Cyclopropanes from carbenes

An example of double carbon-carbon bond formation in an asymmetric synthesis has been developed by Nakamura et al in an interesting paper on the use of an optically active cobalt reagent for producing cyclopropanes from carbenes and alkenes. For example the cyclopropane (51) was prepared in 70% optical yield in this work. Finally, asymmetric syntheses have been achieved photochemically in chiral crystals (cyclobutanes), and in a chiral solvent (heli-cenes). ... 

Cyclopropanations by carbenes from chlorodiazirines were observed in several cases, e.g. with the r-butyl compound. Cyclopropanation and stabilization by ring enlargement and by elimination compete in chlorocyclobutyldiazirine photolysis. 

Cyclopent-2-en-l-one, 2-hydroxy-3-methyl-synthesis, 3, 693 Cyclopentenone, 4-methoxy-formation, 1, 423 Cyclopenthiazide as diuretic, 1, 174 Cyclopent[2,3-d]isoxazol-4-one structure, 6, 975 Cyclophane conformation, 2, 115 photoelectron spectroscopy, 2, 140 [2,2]Cyclophane conformation, 2, 115 Cyclophanes nomenclature, 1, 27 Cyclophosphamide as pharmaceutical, 1, 157 reviews, 1, 496 Cyclopiloselloidin synthesis, 3, 743 Cyclopolymerization heterocycle-forming, 1, 292-293 6H-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine pyrazoles from, 5, 285 Cydopropabenzopyran synthesis, 3, 700 Cyclopropachromenes synthesis, 3, 671 Cyclopropa[c]dnnolines synthesis, 7, 597 Cyclopropanation by carbenes... 

By application of the Simmons-Smith reaction it is possible to synthesize a cyclopropane from an alkene by formal addition of carbene to the carbon-carbon double bond, without a free carbene being present in the reaction mixture the... 

Furthermore, Rhg(CO)16, which can be used advantageously for cyclopropanation of more electron-rich alkenes, furnished only insignificant amounts of cyclopropane from acrylonitrile or ethyl acrylate and ethyl diazoacetate from methacrylonitrile and ethyl diazoacetate, equally low yields of vinyloxazole, cyclopropane and carbene dimers resulted (Scheme 20)145). The use of Rh2(OAc)4 or [Rh(CO)2Cl]2 as catalysts did not change this situation. 

By analogy with cyclopropane formation from carbenes and C=C bonds, azo compounds might be expected to give diaziridines in their reaction with carbenes. Although acyclic ADC compounds react readily with diazoalkanes... 

Calculations [28] on the formation of cyclopropanes from electrophilic Fischer-type carbene complexes and alkenes suggest that this reaction does not generally proceed via metallacyclobutane intermediates. The least-energy pathway for this process starts with electrophilic addition of the carbene carbon atom to the alkene (Figure 1.9). Ring closure occurs by electrophilic attack of the second carbon atom... 

Optically active metal complexes have been recognized as excellent catalysts for the enantioselective cyclopropanation of carbenes with alkenes. Normally, diazo compounds react under metal catalysts in the dark to afford carbenoid complexes as key intermediates. Katsuki et al. have reported the ds-selective and enantioselective cyclopropanation of styrene with a-diazoacetate in the presence of optically active (R,R)-(NO + )(salen)ruthenium complex 80, supported under illumination (440 nm light or an incandescent bulb) [59]. The irradiation causes dissociation of the apical ligand ON + in 80, and thus avoids the splitting of nitrogen from the a-diazoacetate. 

M. D. Cooke, and E. O. Fischer, Proof of the Absence of a Free Carbene in the Preparation of a Cyclopropane from a Metal-Carbene Complex, J. Organomet. Chem. 56, 279-284 (1973). 

This is the other possible cyclic isomer of C3H4 and may be considered as a cyclic carbene. Only the singlet state has been considered, although it is possible that an associated triplet state may be lower in energy. C v symmetry was assumed in the structure determination. The cyclopropylidene skeleton is rather similar to that of cyclopropane, from which... 

Carbene addition occurs in a syn fashion from either side of the planar double bond. The relative position of substituents in the alkene reactant is retained in the cyclopropane product. Carbene addition is thus a stereospecific reaction, since cis and trans alkenes yield different stereoisomers as products, as illustrated in Sample Problem 26.4. 

German chemists have used the method successfully for preparation of dichloro-cyclopropanes from olefins which yield little or no products when the dichlorocarbene is generaied from chloroform and potassium /-bntoxide. TTiey also generated dibromo-carbene in the same way. Cyclopropcnes are obtained in only low yields from acetylenes owing to side reactions. 

Among the methods at hand to synthesize cyclopropane derivatives, carbene addition to alkenes plays a prominent role 63). As a source of vinylcarbenes, cyclopropenes might be useful in this kind of approach. In 1963, Stechl was the first to observe a transition metal catalyzed cyclopropene-vinylcarbene rearrangement64). When treating 1,3,3-trimethylcyclopropene with copper salts, dimerization occurred to give 2,3,6,7-tetramethyl-octa-2,4,6-triene (9), the product from a formal recombination of the corresponding vinylcarbene (Eq. 8). 

The product of thermal isomerization of this cyclopropane, dimethyl (l-naphthyl)malonate, was also formed (5-10%), together withtetramethyl2,3-benzo-ant -tricyclo[5.1.0.0 ]oct-2-ene-5,5,8,8-tetracarb-oxylate (5-15%) and dimethyl 377-benzocycloheptatriene-3,3-dicarboxylate (5-10%) which is likely to arise from an intermediate cyclopropane arising from carbene addition to the 2,3-bond of naphthalene. 

Historically, potassium /er/-butoxide was the first base used for the preparation of 1,1-dibromo-cyclopropanes from bromoform and an alkene. Since generation and cycloaddition of dibromo-carbene to alkenes proceeds rapidly, this method is still in laboratory practice. 

Cyclopropanation from alkenes and carbenes with alkyl gem dihalides and Zn-Cu couple (Simmons-Smith) or Et2Zn (Furukawa) EtgAI (Yamamoto) or Sm (Molander) with high diastereoselectivity (see 1st edition). 

Carbenes with coordination number 1, e.g., alkylidene carbenes. are not considered in this section. They are extensively described in Vol. E19b, p 84. Several examples demonstrate the stereospecificity of their [2 + 1] cycloaddilions to olefins. A few reactions which employ chiral olefins indicate that these are cyclopropanated from the sterically more accessible face (Vol. El9b. p 145). 

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