Schmidt reactions with carbocations

The lack of regioselectivity, the limitation that tertiary or benzylic alcohols must be used as precursors to Schmidt reactions with carbocations, and the harsh Lewis acidic... 

As with alkene precursors, there is often a lack of selectivity in Schmidt reactions of carbocations generated from alcohols under acidic reaction conditions. However, the Renaud group reported the first example of an intramolecular Schmidt reaction involving a primary electrophilic carbon center for the synthesis of (-)-indolizidine under nonacidic conditions fScheme 4.1 liP After activation of the alcohol 31 via triflation, alkyl migration and extrusion of molecular N2 occurred smoothly. After subsequent reduction of 32, the desired structure 33 was obtained in high yield and excellent optical purity (98% ee). This concise approach enabled the synthesis of (-)-indolizidine in seven linear steps and 27% overall yield. 

Pearson, W. H., Walavalkar, R., Schkeryantz, J. M., Fang, W. K., Blickensdorf, J. D. Intramolecular Schmidt reactions of azides with carbocations synthesis of bridged-bicyclic and fused-bicyclic tertiary amines. J. Am. Chem. Soc. 1993,115,10183-10194. 

Schmidt Reactions of Alkyl Azides with Carbocations... 

Scheme 7.23 Intermolecular Schmidt reactions of alkyl azides with carbocations...

Traditionally, relative stabilities of carbocations have been derived from the comparison of the rates of solvolysis reactions following the SN1 mechanism, for which the designation Dm + An has recently been proposed [36], The comparison of solvolytic rate constants for substrates of a large structural variety is hampered by the fact that the published solvolysis rates refer to different solvents, different temperatures, and precursors with different leaving groups. Dau-Schmidt has, therefore, converted solvolysis rates of a manifold of alkyl chlorides and bromides to standard conditions, i.e., soiv of RC1 in 100% EtOH at 25° C (Scheme 6) [37]. Although from a theoretical point of view, ethanol is not an ideal solvent for observing unassisted SN 1-type reactions (nucleophilic solvent participation), it has been selected as the reference solvent because most available experimental data have been collected in solvents of comparable nucleophilicity, a fact which made conversions to 100% ethanol relatively unproblematic [38],... 

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