Carbamates allyl carbonate reactions

Allylic acetates are widely used. The oxidative addition of allylic acetates to Pd(0) is reversible, and their reaction must be carried out in the presence of bases. An important improvement in 7r-allylpalladium chemistry has been achieved by the introduction of allylic carbonates. Carbonates are highly reactive. More importantly, their reactions can be carried out under neutral con-ditions[13,14]. Also reactions of allylic carbamates[14], allyl aryl ethers[6,15], and vinyl epoxides[16,17] proceed under neutral conditions without addition of bases. 

Pd(OAc)2, TPPTS, CH3CN, H2O, Et2NH, 30 min, 89-99% yield. Deprotection can be achieved in the presence of a prenyl or cinnamyl ester, but as the reaction times increase, these esters are also cleaved.Prenyl carbamates and allyl carbonates are cleaved similarly. 

Allylsilanes are available by treatment of allyl acetates and allyl carbonates with silyl cuprates17-18, with antarafacial stereochemistry being observed for displacement of tertiary allyl acetates19. This reaction provides a useful asymmetric synthesis of allylsilanes using esters and carbamates derived from optically active secondary alcohols antarafacial stereochemistry is observed for the esters, and suprafacial stereochemistry for the carbamates20,21. 

An efficient chemoenzymatic route for the synthesis of optically active substituted indolines has been recently developed (Scheme 7.27), and also the alkoxycarbonyla-tion process is more efficient than the acylation reaction. Different lipases have been tested in the alkoxycarbonylation of these secondary amines, GALA being found to be the best biocatalyst for 2-substituted-indolines, and CALB for 3-methylindoline. The combination of lipases with a variety of allyl carbonates and TBME as solvent has allowed the isolation of the carbamate and amine derivatives in a high level of enantiopurity [51]. 

Anodic oxidation of allylsilanes in the presence of nucleophiles results in replacement of a trimethylsilyl group by a nucleophile which is introduced into the allylic carbon. Various oxygen and nitrogen nucleophiles such as alcohols, water, caboxylic acids, p-toluenesulfonic acid, carbamates or a sulfonamide can be employed in this reaction (equations 9—11)11 —13. 

A palladium-based method has been developed for the alkylation of the phenolic oxygen of tyrosine residues. Fig. 5f (61). In this reaction, allylic carbonates, esters, and carbamates are activated by palladium(O) complexes in aqueous solution to form electrophilic pi-allyl complexes. These species react at pH 8-10 with the phenolate anions of tyrosine residues, which results in the formation of an aryl ether and the regeneration of the Pd(0) catalyst. The reaction requires P(m-C6H4S03 )3 as a water-soluble phosphine ligand. Activated pi-allyl complexes that do not react with tyrosine residues undergo P-hydride elimination under the basic conditions to yield diene by-products. A particularly attractive feature of this method is its ability to use substrates with charged groups in the allylic positions. This ability allows hydrophobic substrates, such as lipids, to be solubilized to facilitate protein modification. 

Deallylation. Allyl carbonates and carbamates are readily cleaved " by treatment with Pd(OAc)2. There is a useful chemoselectivity for this reaction in that dimethylallyl esters and cinnamyl esters are not affected. An expedient route to isoflavanones and isoflavones from allyl chroman-4-one-3-carboxylate involves ary-lation with ArPbfOAcfa and treatment with Pd(OAc>2. The latter reaction removes the ester group to give isoflavanones when it is carried out in the presence of PhjP, HCOOH, and EtsN. Isoflavones are obtained when the keto esters are treated with Pd(OAc>2 and PhaPCHjCHaPPhj in refluxing MeCN. 

A mixture of cinnamyl alcohol, phenyl isocyanate, heptanal, tri-n-butylphosphine, and a little Pd(PPh3)4 in acetonitrile refluxed for 5 h - product. Y 82% (E,E E,Z 4 1). The phosphine attacks the less hindered carbon of the intermediate n-allyl complex, and the (E)-geometry of the allyl alcohol is retained for tert. allylic alcohols, reaction requires prior formation of the allyl carbamate ketones react sluggishly. Although stereoselectivity is poor, the method is interesting since intermediate phosphonium salts are formed under neutral conditions. F.e. and polyenes s. N. Okukado et al., Chem. Letters 1988, 1449-52. 

Allylic Carbonates and Carbamates AUyhc carbonates are the most reactive of these derivatives [73]. Oxidative addition of the allyl carbonate A is followed by decarboxylation to afford the positively charged it-allylpalladium complex B and alkoxide, which acts as base for the deprotonation of the nucleophile (Scheme 12.39). The in situ formation of the alkoxide, which is a poor nucleophile, is the reason why no additional base has to be used. In addition, the decarboxylation makes the formation of the n-allyl complex an irreversible process, in contrast to the reactions of acetates. 

AUylic carbamates behave similarly, and they can also be used under neutral conditions [60]. AUylic carbonates are more reactive than acetates, and therefore, chemoselective reactions are possible [73]. As allylation with allyl carbonates proceeds under relatively mild neutral conditions, this protocol finds wide applications for the aUylation of labile compounds, sensitive to acids and bases [74]. 

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. 

Three types of simple 0-nucleophiles have been reported to react with allyl carbonates under Pd catalysis (Scheme 32, Table 3) carboxylatesP and carbamic acid conjugate base,P phenols,P p p and alcohols.As previously stated allylation of nucleophiles with allylic carbonates can be performed in the absence of base, and the total amount of real nucleophile present at any moment in the reaction medium cannot be higher than the amount of palladium added. However, in asymmetric reactions it is sometimes... 

A wide application of Newcomb s method provides a variety of N-heterocyc-lic systems, such as perhydroindoles, pyrrolizidines and aza-brigded bicycles [59, W, 146], The mild reaction conditions are compatible with several funtional groups of the substrate and several trapping agents to functionalize the cyclized product. 2-Substituted pyrrolizidines 132 are accessible by tandem cyclization of iV-allyl-substituted PTOC carbamate 131. In this case the allyl group on the nitrogen serves as an internal trap for the intermediate carbon radical. The Af-methylcyclohept-4-enaminium radical cation, produced from the corres-... 

Allyl esters, carbonates, and carbamates readily undergo C-O bond cleavage upon reaction with palladium(O) to yield allyl palladium(II) complexes. These complexes are electrophilic and can react with nucleophiles to form products of allylic nucleophilic substitution. Linkers based on this reaction have been designed, which are cleavable by treatment with catalytic amounts of palladium complexes [165,166], For the immobilization of carboxylic acids, support-bound allyl alcohols have proven suitable (Figure 3.12, Table 3.7). 

Aresta and Quaranta studied the reactivity of alkylammonium N-alkylcarbamates (RNH3)02CNHR towards a different acylating substrate, such as dimethyl carbonate (DMC) [62a, b]. Carbamate salts (RNH3)02CNHR (R = benzyl, allyl, cyclohexyl), prepared in situ from aliphatic primary amines and C02, reacted with DMC to afford N-alkyl methylcarbamates (Equation 6.6). The reaction requires mild conditions (343-363 K 0.1 MPa C02 pressure) and can be carried out in DMC used as solvent and reagent. At 363 K, carbamate esters were obtained in satisfactory yield (45-92%) with high selectivity, as side products such as ureas, N,N-dialkylcarbamate esters, and alkylated amines were formed in very small amounts. 

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