Enantio- and diastereoselective titanium-TADDOLate catalyzed addition of diethyl and bis(3-buten-1-yl) zinc to aldehydes. A full account with preparative details

Abstract α,α,α′,α′-Tetraaryl-2-mono- and -2,2-disubstituted-1,3-dioxolan-4,5-dimethanolates (TADDOLates) of titanium (IV) are used in substoichiometric amounts for the Lewis acid-mediated enantioselective addition of alkyl groups from organozinc reagents to aldehydes (19 examples). With 0.05 – 0.20 equiv. of the diisopropoxy-Ti-TADDOLate bearing four 2-naphthyl groups and 1.2 equiv. of Ti(OCHMe 2 ) 4 in toluene or ether solution the best results are obtained: ≥ 98 : 2 enantiomer ratios with all types of aldehydes tested (saturated, olefinic, and acetylenic aliphatic, aromatic, and heteroaromatic). The nucleophilic addition occurs from the ( Si )-face of the aldehydes when the ( R,R )-TADDOLate is employed. - With chiral aldehydes, diastereoselective additions of diethyl zinc were achieved (7 examples). In the absence of additional functional groups in the aldehyde the diastereoselectivities are independent of its chirality (“reagent control”, two examples). - The TADDOLate method of adding dialkyl zinc reagents to aldehydes enantioselectively is compared with other Lewis acid or aminoalcohol mediated methods. Full experimental detail and correlations of the absolute configurations of some of the products obtained with literature assignments are given.