Diastereoselective crotylzincation

Indeed, as shown in Scheme 31, highly diastereoselective crotylzincation of t-butoxy-substituted Z-alkenyl lithium affords. sy 3-geminated organodimetal compound with high diastereoselectivity41. Once the alkenyllithium has a secondary allylic substituent, three... 

When the pure (E) isomer of the vinyl lithium 75 is used as starting material, syn-77 is obtained in 81% yield and with 95/5 dr. This diastereoselection can be accounted for by a kinetically favoured (Z) configuration of the crotylzinc species in a chair-like transition state 76 (cf. path c, Scheme 6). However, the metallo ene pathway cannot be ruled out completely and was used sometimes to rationalize the experimental results44. This methodology can also be applied to more functionalized molecules as shown in equation 34.42... 

As shown in Scheme 6, the addition forms two stereogenic centers via the favorable chair-like transition state. The diastereoselective construction of stereogenic centers has been studied extensively by Marek and Normantla. For the control of stereochemistry, one should think about the configuration of allylzinc compounds and the alkenyl metal. Interestingly, a comparison of four possible transition states (Scheme 7) by calculation concludes that Z-crotylzinc bromide is the most favorable transition state. This means that it is not necessary to think about the stereochemistry of crotylzinc bromide as its configuration changes via 1,3-transposition of the zinc atom (Scheme 6)12. 

Based on these investigations, stereochemically defined alkenyllithium is treated with stereochemically undefined crotylzinc to give the adduct diastereoselectively (equation 16)26. Many types of stereoselective reactions will be shown in Section . 

Thus, the alkenyllithium reagent derived from the (X)-y-iodo allylic ether 205 underwent addition of crotylzinc bromide in ether at — 50 °C and, after hydrolysis of the resulting dimetallic reagent, compound 206 was obtained with high diastereoselectivity (anti/syn = 93/7) (equation 101)146. 

Combining substrate-induced diastereoselection and mutual diastereoselectivity, as illustrated for the crotylzincation of the alkenyllithium derived from 209, led to excellent results as the gewt-dimetallic species 217 was obtained in a highly stereoselective fashion. The stereochemical outcome was explained by the addition of the kinetically reactive cisoid metallotropic form of the crotylzinc reagent anti to the propyl group in the chelated allyl alkenylzinc intermediate. After hydrolysis, compound 218 was obtained as a single diastereomer (equation 106)148,149. 

The mutual diastereoselection between the alkenyllithium and the zincated allylic ether turned out to be the same as for a crotylzinc species, and could be rationalized by kinetic addition of a cisoid -alkoxyallylic organozinc compound. 

Although substrate-induced diastereoselection can be conveniently achieved when the alkenylmetal was coordinated by an oxygen atom, other heteroatoms such as sulfur and nitrogen resulted in high inductions as illustrated by the crotylzincation of the organolithium reagents derived from the allylic sulfide 238 or the tertiary amine 239 (equation 117)154. 

Substrate-induced diastereoselective allylzincations essentially rely on coordination of the alkenylmetal by an appropriately located heteroatom, but a zinc-alkene -interaction23 27 can also exert a remarkable stereodirecting effect. Indeed, the alkenyllithium derived from 248, bearing an appropriately located carbon—carbon double bond, underwent highly diastereoselective allyl- and crotylzincations which led after hydrolysis to the corresponding 1,6-dienes 249 and 250. The stereochemical outcome... 

Nevertheless, chiral propargylic amines remain interesting substrates for achieving the diastereoselective addition of substituted allylic organozinc compounds to metallated alkynes. Besides crotylzincation, one example of diastereoselective addition of zincated allyl ethyl ether to 328 has also been reported183. 

Tliis methodology has been generalized to various functionalized molecules y-amino and -arylthio vinylmetals react diastereoselectively with crotylzinc bromide [107] (Scheme 7-93). 

The chelation between zinc and heteroatoms allows a diastereoselective allyl- or crotylzincation of secondary y-heterosubstituted vinyl metals. However, the intramolecular interaction between the metal center and an olefinic site was also described in the case of di(4-pentenyl)zinc [114]. This weak dipolar chelation is the result of the inherent polarity of the Zn - C " bond and the polarity of the double bond (having a partial negative charge on the terminal carbon). Such interactions were evidenced by NMR investigations and the spiro structure of di(4-pentenyl)zinc was postulated to interpret this phenomenon (Fig. 7-1). The oxygen chelation described in Scheme 7-95 is now replaced by a jr-chelation between a vinyl organozinc and an cu-olefinic residue. 

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