Organozinc reagents cyclizations

Feringa and co-workers described the tandem addition-aldol cyclization protocol leading to the formation of 6,6-, 6,7-, and 6,8-annulated bicyclic systems (Scheme 68).39 Using Cu(n)-29 as catalyst and functionalized organozinc reagents as nucleophiles, the conjugate addition reaction followed by aldol cyclization can offer highly enantioselec-tive annulation products (up to 98% ee). This method can be used in the synthesis of carbocyclic compounds, such as steroids, terpenes, and other natural products. 

The high chemoselectivity of organozinc reagents also allowed the use of the functionalized secondary a-acetoxy alkyl bromide 50 which was converted to 34a (equation 19)36, a product previously obtained by the cyclization of a 5-ethylenic primary iodide bearing the acetoxy group at the allylic position (equation 13). 

When the Pd-catalyzed exchange protocol was applied to the 5-alkenyl iodides of type 51, the cyclized organozinc reagents 52 were directly obtained and functionalized by allylation with ethyl 2-bromomethylacrylate after transmetallation with CuCN 2LiCl. The five-membered ring products 53 were obtained with high trans diastereoselectivity, irrespective of the nature of the allylic substituent (R = Ph or OBz) at the allylic position (equation 21)34,39. By contrast, the zinc-induced carbocychzations were found to be moderately cis stereoselective when an acyloxy group was present at the allylic position (see Section II.B.2)29. 

Keller E, Feringa BL. Catalytic enantioselective annulations via 1,4-addition-aldol cyclization of functionalized organozinc reagents. J. Am. Chem. Soc. 1999 121 1104-1105. 

Typical procedure for the cyclization of propargylic organozinc reagents 330... 

Chapter 3 by Jie Jack Li presents a collection of very interesting total syntheses of naturally occurring indole alkaloids where palladium chemistry plays a central role in the syntheses. Five different types of palladium-mediated reactions are treated (I) oxidative cyclization reactions promoted by palladium (II) species (2) transmetallation reactions with organoboranes, organoslannanes, and organozinc reagents (3) inter- and intramolecular Heck reactions (4) reactions with it-allylpalladium as the intermediate and (5) reactions using C-N bond formation as the key step for the synthesis. 

Hajjem and Baccar used cyanomethylimidates as substrates for addition of organozinc reagents to prepare (3-ketoimidates that cyclized to 2,5-disubstituted-oxazoles as shown in Scheme 1.95. For example, addition of an alkenylzinc... 

The reaction proceeds via a radical intermediate and can be used to perform radical cyclizations affording flve-membered rings. However, the products of these reactions are organozinc reagents, which can be reacted with a wide range of electrophiles. 

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