Chiral Aluminum Catalyst System for the Enantioselective Addition of Vinylaluminum Reagents to Aldehydes: Metal Controlled Reversal of Enantioselectivity

Abstract

Ac hiral aluminum catalyst systemh as been developed for the enantioselective vinylation of aldehydes. b,b-Disubstituted (E)-vinylaluminum reagents,g eneratedr egio-and stereoselectively by the carboalumination of terminal alkynes with trimethylalumunim (Me 3 Al),w ere useds traightforwardly without transmetalation to vinyltitanium reagents in the subsequent enantioselective addition to aldehydes with aD PP-H 8 -BINOL-derivedc hiral aluminum catalyst at low catalyst loading (5 mol%). Ther eactiona ffordedt he corresponding enantiomerically enriched secondary allylic alcohols with ar eversalo ft he selectivity observed in closely related reactions catalyzed by ac hiral titanium complex derived from the same ligand.

Stereodivergent Catalysis

“…By using the Zr-catalyzed carboalumination of terminal alkynes with Me 3 Al, it was possible to prepare in situ the corresponding (E)-alkenylaluminum compounds 38, which in the presence of (R)-DPP-H 8 -BINOL (39)-derived Ti catalyst reacted with aldehydes to afford (R)-alcohols 40. 56 However, in the absence of Ti(OiPr) 4 the reversal of enantioselectivity was observed, just by changing Ti by Al as a metal source, giving allylic alcohols (S)-40 57 eodivergence was observed by Fujisawa and co-workers 59 in the synthesis of (+)-deoxybiotin, a precursor of (+)-biotin, starting from the thio derivative of 9. The addition of 1-hexynyllithium in the presence of HMPA gave the anti-adduct in 66% de, whereas the chlorozincacetylide exclusively gave the syn-adduct in 86% yield.…”

“…By using the Zr-catalyzed carboalumination of terminal alkynes with Me 3 Al, it was possible to prepare in situ the corresponding ( E )-alkenylaluminum compounds 38 , which in the presence of ( R )-DPP-H 8 -BINOL ( 39 )-derived Ti catalyst reacted with aldehydes to afford ( R )-alcohols 40 . However, in the absence of Ti­(O i Pr) 4 the reversal of enantioselectivity was observed, just by changing Ti by Al as a metal source, giving allylic alcohols ( S )- 40 (Scheme ).…”