Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

Abstract

Aldol reactions belong to the most frequently used C–C bond forming transformations utilized particularly for the construction of complex structures. The selectivity of these reactions depends on the geometry of the intermediate enolates. Here, we have reacted octyl pentafluoro-λ6-sulfanylacetate with substituted benzaldehydes and acetaldehyde under the conditions of the silicon-mediated Mukaiyama aldol reaction. The transformations proceeded with high diastereoselectivity. In case of benzaldehydes with electron-withdrawing substituents in the para-position, syn-α-SF5-β-hydroxyalkanoic acid esters were produced. The reaction was also successful with meta-substituted benzaldehydes and o-fluorobenzaldehyde. In contrast, p-methyl-, p-methoxy-, and p-ethoxybenzaldehydes led selectively to aldol condensation products with (E)-configured double bonds in 30–40% yields. In preliminary experiments with an SF5-substituted acetic acid morpholide and p-nitrobenzaldehyde, a low amount of an aldol product was formed under similar conditions.

Chemistry of Pentafluorosulfanyl Derivatives and Related Analogs: From Synthesis to Applications

“…However, in this case, the aldol addition is substrate-dependent and p-substituted benzaldehydes with EDG did not yield the desired product, probably due to the instability of intermediates. [80] Scheme 26. Alkylation of aliphatic amines using the SF 5 -containing electrophile.…”

Recent Advances in the Synthesis and Medicinal Chemistry of SF5 and SF4Cl Compounds

“…Scheme 38 Mukaiyama-type aldol reaction of octyl pentafluoro- 6 sulfanylacetate with different aldehydes 36 The Ireland-Claisen [3,3]-sigmatropic rearrangement of allyl esters is useful for the construction of carboxylic acid derivatives.…”

“…Scheme 38 Mukaiyama-type aldol reaction of octyl pentafluoro- 6 sulfanylacetate with different aldehydes 36 The Ireland-Claisen [3,3] sigmatropic rearrangement of allyl esters is useful for the construction of carboxylic acid derivatives. Haufe and co-workers reported the synthesis of 3-arylpent-4-enoic acid derivatives bearing an -SF 5 group by reacting the SF 5 -acetates of p-substituted cinnamyl alcohols with triethylamine, followed by trimethylsilyl triflate (TMSOTf) (Scheme 39).…”

Theoretical investigation of Prolyl‐Histidine‐catalyzed intermolecular aldol reaction

“…[1] It has many applications in chemistry, pharmacy, chemical engineering, biology, and so forth. [2][3][4][5][6][7][8][9][10][11][12][13][14] A variety of catalysts for aldol reactions, including enzymes antibodies and small molecules, have been developed in the past decades. [15][16][17][18][19] The research of asymmetric synthesis reactions catalyzed by small organic molecules such as amino acids and peptides has become a hot topic.…”