A trichloroacetamide

Speziale and his co-workers have carried out comprehensive studies of the reactions of phosphorus compounds. It has been shown 108) that the reaction of N,N-dialkyl-a-trichloroacetamides (127) with phosphites and phosphines gives trichlorovinylamines (128). In general the trialkyl-phosphines gave somewhat higher yields (60 to 83%) and purer products... 

In a later paper Speziale and Smith 109) investigated the reaction of trivalent phosphorus compounds with N-monosubstituted a-trichloro-acetamides and a-trichloroacetamide. The products were imidoyl chlorides (129) and dichloroacetonitrile (130), respectively. The intermediacy of enamines (131) was assumed. For the monosubstituted amides the enamine... 

This synthetic route entails introduction of a trichloroacetamide group into a protected glucose (8) (Scheme 3) which is exchanged by an alkyl chain [13,14]. 

In 2014, an intramolecular atom transfer radical cyclisation (ATRC) between a trichloroacetamide and an anisole or enol acetate moiety was applied to the synthesis of highly functionalized 2-azaspiro[4.5]decanes or morphan compounds, respectively, using the second-generation Grubbs catalyst 20. The procedure was further employed to construct the azatricyclic framework of the immunosuppressant FR901483 by the elaboration of its azatricyclic core [eqn (7.15)]. 

The isolation of 73 was then fully optimized. Upon completion of the etherification reaction, the insoluble trichloroacetamide 68 was filtered, leaving a 17 1 mixture of 18 and 19 as a DCE/heptane solution, together with starting material 10. The solvent was switched to MeOH and the esters were saponified with KOH. The carboxylic acid was isolated after neutralization and the addition of NEt3 which gave the highly crystalline triethylamine solvate 73 as a 40 1 mixture of diastere-omers. Recrystallization from MTBE/heptane gave a 109 1 diastereomeric mixture of 73 in 54% overall yield from 10. This final process was successfully implemented in the pilot plant without incident. 

Alkylation of trifluoro- and trichloroacetamides with a-bromoacetic esters has been utilized for the synthesis of a wide range of a-aminoacetic acids [11-13] (Table 5.13). Hydrolysis of the intermediate a-trihaloacetamidoacetic esters with methanolic potassium hydroxide converts the methyl and ethyl esters directly into the amino carboxylic acids. /-Butyl a-aminoacetates are more stable, but they are hydrolysed under phase-transfer catalytic conditions (see Chapter 9.2). Reaction of the trihaloacetamides with 1,4-dibromobutane and 1,5-dibromopentane and subsequent hydrolysis provides a simple route to pyrrolidine-2-carboxylic acid (75%) and piperidine-2-carboxylic acid (58%) [11, 12],... 

The reduction of the trichloroacetamide derivative 56 with (TMS)3SiH afforded 57 in a 60% yield (Reaction 7.58) [68]. The final product is the result of cyclization and further removal of two chlorine atoms. In fact, 3.5equiv of silane and 1.1 equiv of AIBN are used. 

Allyl imidate esters undergo [3,3] sigmatropic rearrangements to A -allyl amides. Trichloroacetimidates can be easily made from allylic alcohols by reaction with trichloroacetonitrile. The rearrangement then provides trichloroacetamides of iV-allyl-amines.176 177... 

Epoxytrichloroacetimidates 153 also undergo oxazoline ring formation in the presence of a catalytic amount of Lewis acids.Diethylaluminum chloride was found to be superior to boron trifluoride, which tends to further hydrolyze the oxazoline 154 to the trichloroacetamide. Generally, formation of the six-membered ring oxazine 155 is not favored, but it can be a serious side reaction if the epoxide contains substituents that stabilize the incipient cation generated prior to ring closure. Examples from this study are summarized in Table 8 19 (Fig 8 8 Scheme 8.45). 

Reaction of 7V,A-diethyl-2,2,2-trichloroacetamide with trialkyl phosphites or triphenylphosphine to give N, N-diethyl-1,2,2-trichlorovinylamine [152-154],... 

A. N,N-Diethyl-2,2,2-trichloroacetamide. A 1-1. three-necked flask equipped with a stirrer and dropping funnel is charged with 73 g. (1.00 mole) of diethylamine, 500 ml. of ether, and a solution of 40 g. (1.00 mole) of sodium hydroxide in 160 ml. of water. The mixture is stirred and maintained at a temperature of —10° to — 15° by a bath of Dry Ice and acetone while 200 g. (1.10 moles) of trichloroacetyl chloride is added in the course of 1 hour. The cooling bath is removed, the temperature is allowed to rise to 10°, and the organic layer is separated. The aqueous layer is extracted with two 50-ml. portions of ether. The ether extracts are combined, washed with 50 ml. of 5% hydrochloric acid, two 50-ml. portions of 5% sodium bicarbonate solution, and 50 ml. of water, and dried over magnesium sulfate. The ether is removed by distillation at atmospheric pressure. The residue is distilled through a short indented Claisen still head at reduced pressure. N,N-Diethyl-2,2,2-trichloroacetamide is collected at 77-79°/1.5 mm. 1.4902-1.4912 weight 183-200 g. (84-92%). 

N,N-Diethyl-l,2,2-trichlorovinylamine has been prepared by the action of trimethyl, triethyl, or triisopropyl phosphite or triphenylphosphine on N,N-diethyl-2,2,2-trichloroacetamide., These methods require a reaction temperature of 150-160° and several distillations in order to obtain a pure product. Consequently, the yields of the vinylamine are lower than by the present procedure.3... 

The procedure has also been applied to the synthesis of N,N-dimethyl-l,2,2-trichlorovinylamine from trichloroacetamide (60% yield),3 and it probably is a general means of preparing N,N-dialkyl-l,2,2-trichlorovinylamines. The reaction is an unusual one involving reduction of the amide and halogen migration and is of theoretical interest. 

A-f(2E)-4-Benzyl-5-(tetrahydro-2/f-pyran-2-yloxy)pent-2-enyl]-2,2,2-trichloroacetamide (128) [29)... 

Amides with electron-withdrawing substituents can be sufficiently labile towards nucleophilic attack to enable their use as protective groups. This is the case, for example, with trifluoro- [102,290] and trichloroacetamides [163], which are readily hydrolyzed under mild conditions (Figure 10.13). Suitable nucleophiles are hydrazine [291], aliphatic amines, and hydroxide, but if a hydrophobic support has been chosen, it must be borne in mind that the reactivity of alkali metal hydroxides will be reduced because of poor diffusion into the support. Amides of electron-poor amines (e.g. anilides) can also be readily cleaved by nucleophiles [292],... 

Demethoxyerythratidinone (10), one of the simplest of the erythrina alkaloids, was isolated in 1973 by Barton et al. from Erythrina lithosperma [14]. A concise approach to such Erythrina alkaloids using a disfavored 5-endo-trig radical cyclization mediated by nickel powder was described by Zard and coworkers [15]. A-Alkenyl trichloroacetamide 7 was... 

The reactions of TMSA (14) with aldehydes165 23° gives a-trimethylsiloxy-alkyl azides (246, 413-417) they are highly stable against hydrolysis and higher temperatures (Scheme 62). Thermolysis of the azides 246, 413-417 gives directly N-TMS-butyr- (246), valero- (413), capro- (414)-, isobutyr- (415)-, pival- (416) and trichloroacetamide (417), respectively. 

The Overman Rearrangement allows the conversion of readily available allylic alcohols into allylic amines by a two-step synthesis involving the rearrangement of an allylic trichloroacetimidate to an allylic trichloroacetamide with clean 1,3-transposition of the alkenyl moiety. 

Not only trichloroacetate or trichloroacetamide systems can be applied. Weinreb and coworkers reported a few copper-catalyzed 5-exo ATRC of 2,2-dichloro-3-oxo-6-heptenoates using 3.2 mol% CuCI and PPh3 as a ligand [304]. A 1.6 1 mixture of regioisomeric 5-exo and 6-endo products was obtained with low diastereoselectivity. 5-exo Annulations and 6-exo cyclizations gave the products with 1 and 2.7 mol% Cu catalyst in 82-99% and 91% yield, respectively. Ghelfi and colleagues found that dichloroacetaldehyde-derived mixed 0-allylic acetals served... 

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