Regioselectivity, allylic alkylations

A combination of rhodium complexes and phosphates promotes a highly regioselective allylic alkylation of unsym-metric allylic esters, where alkylation occurs at the more substituted allylic terminus of the esters (Equation (46)). As Evans and his co-workers reported, both the regio- and stereochemistry of the starting allylic esters are maintained in the allylic alkylated products (Equation (47)). Thus, the rhodium-catalyzed allylic alkylation takes place at the carbon substituted by a leaving group with net retention of configuration. A variety of carbon-centered... 

An enantioselective rhodium(II)-catalysed intramolecular cyclopropanation, follow- (g) ed by a regioselective allylic alkylation and a diastereoselective rhodium(I)-catalysed 5 + 2-cycloaddition has been reported.102 ... 

Copper salts such as CuCN, CuBr-SMc2 and CuCN-2LiCl were demonstrated to mediate the regioselective allylation, alkylation, and propargylation of the lithium anion of n-butylthiooxazole 128 providing 2,5-disubstituted systems 129. Desulfurization with deactivated W2-Raney nikel produced 5-substituted derivatives <03TL7395>. 

Recently, a new ruthenium catalyst that also provides regioselective allylic alkylation has been reported. In DMF, a highly branched alkylation product of cinnamyl carbonate vsdth malonate anion was obtained in quantitative yield (branched/line-ar = 14/1) within 30 min in the presence of 1 mol% of [(C5Me5)Ru(MeCN)3]PF6 catalyst (Eq. 5.30) [46]. 

Allylic alkylations are among the most widely applied catalytic C-C bond formation reactions in organic chemistry. In the 1980s already mononitrosyl ferrate complexes of type 31 were reported to be active in regioselective allylic alkylations [94, 95]. However, this pioneering work suffered from low turnover numbers and the reaction had to be carried out under CO atmosphere. 

The rhodium-catalyzed [5-1-2] cycloadditions have been used in cascade with other processes to synthesize molecules of more complexity in a single operation. The first example was reported by Martin who developed a cascade sequence involving allylic alkylation and [5-1-2] cycloaddition (see (20)) [42,43]. The catalyst [Rh(CO)2Cl]2 could be used to catalyze both the highly regioselective allylic alkylation and the following intramolecular [5-1-2] cycloaddition. As another example, Wender and co-workers combined intermolecular [5-1-2] cycloaddition with... 

Scheme 3 Tsuji s regioselective allylic alkylation reactions...

Additions of carbon nucleophiles to vinylepoxides are well documented and can be accomplished by several different techniques. Palladium-catalyzed allylic alkylation of these substrates with soft carbon nucleophiles (pKa 10-20) proceeds under neutral conditions and with excellent regioselectivities [103, 104]. The sul-fone 51, for example, was cyclized through the use of catalytic amounts of Pd(PPh3)4 and bis(diphenylphosphino)ethane (dppe) under high-dilution conditions to give macrocycle 52, an intermediate in a total synthesis of the antitumor agent roseophilin, in excellent yield (Scheme 9.26) [115, 116]. 

The protocol of the allylic alkylation, which proceeds most likely via a c-allyl-Fe-intermediate, could be further improved by replacing the phosphine ligand with an M-heterocyclic carbene (NHC) (Scheme 21) [66]. The addition of a ferf-butyl-substituted NHC ligand 86 allowed for full conversion in the exact stoichiometric reaction between allyl carbonate and pronucleophile. Various C-nucleophiles were allylated in good to excellent regioselectivities conserving the 71 bond geometry of enantiomerically enriched ( )- and (Z)-carbonates 87. Even chirality and prochirality transfer was observed (Scheme 21) [67]. 

Allylic alkylation of 3-acetoxy-l,3-diphenylpropene by sodium dimethytmalonate, catalysed by the Pd-allyl complex 115, bearing the non-symmetric phosphonium ylide NHC ligand (5 mol%), proceeds to completion with 100% regioselectivity. 

Allylic alkylations of cinnamyl carbonate by sodium malonate have been studied with a series of ruthenium catalysts, obtained from the azohum salts 126-128 and the ruthenium complex 129 (Scheme 2.25) in MeCN or THF to give moderate yields of mixtures of alkylated products in the allylic and ipi o-carbons (90 10 to 65 35). The observed regioselectivity is inferior to similar ruthenium systems with non-NHC co-ligands. The stereoelectronic factors which govern the observed regioselectivity were not apparent [102]. 

Scheme 2.27 Proposed mechanism to account for the observed regioselectivity in the allylic alkylations catalysed by Fe-NHC complexes. Other co-hgands on Fe are omitted for clarity...

Allylic substitutions with nonstabilized C-nucleophiles are an important domain of organocopper chemistry [51]. However, on close inspection of the literature, it becomes apparent that regioselectivity in favor of the branched allylic alkylation products is only obtained with alkyl copper compounds, while aryl copper compounds mainly give the linear alkylation products. This observation was an incentive for Alexakis et al. [52] to probe the reactions of aryl zinc hahdes in the Ir-catalyzed allylic substitution (Scheme 9.18). 

Evans and Nelson reexamined the rhodium-catalyzed allylic substitution reaction, in which they demonstrated that a triorganophosphite-modified Wilkinson s catalyst facilitates the allylic alkylation of secondary and tertiary aUyhc carbonates with excellent regioselectivity (Eq. 2). This work provided a convenient method for the construction of ternary and quaternary allylic products [11]. Additionally, they demonstrated that the modification of Wilkinson s catalyst with triorganophosphites serves to increase the re-... 

Evans and Kennedy later combined the regioselective rhodium-catalyzed allylic alkylation, using a-substituted malonates, with ring-closing metathesis for the construction of five-, six-, and seven-membered carbocycles (Scheme 10.2) [13]. The combination of these methodologies allowed for the rapid and flexible assembly of carbocycles possessing vicinal ternary-quaternary or quaternary-quaternary stereogenic centers. 

Tab. 10.1 Regioselective and enantiospecific rhodium-catalyzed allylic alkylation of enantiomerically enriched allylic carbonates.

Tab. 10.3 The scope of the regioselective rhodium-catalyzed allylic alkylation with copper(l) enolates.

The regio- and diastereoselective rhodium-catalyzed sequential process, involving allylic alkylation of a stabilized carbon or heteroatom nucleophile 51, followed by a PK reaction, utilizing a single catalyst was also described (Scheme 11.14). Alkylation of an allylic carbonate 53 was accomplished in a regioselective manner at 30 °C using a j-acidic rhodium(I) catalyst under 1 atm CO. The resulting product 54 was then subjected in situ to an elevated reaction temperature to facilitate the PK transformation. 

In 2002, Trost and his co-workers reported a stereospecific ruthenium-catalyzed allylic alkylation reaction (Equation (58)). Treatment of an optically active allylic carbonate with carbon-centered nucleophiles in the presence of a ruthenium complex gives the corresponding allylic alkylated compounds with enantiomeric purity being completely maintained. Additionally, the regioselectivity is revealed not to be highly dependent on the nature of the starting carbonates. 

As described in many reviews, Trost and his co-workers have carried out a pioneering work on the molybdenum-and tungsten-catalyzed allylic alkylation of allylic esters regioselectivity of the reaction is often complementary to the palladium-catalyzed allylic alkylation. The first asymmetric version was disclosed by Pfaltz and Lloyd-Jones in 1995 (Equation (63)). They used a catalytic amount of a novel tungsten complex, prepared from [W(CO)3(MeCN)3] or [W(cycloheptatriene) (COIs] and optically active (diphenylphosphino)phenyloxazolines 57, for the allylic alkylation of 3-aryl-2-propenyl phosphate with dimethyl sodiomalonate to isolate the corresponding branched alkylated compounds as a major isomer with an excellent enantioselectivity (96% ee). Unexpectedly, 3-aryl-2-propenyl carbonates are shown to be unreactive. It is worth noting that an isostructural molybdenum complex does not promote the catalytic alkylation under the same reaction conditions. In contrast, Lloyd-Jones and Lehmann reported the stereocontrolled... 

In sharp contrast to the transition metal-catalyzed allylic alkylation of allylic alcohols and their derivatives (see Chapter 11.03) where 77 -allyl-transition metal complexes are key intermediates, the benzyiic alkylation of benzyiic alcohols and their derivatives catalyzed by transition metal complexes has been quite unexplored, although 7] -benzyl-transition metal complexes have often been considered to explain the regioselectivity of transition metal-catalyzed addition to vinylarenes (Scheme 21). A3,63a... 

There have been no significant advances in the area of platinum-catalyzed allylic alkylations since the first work in 1985 [208], With the platinum complex derived from DIOP, low ee (11%) and modest regioselectivity (4 1) were obtained for the alkylation of (E)-crotyl acetate with dimethyl malonate. 

The regio- and stereo-selective rhodium-catalysed allylic alkylations of chelated enolates have been investigated.25 It has been found that the Rh-catalysed allylic alkylation is as efficient and versatile as the Pd-catalysed version. In reactions of chelated enolates with suitable protecting groups, high yields and selectivities were obtained, and the regioselectivity can be directed by the reaction parameters. 

With 1-alkoxyallenes as proelectrophiles, the palladium-catalysed asymmetric allylic alkylation proceeds with 1,3-dicarbonyl compounds as pronucleophiles with excellent regioselectivity good enantioselectivity (82-99% ee) was obtained with the Trost lig- and. The pH of the medium proved crucial for the reactivity and selectivity. By using the more acidic Meldrum s acids, the reactions required a co-catalytic amount of a Brpnsted acid, such as CF3CO2H. On the other hand, the less acidic 1,3-diketones failed to react under these conditions but the reaction proved to occur in the presence of the weaker benzoic acid, suggesting the need for general base catalysis. Indeed, a mixture of Et3N and PhCOiH proved to be optimal (93-99% ee). A mechanistic model to rationalize these results has been developed.88... 

The ruthenium complex Cp Ru(bipyridyl)Cl has been developed as a catalyst for the first regioselective tandem Michael addition-allylic alkylation of activated Michael acceptors. The net outcome is the decarboxylative insertion of Michael acceptors into allyl /3-keto esters to produce (215). The reaction combines the generation of Ru-tt-allyl and enolate from (213) the enolate is first added to the Michael acceptor (214) and the resulting species is captured by the Ru-tt-allyl.254... 

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