Borylated cyclobutanes via thermal [2 + 2]-cycloaddition

Abstract

A one-step approach to borylated cyclobutanes from amides of carboxylic acids and vinyl boronates is elaborated. The reaction proceeds via the thermal [2 + 2]-cycloaddition of in situ-generated keteniminium salts.

Scheme 1. Retrosynthetic disconnection of borylated cyclobutanes via a [2 + 2]-reaction: photochemical vs. thermal strategies.

Scheme 2. Reaction conditions: (i) vinyl Bpin/allyl Bpin (1.0 equiv.), amide (1.2 equiv.), triflic anhydride (1.4 equiv.), collidine or lutidine (1.4 equiv.), 1,2-dichloroethane, reflux, and 16 h; (ii) aqueous NaHCO₃; (iii) purification (vacuum distillation or column chromatography). The scale of the synthesis: ^a 100–500 mg; ^b 1–7 g; ^c 10–50 g of the isolated product. ^d Product 25 (d.r. = 7 : 1) was obtained with ca. 70% purity. ^e Additional purification by column chromatography provided the pure product 25 as a single diastereomer in 3% yield. ^f Product 26 (d.r. = 2 : 1) was obtained with ca. 50% purity. ^g Additional purification by column chromatography provided the pure product 26 as a single diastereomer in 1% yield. X-ray crystal structures of compounds 14–16, 20, and 22 are shown as thermal ellipsoids at a 50% probability level; carbon – white, oxygen – red, boron – brown, and fluorine – green; hydrogen atoms are omitted for clarity.

Scheme 3. Unexpected synthesis of ketone 33.

Scheme 4. Modifications of borylated cyclobutanes. (a) Synthesis of borylated cyclobutane 23. (b) Synthesis of N-Boc amino boronates 38 and 40. (c) An attempted synthesis of bicyclo[1.1.1]pentanes 41 and 42.

Scheme 5. Synthesis of potassium trifluoroborate salts 6a, 9a, and 13; and diol 44.