Stereo‐ and Enantioselective Synthesis of Propionate‐Derived Trisubstituted Alkene Motifs

Abstract

We report a new method for constructing propionate‐derived trisubstituted alkene motifs in a stereoselective manner. 1‐Substituted 1,1‐di(pinacolatoboryl)‐(E)‐alk‐2‐enes are generated in situ from 1‐substituted 1,1‐di(pinacolatoboryl)alk‐3‐enes through ruthenium(II)‐catalyzed double‐bond transposition. These species undergo a chiral phosphoric acid catalyzed allylation reaction of aldehydes to produce the E isomers of anti‐homoallylic alcohols. On the other hand, the corresponding Z isomers of anti‐homoallylic alcohols are obtained when a dimeric palladium(I) complex is employed as the catalyst for this double‐bond transposition. Thus, both E and Z isomers can be synthesized from the same starting materials. A B−C(sp2) bond remaining with the allylation product undergoes the Suzuki–Miyaura cross‐coupling reaction to furnish a propionate‐derived trisubstituted alkene motif in a stereo‐defined form. The present method to construct the motifs with (E)‐ and (Z)‐alkenes are successfully applied to the syntheses of (+)‐isotrichostatic acid, (−)‐isotrichostatin RK, and (+)‐trichostatic acid, respectively.

α-Boryl Organometallic Reagents in Catalytic Asymmetric Synthesis

“…Suzuki–Miyaura cross-coupling, bromination, and Chan–Lam coupling of the boryl-substituted compounds were illustrated, all of which afforded the desired products in good yields with retention of the Z / E geometry. Propionate-derived trisubstituted alkenes could also be synthesized with this strategy according to a recent report …”

“…Propionate-derived trisubstituted alkenes could also be synthesized with this strategy according to a recent report. 56 In 2020, the Chen group synthesized α,α-disubstituted crotylboronates 100 and developed various stereoselective crotylboration reactions with these reagents. 57 The (E)crotylboronate was synthesized by ruthenium-catalyzed alkene transposition (Scheme 29a), and the (Z)-crotylboronate was obtained through methylation of the corresponding monosubstituted crotylboronate.…”

Recent progress in the catalytic enantioselective reactions of 1,1-diborylalkanes

“…Employing a more structurally complicated a,a-disubstituted gem-diboron reagent as a nucleophile to react with aldehydes, both (E)-and (Z)-isomers of the propionate-derived trisubstituted alkenes can be precisely by using different transition metal catalysts (Scheme 14). 16 Prior to this work, the enantioselective 1,2-addition of the more structurally complicated, a,a-disubstituted gem-diboron reagent has been disclosed by Chen et al in 2020. This new crotylboronate reagent is highly reactive that it reacts with benzaldehyde in the absence of any catalyst to afford the addition product with a 3 : 1 E/Z ratio.…”

Highly Stereoselective Syntheses of α,α-Disubstituted (E)- and (Z)-Crotylboronates

“…Such molecules are challenging to synthesize without resorting to a multistep reaction sequence. However, approaches that permit the stereoselective synthesis of reagent III are rare . Therefore, it is highly desirable to develop practical methods that could solve this problem.…”