Partial Asymmetric Synthesis of Substituted Benzylidenecycloalkanes

Abstract

I85 ( 8 5 ) The Wittig reaction of ( 4 ) with aldehydes affords N-substituted thiocarboxamides (7) of cc,(j-unsaturated acids. Both ( 3 ) and ( 4 ) undergo S-methylation on treatment with methyl iodide; the phosphonium salts ( 5 ) isolated after this reaction can be converted into the ylides ( 6 ) by treatment with sodium methoxide. Starting from ( 6 ) , hydrolysis gives thioimidic acid derivatives (a), Wittig reaction affords the corresponding derivatives of cc,P-unsaturated acids ( 9 ) , and reaction with methyl iodide leads to the substituted vinylphosphonium salts ( 10). Angew. Chem. 77, 609, 651, 850 (1965); Angew. Chem. internat. Edit. 4, 583, 645, 830 (1965 Cycloalkanes having an exocyclic double bond and an even number of C atoms in the ring, which bears a substituent at the greatest possible distance from the double bond, are chiral molecules [type (I)]. The same applies to all cis-disubstituted cycloalkanes with a exocyclic double bond having two identical substituents at equal distances from the double bond [type (2)]. In both cases it is essential that R and Rl + H, although R = RI is possible. We have found that optically active molecules of types (f) and (2) can be obtained by partial asymmetric synthesis, the route selected being a Wittig reaction of the corresponding ketones with optically active alkylidenephosphoranes. We chose benzylidenemethylphenyl-n-propylphosphorane (3) (71, m.p 1 175(70) as the optically active ylide since the absolute configuration of the phosphonium bromide obtained from ( 2 ) on liberation of HBr by sodamide is knownr21.

Asymmetric Ylide Reactions: Epoxidation, Cyclopropanation, Aziridination, Olefination, and Rearrangement

“…In the presence of NaH, ketone 398 reacted with chiral phosphate 399 to give optically active alkene (−)- 400 , which was further saponified to produce the corresponding acid (−)- 401 in >50% optical purity (the result of the asymmetric induction was questioned, however 166a ) (Scheme ). In order to improve the asymmetric induction, the first desymmetrization of ketones by the reaction of a chiral ylide reagent, with a stereogenic center on phosphorus, was realized by Bestmann . The axially dissymmetrical alkene ( S )-(+)- 403 was formed in 43% ee by the olefination of 398 with chiral phosphonium ylide ( R )- 402 .…”

“…In order to improve the asymmetric induction, the first desymmetrization of ketones by the reaction of a chiral ylide reagent, with a stereo-genic center on phosphorus, was realized by Bestmann. 165 The axially dissymmetrical alkene (S)-(+)-403 was formed in 43% ee by the olefination of 398 with chiral phosphonium ylide (R)-402. Bestmann also tried this reaction with tropinone and pseudopelletierine.…”

First Microwave‐Assisted Catalytic Wittig Reaction

“…[17] There are only a few stoichiometric variants of this reaction. [18] However, a catalytic asymmetric version has not been reported so far, to the best of our knowledge. Hence, we prepared prochiral carbonyl compound 4 (Scheme 3).…”

External Chiral Ligand-Mediated Enantioselective Peterson Reaction of α-Trimethylsilanylacetate with Substituted Cyclohexanones

“…The past two decades have witnessed considerable progress in the asymmetric Horner−Wadsworth−Emmons (HWE) and Wittig olefination reactions . Since the first report by Tömösközi and Janzsó in 1962, considerably energetic efforts have been devoted to establish the asymmetric HWE , and Wittig reactions of chirally modified reagents. Some recent work has focused on enantioselectivity using chiral ligands in HWE 6 and Wittig 7 olefinations.…”