Carbamate nucleophiles, allylic substitution

Allylic substitution with free carbamate nucleophiles was not accomplished until advanced catalyst precursors were developed. However, products from substitution with carbamate nucleophiles were generated by a decarboxylative allylation. In this process, the imidodicarbonate was shown to undergo decarboxylation to form the carbamate nucleophile, and reaction of the resulting carbamate with the 7i-allyliridium intermediate formed branched allylic carbamate products (Scheme 17) [92, 95]. 

Scheme 25 Allylic substitution with carbamate nucleophiles...

The preparative electrochemical oxidation of allylsilanes proceeds smoothly and the C-Si bond is cleaved selectively without affecting other allylic C-H bonds [110-113]. This selectivity is ascribed to the selective cleavage of the C-Si bond in the cation radical intermediate. The resulting allyl radical intermediate is further oxidized to give the allyl cation intermediate, which is trapped by nucleophiles such as alcohols, water, carbamates, and tosylamides to give the corresponding allylic substitution products as shown in Eq. (25). Usually, the nucleophiles are introduced to both ends of the allyl cation, and therefore a mixture of two regioisomeric products is formed. 

Allyl carbamates also can serve as amino-protecting groups. The allyloxy group is removed by Pd-catalyzed reduction or nucleophilic substitution. These reactions involve formation of the carbamic acid by oxidative addition to the palladium. The allyl-palladium species is reductively cleaved by stannanes,221 phenylsilane,222 formic acid,223 and NaBH4,224 which convert the allyl group to propene. Reagents... 

Better results were obtained for the carbamate of 163 (entry 3) [75, 80). Thus, deprotonation of the carbamate 163 with a lithium base, followed by complexation with copper iodide and treatment with one equivalent of an alkyllithium, provided exclusive y-alkylation. Double bond configuration was only partially maintained, however, giving 164 and 165 in a ratio of 89 11. The formation of both alkene isomers is explained in terms of two competing transition states 167 and 168 (Scheme 6.35). Minimization of allylic strain should to some extent favor transition state 167. Employing the enantiomerically enriched carbamate (R)-163 (82% ee) as the starting material, the proposed syn-attack of the organocopper nucleophile could then be as shown. Thus, after substitution and subsequent hydrogenation, R)-2-phenylpentane (169) was obtained in 64% ee [75]. 

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). 

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. 

Nucleophiles for the substitution can be generated in situ. For example, a synthesis of allylic carbamates and carbonates is conducted using amines and alcohols under CO2. Since disilanes are cleaved in the presence of Pd(0) complexes, their use in the synthesis of allylsilanes is feasible. 

The Pd(Ph3P)4-catalyzed reaction of various allylic electrophiles with carbon-based nucleophiles is a very useful method for the formation of C-C bonds under relatively mild conditions (eq 17) and has been extensively reviewed elsewhere. >4 The most commonly used electrophilic substrates for Pd(Ph3P)4-catalyzed aUylic substitution reactions are allylic esters, carbonates, phosphates, carbamates, halides, sulfones, and epoxides. 

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