Lewis Acid Mediated Reactions Of Hydroxymethylcyclopropanylam-Ides Derivatives

The chemistry of three-membered rings has come a longway in the 120 odd years, since the first cyclopropane derivatives were synthesized by William Henry Perkin in Munich in the laboratory of the eminent chemist Adolf von Baeyer. At that time, only some five- and mainly sixmembered rings had been found in natural products,and no- body would have anticipated that cyclopropanes are actually abundant in nature. In his book"Terpenes and Camphor", Otto Wallach, another eminent chemist of his time, in 1909 already summarized the chemistry of terpene hydrocarbons like sabinene and thujene in which he identified carbocyclic three-membered rings. Chrysanthemic acid, which was identified by Staudinger and Ruzicka in 1924, was probably the first natural product containing a cyclopropane moiety that exhibited an important biological activity. Ever since, the number of newly discovered cyclopropane natural products has been increasing from year to year.This indicates that the three-membered carbocycle, despite its signifyant ring strain, attributed to it as early as 1885 by Adolf von Baeyer, can be formed rather easily. Most of the simple cyclopropane derivatives are actually prepared by such 1,3-elimination reactions A great advance in the synthesis of cyclopropanes was initiated with the discovery of carbene additions to alkenes in 1955 ,and it is mainly due to the rapid development of carbene chemistry in the second half of thelast century, but also to new photochemical and other strikingly simple transfo- mation leading to three-membered carbocycles, that almost any kind of structure appears to be achievable in cyclopropane chemistry nowadays.Cyclopropanes are extremely versatile building blocks in organic synthesis owing to their ready accessibility and good reactivity. Since the first report by Cloke in 1929 that cyclopropyl ketones can be transformed into dihydrofuran derivatives, the synthetic applications of cyclopropyl ketones have been well studied., Comparatively although the studies on the synthetic utility of cyclopropyl amides are relatively fewer.c-Iminolactones, dihydroquinolin-2-ones, and c-lactames have been synthesized starting from a-hydroxymethylcyclopropanylamides, mediated by SnCl₄/NaI/NEt₃, BF₃·OEt₂, and TiCl₄/NEt₃. The corresponding products were produced, respectively, in high to excellent yields. β-Hydroxymethylcyclopropanylamides have the structure characters of both cyclopropyl amides, and cyclopropyl carbinol. On treatment with an acid, cyclopropyl carbinyl cation intermediate could be formed from cyclopropyl carbinol. This carbocation will undergo either ring expansion to give a cyclobutyl cation or ring cleavage to give a homoallyl cation8 to relieve ring strain.