Diastereoselection allylic zinc reagents

SCHEME 51. Diastereoselective reactions of substituted allylic zinc reagents generated by fragmentation... 

Barbier-type additions are attractive methods because the required allylic halide precursors are often commercially available, and are more stable than a preformed organometallic reagent (Equation 5). The required 2-alkoxycarbonyl allylic zinc reagents can be prepared from zinc powder. Lactonization tends to occur under the reaction conditions however, the diastereoselectivity of the reactions tends to be poor with 3-substituted reagents. Zinc-mediated Barbier-type allylations are mild enough for use with functionalized substrates and can utilize both aldehydes and ketones as substrates. 

The addition of substituted allylic zinc reagents to aldehydes proceeds with moderate diastereoselectivity. Besides, the direct zinc insertion to substituted allylic halides is complicated by radical homocoupling reactions. Both of these problems can be solved by using the fragmentation of homoallylic alcohols. Thus, the ketone 329 reacts with BuLi providing a lithium alcoholate that, after the addition of ZnCb and an aldehyde, gives the expected addition product 330 with an excellent diastereoselectivity. 

Its trapping with various electrophiles provides chiral products, such as 137-139. The deprotection of 139 furnishes the -alkynylaldehyde 140 in 88% ee. The exo-alkylidene acetal 141 is converted similarly to the zinc reagent 142, which can be allylated with an excellent diastereoselectivity (d.r. = 96 4) leading to the ketal 143 (Scheme 44) " . 

Tri-O-benzyl-D-glucose is an efficient and practical chiral auxiliary. If allylic alcohols are fixed as /3-glycosides they can be cyclopropanated by an excess of the diiodomethane/diethyl-zinc reagent with excellent diastereoselectivities. Since the removal of the auxiliary proceeds under mild conditions, this method allows the synthesis of a variety of cyclopropane carbinols in very high enantiomeric excesses96. 

Readily available functionalized aryl siloxanes are also viable cross-coupling partners for Pd(dba)2-catalyzed allylic arylations. A mixture of 5% Pd(dba)2, allylic halide, and in situ-generated aryl zinc reagent produces allylated arenes in high yield. Aryl boronic acids have been converted to allylated arenes as well. Diastereoselective intramolecular Stille-type coupling of two allylic moieties (aUylic acetate and allylic stannane) has been performed in high yield to produce the key intermediate in the synthesis of racemic 10-ep/-elemol (eq 19). ... 

Oppolzer and co-workers have reported that the magnesium-ene reaction is a versatile method for intramolecular addition of allylic magnesium reagents to alkenesP A zinc-600 ° reaction can be initiated by the addition of -BuLi to the tert-butyl ketone 331 followed by the addition of zinc chloride. The resulting zincated spiro-derivative 332 could be quenched with an acid chloride leading to the ketone 333 in 60% and >98% syn-diastereoselectivity (Scheme 2-114). ° ... 

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. 

---