Molybdenum-catalyzed asymmetric reaction

The molybdenum-catalyzed asymmetric reaction differs from the palladium-catalyzed reaction in several ways, the most important of which is the different regios-electivity achieved. Molybdenum-catalyzed reactions favor the most sterically hindered position (Eq. 11.39), in contrast with palladium catalysis. The molybdenum-catalyzed allylations also suffer from significantly lower reactivity. 

A fast and efficient molybdenum-catalyzed asymmetric allylic alkylation under noninert conditions has been reported using MW-accelerated reaction [178]. Inter-molecular hydroacylation of 1-alkenes with aldehydes has been presented as a greener alternative to classical approach using a homogeneous catalyst in toluene. 

The molybdenum-catalyzed asymmetric allylic alkylation can also be carried out under non-inert conditions with microwave activation (eq 5). In comparison to the thermally promoted reaction, reaction times are shorter (5 min vs 4 h). Nevertheless, high yields (87%) and ee (98%) are obtained, the regioselectivity is lower in the microwave reactions (19 1). This can be improved (41 1) by introducing an electron-donating substituent (4-methoxypyridine derivative) into the title ligand. ... 

Oxalactims, for exanple 5//-methyl-2-phenyl-oxazol-4-one, were investigated as synthetically powerful synthons for the construction of a-hydroxy acids via o -deprotonation followed by molybdenum-catalyzed asymmetric allylation and a subsequent hydrolysis of the oxalactim rings. Among the series of the HMDS bases used in tbe Mo-catalyzed asymmetric allylation, LHMDS was found to be tbe base of choice providing better yields, regio- (branched/Unear), diastereo- andenantioselectivity than the corresponding allylation reactions mediated by KHMDS (eq 63). ... 

Just like palladium, the molybdenum-catalyzed reaction has been extended to an asymmetric variant. Following development of the reaction by Trost and co-workers,they reported a concise and efficient synthesis of the HIV therapeutic tipranavir (119). While the key tetrasubstituted centre in compound 115 was constructed by a palladium-boron co-catalyzed DYKAT reaction, the stereogenic centre in nitroaromatic 117 was installed in a molybdenum-catalyzed DYKAT reaction. Both compounds were subsequently elaborated to tipranavir (119). While it has been determined that the molybdenum-catalyzed reaction proceeds with overall retention, the stereochemistry of each step has not been extensively studied. Recent studies have suggested a retention-retention pathway may be in operation. ... 

Hallberg and his co-workers reported in 1999 the first microwave-promoted asymmetric palladium-catalyzed allylic alkylation of acyclic and cyclic allylic esters with dimethyl malonate, using some chiral ligands 57 and 118 (Equations (65) and (55))3 s,l6Sa,i6Sb both cases, microwave irradiation reduces reaction time without any loss of enantio-selectivity. The same group successfully applied this reaction system to the molybdenum-catalyzed allylic alkylation (Equation ((,7)) 60.160 -l60. 

Because asymmetric catalysis enables access to several synthetically important compounds, microwave-assisted molybdenum-catalyzed allylic allylation has been studied using both free and polymer-supported bis-pyridylamide ligands [134]. The microwave-assisted catalytic reaction of 3-phenylprop-2-enyl methyl carbonate with dimethyl malonate in the presence of N,0-bis(trimethylsilyl)acetamide (BSA) and a polymer-bound bis-pyridyl ligand was rather slow, however. 

One good example of the application of this technology is in the AAA reaction of a racemic vinyl epoxide. The epoxide undergoes a dynamic kinetic asymmetric transformation (DYKAT) by reaction with p-methoxybenzyl alcohol, the standard ligand, and a palladium source. The product is obtained in 69% yield and 98% e.e. After further manipulations a key building block for the nonpeptidic protease inhibitor tipranavir was produced. Coupling of this intermediate with a synthon obtained using a molybdenum-catalyzed DYKAT process led to an advanced intermediate in a total synthesis of tipranavir (Scheme 20.14). ... 

Another metal-catalyzed microwave-assisted transformation performed on a polymer support involves the asymmetric allylic malonate alkylation reaction shown in Scheme 12.4. The rapid molybdenum(0)-catalyzed process involving thermostable chiral ligands proceeded with 99% ee on a solid support. When TentaGel was used as as support, however, the yields after cleavage were low (8-34%) compared with the corresponding solution phase microwave-assisted process (monomode cavity) which generally proceeded in high yields (>85%) [30],... 

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... 

---