Asymmetric reactions quaternary carbon center formation

Pd-catalyzed Heck reactions are among the most effective methods for the formation of quaternary carbon centers. Considering the significance and the strategic difficulties associated with the synthesis of quaternaiy carbons, particularly in the optically enriched or pure form, it is not a surprise that the development of catalytic asymmetric Heck reactions has held center stage for the past few years. One of the leading labs in this area is that of Shibasaki, who in 1993 reported a concise total synthesis of eptazodne 23 (Scheme 4).141 Thus, treatment of silyl ether 18 with 10 mol% Pd(OAc>2 and 25 mol% (S)-19 leads to the formation of 20 in 90 % yield and 90% ee As illustrated in Scheme 4, once the quaternary carbon center is synthesized efficiently and selectively, the target molecule is accessed in a few steps. 

The formation of a quaternary carbon center by the radical-mediated allylation of an a-iodolactone was examined for substrate 341 by Murakata, Jono, and Hos-hino [71]. Lewis acids for this reaction were prepared from a bis-sulfonamide and tri-methylaluminum in dichloromethane. Other aluminum compounds were employed in the preparation of the catalyst but all resulted in similar or lower asymmetric induction. The Lewis acid was complexed with the lactone and then the allylation procedure in Sch. 44 was performed. It was found that superior asymmetric induction could be achieved if the Lewis acid was prepared from the ligand with two equivalents of trimethylaluminum. It was also interesting that some turnover could be achieved, as indicated by the data obtained from use of 50 mol % catalyst. 

The asymmetric induction in the formation of 214 stems from an eiiantiodifferentiation of two double bonds. The intramolecular jr-enantiofacial discrimination (cf. Scheme 3-49 for the intermolecular version) has also been successful, as shown by the asymmetric construction of quaternary carbon centers in the preparation of spirooxindoles 217 from 216 (Scheme 3-51). It is amazing that each product enantiomer was obtained selectively by careful choice of reaction conditions and, remarkably, by applying exactly the same enantiomer of the chiral phosphane ligand [122]. 

The asymmetric induction in the formation of362 stems from a differentiation of two enantiotopic double bonds in the same molecule. The intramolecular discrimination between the two enantiofaces of the same double bond (cf Scheme 8.73 for another intramolecular version) has also been achieved, for example, with the asymmetric constmction of quaternary carbon centers in the preparation of spirooxindoles 365 from 364 (Scheme 8.75). It is particularly noteworthy that either of the two product enantiomers could be obtained selectively by careful adaptation of the reaction conditions, yet with exactly the same enantiomer of the chiral phosphine Hgand [205]. 

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