Palladium Catalyzed Asymmetric Three-Component Coupling of Boronic Esters, Indoles, and Allylic Acetates

Abstract

Boronic esters react with 2-lithiated indoles to form boronate intermediates. The boronate reacts with allylic acetates in the presence of (BINAP)Pd catalysts to allylate C3 concurrent with alkyl migration from B to C2 of the indole. Overall, the process is a three-component coupling that joins an allylic acetate, and indole and an organo-B(pin) species to provide substituted indoles and indolines with high enantio-, regio-, and dia-stereo-selectivity.

ortho‐Directing Chromium Arene Complexes as Efficient Mediators for Enantiospecific C(sp2)–C(sp3) Cross‐Coupling Reactions

“…Although there has been ar ecent surge in stereoselective cross-coupling strategies, [2][3][4][5] most of the products presented here are inaccessible by such methods.T hus,t he current method is av aluable addition to the ever-growing arsenal of cross-coupling reactions. Although there has been ar ecent surge in stereoselective cross-coupling strategies, [2][3][4][5] most of the products presented here are inaccessible by such methods.T hus,t he current method is av aluable addition to the ever-growing arsenal of cross-coupling reactions.…”

Enantiospecific Three‐Component Alkylation of Furan and Indole

“…Surprisingly, reactions of boronates derived from stable boronic esters are rare with only a single report very recently disclosed by Ready et al. (with π‐allyl palladium complexes) …”

“…Surprisingly,r eactions of boronates derived from stable boronic esters are rare with only as ingle reportv ery recently disclosed by Ready et al (with p-allyl palladium complexes). [19] Through our simple protocol, indole-derived boronates 15 could be alkylated to introduce ad iverse range of functional groups,i ncluding nitriles, ketones,e sters and unprotected amides, providingf unctionalizedi ndoles 14 a-d in good yields. Various other alkyl boronic esters werealso applied to the coupling reaction, including primary (14 e)a nd enantioenriched chiral secondary (14 f and 14 g)e xamples,a ll proceedingi n high yields and with complete stereospecificity.H owever, using the bulky menthyl boronic ester provided the desired product 14 h in only 18 %yield (albeit with excellent stereospecificity)s howing that steric hindrance has an impact in this reaction.…”

Lewis Acid Catalyzed Stereoselective Dearomative Coupling of Indolylboron Ate Complexes with Donor–Acceptor Cyclopropanes and Alkyl Halides

“…Aggarwal and co-workers recently described an elegant coupling of 2-lithiofuran with various boronic esters as induced by trifluoromethyl radical addition (Scheme 1A). [9] However,m ulticomponent 1,2-boronate rearrangement involving indole activation beyond pallyl chemistry still remains ac hallenge.W ea ssumed that 3alkylation of the indole core in a2-indolylboron ate complex with concomitant 1,2-aryl migration from boron to the indole C2 atom could be achieved by reaction with aL ewis acid activated donor-acceptor (D-A) cyclopropane. Thereactivity of 2-indolylboron ate complexes in coupling reactions was studied in the 1990s by Ishikura and coworkers.…”

“…[8] In the presence of aP dc atalyst, they coupled 2lithiated indoles with trialkyl boranes and allylic acetates to give after oxidative aromatization 2,3-difunctionalized indoles.R ecently,a na symmetric variant of this transformation was developed by Panda and Ready with pinacol boronic esters (Scheme 1B). [9] However,m ulticomponent 1,2-boronate rearrangement involving indole activation beyond pallyl chemistry still remains ac hallenge.W ea ssumed that 3alkylation of the indole core in a2-indolylboron ate complex with concomitant 1,2-aryl migration from boron to the indole C2 atom could be achieved by reaction with aL ewis acid activated donor-acceptor (D-A) cyclopropane. [10][11][12] In contrast to the p-allyl-induced rearrangements in indolylboron ate complexes,i nt he D-A cyclopropane mediated cascades an anion on the acceptor carbon atom of the cyclopropane would be generated that can be trapped by an electrophile, thus culminating in an overall four-component reaction.…”