X-ray Crystal Structures of Intermediates of the Stereoselective (±)-Grandisol Synthesis Based on the Remote Alkylation Protocol

Abstract

Starting from easily prepared (cyclobutylsulfonyl)benzene (1), a stereoselective synthesis of (±)-grandisol, accomplished in nine steps, with an overall yield of ca. 18 %, has been presented by Monteiro and Stefani (Eur J Org Chem 14:2659–2663, 2001). Most of the synthetic intermediates were secured in good to excellent yields as crystalline compounds requiring no or minimal purification, should being amenable to scale up. The structures and absolute stereochemistry of (2), (3), (4a), (5), (8) and (9) were established by IR and NMR (¹H, ¹³C) spectroscopies and confirmed by X-ray diffraction analysis. Compound (2) crystallizes in orthorhombic Pbca, a = 16.0565(5), b = 9.5144(6), c = 23.9728(7) Å, the (3) crystallizes in monoclinic P2₁/c, a = 5.6390(5), b = 17.8630(16), c = 12.8678(12) Å and β = 111.928(7)°, the (4a) crystallizes in monoclinic P2₁/c, a = 5.7002(9) Å, b = 17.2752(14) Å, c = 14.9168(9) Å and β = 109.464(8)°. The other three cyclobutylsulfonyl derivatives crystallize in the same monoclinic space group P2₁/c with cell parameters (5) a = 8.072(4), b = 11.486(9), c = 14.565(8) Å and β = 101.373(4)°, (8) a = 11.3448(2), b = 7.9377(1), c = 18.5329(4) Å and β = 94.147(1)° and (9) a = 37.7571(9), b = 11.4434(3), c = 8.1824(2) Å and β = 90.748(1)°.

Graphical Abstract

X-ray crystal structures of six synthetic intermediates prepared from the stereoselective synthesis of (±)-grandisol.