Alkenes alkyl diazoacetate

The addition of caibenoids derived from alkyl diazoacetates to alkenes has been extensively studied. As two thorough reviews on the subject,1 2 dealing with a detailed comparison of the various catalysts, have recently appeared, only a general summary concerning regioselectivity, competing reactions, dia-stereoselectivity and enantioselectivity will be presented here. 

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... 

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... 

Copper and rhodium complexes catalyze the reaction of alkenes with diazoacetate to give alkyl cyclopropanecarboxylates [13]. In the presence of Cu(acac)2, the reaction of carbohydrate enol ether 20 with methyl diazoacetate afforded a 1 4 mixture of cis- and frani-cyclopropanes 21 and 22 (c -product 21 was obtained with 95% de). When the reaction was catalyzed by CuOTf in the presence of hgand 23, the tranj -product 22 was obtained with 60% de (Scheme 10.4). The absolute configuration of the major diastereomer was not given [19]. 

Bis(camphorquinone-a-dioximato)cobalt(II) (10) has been developed as a catalyst for enan-tioselective cyclopropanation reactions. It allows selective carbene transfer from diazoacetic esters to terminal C-C double bonds which are in conjugation with vinyl, aryl, alkoxycarbonyl or cyano groups, but not to alkyl-substituted alkenes, cycloalkenes, 1,3-dienes and al-lenes. The unusual chemoselectivity and some other experimental observations make the two mechanistic pathways proposed vide supra) questionable for these special carbene-transfer reactions. In contrast, the cobalt(II) complex 11 allows not only the cyclopropanation of styrene but also of oct-l-ene, a nonactivated alkene (ethyl diazoacetate, 35 °C, 3mol% of catalyst yield 50-60%). ... 

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 complexes of these three types of ligands also efficiently catalyzed the formation of highly enantiomeric cyclopropanes from alkyl diazoacetates and styrene, hept-l-ene, and other alkenes. All these results show that the enantio- and diastereospecificity are highly dependent on the size of substituents R in 8.169-8.171 and of methyl groups at the methylene C-atom in 8.169 or of phenyl groups in the... 

Aziridine-2-carboxylic esters are preparecf from hexahydro-l,3,5-triazines with alkyl diazoacetates in the presence of SnCl,. A-Tosylmethylanilines apparently also undergo ionization to generate iminium species that are interceptable by alkenes 1,2,3,4-Tetrahydroquinolines are formed. ... 

Cyclopropanation with alkyl dlazoacetates. Rhodium(Il) acetate is an efficient catalyst for the insertion of carboethoxycarbene into activated C-H-bonds (5, 571-572), but it is less effective than rhodium(II) n-butanoate or pivalate for catalysis of cyclopropanation of alkenes with alkyl diazoacetates, possibly because the latter carboxylates are more soluble in organic solvents. However, rhodium(ll) trifluoroacetate is readily soluble, but it is a poor catalyst for cyclopropanation. The alkyl group of the diazoacetate strongly influences the yields, which are highest with n-butyl diazoacetate. 

Enantioselective Cyclopropanation. Cu(OAc>2 has been used as procatalyst in the asymmetric cyclopropanation of alkenes with alkyl diazoacetates with optically pure imines as cocatalyst (eq 18). ... 

Rhodium(ii) carboxylates are reported to be highly efficient catalysts for the cyclopropanation of alkenes with alkyl diazoacetates. Yields are improved from the procedure using copper trifluoromethane sulphonate. The catalytic co-oligomerization reactions of butadiene with various nitrogen containing moieties was extended and can clearly lead to interesting functionalized molecules (Scheme... 

Cyclopropanations of alkenes with alkyl diazoacetates are catalysed by rhodium(ii) carboxylates, and Sasaki et al have shown that crown ethers have several advantages over quaternary ammoniurq ions for the catalytic synthesis of allene-cyclopropanes from addition of allene-carbenes to olehnic substrates. 

Although copper complexes are widely used as catalysts for cyclopropanation of alkenes with alkyl diazoacetates they are often poor catalysts for reactions with substituted olefins. Rhodium(ii) carboxylates, however, are highly efficient for this reaction (Equation 7). The soluble carboxylates, such as the butanoate and pivalate, are particularly effective catalysts giving excellent yields for a variety of substituted monoenes and dienes. It is interesting to note that the oxidation state of the rhodium plays an important role as can be concluded from the fact that only very low yields of cyclopropanation products are obtained in the presence of Rh oi Rh complexes. 

Syntheses of fluoro-substituted pyrazoles continue to be of interest. Both 3- and 5-fluoropyrazoles (44 and 45, respectively) can be prepared from 43 <96JOC2763>. Treatment of 43 with hydrazine followed by N-alkylation provides 44, whereas reactions with monosubstituted hydrazines afford 45. The 4-(trifluoromcthyl)pyrazoles 47 are obtained from J-trifluoromethyl vinamidinium salt 46 <96TL1829>. The 5-trifluoromethyl-3-carboethoxypyrazoles 49 are obtained from the 1,3-dipolar cycloadditions of trifluoromethyl alkenes 48 with ethyl diazoacetate <96T4383>. 

Palladium(II) acetate was found to be a good catalyst for such cyclopropanations with ethyl diazoacetate (Scheme 19) by analogy with the same transformation using diazomethane (see Sect. 2.1). The best yields were obtained with monosubstituted alkenes such as acrylic esters and methyl vinyl ketone (64-85 %), whereas they dropped to 10-30% for a,p-unsaturated carbonyl compounds bearing alkyl groups in a- or p-position such as ethyl crotonate, isophorone and methyl methacrylate 141). In none of these reactions was formation of carbene dimers observed. 7>ms-benzalaceto-phenone was cyclopropanated stereospecifically in about 50% yield PdCl2 and palladium(II) acetylacetonate were less efficient catalysts 34 >. Diazoketones may be used instead of diazoesters, as the cyclopropanation of acrylonitrile by diazoacenaph-thenone/Pd(OAc)2 (75 % yield) shows142). 

Some remarks concerning the scope of the cobalt chelate catalysts 207 seem appropriate. Terminal double bonds in conjugation with vinyl, aryl and alkoxy-carbonyl groups are cyclopropanated selectively. No such reaction occurs with alkyl-substituted and cyclic olefins, cyclic and sterically hindered acyclic 1,3-dienes, vinyl ethers, allenes and phenylacetylene95). The cyclopropanation of electron-poor alkenes such as acrylonitrile and ethyl acrylate (optical yield in the presence of 207a r 33%) with ethyl diazoacetate deserve notice, as these components usually... 

In the presence of alkenes, photolysis of alkyl (silyl)diazoacetates leads mainly to the formation of cyclopropanes as diastereomeric mixtures4,111,112. With (Z)- and ( )-but-2-ene, the cyclopropanation is not completely stereospecific with respect to the double bond configuration, but gives a small amount of the wrong isomer these results point to the participation of a triplet carbene in the cyclopropanation reaction. Allylic C,H insertion products are also formed their yield increases in the series 1,1-, 1,2-, tri- and tetrasubstituted C=C bond. With 2,3-dimethyl-but-2-ene, the allylic C,H insertion product is formed at the complete expense of the cyclopropane. 

Dirhodium(ll) tetrakis[methyl 2-pyrrolidone-5(R)-oarboxylate], Rh2(5R-MEPV)4, and its enantiomer, Rh2(5S-MEPY)4, which is prepared by the same procedure, are highly enantioselective catalysts for intramolecular cyclopropanation of allylic diazoacetates (65->94% ee) and homoallylic diazoacetates (71-90% ee),7 8 intermolecular carbon-hydrogen insertion reactions of 2-alkoxyethyl diazoacetates (57-91% ee)9 and N-alkyl-N-(tert-butyl)diazoacetamides (58-73% ee),10 Intermolecular cyclopropenation ot alkynes with ethyl diazoacetate (54-69% ee) or menthyl diazoacetates (77-98% diastereomeric excess, de),11 and intermolecular cyclopropanation of alkenes with menthyl diazoacetate (60-91% de for the cis isomer, 47-65% de for the trans isomer).12 Their use in <1.0 mol % in dichloromethane solvent effects complete reaction of the diazo ester and provides the carbenoid product in 43-88% yield. The same general method used for the preparation of Rh2(5R-MEPY)4 was employed for the synthesis of their isopropyl7 and neopentyl9 ester analogs. 

The cyclopropanation of gaseous alkenes, butadiene, and allene (see Section 1.2.1.2.4.2.6.3.3., Table 11, entry 1) by diazoacetic esters can be achieved by passing a vapor-gas mixture of the alkene and the diazo compound at atmospheric pressure through a tubular continuous flow reactor which contains a copper catalyst (ca. 10%) deposited on pumice. In this manner, alkyl cyclopropanecarboxylates were obtained in yields of up to 50% with cop-per(II) sulfate (typical reaction temperature 65-110"C, contact time 3.6 s) or copper(II) oxide (85-200°C, 5s) as catalysts. 

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 ... 

Dawes and Hutcheson [933] examined the asymmetric cyclopropanation of alkenes with methyl or ethyl vinyldiazoesters 7.140 in the presence of a rhodium catalyst bearing 3.60 as ligand. E-Cyclopropanecarboxylates 7.141 are obtained with a high enantioselectivity when using styrenes or simple alkenes (Figure 7.88). Bulkier alkyl diazoesters yield less useful selectivities. The use of the same catalyst in the cyclopropanation of styrene with ethyl diazoacetate gives low selectivities. Rhodium- or osmium-porphyrin-catalyzed cyclopropanations of alkenes by diazoesters also yield poor selectivities [1502,1502a]. 

Cobalt is another metal which has been successfully used in asymmetric cyclopropanation. A chirally modified catalytic system for selective cyclopropanation of phenyl-, vinyl- or alkoxy-carbonyl-conjugated terminal double bonds with diazoacetates is formed from cobalt(ll) chloride and (+)-a-camphorquinonc dioxime27,69 71 and similar systems 09. Best optical yields are achieved with styrene and the bulky 2,2-dimethylpropvl diazoacetate which gives 2,2-dimethylpropyl /ra .v-2-phenyl-l-cyclopropanecarboxylate in 88% ee and the as-isomer in 81%ee7n. No cyclopropanation occurs with alkyl-substituted or cyclic alkenes, cyclic or sterically hindered acyclic 1.3-dienes, vinyl ethers and phenylethyne. 

A very recent report highlights the cross-coupling of Fischer carbene complexes with ethyl diazoacetate to give push-pull alkenes such as 106 at ambient temperature using 15 mol-% CuBr as a catalyst (Scheme 46) [98] alkyl-, alkenyl- (105) and arylcarbenes provided comparable good chemical yields. 

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