Diastereoselective aldol reactions of β-silyloxy ethyl ketones. Application to the total synthesis of bafilomycin A1

Total Synthesis of (−)-Bafilomycin A1: Application of Diastereoselective Crotylboration and Methyl Ketone Aldol Reactions

“…The important biological properties and interesting structural features of these molecules have stimulated considerable interest. Total syntheses of bafilomycin A 1 have been recorded by Evans and Calter [7] and Toshima et al, [8] and syntheses of concanamycin F and hygrolidin have been accomplished by Toshima et al [8] and Yonemitsu et al, [9] respectively. In this communication we report a highly convergent synthesis of bafilomycin A 1 (1) following the strategy summarized in Scheme 1.…”

“…[12] This highly convergent approach would allow for the use of a Suzuki cross-coupling reaction [13] to generate an appropriately protected macrocyclization precursor. While the Stille reaction [14] has found great utility in the assembly of natural products, including in the earlier bafilomycin syntheses, [7,8] there are limited applications of the Suzuki reaction for latestage union of complex intermediates, the most notable of the limited examples being recorded in the palytoxin synthesis by Kishi et al [15] and the rutamycin synthesis by Evans et al [16] The aldol reaction between 2 and 3, which serves as the final CÀC bond forming event in the synthesis, provides an additional opportunity to explore the factors that control the stereochemistry of fragment assembly in methyl ketone aldol reactions. [17] The vinylboronic acid 4 was prepared from olefin 7, which was synthesized from commercially available ester 6 by the previously described diastereoselective allylmetalation sequence (Scheme 2).…”

Asymmetric Total Synthesis of Rhizoxin D

“…[11] This afforded what proved to be the desired aldol adduct 16 as a single stereoisomer. [12,13] Reduction of the C15 oxo group proved problematic, as no hydride reducing agent could be found which would give the desired stereochemical outcome. Ultimately, application of a protocol developed for this specific problem proved successful.…”

Polypropionate Synthesis via Substrate‐Controlled Stereoselective Aldol Couplings of Chiral Fragments

“…In contrast, similar reactions of ethyl ketones with a β-alkoxy stereocenter but lacking an α-stereocenter generally exhibit low diastereoface selectivity in favor of the 1,4-syn-7 adducts [33][34][35][36], as might be expected considering the increased number of low-energy conformers possible for H 2 C-enolate bond (Scheme 6.5). Nonetheless, some highly diastereoselective examples are known [33,37]. The remarkable increase in the diastereoface selectivity of (Z)-6b compared to (Z)-6a has been attributed to differences in the ground-state conformations of the enolates where the former adopts a single conformer that effectively shields its si face [33].…”

“…Nonetheless, some highly diastereoselective examples are known [33,37]. The remarkable increase in the diastereoface selectivity of (Z)-6b compared to (Z)-6a has been attributed to differences in the ground-state conformations of the enolates where the former adopts a single conformer that effectively shields its si face [33].…”