Asymmetric methyl phenyldiazoacetate

Carbenoids derived from the aryldiazoacetates are excellent donor/acceptor systems for the asymmetric cyclopropanation reaction [22]. Methyl phenyldiazoacetate 3 cyclopropanation of monosubstituted alkenes catalyzed by Rh2(S-DOSP)4 is highly diaster-eo- and enantioselective (Tab. 14.5) [22]. Higher enantioselectivities can be obtained when these reactions are performed at -78°C, as the catalyst maintains high solubility and activity at this temperature. The phenyldiazoacetate system has been evaluated using many popular rhodium(II) and copper catalysts the rhodium(ll) prolinates have proven to be superior catalysts for this class of carbenoids [37, 38]. 

Numerous studies have been directed toward expanding the chemistry of the donor/ac-ceptor-substituted carbenoids to reactions that form new carbon-heteroatom bonds. It is well established that traditional carbenoids will react with heteroatoms to form ylide intermediates [5]. Similar reactions are possible in the rhodium-catalyzed reactions of methyl phenyldiazoacetate (Scheme 14.20). Several examples of O-H insertions to form ethers 158 [109, 110] and S-H insertions to form thioethers 159 [111] have been reported, while reactions with aldehydes and imines lead to the stereoselective formation of epoxides 160 [112, 113] and aziridines 161 [113]. The use of chiral catalysts and pantolactone as a chiral auxiliary has been explored in many of these reactions but overall the results have been rather moderate. Presumably after ylide formation, the rhodium complex disengages before product formation, causing degradation of any initial asymmetric induction. 

Considerable interest has been shown in developing asymmetric variants of the Si-H insertion. The chiral auxiUary (Jl)-pantolactone has performed quite well in this chemistry, as illustrated in the formation of 169 in 79% diastereomeric excess (Eq. 19) [28]. A wide variety of chiral catalysts have been explored for the Si-H insertion chemistry of methyl phenyldiazoacetate [29, 117-119]. The highest reported enantioselectivity to date was obtained with the rhodium prolinate catalyst Rh2(S-DOSP)4, which generated 170 with 85% enantiomeric excess (Eq. 20) [120]. 

The full potential of this C-H activation process, as a surrogate Mannich reaction, was realized in the direct asymmetric synthesis of threo-methylphenidate (Ritalin) 217 (Eq. 28) [140]. C-H insertion of N-Boc-piperidine 216 using second-generation Rh2-(S-biDOSP)2 and methyl phenyldiazoacetate resulted in a 71 29 diastereomeric mixture, where the desired threo-diastereomer was obtained in 52% yield with 86% enantiomeric excess. Winkler and co-workers screened several dirhodium tetracarboxami-dates and found Rh2(R-MEPY)4 to be the catalyst that gives the highest diastereoselec-tivity for this reaction [142]. 

The asymmetric allylic C—H bond insertion reaction of 1,4-cyclohexadiene was further improved by Denton and Davies in 2009. Using different donor/ acceptor carbenoids derived from a-aryl-a-diazoketones 25 and a chiral dirhodium complex Rh2(S-PTAD)4 instead of methyl phenyldiazoacetate la and Rh2(S-DOSP)4 in previous work (Scheme 1.6, eqn (1)), the corresponding C—H bond insertion products 26 could be obtained in up to 90% yield and 89% ee in refluxing DMB (Scheme 1.7a). Later, the catalytic efficiency was significantly enhanced by conducting the reaction under solvent-free con-ditions. Since donor/acceptor carbenoids are more stable and less prone to catalyst decay and carbene dimerization, they are suitable for reactions... 

Successful conditions for intermolecular carbene insertions into alkane C-H bonds with diazo esters have been reported under Ag(I) and Ir(III) catalyses. While the argen-tate trinuclear cluster (90) has been shown to catalytically promote such C-H insertion with ethyl diazoacetate, " Ir(III)-based porphyrin catalyst (91) appeared much more efficient using bulky methyl 2-phenyldiazoacetate as an alternative carbene source. Ir(III)-based porphyrin analogue (92) bearing chiral arms promotes carbene insertion with up to 98% yield in an asymmetric manner (up to 98% ee). ... 

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