Grignard reagents kinetic resolution

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

The availability of non-racemic oxepins through tandem catalytic RCM and Zr-catalyzed kinetic resolution has additional important implications. Optically pure heterocycles that carry a heteroatom within their side chain (cf. (S)-14 in Scheme 3) can be used in stereoselective uncatalyzed alkylations. The alcohol, benzyl ether or MEM-ethers derived from (S)-14 readily undergo directed [10] and diastereoselective alkylations when treated with a variety of Grignard reagents [11]. 

Another approach to chiral sulfinates was developed by Pirkle and Hoekstra (108) it is based on incomplete but stereoselective reaction of racemic sulfinates with chiral Grignard reagents. This kinetic resolution affords the unreacted sulfinates enriched in the (5 -enantiomers with optical purities in the 8-64% range. The chiral cyclic sulfinates 66 and 67 were first obtained by this method. 

Hayashi et al.74 described a process of kinetic resolution in the coupling of Grignard reagents R Mgx (having a chiral center at the point of attachment to the metal) with various alkenyl halides under the influence of chiral phosphine-nickel complexes. Chiral amino acid derivatives (35) were used as ligands. 

The kinetic resolution of racemic 1-phenylethyl Grignard reagent 2a was also observed in the cross-coupling with allylic substrates, such as allyl phenyl ether, in the presence of NiC12[(S, .S )-chiraphos (81)] which gave (/ )-4-phenyl-1 -butene (56) with 58% ee [59] (Scheme 8F.19). 

Stereoselective chelate-controlled addition of Grignard reagents to tetrahydrooxepine derivatives (Equation 3) involves Zr-catalyzed kinetic resolution with (i )-[EBTHI]Zr-BINOL (BINOL= l,l -bi-2-naphthol) <1996JA4291, 1997JA6205, 1999JOC854>. 

Selenenylated Grignard reagents, generated by transmetalation with magnesium bromide, have a higher stability than their lithium counterparts. They were enantiomerically enriched by kinetic resolution resulting from reactions with (S)-a-benzyloxypropionaldehyde and benzaldehyde successively [24] (Scheme 22). 

Y. Okamato, K. Suzuki, T. Kitayama, H. Yuki, H. Kageyama, K, Miki, N. Tanaka, and N. Kasai, Kinetic resolution of racemic methylbenzyl methacrylate Asymmetric selective polymerization catalysed by Grignard reagent-(-)-sparteine derivative complexes, /. Am, Chem, Soc., 104 4618 (1982). 

This reaction can be considered a kinetic resolution of a secondary Grignard reagent. However, fortunately, an unreacted enantiomer of the Grignard reagent immediately racemizes to again enter the process of kinetic resolution. Thus, finally all of the Grignard... 

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