Chloroiminium salts, with

Formation of angular-substituted dimethylene-bisimidazole derivatives 386 has been achieved by reaction of the parent bisimidazole 385 with either l-bromo-2-chloroethane or 1,2-dibromoethane (Equation 102) <1997CJC28>. Reaction of the bisimidazole with a bis-chloroiminium salt has also been used to generate a related core structure <2006T731>. 

The Vilsmeier-Haack reagent, a chloroiminium salt, is a weak electrophile. Therefore, the Vilsmeier-Haack reaction works better with electron-rich carbocycles and heterocycles. 

Thus, whilst acid-hydrolysis of 21 provided 27, N-methylation of the former followed by treatment of the resulting chloroiminium salt 29 with aqueous alkali generated 28. A later report [14] described a shorter route to 28 which involved a mild Bischler-Napieralsky reaction of the tertiary carbamate 30 secured from 20 by N-methylation, with a mixture of trifluoro-... 

Starting from the chloroiminium salt we performed the reaction with bis(trimethylsilyl)mercury at low temperature in THF. 

Hexamethylphosphoramide, (MejN)3P=0, reacts with phosgene to give an interesting chlorophosphonium salt, in a manner similar to the formation of chloroiminium salts (Vilsmeier reagents) cf. Sections 10.2.2.3 and 10.2.7 [1638] ... 

Amides, for example Nyv-dimethylcarboxamides, represented by the general formula (109), react with salt (1) to yield chloroiminium salts (110 Scheme 9). Hydrolysis of these salts affords 2-dimethylamino-methylene amide derivatives (111). If group R in salt (110) is hydrogen, further reaction with salt (1) is possible, giving chloroiminium salts (112). Hydrolysis of these salts (112) affords aldehydes (113). 

Another acylation procedure uses iminium salts rather than acyl halides. The Vilsmeier-Haack reaction is a well-known process illustrated by reaction of pyrrole with the POCI3 complex of N,N-dimethylacetamide (207, which can decompose to a chloroiminium salt). The acylation reaction gave 208, which was converted to 2-acetylpyrrole by hydrolysis with aqueous sodium acetate.A synthetic example is taken from Lai s synthesis of indole analogs of mycophenolic acid,l in which 209 reacted with POCI3 and DMF to give a 77% yield of the aldehyde 210. 

Chloroiminium salts produced as shown below are excellent synthons for 1,3-dicarbonyl compounds and can be used in the context of reaction with glycinate. 

For example, efficient syntheses of thioamides and thio-lactams are based on this methodology. Certain types of chloroiminium salts can serve as precursors for high-energy synthetic intermediates. Thus, azomethine ylides were obtained by treatment of -acylamino carboxylic esters with oxalyl chloride (eq 24). ... 

Chloroiminium salts prepared from formaldehyde led to amino-chlorocarbenes when treated with base (eq 25). ... 

The Vilsmeier-H2iack reagent, a chloroiminium salt, is a weak electrophile. Therefore, the Vilsmeier-Haack reaction works better with electron-rich carbocycles and heterocycles. Since pyrrole is very electron-rich, the Vilsmeier-Haack reaction readily takes place. Formylation of methyl pyrrole-2-carboxylate was achieved using the Vilsmeier-Haack reaction. The mechanism is shown below. The resulting methyl 5-formylpyrrole-2-carboxylate, in turn, was converted into nonpeptidic analogues of neurotesin(8-13), which are potential treatment for neuropsychiatric diseases such as schizophrenia and Parkinson s disease. 

Acylation. Acylation is the most rehable means of introducing a 3-substituent on the indole ring. Because 3-acyl substituents can be easily reduced to 3-aLkyl groups, a two-step acylation—reduction sequence is often an attractive alternative to direct 3-aLkylation. Several kinds of conditions have been employed for acylation. Very reactive acyl haUdes, such as oxalyl chloride, can effect substitution directiy without any catalyst. Normal acid chlorides are usually allowed to react with the magnesium (15) or 2inc (16) salts. The Vilsmeier-Haack conditions involving an amide and phosphoms oxychloride, in which a chloroiminium ion is the active electrophile, frequentiy give excellent yields of 3-acylindoles. 

Azetidiniminium salts - ° are available from the reaction of imines with iminium salts derived from tertiary carboxamides. These smoothly react with phosgene "- to yield a-chloroiminium... 

A potentially mote interesting application of the method for asymmetric synthesis - uses chiral a-chloroiminium chlorides as starting material. Best results are obtained with iminium salts derived from (2S)-(methoxymethyl)pyrrolidine. They react with imines in the presence of triethylamine to give opti-... 

Various iminium salts have been studied as reagents for the alcohol to halide transformation (see also 1,173) " for example the chloroiminium phospho-chloridates (75a) and chlorides (75b), prepared from amides with POCI3 and SOCI2, respectively, and the bromoiminium bromides (75c), made from (75b) by treatment with HBr, have been used to convert alcohols to the chlorides and bromides (Scheme 36). 

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