Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π‑Allyls

The
first enantioselective carbonyl crotylations through direct use of
alkynes as chiral allylmetal equivalents are described. Chiral ruthenium­(II)
complexes modified by Josiphos (SL-J009-1) catalyze the C–C
coupling of TIPS-protected propargyl ether 1a with primary
alcohols 2a–2o to form products of
carbonyl siloxy-crotylation 3a–3o, which upon silyl deprotection-reduction deliver 1,4-diols 5a–5o with excellent control of regio-, anti-diastereo-, and enantioselectivity. Structurally related
propargyl ethers 1b and 1c bearing ethyl-
and phenyl-substituents engage in diastereo- and enantioselective
coupling, as illustrated in the formation of adducts 5p and 5q, respectively. Selective mono-tosylation of diols 5a, 5c, 5e, 5f, 5k, and 5m is accompanied
by spontaneous cyclization to deliver the trans-2,3-disubstituted
furans 6a, 6c, 6e, 6f, 6k, and 6m, respectively. Primary alcohols 2a, 2l, and 2p were converted to
the siloxy-crotylation products 3a, 3l,
and 3p, which upon silyl deprotection-lactol oxidation
were transformed to the trans-4,5-disubstituted γ-butyrolactones 7a, 7l, and 7p. The formation of 7p represents a total synthesis of (+)-trans-whisky lactone. Unlike closely related ruthenium catalyzed alkyne-alcohol
C–C couplings, deuterium labeling studies provide clear evidence
of a novel 1,2-hydride shift mechanism that converts metal-bound alkynes
to π-allyls in the absence of intervening allenes.