Reagent controlled addition of chiral sulfur ylides to chiral aldehydes

Abstract

The degree of reagent and substrate control in the reaction of chiral sulfur ylides with chiral aldehydes has been investigated. Specifically, the reactions of the two enantiomers of the chiral benzyl sulfonium salt 1 with glyceraldehyde acetonide were studied in detail. Of the two new stereogenic centers created, it was found that the C 1 stereochemistry was largely controlled by the reagent, whereas control at the C 2 center was dependent on the aldehyde used. In one case, the trans isomer was produced via reversible formation of the intermediate betaine, whereas in the alternative case, the C 2 center was under Felkin Anh/Cornforth control through non-reversible formation of the betaine. Thus, the aldehyde stereocenter influenced the degree of reversibility in betaine formation, which impacted on the stereocontrol at the C 2 position.

Chalcogenides as Organocatalysts

“…With chiral aldehydes and sulfides, match/mismatch effects arise and affect the ease of rotation and thus, the degree of reversibility. 63 (iii) Reversibility is decreased if there is improved solvation of the betaine alkoxide by a metal or a protic solvent, which lowers the torsional rotation barrier. 62 It is important to note that, while all these factors can also have an effect on the reversibility of anti-betaine formation, the effects on syn-betaine formation normally dominate the diastereoselectivity.…”

“…(ii) Increased reversibility also results when the steric hindrance of the ylide and/or the aldehyde is increased, which leads to an increase in the torsional rotation barrier. With chiral aldehydes and sulfides, match/mismatch effects arise and affect the ease of rotation and thus, the degree of reversibility …”

Application of furyl-stabilized sulfur ylides to a concise synthesis of 8a-epi-swainsonine

“…11 In early studies, we had shown that the phenyl-stabilized ylide 2a reacted with glyceraldehyde dimethylacetonide 3 to give the cis epoxide 4a (Scheme 1). 12 In this kinetically controlled reaction, the C 1 stereochemistry is controlled by the chiral sulfur ylide (reagent control) and the C 2 stereochemistry is controlled by the substrate. We reasoned that if we could effect the same type of reaction with the related furylstabilized ylide 2b to give epoxide 5a, then following ring opening by NH 3 and application of the Achmatowicz reaction we should arrive at piperidine 7a (Scheme 2).…”

Bicyclo[2.2.1]heptan-2-one, 7,7-Dimethyl-1-(1S,3S,4R)-2-thiabicyclo[2.2.1]hept-3-yl-, (1S,4R)

“…Phenyl-stabilized chiral sulfur ylide, generated by deprotonation of benzyl sulfonium salt with P 2 base, reacts with five-membered ring hemiaminals to give an intermediate trans-functionalized epoxide, which upon heating leads to functionalized pyrrolidines with high enantioselectivity and diastereoselectivity and in high yield (eq 7). 12 The degree of reagent and substrate control in the reaction of chiral sulfur ylides, generated from sulfonium salts, with chiral aldehydes (glyceraldehyde acetonide and meroquinene aldehyde) has also been investigated. In the case of the reaction of phenyl-stabilized ylide with glyceraldehyde acetonide, it was found that the C 1 stereochemistry was largely controlled by the reagent, whereas control at the C 2 center was dependent on the aldehyde used (eq 9).…”