Regioselectivity diazoalkane cycloaddition reactions

Whereas the Rh2(OAc)4-catalyzed addition of diazoalkanes to propargyl alcohols readily gives the insertion of the carbene into the 0-H bond, with only a small amoimt of cyclopropenation of the resulting propargylic ether [54] the 2-diazopropane 59 reacts at 0 °C with l,l-diphenyl-2-propyn-l-ol 62a in dichloromethane and exclusively gives, after 10 h of reaction, only the adduct 63a isolated in 75% yield and corresponding to the regioselective 1,3-dipolar cycloaddition of the 2-diazopropane to the alkyne C - C bond (Scheme 15). 

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. 

Although from the conceptual point of view such a simple qualitative picture is completely clear, the practical discrimination between the individual alternative reaction paths can be, in a given case, quite complicated. The best that can be done in these cases is to calculate the energies of the molecular oibitals by some quantum chemical method. The typical example where such subtle effects of the quantitative nature play the role is the regioselectivity of 1,3 dipolar cycloadditions [44,45], which is the cycloaddition of substituted alkenes, called in this coimection dipolarophiles, with the so-called 1,3 dipoles as, e.g., azides, diazoalkanes, nitriloxides, nitrones and some other, usually rather unstable species. 

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