Carbenes reactions with esters

Numerous authors189-191 have compared the reactions of Fischer carbene complexes with nucleophiles to the corresponding reactions of carboxylic esters.183,185-187 Our view is that there is much more resemblance between the reactions of Fischer carbene complexes and SNV reaction than between the reactions of Fischer carbene complexes and reactions with esters because in the latter reactions there are no strong resonance effects. 

Furan and thiophene undergo addition reactions with carbenes. Thus cyclopropane derivatives are obtained from these heterocycles on copper(I) bromide-catalyzed reaction with diazomethane and light-promoted reaction with diazoacetic acid ester (Scheme 41). The copper-catalyzed reaction of pyrrole with diazoacetic acid ester, however, gives a 2-substituted product (Scheme 42). 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Carboxylic esters undergo the conversion C=0— C=CHR (R = primary or secondary alkyl) when treated with RCHBr2, Zn, and TiCl4 in the presence of A,A,A, iV -tetramethylethylenediamine. Metal carbene complexes R2C=ML (L = ligand), where M is a transition metal such as Zr, W, or Ta, have also been used to convert the C=0 of carboxylic esters and lactones to CR2. It is likely that the complex Cp2Ti=CH2 is an intermediate in the reaction with Tebbe s reagent. 

One such agent is prepared by NBS and peroxide bromination of ethyl 4-chiorophenylacetate (108) to give 109. This is converted by sodium hydride to the benzylic carbene, which is inserted into the double bond of ethyl acrylate to give cis-cyclopropane 110. Partial saponification cleaves the less hindered ester moiety to give 111. This is next converted to the alkoxyimide (112) on reaction with diethyl carbonate and diammonium phosphate. Stronger base (NaOEt)... 

A variety of silicon-functionalized diazoacetic esters are available by reacting (trifloxysilyl)- or (chlorosilyl)diazoacetic esters with appropriate nucleophiles [1]. Thermally, photochemically, or transition metal induced intramolecular carbene reactions of these novel diazoesters lead to four-, five-, and six-membered silaheterocycles. 

Scheme 7.19). Prototropic shift of the initial adduct to produce ROCHCl2 and, subsequently, the formate ester is a less favourable pathway. Alternatively, the carbon monoxide-separated ion-pair can lose a proton leading to an alkene, or cycloadducts derived from further reaction with the carbene. The formation of rearranged products from the reaction of 1 -hydroxymethyladamantane suggests that a relatively unencumbered carbenium cation can also be generated, which leads to a Nametkin rearrangement of the system [4]. 

The reaction of 2- and 4-hydroxyadamantane-l-carboxylic esters with dibromo-carbene produces the corresponding 2- and 4-bromo derivatives (10-20%). Slow hydrolysis of the ester groups may also occur under the basic conditions. l-Acetyl-4-hydroxyadamantane yields 4-bromoadamantane-l -carboxylic acid (37%), as a result of a concomitant reaction with dibromocarbene and a haloform-type reaction [8]. 

Thermolysis of the oxadiazoline (123) gives rise to the corresponding dialkoxy-carbene, which can be trapped by reaction with f-butanol to form orthoesters. The formation of a regioisomeric mixture of esters was explained by fragmentation of the carbene to radicals (124) which recombine at either end of the allyl system. 

Wenkert and Khatuya (51) examined the competition between direct insertion of a carbene into furan (via cyclopropanation) and ylide formation with reactive side-chain functionality such as esters, aldehydes, and acetals. They demonstrated the ease of formation of aldehyde derived carbonyl ylides (Scheme 4.30) as opposed to reaction with the electron-rich olefin of the furan. Treatment of 3-furfural (136) with ethyl diazoacetate (EDA) and rhodium acetate led to formation of ylide 137, followed by trapping with a second molecule of furfural to give the acetal 138 as an equal mixture of isomers at the acetal hydrogen position. 

An alternative approach in the asymmetric catalysis in 1,3-dipole cycloaddition has been developed by Suga and coworkers. The achiral 1,3-dipole 106 was generated by intramolecular reaction of an Rh(ii) carbene complex with an ester carbonyl oxygen in the Rh2(OAc)4-catalyzed diazo decomposition of <9-methoxycarbonyl-o -diazoacetophenone 105 (Scheme 12). The asymmetric induction in the subsequent cycloaddition to G=G and G=N bond was achieved by chiral Lewis acid Sc(iii)-Pybox-/-Pr or Yb(iii)-Pybox-Ph, which can activate the dipolarophile through complexation. With this approach, up to 95% ee for G=0 bond addition and 96% ee for G=G bond addition have been obtained, respectively. ... 

When the diazoesters (240) and (241) were thermally decomposed in the presence of copper(II) acetoacetate ester as catalyst, an intermolecular carbene reaction occurred, the resulting benzo[c]furans (242) and (243) were not isolated but were trapped as the Diels-Alder adducts with N- methylmaleimide and dimethyl acetylenedicarboxylate (76CL287). 

Diazothioxanthene is the usual precursor for the thioxanthylidene carbene, which can be shown to have a nucleophilic character. It adds to fumaric or maleic esters to form cyclopropyl compounds, but does not react with cyclohexene (78JOC3303). Reaction with alkyl phosphites is a very useful means of preparing the phosphonate derivatives (72JIC985). 

As with the Aratani catalysts, enantioselectivities for cyclopropane formation with 4 and 5 are responsive to the steric bulk of the diazo ester, are higher for the trans isomer than for the cis form, and are influenced by the absolute configuration of a chiral diazo ester (d- and 1-menthyl diazoacetate), although not to the same degree as reported for 2 in Tables 5.1 and 5.2. 1,3-Butadiene and 4-methyl- 1,3-pentadiene, whose higher reactivities for metal carbene addition result in higher product yields than do terminal alkenes, form cyclopropane products with 97% ee in reactions with d-men thy 1 diazoacetate (Eq. 5.8). Regiocontrol is complete, but diastereocontrol (trans cis selectivity) is only moderate. 

Dioximato-cobalt(II) catalysts are unusual in their ability to catalyze cyclopropanation reactions that occur with conjugated olefins (e.g., styrene, 1,3-butadiene, and 1-phenyl-1,3-butadiene) and, also, certain a, 3-unsaturated esters (e.g., methyl a-phenylacrylate, Eq. 5.13), but not with simple olefins and vinyl ethers. In this regard they do not behave like metal carbenes formed with Cu or Rh catalysts that are characteristically electrophilic in their reactions towards alkenes (vinyl ethers > dienes > simple olefins a,p-unsaturated esters) [7], and this divergence has not been adequately explained. However, despite their ability to attain high enantioselectivities in cyclopropanation reactions with ethyl diazoacetate and other diazo esters, no additional details concerning these Co(II) catalysts have been published since the initial reports by Nakamura and Otsuka. 

The fact that the intrinsic rate constants for nucleophilic addition to Fischer carbene complexes are relatively low, for example, much lower than for most reactions with comparable vinylic substrates or carboxylic esters,188 constitutes strong evidence for the presence of substantial transition state imbalances. However, there have only been a few studies of substituent effects that demonstrate the imbalance directly by showing a uc > p uc or by providing an estimate of its magnitude from the difference a uc - p uc. One such study is the reactions of 76-Cr-Z and 76-W-Z with HC CCII20 and C.F3CH20, 183 It yielded a Llc 0.59 and p ]uc< 0.46 for 76-Cr-Z, and a[juc 0.56 and 0 42 for 76-W-Z, i.e., a ue > p uc as expected. 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

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