Transfer of Carbamate Group to Alkyl Halides

Despite the great number of metal-carbamates isolated to date, the transfer of a carbamic group from a metal center to an alkylating agent such as an alkyl halide or diatkyl sulfate has been documented in only a few cases [1, 2]. 

In some initial studies [45], Saegusa and coworkers reported the synthesis of methylurethanes by the reaction of copper) I) -carbamates with methyl iodide. H ere, the carbamate formation occurred only in the presence of a bulky o-donor ligand, 

Yoshida et al. were the first to report the synthesis of carbamate esters by the direct reaction of aliphatic amines, C02 and alkyl halides [47]. The process involved the O-alkylation of intermediate alkylammonium carbamate salt, and required relatively, severe conditions (333-393 K 4MPa C02), long reaction times (1-2 days) and an excess of amine (2.5 equiv.) with respect to the alkylating agent. The method was shown to be effective only with secondary aliphatic amines which, however, were converted into organic carbamates in low to moderate yield and with modest selectivity because of significant side-formation of N-alkylation products. 

Aresta and Quaranta focused on the direct synthesis of carbamate esters by the reaction of aliphatic primary amines with alkyl halides in the presence of C02. Under the conditions used (293-353 K 0.1 MPa C02 solvent = tetrahydrofuran (THF), MeOH, PhCH3/CH2Cl2 mixtures), the formation of carbamate ester was 

Inorganic bases have been also employed in this system. When Butcher first used alkali carbonates [50], it was reported that, in DMF and at ambient temperature, the carbamation of primary and secondary aliphatic amines (or also arylamines) with alkyl halides under a C02 atmosphere (0.1 MPa) was effectively promoted by Cs2C03 [50, 51]. The Cs+ cations in the solvent used (DMF) did not form ion pairs with counterions, and favored the formation of naked carbamate anions that were more reactive at the O-ends with alkyl halides. Jung further found that the addition of tetrabutylammonium iodide (TBAI) to the system RR NH/ C02/RX/Cs2C03/DMF promoted the carbamation process with a higher yield and selectivity with respect to N-alkylation [51]. The process has been successfully extended to the synthesis of carbamate functionalities on solid phases. In this case, resin-bound carbamates are readily released from the resin by treatment with LiAlH4 in THF, yielding the respective N-methyl secondary amines [51]. 

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