Sulfinylimidates as Chiral Amide Equivalents for Irreversible, Asymmetric Aldol Reactions

Abstract

A highly selective N-sulfinylimidate aldolization has been developed under mildly basic conditions leading to diastereopure products of high synthetic potential. The innate reversibility of this aldolization was suppressed by the use of titanium as the Lewis acid. An application of this methodology via the synthesis of a potential neurotransmitter reuptake inhibitor is illustrated.

Asymmetric Synthesis of δ‐Chloro‐β‐amino‐N‐sulfinyl Imidates as Versatile Chiral Building Blocks for the Synthesis of 2,3‐Disubstituted Piperidines

“…Condensation of ( R S )‐ tert ‐butanesulfinamide ( 6 ) and orthoester 7 with a catalytic amount of p TsOH without solvent gave imidate ( R S )‐ 8 in high yield (Scheme ). A single isomer was observed, which, based on recent literature data, we assigned with an E configuration 18…”

“…Over the last decade, chiral N ‐sulfinamides have proved to be among the most efficient classes of chiral auxiliaries in asymmetric synthesis 15. In particular, N ‐( tert ‐butanesulfinyl)imidates are very useful chiral enolate precursors for Michael addition,16 α‐alkylation,17 and aldol addition 18. Recently, our group demonstrated asymmetric, highly anti ‐selective Mannich‐type reactions of α‐methyl‐ and α‐chloro‐ N ‐sulfinyl imidates across N ‐tosyl aldimines 15f,15g.…”

Iminoiodane- and Brønsted Base-Mediated Cross Dehydrogenative Coupling of Cyclic Ethers with 1,3-Dicarbonyl Compounds

“…1). This test gave 4n along with a 1:1 mixture of 2a and 3n in 35% and 43% yield, respectively, with the latter two adducts being obtained, presumably, from a competitive retro-Mannich-type pathway [113,114,115,116,117,118]. The role of DBU in mediating the cyclization of the 1,4 amino aldol was also supported by our findings showing the recovery of the substrate on treating it to the standard conditions in the absence of the Schiff base (Scheme 3, Equation (2)).…”

Highly Diastereoselective and Irreversible Aldol Reactions of N-Sulfonylimidates

“…We have recently studied the aldolization of sulfinylimidates, and found that the high reversibility of the reaction could be overcome by using a titanium Lewis acid. 5 We wondered whether the parent sulfonylimidates would show a similar pattern of reactivity. We report herein the successful aldol reaction of sulfonylimidates under mild basic conditions, with the aid of titanium salts to stabilize the products and prevent retro-aldolization.…”

“…We report herein the successful aldol reaction of sulfonylimidates under mild basic conditions, with the aid of titanium salts to stabilize the products and prevent retro-aldolization. 5…”