Trichloroacetyl chloride, synthesis

Trichloroacetyl chloride, with pyrrole to give pyrrol-2-yl trichloro-methyl ketone, 51,100 Triethylamine, in synthesis of diazoketones, 50, 77... 

The characteristic pyrolytic process for acid chlorides is loss of HC1 and this occurs for the bicyclic example 235 on FVP at 800 °C to give cyclohexa-1,2-diene 238 by way of the ketene 236 and carbene 237 as shown113. The product can be directly observed by low-temperature IR and forms a [2 + 2] dimer on warming up. FVP of >-toluoyl chloride 239 at 630 °C also results in loss of HC1 to provide a dependable large-scale synthesis of benzocyclobutenone 240 in excellent yield114. Pyrolysis of trichloroacetyl chloride, CI3C—COC1, over a bed of zinc at 420 °C results in dechlorination... 

The Staudinger ketene cycloaddition was utilized as the key reaction in the synthesis of a number of bakkane natural products in the laboratory of A.E. Greene. Dichloroketene was generated in situ from trichloroacetyl chloride by zinc-copper alloy in the presence of phosphorous oxychloride. The [2+2] cycloaddition between dichloroketene and 1,6-dimethylcyclohexene gave the product in high yield and excellent regio- and diastereoselectivity. The cycloadduct was successfully converted to (+)-bakkenolide A. 

The synthesis of unnatural (+)-mesembrine (387) through the asymmetric synthesis of methyl (i )-l-[(3,4-dimethoxy)phenyl]-4-oxocyclohex-2-enyl acetate (390) by cycloaddition of enantiomerically pure vinyl sulfoxide with dichloroketene has been performed 189) (Scheme 43). Vinyl sulfoxide 388 [prepared by conjugate addition of enantiopure acetylenic sulfoxide with (3,4-dimethoxy)phenylcopper] reacted with trichloroacetyl chloride in the presence of freshly prepared zinc-copper couple in THF at 0°C to produce a mixture of mono- and dichloro lactones 389. Reduction of 389 with zinc in acetic acid followed by cyclization and methylation afforded methyl IR-[(3,4-dimethoxy)phenyl]-4-oxocyclohex-2-enyl acetate (390), treatment of which with methylamine brought about amidation and concomitant intramolecular Michael addition to provide 2-oxo-mesembrine (391). Successively, 391 was transformed to (+)-mesembrine (387) in 79% yield (three steps ketalization of an oxo group, reduction of lactam, and deketali-zation)(/S9). 

This novel strategy was applied to a synthesis of ( + )-aspidospermidine. In this approach, enantiomerically pure sulfoxide 242 was treated with trichloroacetyl chloride in the presence of zinc-copper couple (Zn-Cu) to give lactone 243 in 78% yield (Scheme 44) (02JA13398). Removal of the chloro substituents followed by the... 

The addition of cyanogen chloride to carboxylic acid chlorides is another useful method of synthesis for acyl and aroylcarbonimidoyl dichlorides. For example, trichloroacetyl chloride reacts readily with cyanogen chloride at 50°C in an autoclave to yield the corresponding carbonimidoyl dichloride (LXVII) However, on standing, gradual dissociation into the starting materials was observed... 

A vigorously stirred mixture of trichloroacetyl chloride and dry pyridine cooled to —10° under N2, ethyl vinyl ether added, and stirring continued for 12 h at 0-25° -> l,l,l-trichloro-4-ethoxy-3-buten-2-one (Y 92-7%), added dropwise to a stirred mixture of K2CO3 and dry methanol over 30 min with cooling, and stirred at room temp, for 10 h methyl 3-ethoxy-3-methoxypropanoate (Y 80%). F..e.s. L.-F. Tietze et al., Synthesis 1988, 274-7. 

Disubstituted pyrroles lacking substituents at the 3- and S-positions are often required in porphyrin synthesis, and these can now be prepared from pyrrole itself. Thus, trichloroacetylation or trifluoroacetylation of pyrrole affords the 2-trihaloacetylpyrrole 8, which can be converted into the corresponding esters 9, carboxylic acids, or amides. The amides have been acetylated, or formylated, at the 4-position specifically, and the resulting acyl pyrroles (10) have been reduced to the alkyl pyrroles (11). This general procedure has now been improved by direct Friedel-Crafts formylation of the trichloroacetylpyrrole (8a) with dichloromethyl methyl ether (aluminium chloride) to the diacylpyrroles... 

The a-l,2-d5-glycosyl azides are synthesized by reaction of 3,4,6-tri-O-acetyl-2-O-trichloroacetyl-p-D-glucopyranosyl chloride (for the synthesis of this compound, see reaction 4.57) with sodium azide in hexamethylphosphoramide (HMPA) at 20°C [59] (reaction 4.55). 

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