Alkyl diazoacetates, enantioselective cyclopropanations, copper

Enantioselective carbenoid cyclopropanation can be expected to occur when either an olefin bearing a chiral substituent, or such a diazo compound or a chiral catalyst is present. Only the latter alternative has been widely applied in practice. All efficient chiral catalysts which are known at present are copper or cobalt(II) chelates, whereas palladium complexes 86) proved to be uneflective. The carbenoid reactions between alkyl diazoacetates and styrene or 1,1 -diphenylethylene (Scheme 27) are usually chosen to test the efficiency of a chiral catalyst. As will be seen in the following, the extent to which optical induction is brought about by enantioselection either at a prochiral olefin or at a prochiral carbenoid center, varies widely with the chiral catalyst used. 

It has already been mentioned that prochirality of the olefin is not necessary for successful enantioselective cyclopropanation with an alkyl diazoacetate in the presence of catalysts 207. What happens if a prochiral olefin and a non-prochiral diazo compound are combined Only one result provides an answer to date The cyclopropane derived from styrene and dicyanodiazomethane shows only very low optical induction (4.6 % e.e. of the (25) enantiomer, catalyst 207a) 9S). Thus, it can be concluded that with the cobalt chelate catalysts 207, enantioface selectivity at the olefin is generally unimportant and that a prochiral diazo compound is needed for efficient optical induction. As the results with chiral copper 1,3-diketonates 205 and 2-diazodi-medone show, such a statement can not be generalized, of course. 

Enantioselection can be controlled much more effectively with the appropriate chiral copper, rhodium, and cobalt catalyst.The first major breakthrough in this area was achieved by copper complexes with chiral salicylaldimine ligands that were obtained from salicylaldehyde and amino alcohols derived from a-amino acids (Aratani catalysts ). With bulky diazo esters, both the diastereoselectivity (transicis ratio) and the enantioselectivity can be increased. These facts have been used, inter alia, for the diastereo- and enantioselective synthesis of chrysan-themic and permethrinic acids which are components of pyrethroid insecticides (Table 10). 0-Trimethylsilyl enols can also be cyclopropanated enantioselectively with alkyl diazoacetates in the presence of Aratani catalysts. In detailed studies,the influence of various parameters, such as metal ligands in the catalyst, catalyst concentration, solvent, and alkene structure, on the enantioselectivity has been recorded. Enantiomeric excesses of up to 88% were obtained with catalyst 7 (R = Bz = 2-MeOCgH4). 

The ruthenium(ll) complex 20175c,d and the cobalt complexes 21179a and 22197b are also able to produce remarkable enantioselectivities in intermolecular cyclopropanation reactions. For the cyclopropanation of styrene with alkyl diazoacetates, the following ee-values have been reported 20 /t/V-buty , 94% (trans), 85% (cis), /-menthyl, 95% (as), 76% (trans), /-menthyl, 86% (cis), 95% (trans) 21 ethyl, 75% (cis), 20% (trans) 22 tert-butyl, 73% (trans). It is interesting to note that a catalyst analogous to 20, but with copper(II) triflate instead of ruthenium, displayed only low enantiocontrol.220b... 

Chiral dirhodium(II) carboxamidates are preferred for intramolecular cyclopropanation of allylic and homoallylic diazoacetates (Eq. 2). The catalyst of choice is Rh2(MEPY)4 when R " and R are H, but Rh2(MPPIM)4 gives the highest selectivities when these substituents are alkyl or aryl. Representative examples of the applications of these catalysts are listed in Scheme 15.1 according to the cyclopropane synthesized. Use of the catalyst with mirror image chirality produces the enantiomeric cyclopropane with the same enantiomeric excess [33]. Enantioselectivities fall off to a level of 40-70% ee when n is increased beyond 2 and up to 8 (Eq. 2) [32], and in these cases the use of the chiral bisoxazoline-copper complexes is advantageous. 

Reissig and coworkers have devised an indirect method of enantioselective alkylation of ketones via cyclopropanation of silyl enol ethers in the presence of the chiral copper catalyst 16, followed by ring opening to provide the substituted ketones. Overall, the transformation corresponds to alkylation of ketones using methyl diazoacetate as the electrophile. Enantioselectivities up to 88% were realized in the cyclopropanation of aryl substituted olefins, Eq. (20) [63,64]. 

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