Molybdenum allylic substitution

When the chiral molybdenum allyl-substituted enone 147 was treated with lithium dimethylcuprate formation of adduct 148 vtith fair selectivity was observed (Scheme 6.29) [69]. Interestingly higher selectivities were obtained in the presence of boron trifluoride etherate. It is assumed that Lewis acid coordination induces the s-trafxs reactive conformation 149 [64]. Consequently nudeophile attack anti to the molybdenum fragment should afford the major diastereomer 148. 

Chiral pyridine-based ligands were, among various Ar,AT-coordinating ligands, more efficient associated to palladium for asymmetric nucleophilic allylic substitution. Asymmetric molybdenum-catalyzed alkylations, especially of non-symmetric allylic derivatives as substrates, have been very efficiently performed with bis(pyridylamide) ligands. 

An interesting allylic substitution reaction of ( )-cinnamyl methyl carbonate 143 has been examined by Pfaltz s group. The use of a molybdenum complex of ligand 144 resulted in 145 in 88% yield with an ee of 99% [for the (R) isomer] (Fig. 9.45). 

Metals other than palladium and molybdenum can be used for allylic substitution reactions. For example, nickel in the presence of the oxazolinylferrocenylphosphine 9 provides good asymmetric induction for the reaction of a Grignard reagent with allylic electrophilic systems such as acetates.151... 

The various allylic substitution reactions are illustrated in a synthesis of Tipranavir (11), an HIV protease inhibitor. A palladium-catalyzed opening of a vinyl epoxide set the quaternary stereogenic center (Scheme 22.23). A molybdenum-catalyzed allylic nuclophilic displacement was used to access the benzylioc stereogenic center (Scheme 22.24).153... 

Keywords Allylic substitution, Allylation, Allylic alkylation, Jt-Allyl complexes, Palladium, Molybdenum, Ruthenium, Iridium... 

The lithium cuprates 39, prepared from a- and P-2-deoxy-D-glucopyranosyl-stannanes a- and P-38 are configurationally stable and provide the corresponding Michael addition products 40 on reaction with methyl vinyl ketone [Eq. (14)] [27]. The cuprates a-39 [28] and 41 [29] have been used by Kocienski et al. for allylic substitution at q -molybdenum complexes. 

The first conventional catalysts based on tungsten and molybdenum complexes exhibited very low activity in the homo-metathesis of allylic-substituted silanes [2]. 

Several recent studies have revealed the dichotomous relationship between the regioselectivity of reactions of unsymmetrical allyl complexes of palladium and that of reactions of unsjmmetrical allyl complexes of other metals. An isolated molybdenum-allyl complex containing an allyl group derived from methyl cinnamyl carbonate (PhCH=CHCH2C)COjMe) reacts with the sodium salt of dimethyl malonate in the presence of a source of CO to generate the branched substitution product (Equation 11.41). The addition of nucleophile to this allyl complex has been shown to occur by retention of configuration, perhaps by initial attack at the metal, rather than the more common external attack at Are allyl group. ... 

Much effort has been devoted to developing catalysts that control the enantioselectiv-ity of these substitution reactions, as well as the regioselectivity of reactions that proceed through unsymmetrical allylic intermediates. A majority of this effort has been spent on developing palladium complexes as catalysts. Increasingly, however, complexes of molybdenum, tungsten, ruthenium, rhodium, and iridium have been studied as catalysts for enantioselective and regioselective processes. In parallel with these studies of allylic substitution catalyzed by complexes of transition metals, studies on allylic substitution catalyzed by complexes of copper have been conducted. These reactions often occur to form products of Sj 2 substitution. As catalylic allylic substitution has been developed, this process has been applied in many different ways to the synthesis of natural products. ... 

A vast majority of the allylic substitution reactions have been reported with palladium catalysts. However, complexes of other metals also catalyze allylic substitution reactions. In particular, complexes of molybdenum,tungsten, ruthenium, rhodium, and iridium " have been shown to catalyze the reactions of a variety of carbon nucleo-pliiles. In addition, complexes of ruthenium, rhodium, and iridium catalyze the reactions of phenoxides, alkoxides, amines, and amine derivatives. " The regioselectivity of the allylic substitution process witli these metals can often complement the regioselectivity of the reactions catalyzed by palladium complexes. The regioselectivity... 

The enantioselective allylic substitution has also been conducted with vmsymmetrical allylic electrophiles, as shown in Equation C of Scheme 20.10. In this case, enantioselectivity is dictated by the face to which the metal is bound and the resulting face of the allyl group that suffers nucleophilic attack. Complexes of many different metals have been studied for this type of reaction, and complexes of molybdenum and iridium are particularly selective for this class of of substitution."- - " ... 

Figure 20.3. Ligands for enantioselective, molybdenum-catalyzed allylic substitution.

Stable enolates such as diethyl malonate anions react with allyl sulfones (or acetates) in the presence of nickel complexes to give a mixture of the a- and /-product83. The regioselectivity is generally poor in the nickel-catalyzed reaction, but the molybdenum-catalyzed reaction is selective for alkylation at the more substituted allylic site, thereby creating a quaternary carbon center84. 

Trost and Hachiya [140] studied asymmetric molybdenum-catalyzed alkylations. Interestingly, they noticed that the regioselectivity of this transformation performed with a non-symmetric allylic substrate varied according to the nature of the metal Pd-catalyzed substitutions on aryl-substituted allyl systems led to attack at the less substituted carbon, whereas molybdenum catalysis afforded the more substituted product. They prepared the bis(pyridylamide) ligand 105 (Scheme 55) and synthesized the corresponding Mo-complex from (C2H5 - CN)3Mo(CO)3. With such a catalyst, the allylic... 

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