Diastereoselective allylzincation

Scheme 40 Diastereoselective addition of y-substituted allyllithium and allylzinc reagents to a chiral diimine...

The high diastereoselectivity observed is remarkable, particularly in view of the fact that addition of substituted allylzinc halides to aldehydes usually occurs without diastereoselectivity31. The high level of stereoselectivity in the allylation reaction was rationalized by a Zimmermann-Traxler chair-like transition state30. 

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. 

An alkoxy group at the -position induces a cyclopropanation reaction of the dimetallic species as shown in equation 46. The formation of the gem-dimetal species proceeded diastereoselectively as described above. The ring closure proceeds with inversion of configuration to form stereospecifically the cyclopropane ring. An alkoxy substituent at the -position of the allylzinc reagent also induces the cyclopropanation reaction (equation 47)61a 72. 

Metallated allylic ethers can also be used as partners in allylzincations of alkenyl-metals144. Allyl methyl ether could be metallated with s-BuLi in ether provided that TMEDA was present and, after transmetallation with ZnBr2, addition to the alkenyl-lithium derived from 205 proceeded slowly at room temperature. Nevertheless, after hydrolysis the corresponding allylic ether 227 was obtained with high diastereoselectivity (equation 110)146. 

Substrate-induced diastereoselection has also been achieved in the case of alkenyllithium reagents derived from (Z)-5-iodo homoallylic ethers152,153. Thus, the allylzincation of the alkenyllithium derived from 230 proceeded efficiently in ether at — 20 °C and led after hydrolysis to 231 as a single diastereomer (equation 112). 

For alkenylmetals bearing two stereocenters at both the allylic and homoallylic positions, two situations have to be distinguished depending on their relative influence (matched or mismatched) with respect to the stereochemical outcome of the allylzincation. Not surprisingly, in the matched case, as illustrated for substrate 232, the diastereoselectivity was excellent and 233 was obtained as a single diastereomer. The allyl moiety was delivered anti to both the allylic and homoallylic substituents in the chelated allyl alkenylzinc species (equation 113). 

Interestingly, in the mismatched manifold, the diastereoselectivity seemed to be controlled by the more remote homoallylic stereocenter. The allyl moiety was apparently delivered syn to the allylic substituent, as illustrated for the allylzincation of the organo-lithium derived from 234 which led to 235 with high diastereoselectivity (equation 114). 

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... 

Allylzincation of alkenylmetals provides a useful entry to the diastereoselective synthesis of sp3 yem-dirnclallic species that can react with two different electrophiles in a one-pot protocol, leading to elaborated acyclic structures with control of the configuration of up to three adjacent stereocenters, as well as to cyclopropanes bearing various substitution patterns126,163. 

By this way, from two prochiral vinylic carbon atoms, two stereogenic centres were created with good diastereoselectivity. Knowing that the chelation between zinc and heteroatoms in w-heterosubstituted dialkylzinc reagents has already been shown by NMR studies,14 the allylzincation of substituted y-heterosubstituted vinyl metals has been studied.13,15 In all cases, the chelation promotes a difference between the two prochiral faces of the vinyl moiety since one is shielded by the alkyl group, and then the allyl13,15,16 or the substituted allylmetal13,1517 (Equation 7.4 and Protocol 6) reacts diastereoselectively. 

The issue of double stereodifferentiation has also been addressed with a substituted allylzinc bromide, e.g., cinnamyl bromide, and leads to modest diastereoselectivity. Indeed, the C(3)/C(4) diastereoselectivity was 73 27 with 60% ee as described in Scheme 7-118, but the use of a bulkier BOX ligand (R = /-Bu) improved the latter to 97% ee whereas the C(3)/C(4) selectivity remained at 81 19 [136] (Scheme 7-118). 

Scheme 7-118 Enantio- and diastereoselective allylzincation of a cyclopropenone ketal. by coordination with chiral amines.

Allylation. The reagent can be generated by an in situ fragmentation of allyldi-t-butylcarbinol on treatment with BuLi followed by Li/Zn exchange with ZnBr. The reaction of these allylzinc species with aldehydes is highly diastereoselective ... 

Diastereoselective allylzincations of achiral cyclopropenone acetals, addressing the control of the relative configuration at the newly formed C-C bond (centers C3 and C4) and of chiral derivatives such as 20 (R = H), addressing chirality transmission through a spiro carbon center, have been investigated. In the presence of bis(oxazoline) ligands, enantioselective reactions of this kind can also be performed. ... 

The presence of a substituent at C-2 of the allyl unit also influences the stereoselectivity of allylzinc reactions, in the same way that C-2 substituents influence the reactions of allylchromium (109) and (110) (Schemes 22 and 23). For example, the — ZnBr derivative corresponding to (109) displays syn diastereoselectivity comparable in the best cases to that realized with (109). The reaction of (130) with Zn(Cu) in dilute solution similarly provides (131) with syn stereochemistry about the new C—C bond. Type III diastereoselectivity has been demonstrated in this series, as the ( )-isomer of (130) provides a 3.8 1 mixture of (131) and the corresponding trans-fused lactone. ... 

Diastereoselective reactions of oxime (198) and phenylsulfenimines such as (201) with allyl metal reagents have been described (Scheme 33). The reaction of (198) and allylboronate (144) provides (199) with modest selectivity, while excellent diastereoselectivity was realized in the reactions of (201) and its C-2 epimer with the allylzinc reagent." The corresponding ketone derivatives, however, gave 70 30 mixtures of (204) and (205) upon reaction with diallylzinc, while with allyl Grignard, (205) is almost the exclusive product." The latter result is suggestive of a chelated transition state. 

Organozinc chlorides. To avoid generation of dibenzyls during preparation of benzylic zinc reagents from ArCH2Cl in THF, a protocol exploits the beneficial effect of LiCl. Allylzinc chlorides are similarly available, and they add to carbonyl compounds with excellent diastereoselectivity. ... 

Scheme 10.125 Diastereoselective carbocupration/ketone allylzincation of terminal unactivated alkynes [106].

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