Allyl carbonates deprotection

This electrochemical oxidation mediated by NHPI was applicable to benzylic carbons, allylic carbons, deprotection of acetals, oxidative cleavage of cyclic acetals and amide to afford benzoylated compounds, enones ", carbonyl compounds, -hydroxyethyl esters and imides, respectively (equations 31-35). 

Alkyl allyl ethers are difficult to cleave. Therefore alcohols are protected as allyl carbonate. Deprotection of tlie cyclic carbonate 471 with HC02H/Et3N proceeded regioselectively at room temperature to afford the <5-hydroxy ester 472. The electronic effect is crucial in this case and hydride attacked an electron deficient carbon [176]. 

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. 

Allyl carbonate esters are also useful hydroxy-protecting groups and are introduced using allyl chloroformate. A number of Pd-based catalysts for allylic deprotection have been developed.209 They are based on a catalytic cycle in which Pd° reacts by oxidative addition and activates the allylic bond to nucleophilic substitution. Various nucleophiles are effective, including dimedone,210 pentane-2,4-dione,211 and amines.212... 

Chemically modified P-cyclodextrins were successfully used to accelerate the deprotection of various water insoluble allylic carbonates in genuine two-phase systems without organic cosolvents. The cyclodextrins act not only as reverse phase transfer agents but may increase the selectivity of the reactions through molecular recognition [59-60] (see also Chapter 10). 

Allyl carbonates can be cleaved by nucleophiles under palladium(O) catalysis. Allyl carbonates have been proposed for side-chain protection of serine and threonine, and their stability under conditions of /VT moc or /V-Boc deprotection has been demonstrated [107]. Prolonged treatment with nucleophiles (e.g., 20% piperidine in DMF, 24 h) can, however, lead to deprotection of Alloc-protected phenols [108,109]. Carbohydrates [110], tyrosine derivatives [107], and other phenols have been protected as allyl ethers, and deprotection could be achieved by palladium-mediated allylic substitution (Entry 9, Table 7.8). 9-Fluorenyl carbonates have been used as protected intermediates for the solid-phase synthesis of oligosaccharides [111]. Deprotection was achieved by treatment with NEt3/DCM (8 2) at room temperature. 

To this end, the singly protected triol 1 was convergently coupled to the iso-propylidene-protected carboxylic acid 2 shown in Fig. 4.27. The resulting protected allyl carbonate 3 was deprotected with Pd(PPh3)4 in the presence of mor-... 

Alcohols are protected as allyl ethers, which are difficult to cleave with the Pd catalyst and deprotected by other methods [149]. Alcohols are conveniently converted to allyl carbonates 334 by treatment with allyl chloroformate (333). The allyl carbonates are deprotected using HCO2H [150], and HSnBu3 [151]. This method is called the AOC (allyloxycarbonyl) method. Phenols are protected as allyl phenyl ethers, which can be cleaved with HSnBu3 [152]. 

It is noteworthy that Takeda and coworkers (Ref. 154) recently proposed allyl isopropenyl dicarbonate made from isopropenyl chloroformate and sodium allyl carbonate as a convenient reagent for the preparation of allyl esters of carboxylic acids. Allyl isopropenyl dicarbonate reacts with carboxylic acids in the presence of DMAP under mild neutral conditions to give allyl esters in high yields. Allyl esters which could be deprotected by palladium catalysts are especially useful in the case of unstable compounds under acid or basic conditions, for example O-glycopeptides, penicillin derivatives, etc. 

Allyl alkyl carbonates, prepared from various alcohols except simple primary ones, are converted into aldehydes or ketones in the presence of a phosphine-free palladium catalyst. Acetonitrile as coordinating solvent is necessary for the success of this reaction. A mechanism via palladium alkoxides was proposed (Scheme 8). Ruthenium hydride complexes work similarly. A similar mechanism operates for the palladium-catalyzed decomposition of allylic carbonates. The reaction can be utilized for the mild deprotection of amines, e.g., for peptide synthesis shown in equation (20). 

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... 

Another way of achieving chemoselectivity is the use of catalytic amounts of chemically modified (methylated) /3-cyclodextrins as counterphase transfer agents (203). Such way the deprotection of neat, water insoluble allylic carbonates was achieved (without an organic solvent) with up to 300 times increase in the rate related to the cyclodextrin-free reactions. Furthermore, molecular recognition of the substrates by the cyclodextrin resulted in large differences between the rates of deprotection of the various substrates, for example, phenylbenzene allyl carbonates reacted considerably faster than naphtylmethyl allyl carbonates. 

However, we should mention that use of allyl carbonates to protect alcohols, including deprotection under Pd(0) catalysis, was reported in 1981 by Guibd and Saint M Leuxt (Scheme 5). The same strategy to protect and deprotect amines was reported by Jeffrey and McCombie in 1982 and patented by McCombie in 1980 with an application to the... 

When Pd-catalyzed deprotection of an allyl ester is conducted in the presence of external carboxylic acid nucleophile, an equilibrium between two different allyl esters is established. Several strategies have been developed to perturb this equilibrium far enough to ensure complete deprotection. Use of a large excess of acetic acid has been shown to effect the deprotection of allyl carbonates and aUyl phosphates. Another approach employs the soluble carboxylate salt potassium 2-ethylhexanoate (Scheme 3) for the deprotection of allyl carboxylic esters. Precipitation of the desired potassium carboxylate is used to perturb the equihbrium in the direction of products. Because these deprotection conditions are essentially neutral, they have been employed in the deprotection of particularly sensitive allyl esters. ... 

Since the initial studies of Tsuji and Trost, it has been known that Tr-allylpalladium complexes react irreversibly with active methylene compounds to form new carbon-carbon bonds. Applying this information, Kunz introduced dimedone and A,A-dimethylbarbi-turic acid (NDMBA) as nucleophiles in the Pd-catalyzed deprotection of allyl carbamates and carbonates. The presumed catalytic cycle for this process is shown in Scheme 4. Dimedone and NDMBA have also been employed as nucleophiles in the deprotection of aUyl esters. Dimethyl malonate has also been used occasionally in allyl carbamate deprotection, although it appears to be less reactive than the other carbon nucleophiles.f ... 

Deprotection of allyl carbonates has been accomplished using a wide variety of nucleophiles (Scheme 9), including formate, sodium borohydride, tri-n-butyl hydride, dimedone, diethylamine, and sodium azide. A recent, noteworthy development is the use of sulfinic acids as nucleophiles in the deprotection of allyl carbonates. Not only were allyl carbonates quantitatively deprotected in 30 min, but the authors also reported the successful deprotection of an allyl ether using catalytic palladium(O). Should this result prove to be general, it would represent in a major development in allyl-based protection of alcohols. 

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. 

Hydroxylysine (328) was synthesized by chemoselective reaction of (Z)-4-acet-oxy-2-butenyl methyl carbonate (325) with two different nucleophiles first with At,(9-Boc-protected hydroxylamine (326) under neutral conditions and then with methyl (diphenylmethyleneamino)acetate (327) in the presence of BSA[202]. The primary allylic amine 331 is prepared by the highly selective monoallylation of 4,4 -dimethoxybenzhydrylamine (329). Deprotection of the allylated secondary amine 330 with 80% formic acid affords the primary ally-lamine 331. The reaction was applied to the total synthesis of gabaculine 332(203]. 

It was considered of interest to utilize dianion 26 <89PHC(1)1> as a potential three carbon allyl anion fragment to react with 6 with a view to develop a new synthesis of 2,3-substituted and fused carbazoies 28 involving protection, activation and deprotection of the... 

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