Sulfinyl anions chiral

Papageorgiou and Benezra204 treated chiral r-butyl (-)-(S)- and ( + )-(R)-2-(p-tolylsulfinyl)propionate with an aldehyde, then pyrolyzed the mixture and obtained chiral a-(hydroxyalkyl)acrylate in 75% e.e. Similarly, condensation of the anion of ( + )-(R)-3-(p-tolylsulfinyl)propionic acid 159 with aldehydes was found to give the diastereomeric [i-sulfinyl-y-lactones, (+)-(Sc4,Rc5,Ps)-160a and ( + )-( c4,Sc5,l s)-160b in an approximate ratio of 60 40205. 

A highly stereoselective synthesis of the (3-substituted P-amino sulfone 271 involves the addition of a sulfonyl anion, derived from A-PMB sultam 268 upon treatment with NaHMDS, to chiral A-sulfinyl imine (5)-269 <06OL789>. Removal of the A-sulfinyl followed by basic workup affords amine 271. The stereochemical outcome of the adduct 270 was established via proton NMR analysis of the Mosher s amide derived from 271. 

Methyl chloroacetate reacts with the anion of (7 )-methyl p-tolyl sulfoxide to give the corresponding 8-chloro-p-keto sulfoxide (eq 10), which can be easily transformed into the corresponding 3-hydroxy sulfoxide which gives, in presence of a base, the optically active a-sulfinyl epoxides. As illustrated here, a-sulfinyl epoxides can be opened by cuprates, leading to chiral homoallylic alcohols. ... 

In their route to (- )-3, Hua and his coworkers demonstrated Ae usefiilness of chiral a-sulfinyl ketimine anions as intermediates in alkaloid synthesis (Scheme 4) (43). Treatment of the anion of 28 with (S)-( - )-menthyl p-toluenesulfinate afforded a 1 1 mixture of the separable diastereomers 29 and 30, while use of (/ )-( + )-menthyl p-toluenesulfinate afforded the enantiomers ent-29 and ent-30. Conjugate addition of the anion of 30 to methyl 2-(rerr-butoxycarbonylamino)acrylate was followed by spontaneous cyclization to give the unsaturated indolizidines 31 and 32 in a ratio of 2 3. Similar treatment of the anion of ent-29 yielded 33 and 34 in the ratio 1 2. Both sets of indolizidine diastereomers were readily separated by chromatography. The synthetic routes converged when reduction of either 32 or 33 with Raney nickel gave the same 5-oxoindolizidine 35, fiom which ( - )-slaihimine... 

Madec and Poli recently reported that sulfenate anions can also be used as nucleophiles in catalytic formation of C ryi-S bonds, generating sulfoxides [103]. The sulfenate anions are generated in situ by base-induced elimination of (3-sulfinyles-ters [136]. These groups subsequently developed an enantioselective variant, allowing the asymmetric synthesis of sulfoxides with up to 83% ee (16) [105]. Chiral sulfoxides are present in a variety of pharmaceuticals and are widely used in asymmetric catalysis [137-141]. Likewise, Madec and Poli found that sulfenate anions can be used to generate Csp -S bonds in Pd-catalyzed allylic alkylation [ 142]. o... 

Hua rationalizes the stereoselectivity observed in Scheme 4.21 by reference to a planar species. Hua proposes that (37a) and (37b) both generate the same sp -p hybridized a-sulfinyl carbanion on deprotonation. Scheme 4.23 illustrates the suggested transition states for addition of conformeric anions to butyraldehyde. Transition state A appears to be the most favourable and leads to the major product isomer (39a). Transition state B (related to A simply by attack of the aldehyde from the opposite apex of the p-orbital) shows slightly more steric hindrance between the five-membered ring and the butyryl chain and leads to (39b). Both transition states A and B give rise to the (5) configuration at the new alcohol chiral centre. 

Dialkylformamides and EDA (lithium diisopropylamide) react to give carbamoyl anions (42, with contributions from C-lithiated anion and 0-lithiated carbene forms). Addition of such anions to chiral Al-sulfinyl aid- and ket-imines provides a-amino amides. The method avoids the unmasking of the nucleophile found in other approaches. i C-NMR confirms the unusual nature of the carbon of the anion (42). 

Davis and coworkers have exploited the reactions of chiral JV-sulfinyl-amines in the synthesis of numerous alkaloids. Their route to (—)-epimyr-tine (1098) began with the diastereoselective addition of the enolate anion of methyl acetate to the (Ss)-(4-)-sulfmimine (+)-1128, from which the (Ss,S)-p-amino ester derivative (- -)-1129 was obtained in better than 97% de (Scheme 144). After Claisen condensation of 1129 with ierf-butyl acetate, the sulfmyl group was removed from the resulting P-keto ester (4-)-1130 by treatment with acid, the desuhinylated product then undergoing Mannich cyclization with acetaldehyde. The relative stereochemistry of the sole product, 2,6-a5-disubstituted piperidine (4-)-1131, was corroborated by nOe experiments, which indicated that no epimerization at the stereogenic centers had occurred. After hydrolysis and decarboxylation of... 

In 1989, Prakash and co-workers reported that (trifluoro-methyl)trimethylsilane can be activated by a Lewis base to form the trifluoromethyl anion in situ, which could subsequently add to both carbonyls and imines. More recently, it has been demonstrated that the asymmetric addition of the trifluoromethyl anion to imines can be directed by sulfinyl chiral auxiliaries, whereas the addition to ketones can be controlled through the use of menthol " and isosorbide ° derived chiral auxiliaries. 

Addition of lithiated alkoxy ethynyl anion with chiral Al-sulfinyl imines proceeds with dr >95 5, which can be reversed in the presence of BF3. Excellent diastereoselec-tivity has been reported for zinc-mediated addition of methyl and terminal alkynes to chiral IV-f-butanesulfinyl ketimines (to form 3-amino oxindoles). Zinc-BINOL complexes have been used to achieve enantioselective addition of terminal alkynes to N-(diphenylphosphinoyl)imines (up to 96% cc) and terminal 1,3-diynes to IV-arylimines to trifluoropyruvates (up to 97% yield and 97% ee). ... 

---