Stereoselective Construction of Acyclic Carbon Chains by a One‐Pot Coupling Process Based on Alkenyloxazoline–Titanium Complexes

Abstract

Oxazoline is known as a versatile functional group in organic synthesis for the activation of substrates and for asymmetric synthesis.[1] Complexation of organic compounds having this group with transition metals may lead to the development of unique synthetic transformations, [2] but an olefin complex such as the one in Scheme 1 (M = metal) [3] has not been investigated. We report here that titanation of alkenyloxazolines proceeds nicely to give novel olefin-titanium complexes (Scheme 1, M = Ti(OiPr) 2 ), which subsequently allow for a diastereoselective multicomponent coupling process and an asymmetric coupling reaction. Treatment of alkenyloxazoline 2[4] with a titanium(ii) alkoxide reagent 1 formed from Ti(OiPr) 4 with two equivalents of iPrMgCl, [5] generates olefin complex 3, [6] which underwent a coupling reaction with 1-octyne (4) to give titanacycle 6 (R = C 6 H 13 ; Scheme 2). Intermediates 3 and 6 were identified by deuteriolysis.[7] The carbon-titanium bond a to the oxazoline (rather than the vinyl-titanium bond) of 6 selectively reacted with the octanal to give, after hydrolytic work-up, a single regioisomer 8 having exclusively an Eolefinic bond. Surprisingly, the crude reaction mixture contained this adduct 8 together with a very small amount of one of the four possible diastereoisomers (d.r. = 96:4) arising from the three consecutive stereogenic centers. Compound 8 could be readily separated from this minor isomer [8] by flash chromatography on silica gel to give a pure sample in 66 % yield. The stereochemistry of 8 was determined (as depicted) by derivatization. [7] A stereochemical course from 2 to 8 is proposed in the Supporting Information. [7] Analogously, the sequential treatment of 2 with silylacetylene 5 and nonanal Scheme 1. Generation of the olefin-metal complex.Scheme 2. Four-component coupling process.