Aldehydes alkynylzinc addition

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

Addition to aldehydes. Qrganozinc addition to aldehydes with BINOLs as catalysts likely involves precoordination. 3,3 -Disubstituted BINOLs, especially with substituents providing additional ligating groups, are found to be highly effective, as exemplified by the use of 1 and 2 in reaction of Et2Zn and alkynylzincs (in situ), respectively. 

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... 

Similar observations have been made with the addition of alkynylzinc reagents to aldehydes in the presence of the lithium salt of Wmethylephedrine (26)28. Whereas addition of 2-phenyl-ethynylzinc bromide to an aromatic aldehyde led to the chiral alcohol in 88% ee, addition of ethyl(2-phenylcthynyl)zinc afforded the same alcohol with only 42% ee. 

Addition of Aryl-, Alkenyl- and Alkynylzinc Reagents to Aldehydes... 

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. 

The synthesis of a new enantiopure, conformationally constrained 1,4-amino alcohol (25) has been reported, starting from commercially available reagents from the chiral pool.107 This 1,4-amino alcohol has been used as a chiral ligand in the addition of Et2Zn to aldehydes (best ee 98%) and in the synthesis of chiral propargylic alcohols (best ee 70%) by alkynylzinc species. 

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... 

Asymmetric additions of alkynylzinc reagents (pyridines and alkaloids as N-containing ligands) to aldehydes and ketones 03T9873. 

A polymer with repeating 6,6 -dibutyl-BINOL units that are linked to each other at C-5 and C-5 has been synthesized. The Ti-complex of the polymer catalyzes the addition of alkynylzinc species to aldehydes. ... 

Methylmagnesium bromide modified by ZnCl2 reacts with aldehydes in the presence of the Ti alkoxide derived from 51. It leads to chiral 2-alkanols. A Ti(IV) complex of the C2-symmetric isophthalamide 52 and a diastereomer of 42 catalyze the addition of alkynylzinc reagents to aldehydes, whereas the polymer-linked hydroxy-imine 53 alone is used for the same purpose. ... 

Alkynylzinc reagents. The direct alkynylation of aldehydes is subject to asymmetric induction in the presence of a chiral base such as (-l-)-Af-methylephedrine. Addition to the C=N bond of A-tosylimines and nitrones by this procedure is also successful. ... 

Asymmetric addition of alkynylzinc reagents to aldehydes has been developed with A-methylephedrine (or other chiral amino alcohol) as the chiral ligand. The alkynylzinc reagent is prepared in situ from the terminal alkyne and this allows use of the metal salt (zinc triflate) as a catalyst in substoichiometric amount (1.145). 

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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