesis of either syn- or anti - stereodefined oxazolidin-4-ones in high d.r . , yield and ee . 
 additionally , the oxazolidin-4-one products have been derivatised to afford functionalised enantioenriched building blocks .