Carbamates from alkoxides

Carbamates can also be obtained from die carbamoyltriazole of a secondary amine by reaction with an alkoxide, as the following example shows [215]... 

The five-membered ring can also be formed by intramolecular nucleophilic attack of an alkoxide on a carbamate such as for the formation of 196 from 195 <1997T9553>, by dehydration of fV-carbamate-pipecolic acid derivatives <2002EJO3936>, by treatment of amino-amides under Eschweiler-Clarke conditions <1999TA3371>, or by treatment of hydroxyl aminonitriles with silver trifluoroacetate <2002JA2951> (Scheme 57). 

Aluminum porphyrins with alkoxide, carboxylate, or enolate can also activate CO2, some catalytically. For example, Al(TPP)OMe (prepared from Al(TPP)Et with methanol) can bring about the catalytic formation of cyclic carbonate or polycarbonate from CO2 and epoxide [Eq. (6)], ° - and Al(TPP)OAc catalyzes the formation of carbamic esters from CO2, dialkylamines, and epoxide. Neither of the reactions requires activation by visible light, in contrast to the reactions involving the alkylaluminum precursors. Another key difference is that the ethyl group in Al(TPP)Et remains in the propionate product after CO2 insertion, whereas the methoxide or acetate precursors in the other reactions do not, indicating that quite different mechanisms are possibly operating in these processes. Most of this chemistry has been followed via spectroscopic (IR and H NMR) observation of the aluminum porphyrin species, and by organic product analysis, and relatively little is known about the details of the CO2 activation steps. 

Carbamates have been prepared by heating ethyl carbamate with a higherboiling alcohol in the presence or absence of catalysts [31-33], Aluminum iso-propoxide has been reported [34] to be an excellent catalyst for the interchange reaction between ethyl carbamate and benzyl alcohol. The interchange reaction is also effective for /V-alkyl carbamates as well as unsubstituted carbamates [35]. This catalyst is effective in preparing mono- and dicarbamates in excellent yields from primary and secondary alcohols and diols. Other effective catalysts are dibutyltin dilaurate [36], dibutyltin oxide [37], sulfuric acid or p-toluenesulfonic acid [31], and sodium metal (reacts with alcohols to give the alkoxide catalyst) [33]. 

The synthesis of hydroxycarbamates from secondary aliphatic amines, C02 and epoxides has been found to be catalyzed by (5,10,15,20-tetraphenylporphinato) aluminum(III) acetate, AI(TPP)(02CCH3) [80], Scheme 6.14 illustrates the mechanism proposed for the catalytic process, which can be carried out under not severe conditions (293-343 K 0.1-5 MPa C02 pressure). The key step here is the insertion of epoxide into the Al-O bond of the A1-carbamate A (Scheme 6.14), which preliminarily forms by the reaction of A1(TPP)(02CCH3) with the amine and C02. Protolytic cleavage of the Al-alkoxide bond in the insertion product, C, by dialkylcarbamic acid regenerates the catalytkally active carbamato-species A and... 

Catalytic DBB29 avoids the need for such vigorous conditions, and allows benzyl48 and allyl lithiums to be formed from silyl ethers,49 mesylates50 triflates,51 carbamates and carbonates,9 and even directly from lithium alkoxides.49... 

Alternatively, carbamate anions like those involved in the formation of 13 can be generated efficiently by trapping the alkoxide of zwitterionic 7t-allylpalladium complexes from vinyl epoxides with isocyanates55 57. Table 6 shows that cyclic vinyl epoxides lead exclusively to 2-oxazolidinones with retention of configuration which is independent of isocyanate substitution. Triisopropyl phosphite is the ligand of choice to assure a high turnover number. 

If the mechanism of the catalysis of isocyanate-alcohol reaction by tin carboxylates does indeed proceed via the alkoxide as proposed by Bloodworth and Davies (11), then the synergism of the amine to tin can readily be explained from the above equilibrium. The amine will assist in the alcoholysis step and speed up the decomposition of the tin-carbamate complex by the alcohol to the urethane and tin alkoxide. 

Aryl carbamates are superior to alkyl carbamates as AChEls, because they have better affinity for AChE and, therefore, carbamylafe AChE more efficiently. Physostigmine and other aryl carbamates exhibit inhibition constants (Ki) on the order of 10 to 10 ° M and are three to four orders of magnitude more effective than alkyl carbamates, such as carbachol (Ki - 10 M). This is to be expected, because phenoxide anions are more stable than and, hence, are better leaving groups than alkoxide anions. Phenoxide anions are stabilized through resonance with the aromatic ring. Thus, the therapeutically effective carbamate inhibitors of AChE are derived from phenols. 

The modification of the HR that employs alkoxide, often methoxide, is usually an efficient route to carbamates. For example, methyl carbamates 67-72 are synthesized from the corresponding primary amides using bromine and sodium methoxide. Carbamate 68 is used in a synthesis of phenanthroviridin aglycon, and cyanoester 70 is a key feature in the commercial synthesis of the DuPont herbicide azafenidin. Carbamate ester... 

Reactions that proceed under neutral conditions are highly desirable. An important event in TT-allylpalladium chemistry is the introduction of highly reactive allylic carbonates (Sect. V.2.1.3), Their reactions can be carried out under mild neutral conditions. " Also, reactions of allylic carbamates, " allyl aryl ethers, and vinyl epoxides proceed without addition of bases. As shown by the mechanism in Scheme 6, the oxidative addition of allyl methyl carbonates is followed by decarboxylation as an irreversible process to afford TT-allylpalladium methoxide, and the generated methoxide picks up a proton from pronucleophiles (NuH), such as active methylene compounds. This in situ formation of the alkoxide is the reason why the reaction of aUyl carbonates can be carried out without addition of bases from outside. Alkoxides are rather poor nucleophiles, and alkyl allyl ethers are not formed from them. In addition, formation of TT-allylpalladium complexes from allylic carbonates involving decarboxylation is irreversible. In contrast, the formation of TT-allylpalladium acetate from allyl acetate is reversible. 

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