Chiral aryl Grignard reagent

Preparation of the chiral biphenyls and binaphthyls with high enantiose-lectivity can be achieved via substitution of an aromatic methoxyl group with an aryl Grignard reagent using oxazoline as the chiral auxiliary.38 Schemes 8-10 and 8 11 outline the asymmetric synthesis of such chiral biaryl compounds. 

F.2.2. Asymmetric Cross-Coupling of Aryl Grignard Reagents Forming Axially Chiral Biaryls... 

In a parallel study, it was found that chelating chiral diamines 208 or 209 are well suited as ligands to promote Kumada-type couplings of primary and secondary alkyl halides 202 with aryl Grignard reagents 203 (entry 4) [281]. This reaction was applicable to alkyl bromides and alkyl iodides, while alkyl chlorides gave only low yields. Acetal and ester functions are tolerated. A notable feature is the stereoretentive arylation of fra s-a-bromo acetals with excellent diastereo-selectivity. The involvement of radicals is supported by the stereoconvergent formation of cxo-phenvI norbornane from both endo- or exo-bromonorbomane (cf. Part 1, Fig. 9) and radical 5-exo cyclizations (see below). 

Preparative Methods chiral titanates are usually prepared by mixing dichlorodiisopropoxytitanium and a chiral 1,4-diol in toluene. Other solvents such as ether and dichloromethane can also be employed. The alcohol exchange reaction takes place immediately at rt. Wherever necessary, liberated isopropyl alcohol is removed by azeotropic removal with toluene. The chiral 1,4-diols are prepared from dimethyl (or diethyl) tartrate by a two-step procedure comprising acetalization followed by the addition of an aryl Grignard reagent. ... 

Addition-elimination. Axially chiral l,l -biphenyl-2-carboxylate esters are obtained by the reaction of 2-menthoxybenzoates with aryl Grignard reagents. Conjugate addition followed by elimination of a malonic ester unit constitutes a useful method for the access to (Z)-alkenes. The reagents are 1,1-dimetalloalkanes. 

Axially chiral biaryls can be also prepared by nucleophilic substitution of tri-carbonylchromium complexes of 2-methoxy-benzoates with aryl Grignard reagents [65]. 

Around the time of Solladie s initial work on 3-ketosulfoxide reduction, Cinquini reported an enantioselective route to chiral amines by reduction of non-racemic N-alkylidene sulfinamides [36]. The A-alkylidene sulfinamide substrates were readily prepared in one pot by addition of alkyl or aryl Grignard reagents to a nonenolizable aromatic nitrile to yield an imino-Grignard intermediate which was allowed to react with (5 )-(-)-menthyl p-toluene sulfinate (Scheme 4.25). The resulting A-alkylidene sulfinamides were found to be enantiomerically pure and of (S) configuration. 

A mild method has been developed for the asymmetric synthesis of a variety of chiral diarylmethylamines via the addition of aryl Grignard reagents to chiral A-2,4,6-triisopropylbenzenesulfinylimines in high yields and high diastereo-selectivitiesJ (g) Higher stereoselectivities are obtained for most of the examples studied when the (g) reactions are performed at ambient temperature as compared to cryogenic conditions (> 95 5 dr). 

Preparation of thiol esters of highly elaborated phosphoranes with thiopyridyl chloroformate has been reported. Treatment of the thiol ester with an aryl Grignard reagent gives the corresponding ketone without epimerization of the chiral centers (eq 7). ... 

In the biphenyl series, axially chiral tri- and tetra-orf/jo-substituted biphenyls 43 are successfully prepared with excellent optical yields from 2-f-butylphenyl 2-(-)-menthoxybenzoic esters 41 and aryl Grignard reagents 42 (Scheme 8.8) [36]. The steric bulk of the ester group prevents the undesired nucleophilic attack of the carbonyl by the aryl Grignard. 

Selim KB, Matsumoto Y, Yamada K, Tomioka K (2009) Efficient chiral N-heterocyclic carbene/copper(I)-catalyzed asymmetric allylic arylation with aryl Grignard reagents. Angew Chem Int Ed 48 8733-8735... 

---