Cyclopropanation alkyl diazoacetate

The change in selectivity is not credited to the catalyst alone In general, the bulkier the alkyl residue of the diazoacetate is, the more of the m-permethric acid ester results 77). Alternatively, cyclopropanation of 2,5-dimethyl-2,4-hexadiene instead of l,l-dichloro-4-methyl-l,3-pentadiene leads to a preference for the thermodynamically favored trans-chrysanthemic add ester for most eatalyst/alkyl diazoacetate combinations77 . The reasons for these discrepandes are not yet clear, the interplay between steric, electronic and lipophilic factors is considered to determine the stereochemical outcome of an individual reaction77 . This seems to be true also for the cyclopropanation of isoprene with different combinations of alkyl diazoacetates and rhodium catalysts77 . 

Diverging results have been reported for the carbenoid reaction between alkyl diazoacetates and silyl enol ethers 49a-c. Whereas Reissig and coworkers 60) observed successful cyclopropanation with methyl diazoacetate/Cu(acac)2, Le Goaller and Pierre, in a note without experimental details u8), reported the isolation of 4-oxo-carboxylic esters for the copper-catalyzed decomposition of ethyl diazoacetate. According to this communication, both cyclopropane and ring-opened y-keto ester are obtained from 49 c but the cyclopropane suffers ring-opening under the reaction conditions. 

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. 

In the presence of catalytic amounts of 207a and at moderate temperatures (—15 to +30 °C), the cyclopropanes derived from styrene and various alkyl diazoacetates were obtained in good yields (80-95 %) with remarkably high enantiomeric excess for both the cis(lS, 2R) and the transilS, 2S) isomer. With increasing steric bulk of the rater substituent (methyl -> neopentyl), both the trans/cis ratio (0.69 - 2.34) and the optical yield (61 ->88% for the /raws-cyclopropane at 0 ° ) became higher 88,95). 

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. 

In the simplest case, the reaction of allyl diazoacetate, the catalyst (iS )-198 or (f )-198 in a concentration as low as 0.1 mol% can still catalyze the formation of enantiomeric-3-oxabicyclo[3.1.0]hexan-2-ones with 95% ee (Scheme 5-60). Substituted alkyl diazoacetates undergo intramolecular cyclopropanation, with similarly high enantiomeric excess (Scheme 5-61).110... 

Cyclopropanation and Cyclopropenation. At this time, intermolecu-lar cyclopropanation with alkyl diazoacetates is best accomplished with cobalt cat-... 

Rhodium(II) acetate appears to be the most generally effective catalyst, and most of this discussion will center around the use of this catalyst with occasional reference to other catalysts when significant synthetic advantages can be gained. Cyclopropanation of a wide range of alkenes is possible with alkyl diazoacetate, as is indicated with the examples shown in Table l.l6e>37 The main limitations are that the alkene must be electron rich and not too sterically crowded. Poor results were obtained with trans-alkenes. Comparison studies have been carried out with copper and palladium catalysts and commonly the yields were lower than with rhodium catalysts. Cyclopropanation of styrenes and strained alkenes, however, proceeded extremely well with palladium(ll) acetate, while copper catalysts are still often used for cyclopropanation of vinyl ethers.38-40... 

The reaction of N-alkylated pyrroles with carbenoids leads exclusively to substitution products. Due to the pharmaceutical importance of certain pyrrolylacetates, the reaction with alkyl diazoacetates (Scheme 45) has been systematically studied using about 50 different catalysts.13 Both the 2- and 3-alkylated products (216) and (217) could be formed and the ratio was dependent on the size of the JV-alkyl group and ester and also on the type of catalyst used. This has been interpreted as evidence that transient cyclopropane intermediates were not involved because if this were the case, the catalyst should not have influenced the isomer distribution. Instead, the reaction was believed to proceed by dipolar intermediates, whereby product control is determined by the position of electrophilic attack by the carbenoid. Similar alkylations with dimethyl diazomalonate gave greater selectivity and yields.164... 

A vast array of chiral catalysts have been developed for the enantioselective reactions of diazo compounds but the majority has been applied to asymmetric cyclopropanations of alkyl diazoacetates [2]. Prominent catalysts for asymmetric intermolecular C-H insertions are the dirhodium tetraprolinate catalysts, Rh2(S-TBSP)4 (la) and Rh2(S-DOSP)4 (lb), and the bridged analogue Rh2(S-biDOSP)2 (2) [7] (Fig. 1). A related prolinate catalyst is the amide 3 [8]. Another catalyst that has been occasionally used in intermolecular C-H activations is Rh2(S-MEPY)4 (4) [9], The most notable catalysts that have been used in enantioselective ylide transformations are the valine derivative, Rh2(S-BPTV)4 (5) [10], and the binaphthylphosphate catalysts, Rh2(R-BNP)4 (6a) and Rh2(R-DDNP)4 (6b) [11]. All of the catalysts tend to be very active in the decomposition of diazo compounds and generally, carbenoid reactions are conducted with 1 mol % or less of catalyst loading [1-3]. 

A. J. Hubert, A. F. Noels, A. J. Anciaux, and Ph. Teyssie (1976) Rhodium(II) carboxylates novel highly efficient catalysts for the cyclopropanation of alkenes with alkyl diazoacetates, Synthesis 9 600-602... 

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). 

Copper-, rhodium-, palladium-, and ruthenium-catalyzed cyclopropanation with diazoacetic esters is possible for a wide range of electron-rich alkenes, including alkylated acyclic alkenes, cycloalkenes, styrenes, 1,3-dienes, enol ethers, enol acetates, and ketene acetals (examples are given in this section, in Houben-Weyl Vol.E19b, ppl099-1155 and in refs 2, 152, 155 and 184). Furthermore, the construction of cyclopropanes with additional strain is possible, for example ... 

A .A -Dialkyl enamines yield alkyl 2-dialkylaminocyclopropane-l-carboxylates in low yield only, or, more typically, not at all. In contrast, less nucleophilic enamines, such as 77-acyl enamines (see Houben-Weyl, Vol. El9b, p 1153), A-acyl-2,3-dihydropyrroles, 77-acyl-l,2,3,4-tetrahydropyridines and A W-bis(trimethylsilyl) enamine 15, are cyclopropanated by diazoacetic esters without problems, e.g. formation of 16. In contrast to ( )-15, the Z-isomer and related trisubstituted enamines are cyclopropanated only in low yield (5-10%). ... 

The carbenoid reaction between alkyl diazoacetates and enol ethers, enol acetates and silyl enol ethers furnishes P-oxycyclopropane carboxylates (see Tables 2, 4, 5, 6, 7 and Scheme 5). The recently recognized synthetic versatility of these donor/acceptor-substituted cyclopropanes i 2,io3) (precursors of 1,4-dicarbonyl and P, 7-unsaturated carbonyl compounds, 4-oxocarboxylic acids and esters, among others) gave rise to the synthesis of a large number of such systems with a broad variation of substituents p-acetoxycyclopropanecarboxylates , p-alkoxy- or p-aryloxysubstituted cyclopropanecarboxylates 2-alkoxy-1-methyl-1-cy-... 

Diazomalonic esters, in their behavior towards enol ethers, fit neither into the general reactivity pattern of 2-diazo-l,3-dicarbonyl compounds nor into that of alkyl diazoacetates. With the enol ethers in Scheme 17, no dihydrofurans are obtained as was the case with 2-diazo-l,3-dicarbonyl compounds. Rather, copper-induced cyclopropanation yielding 70 occurs with ethoxymethylene cyclohexane However,... 

A number of diazo compounds are known to be decomposed by Zn(II), Co(II), Co(ni) and Rh(III) complexes of porphyrins (409) to give 1 1 and 1 2 adducts between the porphyrin and the formal carbene unit. Depending on the metal ion, different products may result (Scheme 42) Zinc octaethylporphyrin or meso-tetraphenylporphyrin yield N-alkylated porphyrins 410 with ethyl diazoacetate and ethyl 2-diazopropionate In the latter case, a homoporphyrin 411 is obtained additionally. Cu(I)-catalyzed decomposition of diazomethane or alkyl diazoacetates in the presence of zinc me.yo-tetraphenylporphyrin leads to cyclopropanation of a pyrrolic pp double bond, besides an N-alkylated product of type 410 The... 

Inspired by the work of Nozaki and coworkers (Scheme 2) [14], a number of research groups initiated a search for more efficient catalysts for enantioselective cyclopropanation. The most spectacular advances were made by Aratani and coworkers whose aim was to develop a catalyst for the industrial production of pyrethroids [15,16,17,18,49]. After extensive evaluation of many different sal-icylaldimine ligands, they eventually found a practically useful catalyst which gave moderate to high enantioselectivities in the cyclopropanation of various olefins with alkyl diazoacetates (Scheme 5 and Table 1). 

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... 

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