Copper-Catalyzed Asymmetric Reductive Allylation of Ketones with 1,3-Dienes

Abstract

A catalytic chemo-, regio-, and enantioselective allylation of ketones with 1,3 dienes in the presence of (R,R)-Ph-BPE ligated Cu catalyst and hydrosilane is presented. This method provides a straightforward and alternative avenue to synthesize chiral homoallylic tertiary alcohols with 1,3-dienes as the latent allylic nucleophiles and avoids the traditional reliance on stoichiometric quantities of allylmetal reagents. This transformation proceeds under very mild conditions and displays good functional group tolerance and could be performed on a gram-scale.

Allenes and Dienes as Chiral Allylmetal Pronucleophiles in Catalytic Enantioselective C=X Addition: Historical Perspective and State‐of‐The‐Art Survey

“…A report by Xiong on copper‐(Ph‐BPE)‐catalyzed diene‐ketone reductive coupling under essentially identical conditions appeared contemporaneously (Scheme 8, Eq. D) [47c] . The copper‐(Ph‐BPE) catalyst system is also effective for reductive coupling of dienes with aldehydes, provided the aldehyde is introduced slowly via syringe pump to suppress competing reduction (Scheme 8, Eq.…”

Cobalt-Catalyzed Diastereo- and Enantioselective Allyl Addition to Aldehydes and α-Ketoesters through Allylic C–H Functionalization

“…Although generation of allyl-Cu intermediates from Cu-H [37][38][39][40][41] or Cu-B 42,43 addition to polyunsaturated hydrocarbons or deprotonation [44][45][46] followed by enantioselective addition to carbonyl compounds has been studied, access to nucleophilic allyl-metal complex from direct oxidative cleavage of the inert allylic C-H bond of simple alkenes and subsequent enantioselective addition to carbonyls promoted by a single multi-tasking catalyst remained unknown. Inspired by Sato's works (Figure 1b), [47][48][49][50] we envisioned that Co(I)-Me complex I in situ produced from AlMe 3 and Co(II) salt coordinates with the alkene moiety chemoselectively (vs. aldehyde) and facilitates the oxidative insertion to the allylic C -H bond to provide the h 3 -Co(III)-allyl complex III.…”

Copper(I)-Catalyzed Regioselective Asymmetric Addition of 1,4-Pentadiene to Ketones

“…One of the notable reactions was the copper(I)-catalyzed asymmetric reductive allylation of ketones with 1,3-dienes. 34,36 Strikingly, the coupling partner was expanded to CO 2 under copper(I) catalysis, which also produced chiral homoallyl alcohols after extensive reduction. 39,40 One of the most direct methods for the synthesis of 1,3dienes is the transformation based on 1,4-dienes.…”

“…Moreover, 1,3-dienes are a class of synthetically versatile compounds in organic chemistry, which are easily converted into highly functionalized molecules via diversified strategies based on transition metal catalysis or photoredox catalysis. − The reductive coupling between 1,3-dienes and carbonyl compounds or imines is particularly appealing, which affords synthetically useful homoallylic alcohols or amines . Various catalytic systems based on different transition metal catalysts, including Ni, − Ru, − Rh, − Ir, − and Cu, − were disclosed. One of the notable reactions was the copper­(I)-catalyzed asymmetric reductive allylation of ketones with 1,3-dienes. , Strikingly, the coupling partner was expanded to CO 2 under copper­(I) catalysis, which also produced chiral homoallyl alcohols after extensive reduction. , …”