Trichloroacetamides synthesis

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 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. 

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. 

Both 4,5-dihydrooxazoles 3 and 5,6-dihydro-4f/-l,3-oxazines 2 obtained by halocyclization of imidates are cleaved under neutral Or acidic conditions to give trichloroacetamides or amino alcohols which constitute building blocks for the total synthesis of antibiotics and natural products with biological activity144. 

The rearrangement of allyl trichloroacetimidate into allyl trichloroacetamide (Overman rearrangement) has been used for the synthesis of amino sugars. For example, the trichloroace-... 

C. Gallo-Rodriguez, L. Gandolfi, andR. M. de Lederkremer, Synthesis of /j-D-Gal /-(l-3)-D-GlcNAc by the trichloroacetamidate method and of / -D-Gal/-(l-6)-D-GlcNAc by SnCL -promoted glycosyla-tion, Org. Lett., 1 (1999) 245-247. 

Figure 2.15 Automated solid phase oligo-/polysaccharide synthesis. Glycosyl donor (A) is coupled to a solid phase Merrifield-like resin through an alkenyl alcohol linker. The double bond allows for clean removal of product at the end of solid phase synthesis by metathesis using Grubb s catalyst in the presence of ethylene gas. For protecting groups, see Fig 2.13. Trimethyl silyltriflate (TMSOTf) activates the glycosyl donor through controlled removal of the trichloroacetamidate.

Attempts to stabilise nucleic acid-RNA duplexes both in binding affinity and nuclease resistance continue to be been dominated by modifications to the 2 -hydroxyl substituent. In this regard the synthesis of the naturally occurring 2 -0-methyl ribonucleosides has historically received much attention. An efficient synthesis of 2 -0-alkyl ribonucleosides has been reported by Chanteloup et ul. Suitably protected 2-0-alkyl-P-ribosyl trichloroacetamide (130) can be synthesised from D-... 

Reports on three useful transition metal catalysed cyclization routes to nitrogen heterocycles have appeared this year. In an extension of their earlier work on the synthesis of trichlorlnated T-butyrolactams by copper- or ruthenium-catalysed cyclization of -allyl-trichloroacetamides, Itoh and co-workers have now shown that... 

The synthesis of a fully functionalized cyclopentane core structure of pactamycin, a potent antitumor antibiotic, involves Overman rearrangement as a key reaction. Heating a mixture of potassium carbonate and the imidate derived from allylic alcohol 68 in p-xylene yields the desired trichloroacetamide 69 as a single isomer in 90% yield from 68. In this reaction, potassium carbonate is a crucial additive as no desired product is obtained when the same reaction is carried out without potassium carbonate. Trichloroacetimidate 69 has been elaborated into the tricyclic compound 70 which contains all the carbon atoms for the core cyclopentane of pactamycin,... 

Acetamides have been prepared in moderate to good yield from alcohols by reaction with acetonitrile and sulphuryl chloride. It has been found that the hydrolysis of nitriles to amides can be effected in excellent yield using potassium hydroxide in t-butanol if the amide produced is relatively insoluble in water. Experimental details for the large scale anodic oxidation of iV-formyl derivatives of amines to a-methoxyalkylamides have been recorded, and an interesting synthesis of trichloroacetamides from allylic alcohols via a thermal [Att + 2a] rearrangement has been described (Scheme 50). ... 

Synthesis of Tetra- and Higher Saccharides.- Cellotetraose has been synthesized using the trichloroacetamidate method the adopted procedures involved the use of the trisaccharide derivative (64)... 

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)]. 

PALLADIUM- AND NICKEL-CATALYZED STEREOSELECTIVE SYNTHESIS OF GLYCOSYL TRICHLOROACETAMIDES AND THEIR CONVERSION TO a- AND P-UREA GLYCOSIDES... 

FIGURE 15.6 Optimization for stereoselective synthesis of p-iV-glycosyl trichloroacetamide with o-donor ligands. 

Related to the Overman esterification is the Overman rearrangement. The latter 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. Although this rearrangement can be thermally driven, addition of palladium salts lower the needed temperature. Chiral ligands such as proline-based diamines would lead to enantioenriched material. ... 

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