Palladium-catalyzed chemoselective allylic substitution, Suzuki-Miyaura cross-coupling, and allene formation of bifunctional 2-B(pin)-substituted allylic acetate derivatives

Abstract

A formidable challenge at the forefront of organic synthesis is the control of chemoselectivity to enable the selective formation of diverse structural motifs from a readily available substrate class. Presented herein is a detailed study of chemoselectivity with palladium-based phosphane catalysts and readily available 2-B(pin)-substituted allylic acetates, benzoates, and carbonates. Depending on the choice of reagents, catalysts, and reaction conditions, 2-B(pin)-substituted allylic acetates and derivatives can be steered into one of three reaction manifolds: allylic substitution, Suzuki-Miyaura cross-coupling, or elimination to form allenes, all with excellent chemoselectivity. Studies on the chemoselectivity of Pd catalysts in their reactivity with boron-bearing allylic acetate derivatives led to the development of diverse and practical reactions with potential utility in synthetic organic chemistry.

Keywords: allenes; allylic substitution; chemoselectivity; cross-coupling; palladium.

Figure 1

Catalytic cycles of Tsuji-Trost allylic substitution (right-hand cycle) and Suzuki-Miyaura cross-coupling (left-hand cycle).

Figure 2

Potential reactions of 2-B(pin)-substituted allylic esters.

Figure 3

Plausible catalytic cycle for allene formation.

Scheme 1

One-pot synthesis of 2-B(pin)-substituted allylic acetates.

Scheme 2

2-B(pin)-substituted allylic substitution products as synthons for α-electrophilic carbonyl substrates.

Scheme 3

2-B(pin)-substituted allylic substitution products as synthons for α-electrophilic carbonyl substrates.

Scheme 4

Kinetic resolution of 2-B(pin)-substituted allylic alcohol 4 to prepare enantioenriched 2-B(pin)-substituted allylic acetate 1f.

Scheme 5

Allylic substitution of enantioenriched 1f with morpholine followed by oxidation with sodium perborate.

Scheme 6

A. Kazmaier’s one-pot allylic amination/Stille couplings. B. Pucheault’s tandem Tsuji-Trost allylic substitution/Suzuki-Miyaura cross-couplings.

Scheme 7

Precedents for oxidative addition of aryl halides in the presence of allylic acetates. See text for discussion.

Scheme 8

Suzuki-Miyaura Cross-Coupling of 2-B(pin)-substituted Allylic Acetate 1a.

Scheme 9

Gram scale Suzuki-Miyaura cross-coupling reaction of 1e.

Scheme 10

A. Tanaka’s palladium-catalyzed elimination reaction with diethylzinc. B. Kazmaier’s 2-Sn(n-Bu)₃ elimination of 2-stannylated allylic acetates and phenoxides to form terminal allenes.