Alkene derivatives diazoacetates

CO)2Fe (THF) BFT A transition state model for the syn stereoselective cyclo-propanations of alkenes with diazoacetic ester by Rh-porphyrin catalysts has been proposed. Alkenes , conjugated dienes and enol ethers are stereoselectively cyclopropanated with Rh(II) -stabilized 1- (alkoxycarbonyl)vinyl carbenoids derived from the diazo precursors and Rh2(OAc)4 (equation 95). The Cu(acac)2-catalyzed reactions of Me3SiCH2COCHN2 with alkenes provide the expected adducts in good yields ". ... 

Enantioselective Cyclopropanation of Alkenes. Cationic Cu complexes of methylenebis(oxazolines) such as (1), which have been developed by Evans and co-workers, are remarkably efficient catalysts for the cyclopropanation of terminal alkenes with diazoacetates. The reaction of styrene with ethyl diazoacetate in the presence of 1 mol % of catalyst, generated in situ from Copper(I) Trifluoromethanesulfonate and ligand (1), affords the (rans -2-phenylcyclopropanecarboxylate in good yield and with 99% ee (eq 3). As with other catalysts, only moderate transicis selectivity is observed. Higher transicis selectivities can be obtained with more bulky esters such as 2,6-di-r-butyl-4-methylphenyl or dicyclohexylmethyl diazoacetate (94 6 and 95 5, respectively). The efficiency of this catalyst system is illustrated by the cyclopropanation of isobutene, which has been carried out on a 0.3 molar scale using 0.1 mol % of catalyst derived firom the (R,R)-enantiomer of ligand (1) (eq 4). The remarkable selectivity of >99% ee exceeds that of Aratani s catalyst which is used in this reaction on an industrial scale. 

Carbenes and substituted carbenes add to double bonds to give cyclopropane derivatives ([1 -f 2]-cycloaddition). Many derivatives of carbene (e.g., PhCH, ROCH) ° and Me2C=C, and C(CN)2, have been added to double bonds, but the reaction is most often performed with CH2 itself, with halo and dihalocarbenes, " and with carbalkoxycarbenes (generated from diazoacetic esters). Alkylcarbenes (HCR) have been added to alkenes, but more often these rearrange to give alkenes (p. 252). The carbene can be generated in any of the ways normally used (p. 249). However, most reactions in which a cyclopropane is formed by treatment of an alkene with a carbene precursor do not actually involve free carbene... 

Trifluoromethyl-substituted pyrazoles are easily obtained using trifluoromethyl-alkynes as dipolarophiles (Table 8.2, entry 9). Thus, treatment of 4,4,4-trifluorobut-2-ynoic acid with excess diazomethane gave methyl 4-(trifluoromethyl)pyrazole-4-carboxylate (45%) accompanied by its N - (32%) and -methylated (6.5%) derivatives (267). Another convenient route to CF3-substituted pyrazoles involves dipolar cycloaddition of appropriately CF3-substituted alkenes followed by eliminative aromatization (76,77,268). For example, the reaction of alkenes such as (CF3)2C=C(H)COAr with ethyl diazoacetate gave 4-aroyl-5-trifluoromethylpyra-zole-3-carboxylates (268). 

The formation of cyclopropane derivatives by photolysis of diazoalkanes in the presence of alkenes is believed to occur by photolytic decomposition of the diazoalkane to yield the carbene, followed by addition of this carbene to the alkene. Cycloaddition of this type has been reported in furan, dihydrofuran, and thiophene.198 Thus, photolysis of ethyl diazoacetate in thiophene yields the bicyclic sulfur heterocycle (215). Alternatively, photolysis of 3-diazo-l-methyl-oxindole (216) in cyclohexene leads to the formation of two isomers which are thought to have the spirocyclopropyl structure (217) photolysis in ethanol yields 3-ethoxy-1-methyloxindole.194... 

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. 

The first chiral transition-metal catalyst designed for an enantioselective transformation was applied to the reaction between a diazo ester and an alkene to form cyclopropanes [1]. In that application Nozaki and coworkers used a Schiff base-Cu(II) complex (1), whose chiral ligand was derived from oc-phenethylamine, to catalyze the cyclopropanation of styrene with ethyl diazoacetate (Eq. 5.1) [2],... 

Reaction of diazoalkanes with thiocarbonyl compounds, which may be considered an extension of Pechmann s synthesis, forms 1,2,3-thiadiazole derivatives (75SST(3)67o). For example, methyl dithioacetate reacts with diazomethane to form a mixture of thiadiazole isomers and thiirane the latter often is the main product of this type of reaction (equation 26). O-Ethyl thionoacetate reacts with ethyl diazoacetate to form a substituted thiadiazole (equation 27). However, an aryl thionoester reacts with diazomethane to yield a 1,2,3-thiadiazole derivative which is only formed as an intermediate (31) and then rapidly decomposes to alkene (Scheme 5). 

In contrast to the carbene and carbenoid chemistry of simple diazoacetic esters, that of a-silyl-a-diazoacetic esters has not yet been developed systematically [1]. Irradiation of ethyl diazo(trimethylsilyl)acetate in an alcohol affords products derived from 0-H insertion of the carbene intermediate, Wolff rearrangement, and carbene- silene rearrangement [2]. In contrast, photolysis of ethyl diazo(pentamethyldisilanyl)acetate in an inert solvent yields exclusively a ketene derived from a carbene->silene->ketene rearrangement [3], Photochemically generated ethoxycarbonyltrimethyl-silylcarbene cyclopropanates alkenes and undergoes insertion into aliphatic C-H bonds [4]. Copper-catalyzed and photochemically induced cyclopropenation of an alkyne with methyl diazo(trimethylsilyl)acetate has also been reported [5]. 

For the cyclopropanation of terminal mono- and disubstituted alkenes, the cationic Cu complex derived from ligand (1) is clearly the most efficient catalyst available today, giving consistently higher enantiomeric excesses than related neutral semicorrin or bisoxazoline Cu complexes of type (3), - which can induce enantiomeric excesses of up to 92% ee in the cyclopropanation of styrene with ethyl diazoacetate. High enantioselectivities, ranging between the selectivities of the Evans catalyst (eq 3) and complex (3) (M = Cu, R = t-Bu), have also been observed with cationic Cu complexes of azasemicorrins. ... 

The carbene derived by metal-catalysed decomposition of ethyl diazoacetate attacks alkenes to introduce a two-carbon fragment into a cyclopropane—an industrial synthesis of ethyl chrysanthe-mate, a precursor to the pyrethrin insecticides (see p. 000), uses this reaction. The diene in the starting material is more nucleophilic (higher-energy HOMO see Chapter 20) than the single alkene in the product, so the reaction can be stopped after one carbene addition. 

Enantioselective carbenoid cyclopropanation of achiral alkenes can be achieved with a chiral diazocarbonyl compound and/or chiral catalyst. In general, very low levels of asymmetric induction are obtained, when a combination of an achiral copper or rhodium catalyst and a chiral diazoacetic ester (e.g. menthyl or bornyl ester ) or a chiral diazoacetamide ° (see Section 1.2.1.2.4.2.6.3.3., Table 14, entry 3) is applied. A notable exception is provided by the cyclopropanation of styrene with [(3/ )-4,4-dimethyl-2-oxotetrahydro-3-furyl] ( )-2-diazo-4-phenylbut-3-enoate to give 5 with several rhodium(II) carboxylate catalysts, asymmetric induction gave de values of 69-97%. ° Ester residues derived from a-hydroxy esters other than ( —)-(7 )-pantolactone are not as equally well suited as chiral auxiliaries for example, catalysis by the corresponding rhodium(II) (S )-lactate provides (lS, 2S )-5 with a de value of 67%. 

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). 

In 1990, Brunner [5], McKervey [6], and Ikegami [7] and their respective coworkers independently introduced chiral rhodium(II) carboxylates for asymmetric diazocarbonyl transformations. At that time the only chiral rhodium(II) carboxylates known were those derived from (R) and (S)-mandelic acid which had been prepared by Cotton and co-workers [8] for structural and chiroptical studies. Enantiopure carboxylates (1) on a dirhodium core (substituents varied from H, Me, and Ph to OH, NHAc, and CFj) were assessed by Brunner [5] for enantioselective cyclopropanation of alkenes with ethyl diazoacetate. McKervey... 

The copper-catalyzed cyclopropanation of alkenes with diazoalkanes is a particularly important synthetic reaction (277). The reaction of styrene and ethyl diazoacetate catalyzed by bis[/V-(7 )- or (5)-a-phenyl-ethylsalicylaldiminato]Cu(II), reported in 1966, gives the cyclopropane adducts in less than 10% ee and was the first example of transition metal-catalyzed enantioselective reaction of prochiral compounds in homogeneous phase (Scheme 90) (272). Later systematic screening of the chiral Schiff base-Cu catalysts resulted in the innovative synthesis of a series of important cyclopropane derivatives such as chrysanthemic acid, which was produced in greater than 90% ee (Scheme 90) (273). The catalyst precursor has a dimeric Cu(II) structure, but the actual catalyst is in the Cu(I) oxidation state (274). (S)-2,2-Dimethylcyclopropanecar-boxylic acid thus formed is now used for commercial synthesis of ci-lastatin, an excellent inhibitor of dehydropeptidase-I that increases the in vivo stability of the caibapenem antibiotic imipenem (Sumitomo Chemical Co. and Merck Sharp Dohme Co.). Attempted enantioselective cyclopropanation using 1,1-diphenylethylene and ethyl diazoacetate has met with limited success (211b). A related Schiff base ligand achieved the best result, 66% optical yield, in the reaction of 1,1-diphenylethylene and ethyl diazoacetate (275). 

Formation of cyclopropanecarboxylic e derived from diazoacetates with alkenes is 1 bipyridine (2) [complexed to Cu] and a bi Ru]. ... 

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