Nitrones double asymmetric induction

The 1,3-dipolar cycloadditions of nitrones (551), (595), (614), (615) and their enantiomers (595 ent), (614 ent), (615 ent) (Fig. 2.40) to a.p-unsaturated y-lactones, such as achiral D7 g and D-glycero D7 h, provide an interesting example of double asymmetric inductions. The reactions are kinetically controlled. However, on heating and at longer reaction times, the reversibility of the cycloaddition (595 + D7 h) was observed, and the presence of a more stable thermodynamic product (620) was detected. Moreover, in the case of lactone D7 h, a... 

Langlois and co-workers (179) found the same exo stereochemical preference through double asymmetric induction of a related ene-lactone (1 )-145 with their well-explored and efficient camphor-derived oxazoline nitrone (150-146 (Scheme 1.32). They found the cycloaddition components form a matched pair and allowed kinetic resolution of the racemic lactone in up to 70% enantiomeric excess (ee). They suggest the selectivity for exo adduct 147 arises through destabilization of the endo transition state by a steric clash between dipolarophile ring hydrogens and the bornane moiety. 

The chemo-, regio-, and stereo-selective 1,3-dipolar cycloaddition of C-aryl-iV-phenylnitrones with 3,5-bis(arylidine)-l-methylpiperidin-4-ones produced mono- and bis-spiroisoxazolidines, with the former predominating.52 The 1,3-dipolar cycloaddition of five-membered cyclic nitrones with a, fl-unsaturated y-lactones provides an interesting example of a double asymmetric induction.53 Eu(fod)3 catalysed the ... 

With both substituted nitrones and substituted lactones, double asymmetric induction can increase the stereoselectivity of the cycloaddition. For example, the cycloaddition of nitrone 239 with lactone 240, which represents a matched set, provides only cycloadduct 241 in 81% yield (Scheme 46) (2006TA68). Alternatively, the reaction of mismatched set 243 and 240 produced a mixture (45 32 23) of 244, 245, and 246 in 77%... 

Achiral ester-substituted nitrones as well as chiral nitrones can be employed in diastereoselective asymmetric versions of tandem transesterification/[3 + 21-cycloaddition reactions, as shown in Scheme 11.54 (174). High diastereoselectivity and excellent chemical yields have been observed in the reaction with a (Z)-allylic alcohol having a chiral center at the a-position in the presence of a catalytic amount of TiCl4- On the other hand, the reaction with an ( )-allylic alcohol having a chiral center at the a-position, under similar conditions, affords very low selectivities. Tamura et al. has solved this problem with a double chiral induction method. Thus, high diastereoselectivity has been attained by use of a chiral nitrone. 

Asymmetric induction can be also accomplished through the use of a chirally modified nitro olefin. Sugar-based nitroalkenes participate in thermal [4 + 2] cycloaddition to form enantiomerically pure nitronates [55,97]. Alternatively, diastereoselective cycloadditions are possible with chiral nitroalkenes as illustrated on Scheme 16.15 [47]. The tandem double intramolecular cycloaddition of enantiopure nitro-alkene 62 containing a single stereogenic center provides nitroso acetal 63 with high diastereoselectivity (relative to the existing center) in moderate yield. The product is isolated as a mixture of isomers that is formed due to epimerization of the intermediate nitronate (not shown) and used toward total synthesis of daphnilactone B. 

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