Regioselectivity chiral dipolarophiles

The asymmetric induction on the 1,3-dipolar cycloaddition reaction of carbonyl ylides has also been studied using chiral dipolarophile. The Rh2(OAc)4-catalyzed reactions of o-(methoxycarbonyl)diazoacetophenone 89 with enantiomerically pure vinyl sulfoxides 103 afforded 4,10-epoxybenzo-[4,5]cyclohepta[l,2-c]furan-3,9-dione 105, in good or moderate yield with complete regioselectivity [113]. The endo stereoisomer 105a is favored with respect to the exo isomer 105b and interestingly, high diastereoselectivity and complete enantioselectivity have been achieved (Scheme 32). 

Another approach to obtain pure enantiomers of isoxazolines involves the use of chiral acrolein aminals, formed with A.A -substituted diaminodiphenylethanes (194). Thus, with this chiral imidazolidinyl auxiliary in the p-position, and with unsaturated esters serving as the dipolarophile, benzonitrile oxide afforded only one regioisomeric cycloadduct with good stereoselectivity (194) (Scheme 6.40). When the analogous A,A -dimethyl auxiliary was chosen, excellent stereoselectivity was accompanied by poor regioselectivity (194). 

Dipoles are the three-atom components of [3+2]-cydoadditions. These are 4n electrons species, so [3+2]-cycloadditions are thermally allowed according to the rules of orbital symmetry [624g], The interactions between the frontier orbitals of the two partners are of prime importance, and concerted reactions take place in a supra-suprafacial fashion. When the 1,3-dipoles are not symmetrical, their reactions with unsymmetrical dipolarophiles may give regioisomers. Lack of regioselectivity limits some types of cycloadditions. Chirality can be introduced other on the dipole or on the dipolarophile. 

The reactions of diazoalkanes 9.21 with alkenes lead to pyrazolines 9.22, which are thermally transformed into cyclopropanes. Similar transformations occur during thermal reactions of diazoesters. The use of diazoesters of chiral alcohols did not give useful results, so chiral residues have been introduced on the olefin dipolarophile. Meyers and coworkers [327] carried out the reaction of diazomethane 9.21 (R = R = H) and diazopropane 9.21 (R = R = Me) with chiral lactams 1.92 (R = i-Pr or ferf-Bu, R = Me). These 1,3-dipolar cycloadditions are regioselective, but only CH2N2 leads to an interesting stereoselectivity (Figure 9.9). Morever, when the RM substituent of lactam 1.92 is H, the reaction is no longer stereoselective. 

Scheme 13). The 1,3-dipolar cycloaddition of diethyl fumarate with the chiral and enantiomerically pure )3-fluoromethyl nitrone (R)- 35) produced two diastereoiso-meric isoxazolidines, (3f ,45,5iS,l f )-(36) and (35,4f ,5/f,T/()-(37) in a 5.5 1 ratio in 72% overall yield (Scheme 14). The 3 -I- 2-cycloaddition of nitrones with unsaturated methyl sulfones yields substituted isoxazolidines whose regiochemistry depends on the nitrone and the vicinal electron-withdrawing group of the dipolarophile. The 3 -I- 2-cycloaddition of sugar nitrones with sugar nitro alkenes produces 4,5-fra s-4-nitroisoxazolidines with complete regioselectivity and stereoselectivity. MO... 

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