Enantioselective Additions with Chiral Propargyl Reagents

Enantioselective Additions with Chiral Propargyl Reagents... 

Even if hundreds of chiral catalysts have been developed to promote the enantioselective addition of alkylzinc reagents to aldehydes with enantioselectivities over 90% ee, the addition of organozinc reagents to aldehydes is not a solved problem. For example, only very few studies on the addition of vinyl groups or acetylides and even arylzinc reagents to aldehydes have been published, in spite of the fact that the products of these reactions, chiral allylic, propargylic and aryl alcohols, are valuable chiral building blocks. 

Alkynylation of Ketones. By combining catalytic amounts of copper(II) triflate and camphorsulfonamides an effective chiral catalyst system is produced, which is effective in the production of tertiary propargylic alcohols, with good to excellent enantioselectivities. These reactions represent a highly enan-tioselective catalytic addition of alkynyl zinc reagents to simple ketones (eq 43). 

Propargylic zinc derivatives react with aldehydes or ketones with variable selectivity affording a mixture of allenic and homopropargylic alcohols [135]. However, under appropriate reaction conditions, high enantioselectivities and diastereo-selectivities can be achieved. Marshall and coworkers have shown that chiral propargylic mesylates such as 188 are converted to allenylzinc reagents 189 through treatment with a Pd(0)-catalyst. Their addition to an aldehyde such as 190... 

Complexation of propargyl aldehydes to cobalt also enhances the reactivity and enantioselectivity of the addition of alkylzinc reagents. This fact was used to create non-racemic enyne-ol 88 reacting the aldehyde 86 with bis-homoallylzinc in the presence of a chiral frzs-(sulfonamide) and Ti(OlPr)4. The resulting complexed substrate 87 underwent the PKR promoted by TMANO in a one pot fashion (Scheme 25) [122]. 

Carbonyl Allylation and Propargylation. Boron complex (8), derived from the bis(tosylamide) compound (3), transmeta-lates allylstannanes to form allylboranes (eq 12). The allylboranes can be combined without isolation with aldehydes at —78°C to afford homoallylic alcohols with high enantioselectivity (eq 13). On the basis of a single reported example, reagent control might be expected to overcome substrate control in additions to aldehydes containing an adjacent asymmetric center. The sulfonamide can be recovered by precipitation with diethyl ether during aqueous workup. Ease of preparation and recovery of the chiral controller makes this method one of the more useful available for allylation reactions. 

In the field of nucleophilic additions to arenechromium tricarbonyls [50], the chromium complex of phenyloxazohne adds various organohthium reagents re-gio- and enantioselectively in the presence of (-)-sparteine (or chiral 1,2-di-ethers). The hthium adduct thus formed has been trapped with propargyl bromide, leading to a frans-disubstituted cyclohexadiene of high ee [51] (Scheme 30). 

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