Practical, efficient, and broadly applicable synthesis of readily differentiable vicinal diboronate compounds by catalytic three-component reactions

Abstract

A practical, efficient and broadly applicable catalytic method for synthesis of easily differentiable vicinal diboronate compounds is presented. Reactions are promoted by a combination of PCy₃ or PPh₃, CuCl and LiOt-Bu and may be performed with readily accessible alkenyl boronate substrates. Through the use of an alkenyl-B(pin) (pin = pinacolato) or alkenyl- B(dan) (dan = naphthalene-1,8-diaminato) starting material and commercially available (pin)B- B(dan) or B₂(pin)₂ as the reagent, a range of vicinal diboronates, including those that contain a B-substituted quaternary carbon center, may be prepared in up to 91% yield and with >98% site selectivity. High enantioselectivities can be obtained (up to 96:4 er) through the use of commercially available chiral bis-phosphine ligands for reactions that afford mixed diboronate products.

Keywords: Allylic substitution; Boron; Catalysis; Copper; Enantioselective synthesis; Vicinal diboron compounds.

Scheme 1

Related previous work and the basis for the present studies.

Scheme 2

Reactions with 2-substituted allylic phosphates. See the Supporting Information for experimental and analytical details.

Scheme 3

Functionalization through chemoselective oxidation and cross-coupling. See the Supporting Information for experimental and analytical details.

Scheme 4

Functionalization through catalytic Z-selective cross-metathesis reactions. See the Supporting Information for experimental and analytical details.

Scheme 5

Catalytic enantioselective variants. For 3, 1.5:1 ratio of vinyl– B(pin): allylphosphate was used; see the Supporting Information for experimental and analytical details.