Palladium-catalyzed allyl transfer

Coupling of vinyl halides with allyl alcohols/ Palladium-catalyzed coupling of vinyl halides with allylic alcohols under usual Heck conditions results in a complex mixture of products. Addition of silver carbonate and a phase-transfer catalyst can result in a palladium-catalyzed coupling of vinyl halides with a primary allylic alcohol to give a y, -enal, with retention of configuration of the vinyl halide. 

The allylic HYCRAM derivative was subsequently modified by insertion of a standard amino acid between the aminomethyl resin and the hydroxy butenoic acid moiety. Using this allylic anchor, the resin-linked, glycosylated HIV peptide T-derivative 164 was synthesized by application of Fmoc amino protection and sidechain protection with lert-butyl groups. The lac-tosamine peptide T (165) could be released from the resin by application of the palladium(0)-catalyzed allyl-transfer reaction to V-methyl aniline as the allyl acceptor. 

FIGURE 3.13 Cleavage of an allyl-based protector (Stevens Watanabe, 1950) by palladium-catalyzed allyl transfer to a nucleophile in the presence of a proton donor.27-28... 

Common protectors of hydroxyls are benzyl and 2-bromobenzyl for Boc chemistry and tert-butyl for Fmoc chemistry. Trityl provides a third level of selectivity for both chemistries because it can be removed by mild acid (1% CF3C02H in CH2C12), which does not affect tert-butyl based protectors. O-Allyl is not removable by palladium-catalyzed allyl transfer, so it is not appropriate. Protection by acyl such as benzyloxycarbonyl is possible, but 0 -acyl protectors can be problematic because of their tendency to shift to adjacent amino groups (see Section 6.6) and... 

Diethylamine (11) is an inexpensive base that removes fluorenylmethyl-based protectors without forming an adduct with the liberated moiety, and it can be eliminated by evaporation. It has been employed as nucleophile for palladium-catalyzed allyl-transfer reactions (see Section 3.13). 

While alkyl halides are typically employed as an electrophile for this transformation, Takemoto developed palladium-catalyzed asymmetric allylic alkylation of 1 using allylic acetates and chiral phase-transfer catalyst 4k, as depicted in Scheme 2.5 [ 2 3 ]. The choice of triphenyl phosphite [(PhO)3P] as an achiral palladium ligand was crucial to achieve high enantioselectivity. 

Takemoto and coworkers extended their palladium-catalyzed asymmetric allylic alkylation strategy using allyl acetate and chiral phase-transfer catalyst to the quaternization of 13 [23b]. A correct choice of the achiral palladium ligand, (PhO P, was again crucial to achieve high enantioselectivity and hence, without chiral phosphine ligand on palladium, the desired allylation product 15 was obtained with 83% ee after hydrolysis of the imine moiety with aqueous citric acid and subsequent benzoylation (Scheme 2.12). 

Palladium-catalyzed methylene transfer from diazomethane has proved effective for the cyclopropanation of 1-alkenylboronic acid esters allylic alcohols and amines 1-oxy-l,3-butadienes and allenes " Readily accessible iron complex (CO)2FeCH2S Me2 BF4 35 undergoes direct reaction with a range of alkenes to give cyclopropanes (equation 67) The salt is sensitive to steric effects and the reaction proceeds... 

Reactions with Sulfur Nucleophiles. The use of sulfur nucleophiles in palladium-catalyzed allylic substitution reactions is less well documented than that of carbon, nitrogen and oxygen nucleophiles. The asymmetric synthesis of allylic sulfones utilizing a catalytic phase transfer system has been used to produce (35)-(phenylsulfonyl)cyclohex-l-ene on a 45 g scale (eq 10). In many cases, it has been reported that allylic carbonates are more reactive than allylic acetates in asymmetric allylic substitution... 

In both schemes cis insertion is the most hypothetical step. Cossee has assumed 164) that similar processes take place during olefin polymerization in the presence of Ziegler-Natta catalysts, and in some other reactions catalyzed by the transition metal compounds. This author came to the conclusion 165) that the d orbitals of the metal combine with the migrating group to facilitate such processes. In the course of 7r-allyl transfer the palladium orbitals overlap with the antibonding orbitals of double bond of the <7-bonded allyl group so as to favor an insertion reaction. 

Scheme 11 Palladium-Catalyzed Transfer of an Allyl Group to a Nucleophilel ...

AUyl-based handles 19 are very useful systems since cleavage of the protected peptide from the resin can be achieved under practically neutral conditions by palladium(0)-catalyzed allyl transfer to weakly basic nucleophiles.These conditions are, in principle, compatible with both of the major SPPS strategies. 

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