Enantioselective addition alkynylzincs

Enantioselective addition of alkynyl groups to aldehydes and ketones afford enantioen-riched alkynyl alcohols62. Early approaches to the catalytic enantioselective addition of dialkynylzincs and alkynylalkylzincs to aldehydes employed catalytic amounts of chiral amino alcohol63 and amino pyridine64. Stoichiometric enantioselective addition of alkynylzinc halide is reported using the lithium alkoxide of IV-methylephedrine65. 

Enantioselective Addition of Cyanomethylzinc Bromide, Reformatsky Reagent, and Alkynylzinc Reagents to Aldehydes. The enantioselective additions of cyanomethylzinc... 

Dialkylzincs are much less reactive than phenyl or alkynylzincs. In 2002, Kozlowski et al. developed a chiral salen-based catalyst 62 that can promote the diethylzinc addition to a-ketoesters in high yield, [Eq. (13.38)]. In their catalysis, titanium acts as a Lewis acid, and amine nitrogen acts as a Lewis base (63). The enantioselectivity was up to 78% ee ... 

In addition to amino alcohols, numerous other ligands such as amines, amino thiols, diols, disulfides, and dis-elenides have been developed and tested. Several have shown a very good enantioselectivity for dialkylzinc additions to a variety of aldehydes. In contrast, the addition of aryl-, vinyl-, and alkynylzinc compounds was not so extensively studied and more work is stiU needed in... 

Figure 64 Structure of some enantioselective ligands for vinyl- and alkynylzinc additions to aldehyde...

Hoveyda and Snapper reported that the addition of mixed alkynylzinc reagents to various aryl imines can be catalyzed by Schiff base ligand 52 and zirconium tetraisopropoxide to afford the protected propargylamines in good yields and enantioselectivities [130]. The oxidative removal of the o anisidyl group affords the propargylamine without any racemization (Scheme 1.40). 

Alkynylzinc addition to ArCHO can also be carried out in the presence of 3, whereas the disilyl derivative 4 catalyzes enantioselective Reformatsky reaction on ketones (with ee up to 90%)" which operates by a ftee radical mechanism (requiring air to initiate the reaction). 

BINOL is an effective ligand in the titanium-catalysed asymmetric addition of alkynylzinc reagents to aldehydes. Aromatic, aliphatic and a,P-unsaturated aldehydes such as (6.35) are converted into the propargylic alcohol with 91-99% ee using the alkynylzinc, generated from phenylacetylene and diethylzinc. Carriera and coworkers have developed an enantioselective alkynylzinc addition that is also... 

S)-BINOL-Ti was also shown to be an effective chiral catalyst for the catalytic asymmetric addition of alkynylzinc to inactivated simple ketones with good to excellent enantioselectivities [63] (Scheme 14.12). The same reaction has been furnished by using lithium phenylacetylide as the nucleophile under the catalysis of titanium complex prepared from BINOL and ClTi(O Pr)3 [64]. 

Use as a Dual Catalyst in Addition of Alkynylzinc Species to Aldehydes. A dual Lewis acid/base system was reported involving NMI, Ti(OiPr)4, and (/f)-BINOL in the enantioselective alkynylation of aldehydes with diethylzinc at room temperature. Other methods to access these products have been hindered by the need for higher temperatures to generate the alkynylzinc species. A variety of propargy lie alcohols could be prepared from aromatic aldehydes in high yields and with excellent enantioselectivities (eq42). ... 

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