Zinc enolates cyclization

The method involves a regioselective, trans-diastereoselective, and enantioselective three-component coupling, as shown in Scheme 7.26. In this case, the zinc enolate resulting from the 1,4-addition is trapped in a palladium-catalyzed allyla-tion [64] to afford trans-2,3-disubstituted cyclohexanone 96. Subsequent palladium-catalyzed Wacker oxidation [82] yields the methylketone 97, which in the presence of t-BuOK undergoes an aldol cyclization. This catalytic sequence provides the 5,6-(98) and 5,7- (99) annulated structures with ees of 96%. 

However, an even more efficient access to functionalized pyrrolidines was developed relying on a zinc enolate cyclization (see Section V.B). 

It is also worth mentioning that such cyclizations could be achieved for a-aminoesters bearing the amino group located outside of the chain. Indeed, Chemla and coworkers recently reported that the a-aminoester 421 successfully underwent a zinc-enolate cyclization, according to the standard conditions, and afforded after hydrolysis the five-membered ring tertiary amine 422 as a 80/20 mixture of diastereomers (equation 182)264. 

The zinc-enolate cyclizations are not restricted to a-aminoesters as /3-aminoesters have also been successfully involved in such reactions275. The preformed lithium enolate generated by treatment of the /J-arninoester 423 with LDA had to be added dropwise to an ethereal solution of ZnBr2 in order to avoid a competing /3-elimination reaction induced by the zinc enolate. this reverse addition protocol was respected, a smooth carbocyclization reaction occurred and provided, after hydrolysis, the substituted 3-carbomethoxypyrrolidine 424 as a 87/13 mixture of diastereomers (equation 183). 

Zinc(O) is capable of reducing alkyl halides. The interplay of the reductive action of zinc and the ability of aluminum Lewis acids to activate the carbonyl group enabled effective generation of aluminum enolates from a-bromo carbonyl compounds (Scheme 6.25) [45]. This method is convenient for aldol cyclization reaction, producing macrolactones in moderate to high yields. Note that the possibility of a zinc enolate, rather than the aluminum enolate, promoting the actual reactions could not be excluded. 

Zinc enolates of (V -bissilylglycine esters, according to van Koten and coworkers, condense with N-silylimines with high anti selectivity (Table 20 entries 18-20). °° These results parallel those previously described in Section 4.1.3.2.2.i using N-ary - and A/-alkyl-imines and are consistent with a C(Z,E)t transition state. Reactions of N-silylimines are slightly less anti selective, however, than those of N-aryl- and A/-alkyl-imines. Retroaldolization prior to cyclization has been cited as a possible cause for the erosion in stereoselectivity based on the slow rates of cyclization found in the reactions of entries 19 and 20. 

The intramolecular ene reaction with an enol as the ene component is known as the Conia reaction. Very high temperatures are normally required and more efficient is the use of a cobalt catalyst or the use of a zinc enolate. Thus, formation of the zinc enolate 257 from the ester 256 promoted cyclization at room temperature to give, after quenching the intermediate organozinc species with a proton, the cis pyrrolidine 258 (3.164). 

In the synthesis of lumisterin steroid a D ABCD approach was used [151]. A key step is the Co-induced cyclization of cyclopentanoid ene-diynes prepared by thioalkylation of 2,3-substituted cyclopentanone zinc enolates with a-chlorosulfides. 

Although direct oxidation is sometimes possible (54CCC282), N- or S-oxides and dioxides are normally prepared by indirect routes. 3,6-Dihydro-l,2-oxazines can be reduced catalyti-cally to their tetrahydro derivatives, but zinc and acetic acid cause ring fission to 4-aminobut-3-enols which cyclize to dihydropyrroles (54MI22700). 

Substitution of the acetate group at the C-3 position of the /3-sultam 105 can occur by reaction with silyl enol ethers in the presence of zinc iodide or zinc chloride. When the diazo compound is used, after desilylation with tetrabutyl-ammonium fluoride (TBAF), photochemical cyclization gives the bicyclic /3-sultam 106 as a mixture of two cis/ fra -diastereoisomers. When silyl enol ethers derived from cyclic ketones are used, the substitution product is stabilized by a retro-Michael-type reaction leading to open-chained sulfonamides 107 (Scheme 31) <1997LA1261>. 

Carboxylic acids (511) and their chlorides, anhydrides, amides, esters and nitriles, condense with o-aminothiophenols (507) or their zinc salts, affording 2-substituted benzothiazoles (513), the only exception being acetic acid. The intermediate o -acylaminothioph-enols (512) could be isolated and readily cyclized. The activation of carboxylic acids in... 

Subsequent hydroboration of endocyclic enol ether 5 proceeded stereoselectively to give alcohol 6, which was further oxidized with tetra- -propylammorrirrm perrutherrate (TRAP) and A-me% lmorpho-line 7V-oxide (NMO) (Ley et al. 1994) to afford ketone 7. Oxidative removal of the /r-methoxyberrzyl (PMB) group followed by treatment with ethanethiol and zinc triflate effected cyclization of the D-ring... 

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