Enantioselective Synthesis of (E)‐δ‐Boryl‐Substituted anti‐Homoallylic Alcohols Using Palladium and a Chiral Phosphoric Acid

Abstract

(E)-δ-Boryl-substituted anti-homoallylic alcohols are synthesized in a highly diastereo- and enantioselective manner from 1,1-di(boryl)alk-3-enes and aldehydes. Mechanistically, the reaction consists of 1) palladium-catalyzed double-bond transposition of the 1,1-di(boryl)alk-3-enes to 1,1-di(boryl)alk-2-enes, 2) chiral phosphoric acid catalyzed allylation of aldehydes, and 3) palladium-catalyzed geometrical isomerization from the Z to E isomer. As a result, the configurations of two chiral centers and one double bond are all controlled with high selectivity in a single reaction vessel.

Cooperative Use of Brønsted Acids and Metal Catalysts in Tandem Isomerization Reactions of Olefins

“…Murakami and co‐workers also reported a conceptually similar methodology for the asymmetric synthesis of homoallylic alcohols comprising an unsaturated organoboron moiety from 1,1‐di(boryl)alk‐3‐enes 21 (Scheme a) . The motivation for developing a double bond transposition on these substrates was to simplify access to 1,1‐di(boryl)alk‐2‐enes, the synthesis of which can be cumbersome.…”

Efficient synthesis of the key chiral alcohol intermediate of Crizotinib using dual‐enzyme@CaHPO4 hybrid nanoflowers assembled by mimetic biomineralization

“…5 Within all methods mentioned above, highly enantioselective organo-catalysts play a key role in forming the chiral center. 4,6 The same rule also applies to the chemical synthesis of chiral intermediates (S)-1-(2,6-dichloro-3-fluorophenyl) ethyl alcohol. 7,8 Chemical catalysis is always considered to be of high pollution, low efficiency, and high costs (for catalysts and equipments).…”

“…9,10 Aldehyde/ketone reductase and alcohol dehydrogenase are major biocatalysts catalyzing the reduction of ketone and aldehyde substrates to chiral alcohol. 11 Compared with chemical catalysis reaction, 6,8 chiral alcohol from enzymatic reactions always has a higher ee (%) value and higher optical purity. 12 The major challenges for enzymatic synthesis of chiral alcohol intermediates lie in difficult recovery of free enzymes and low tolerance to the environmental conditions of catalysis reaction.…”

Cu‐Catalyzed Diastereo‐ and Enantioselective Reactions of γ,γ‐Disubstituted Allyldiboron Compounds with Ketones

“…Our approach centers on the development of a catalyst-controlled 1,2-addition of g,g-disubstituted allyldiboronate esters to ketones. [10] 1,1-Diboron reagents represent a nascent class of functional reagents for the enantioselective synthesis of alcohols and amines. [11] In this regard, we envisioned a catalytic reaction that begins with an enantioselective S E 2' transmetalation between in situ generated (L)-Cu-OMe and a stereodefined allyldiboron (e.g., 2).…”