Allylic carbonates and carbamates

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. 

Various water-insoluble substrates are deprotected smoothly in water using water-soluble ligand (TPPTS, II-l) in the presence of cyclodextrin [181]. Deprotection of allyl carbonates and carbamates can be carried out in MeCN/H20 using TPPTS as a ligand and Et2NH as the scavenger [182]. Chemoselective removal of allyl carbamate in a base-sensitive cephalosporin 478 was achieved with 1 % Pd(0)/TPPTS at room temperature to afford 479, and then the prenyl carboxylate... 

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. 

Protection of alcohols and amines as allylic carbonates and carbamates is at the origin of the topic of this section (see Sect. A and Scheme The mixed allylic carbonate is... 

Of special importance in p-lactam antibiotic chemistry is the easy removal of carboxylate protecting groups under mild and selective conditions. Attractive, therefore, is the use of Pd -catalysed cleavage of (allyloxy)carbonyl functional groups (Scheme 9). The process is also useful for the deprotection of allylic carbonates and carbamates. 

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]. 

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). 

Fig. 10.3-8 Tyrosine modification using palladium jr-allyl chemistry, (a) Allylic acetates (shown), carbonates, and carbamates can be activated by palladium(O) in aqueous solution to yield electrophilic 7r-allyl complexes. These species alkylate tyrosine residues with high...

Deallylations. The facile cleavage of the allyl group from esters, carbonates, and carbamates by nucleophiles (amines and thiols) in the presence of a Pd(0) complex makes them useful derivatives for protection purposes. 

A 7i-allyl species like allylic acetates, carbonates, and carbamates are inert towards amino acid functionalities until they are activated with a palladium catalyst like palladium acetate and triphenylphosphine tris(sulfonate) as a water-soluble ligand [138, 139]. With a palladium catalyst, the phenolate oxygen of tyrosine will be alkylated. The conjugate is an aUyl aryl ether (14) (Table 4). 

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. 

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-... 

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. 

Treatment of silyl ethers of allyl alcohol, and some simple derivatives, with t-BuLi in THF-HMPA, followed by a suitable electrophile, has been shown to give the 1,4-retro-Brook rearrangement products, which are ethers, carbonates or carbamates of... 

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. 

Leaving groups in the Tsuji-Trost reaction include acetates, halides, ethers, carbonates, sulfones, carbamates, epoxides, and phosphates. Reviews (a) Tsuji, J. In Handbook of Organopalladium Chemistry for Organic Synthesis, Negishi, E. deMeijere, A., Eds. Wiley-lnterscience New York, 2002 Vol II, Palladium-Catalyzed Nucleophile Substitution Involving Allyl Palladium, Propargyl-palladium and Related Derivatives, pp. 1669-1687. (b) Frost C. G. Howarth, J. Williams, J. M. J. Tetrahedron Asymmetry 1992, 3, 1089-1122. 

Pd(0Ac)2, TPPTS, CH3CN, H2O, EtjNH, 96-100% yield. The allyl carbamate (alloc) group can be cleaved in the presence of the prenyl ester. These conditions will also cleave allyl carbonates, cinnamyl esters, and prenyl carbamates. ... 

The corresponding imide can be formed if the medium is hexane. Amines can be protected as their allyl carbamates by formation with diallyl carbonate and a lipase... 

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