A Regio- and Enantioselective CuH-Catalyzed Ketone Allylation with Terminal Allenes

Abstract

We report a method for the highly enantioselective CuH-catalyzed allylation of ketones that employs terminal allenes as allylmetal surrogates. Ketones and allenes bearing diverse and sensitive functional groups are efficiently coupled with high stereoselectivity and exclusive branched regioselectivity. In stoichiometric experiments, each elementary step of the proposed hydrocupration-addition-metathesis mechanism can be followed by NMR spectroscopy.

Regiodivergent Copper Catalyzed Borocyanation of 1,3‐Dienes

“…This in situ, catalytic generation and use of allyl metal species circumvents many problems associated with the preparation of stoichiometric allyl metals. As such, allyl coppers generated from 1,3‐dienes (and other unsaturated carbon frameworks) react with electrophilic coupling partners under mild conditions, with excellent functional group tolerance, leading to densely functionalized and versatile products . For example, copper catalyzed borylative processes of 1,3‐dienes exist where the allyl copper is protonated,, quenched with imines or Michael acceptors, or utilized in palladium catalyzed arylation ,…”

“…Unfortunately, non‐symmetrically substituted 1,3‐dienes present acute challenges in terms of regiocontrol: borocupration can occur at different positions—4,3‐, 4,1‐, 1,2‐ and 1,4‐borocupration—which is further complicated by the possibilty of S E and S E ′ (alpha and gamma) reaction modes of the generated allyl copper (Scheme ). Crucially, if regioselectivity during borocupration could be controlled by a simple change in ligand, then different products would be accessible from the same simple starting materials .…”

Copper‐Catalyzed Tandem Hydrocupration and Diastereo‐ and Enantioselective Borylalkyl Addition to Aldehydes

“…Aldehyde compounds including α,β‐unsaturated carbonyl compounds are highly reducible substrates by Cu−H catalysts, causing chemoselectivity issues. Consequently, the successful copper‐catalyzed reductive couplings with carbonyls have been reported with active olefins such as alkenylazaarenes, enynes, and allenes in combination with ketones. To the best of our knowledge, the use of aldehydes as carbonyl electrophiles has not been reported in copper‐catalyzed asymmetric reductive coupling.…”

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.…”