Enantioselective allylzincation

Nakamura et al.141 reported a closely related reaction, that is, the enantioselective addition of allylzinc reagent to alkynyl ketones catalyzed by a bisox-azoline catalyst 137. High ee values were obtained in most cases (Scheme 2-55). 

TABLE 9.33. ENANTIOSELECTIVE ADDITION OF ALLYLZINC REAGENTS TO CYCLIC IMINES ... 

Bis(oxazoline) ligands have been shown to be useful in the many carbon-carbon bond-forming reactions previously listed. They have also been used in a myriad of other carbon-carbon bond-forming reactions. For example, Nakamura and coworkers used bis(oxazoline) ligands ent-2, ent-22, and ent-39 in ligand-induced enantioselective allylzincation. This reaction consisted of the transformation of the cyclopropenone acetal 198 into allylic cyclopropanone acetal 199 in yields ranging from 73 to 90% with selectivities from >98 2 for the isomer shown to 1 99 (Fig. 9.57). 

Addition of an allylic zinc reagent to cyclic aldimines has been reported129. Lithiated bisoxazoline 61 and allylzinc reagent form the reactive species, which adds to a cyclic aldimine enantioselectively with up to 97.5% (equation 29)129. 

The first example of enantioselective allylzincation of an alkene was also reported for the cyclopropenone ketal 78 as substrate. The chiral allylzinc complex 135 was prepared from the corresponding bis-oxazoline derived from (,V)-valine by deprotonation with n-BuLi and transmetallation with allylzinc bromide. This reagent reacted with 78 and afforded the allylated product 136 with high optical purity ( = 99%) (equation 66)101. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

Table 2 Ligand-induced enantioselective allylzincation of cyclopropyl acetals ...

The chiral allylzinc complex also reacts with chiral aldimines to afford allylated secondary amines in high enantioselectivity. For the acyclic (E)-benzaldehyde IV-phenylimine, the amine was... 

Enantioselective allylmetallation of chiral cyclopropene ketal is also possible [135] as well as allylmetallation of the achiral ketal but with the acid of chiral bisoxazoline (BOX) ligands [136] (Scheme 7-117). The chiral allylzinc reagents were much more reactive than the parent allylzinc bromide. 

Reaction of the homochiral organozinc reagent 24 or its antipode 25 to cyclopropenone acetals leads to enantioselective allylzincation (see Table 5). ... 

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 enantioselective asymmetric allylation of imines has been a synthetic challenge, the initial solutions of which required stoichiometric amounts of chiral allylbor on [87], allylsilane [88], allylzinc [89], or allylindium reagents [90]. Itsuno showed that a chiral B allyloxazaborolidine derived from norephedrine could add to the N trimethylsilyl imine prepared from benzaldehyde in high yield and enantiomeric excess (Scheme 1.22) [91]. Brown later reported that B allyldiisopinocamphenylbor ane is also very effective for the allylation of the same electrophiles, but the addition of a molar amount of water is necessary to obtain high yields [92]. The diastereo and... 

Following their earlier findings on the enantioselective allylzincation of cy-clopropenone acetals [43], Nakamura and co-workers investigated the same reaction with imines of aromatic aldehydes [44]. In an initial experiment, ( )-ben-zaldehyde N-phenyl imine (59) was treated with preformed chiral allylic zinc reagent 57a (R=z-Pr) obtained by mixing a lithiated bis(oxazoline) (55, R=z-Pr) with an allylic zinc bromide (56a) (Scheme 22). The allylation product was obtained in 95% yield, but the enantioselectivity was only 6% ee. Fortunately, the enantioselective allylzincation of Z- (i.e., cyclic) aldimines was more successful. 

Another interesting enantioselective transformation under high pressure was reported by E. Nakamura et al. in the construction of quaternary carbon centers by allylzincation [84]. The allyl zink reagent, 185 possessing an anionic bisoxazoline (BOX) ligand was used to deliver the allyl nucleophile to the alkene 184 regio-... 

Cyclopropanone acetals with a quaternary carbon atom in chiral form can be established by addition of bisoxazoline-ligated allylzinc reagents to the cyclopropenes.The t-BuLi/(-)-sparteine combination favors Br-Li exchange and also promotes enantioselection in the intramolecular addition of aryllithium to an o-alkenyl side chain (e.g., indoline synthe-j.ijj) I28.I29 Moderate asymmetric induction is shown in the hydroarylation of norbomene in the presence of 63. 

Addition to C=X bond. Allylzinc reagents add to the carbonyl group of p-keto phosphonates. With respect to a catalytic enantioselective synthesis of chiral pyrimidyl carbinols, an automultiplication phenomenon is elucidated. ... 

A nickel-catalyzed carbozincation in which an allylzinc adds across the double bond of an unsaturated acetal has also been reported (Scheme 79). ] This procedme effectively provides a reverse-polarity approach to the functionalization of unsaturated carbonyl derivatives. Non-allylic Grignard reagents, however, add to cychc unsaturated acetals with the opposite regiochemistry. This latter procedure provides the basis for an enantioselective conjugate addition to cyclic enones (in 53% ee for the cyclopentenyl substrate and 85% ee for the cyclohexenyl homologue). ... 

---