Lewis Base-assisted Arylation of Unsaturated Carbonyls

Abstract

The combination of Lewis bases with α,β-unsaturated carbonyls allows the in-situ generation of enolates without the need for strong Brønsted bases. Recently developed synthetic methods employ this approach for arylation followed by elimination of the Lewis base, regenerating the alkene. This strategy has been deployed for formal α- or β-C-H arylation in different contexts, namely (a) transition metal catalysis, (b) rearrangement reactions utilizing hypervalent main group elements and (c) organocatalysis. This concept article provides an overview of the developed strategies, highlighting and contextualizing their features.

Keywords: C−C coupling; Lewis bases; aromatic substitution; organocatalysis; rearrangement.

Scheme 1

A) Lewis base‐induced enolate formation and its reaction with an electrophile. B) Necessary reversibility of Lewis base‐electrophile adduct formation. LB=Lewis base.

Scheme 2

Selected examples for Lewis base‐assisted, non‐Morita−Baylis−Hillman α‐functionalization reactions of unsaturated carbonyls. TMS=trimethylsilyl.

Scheme 3

A phosphine‐catalyzed arylation method using an aryl bismuth(V) complex as the electrophile. Ar=aromatic substituent.

Scheme 4

A palladium‐catalyzed coupling of DABCO‐generated enolates to aryl triflates. CPhos=2‐dicyclohexylphosphino‐2’,6’‐bis(N,N‐dimethylamino)biphenyl, JohnPhos=(2‐biphenyl)‐di‐tert‐butylphosphine.

Scheme 5

Arylation of nitriles, oxazoline and ketones through [3,3]‐sigmatropic rearrangements using highly electrophilic, in situ generated, S(IV) and I(III) species. TFA=trifluoroacetate.

Scheme 6

Umpolung of α,β‐unsaturated ketones delivering α‐tosyloxy products 26 and the possibility to access 28 through metal‐catalyzed processes.

Scheme 7

Synthesis of α‐aryl acrylamides via Smiles rearrangement mediated by DABCO.

Scheme 8

NHC‐catalyzed Aryl migration into the β‐position of methacrylamides. R′=o,o′‐dimethyl‐p‐methoxy phenyl.