Catalytic asymmetric synthesis of cyclopropanecarboxylic acids: an application of chiral copper carbenoid reaction

Abstract

Reaction of alkyl diazoacetate with an olefin catalyzed by a chiral copper complex gives an optically active alkyl cyclopropanecarboxylate. This chiral copper carbenoid reaction was successfully applied to the synthesis of industrially valuable cyclopropanecarboxylic acids: (÷)-trans-chrysanthem ic acid, (÷)-cis-permethrinic acid and (+)-2,2-dimethylcyclopropanecarboxylic acid. A series of effective catalysts, chiral Schiff base-copper complexes, was prepared starting with an optically active a-amino acid to achieve more than 90% e.e. of the products. The chirality of the products was correlated with that of the catalyst on the basis of metallacyclobutane intermediates. CHIRAL COPPER CARBENOID REACTION (ref. 1) AND ITS APPLICATION TO CHRYSANTHEMIC ACID SYNTHESISIn 1966, the first example of asymmetric catalysis (ref. 2) by means of a soluble transition metal complex was reported by Prof. Nozaki and his coworkers. They decomposed ethyl diazoacetate in styrene in the presence of chiral copper complex (1) as a catalyst to give the products, trans-and cis-2-phenyl-cyclopropanecarboxylate (3 and 4), both in an optically active form (Eq 1). This finding demonstrated that the carbene derived from ethyl diazoacetate is not free but is combined with the chiral copper complex to form a carbene-copper complex (ref. 3), which is responsible for the asymmetric induction. Furthermore, the reaction provided a new method for the preparation of optically active cyclopropane derivatives of practical value, although the enantiomeric excess (e.e.) attained at that time was less than 10%.

Asymmetric Cyclopropanation of Styrene Catalyzed by Cu–(Chiral Schiff-Base) Complexes

“…According to the proposed mechanism of asymmetric cyclopropanation, 6 metal-carbenes (A1 and A2) (Scheme 1) are involved as the intermediates. Approach of the alkene to the metal-carbene occurs from the less hindered side, giving rise to the enantioselectivity.…”

“…Among the efficient catalysts which have been developed, copper-Schiff base complexes derived from chiral amino alcohols are of particular significance because they are effective for the intermolecular cyclopropanation of various substituted olefins including mono-, di-, and trisubstituted olefins, as well as for intramolecular cyclopropanation. [3][4][5][6][7][8] The successful industrial application of this kind of catalysts in the synthesis of chiral 2,2-dimethylcyclopropanecarboxylic acid makes it a significant achievement in asymmetric catalysis. 9 Even though it has received so much attention, to our knowledge, modification of this kind of catalyst to obtain higher enantioselectivity had only focused on the modification of chiral amino alcohols until 1999, Cai reported that copper-Schiff base complexes derived from 2-hydroxyl-5-methyl-1,3-benzenebisaldehyde were used as the catalyst.…”

First X‐ray Structure of a N‐Naphthaloyl‐Tethered Chiral Dirhodium(II) Complex: Structural Basis for Tether Substitution Improving Asymmetric Control in Olefin Cyclopropanation

“…[1, 2] In the case of the paddle-wheel dirhodium(II) catalysts based on amino acid derived ligands, enantioselectivity arises from the concerted control of the carbene-transfer step (metal to olefin) offered by the chiral ligand set flanking an axial coordination site of the dirhodium complex. A recent report discussed the role of the chiral crown cavity of the well-known Hashimoto catalyst [Rh 2 {(S)-pttl}4] (pttl = N-phthaloyl-(S)-tert-leucinate) formed by the four N-phthaloyl units in this regard, Scheme 1.…”

“…This stems not only from being the reaction in which asymmetric catalysis by transition metals was first demonstrated, but also because of its prevalence in natural-product-based and synthetic drugs. [1] Once this principle was demonstrated, highly selective catalysts were developed, mainly based on Cu I and Rh II associated with appropriate chiral nonracemic ligands.…”

Theoretical Insights into the Role of a Counterion in Copper‐Catalyzed Enantioselective Cyclopropanation Reactions

“…The use of catalysts based on copper is particularly attractive because of their high efficiency in asymmetric cyclopropanation reactions [4] and their relatively low cost in comparison with other metal derivatives, such as catalysts based on rhodium [5] or ruthenium. [6] Various chiral ligands have been described for the enantioselective versions of the cyclopropanation reaction, including salicylaldimines, [7] salicylaldehyde±amino acid derivatives, [8] and semicorrins. [9] The best results have been obtained with bis(oxazolines)-described independently by Evans and co-workers [10] and Masamune and co-workers [11] -which can lead to almost complete enantioselectivity (up to 99 % ee) when their complexes with Cu I or Cu II are used in cyclopropanation reactions.…”