Stereoselectivity in Nucleophilic Additions to 3-Azidoalkanals

Abstract

The stereoselectivity of nucleophilic additions to 3-azidoalkanals was investigated. Non-chelating, BF(3)·OEt(2)-mediated Sakurai addition to 3-azidoalkanals afforded 1,3-anti products, whereas use of a chelating Lewis acid, TiCl(4), resulted in 1,3-syn products with moderate selectivity. A boat-like chelation structure of the 3-azidoalkanal with the Lewis acid is proposed to be consistent with the 1,3-syn selectivity of the reactions. Mukaiyama aldol addition to 3-azidohexanal generated 1,3-anti products regardless of the chelating ability of the Lewis acid.

Stereoselectivity in (Z)‐Vinylmetal Additions to the Dictyostatin C1–C9 β‐Silyloxy Aldehyde

“…The results obtained in this work (Table 3) and literature precedents (Table 1) [6,10,11,21] suggest that models A2 and/ or B (Si face attack, half-chair-like transition state), which lead to the 1,3-syn diastereomer, can make a substantial impact in these addition reactions.…”

Stereoselective Acetate Aldol Reactions

“…Most of the aldol reactions involving such aldehydes proceed in accordance with these expectations, but systematic studies on the addition of enolsilanes (42) to α-chloro, α-hydroxy, and α-amino aldehydes (43)(44)(45) revealed that their diastereoselectivity is dependent significantly on the α-heteroatom and the steric bulk of nucleophiles (Scheme 1.21) [38][39][40]. Thus, additions of acetone-derived enolsilane (42a) to aldehydes (43) and (44) possessing an electronegative α-heteroatom such as chlorine or oxygen afforded the corresponding 3,4-anti aldols (46a) and (47a) (dr 60 : 40 and 82 : 18, respectively), whereas more sterically hindered pinacolone-derived enolsilane (42c) gave under the same conditions 3,4-syn aldol (46c) or equimolar mixtures of 3,4-anti and syn diastereomers (47c).…”

“…As illustrated in Scheme 1.23, most of the aldol reactions of silyl enol ethers (42) with β-hydroxy, β-chloro, and β-azido aldehydes (49) corresponding 3,5-anti aldols (50) in high diastereomeric ratios regardless of the chelating ability of the Lewis acid and the hydroxyl protecting group [42][43][44].…”

The remarkable journey of catalysts from stoichiometric to catalytic quantity for allyltrimethylsilane inspired allylation of acetals, ketals, aldehydes and ketones

“…Huh et al 56 studied the stereoselectivity of nucleophilic addition of allylsilane to 3-azidoalkanals in the presence of chelating and non-chelating Lewis acid. Chelating Lewis acid TiCl 4 produced 1,3-syn product while non-chelating BF 3 -OEt 2 gave 1,3-anti product (Scheme 36).…”