Ring-modifying reactions

Anilines react with ct-haloacetophenones to give 2-arylindoles. In a typical procedure an W-phenacylaniline is heated with a tw o-fold excess of the aniline hydrobromide to 200-250°C[1]. The mechanism of the reaction was the subject of considerable investigation in the 1940s[2]. A crucial aspect of the reaction seems to be the formation of an imine of the acetophenone which can isomerize to an aldimine intermediate. This intermediate apparently undergoes cyclization more rapidly (path bl -> b2) than its precursor (Scheme 7.3). Only with very reactive rings, e.g, 3,5-dimethoxyaniline, has the alternative cydiz-ation (path al a2) to a 3-arylindole been observed and then only under modified reaction conditions[3],... 

By a modified Bischler-Napieralsky reaction, 6 -nitrophenylaceto-jS-3 4-methylenedioxyphenylethylamide, resulting from the condensation of -3 4-methylenedioxyphenylethylamine with 2-nitrophenylacetyl chloride, was converted into 6 nitro-l-benzyl-6 7-methylenedioxy-3 4-dihydroisoquinoline. The methiodide of the latter was reduced with zinc and hydrochloric acid to 6 -amino-l-benzyl-2-methyl-6 7-methylenedioxy-1 2 3 4-tetrahydro/soquinoline dihydrochloride, which by the Pschorr ring-closure reaction, produced dZ-roemerine (IV, p. 317), m.p. 85-7°. By treatment in succession with d- and Z-tartaric acids, the dZ-base was resolved into Z- and tZ-forms. Synthetic Z-roemerine is dimorphic, m.p. 85-7° and 102°, and has [aju — 79-9° (EtOH), these constants being in good agreement with those of the natural base. 

A very powerful inhibitor, which is a bicyclic analogue of (33), is 6-acetamido-6-deoxycastanospermine (49), a compound synthesized from castanospermine and tested by Liu and co-workers [99]. This compound, amongst many other 6-modified castanospermine derivatives, was also prepared by the Furneaux team [100]. Furthermore, by controlled ring-contraction of suitably substituted castanospermine derivatives, these workers gained access to 8-acetamido-8-deoxyaustraline (50), a byciclic analogue of l-acetamido-l,2,5-trideoxy-2,5-imino-D-mannitol (44). This ring contraction reaction, which proceeds via a tricyclic aziridinium intermediate, is based on the same principle as the approach by Peter et al. to compound (45) [95]. 

Some related ring-expansion reactions utilizing a modified version of the pinacol rearrangement, as shown for the formation of 8,45 9,46 and 10,47 have been performed. In particular,... 

Carbometallation is a term coined for describing chemical processes involving net addition of carbon-metal bonds to carbon-carbon Jt-bonds [1] (Scheme 4.1). It represents a class of insertion reactions. Whereas the term insertion per se does not imply anything chemical, the term carbometallation itself not only explicitly and clearly indicates carbon-metal bond addition but also is readily modifiable to generate many additional, more specific terms such as carboalumination, arylpalladation, and so on. In principle, carbometallation may involve addition of carbon-metal double and triple bonds, that is, carbene- and carbyne-metal bonds, as well as those of metallacycles. Inasmuch as alkene- and alkyne-metal Jt-complexes can also be represented as three-membered metallacycles, their ring expansion reactions via addition to alkenes and alkynes may also be viewed as carbometallation processes (Scheme 4.1). 

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