The Insertion of Carbenes

Rh(Por)l (Por = OEP. TPP, TMP) also acts as a catalyst for the insertion of carbene fragments into the O—H bonds of alcohols, again using ethyl diazoacetate as the carbene source. A rhodium porphyrin carbene intermediate was proposed in the reaction, which is more effective for primary than secondary or tertiary alcohols, and with the bulky TMP ligand providing the most selectivity. ... 

The equilibrium interconversion between an ethylene phosphite and a bicyclic spirophosphorane is shown to proceed by the insertion of the phosphite into the labile O-H bond of the hydroxyethyl ester. The mechanism is similar to the insertion of carbenes or nitrenes. Energy relationships of reaction intermediates were studied by MO RHF, MP2(full), MP4SDTQ, and DFT calculations. In most cases, they predicted that hydroxyethyl ethylene phosphates were more stable than the strained spirophosphoranes, which is not supported by the experimental evidence. The best correspondence to experimental data was obtained by DFT calculations with Perdew-Wang correlation functions <2003JST35>. 

Electrophilic carbene complexes can react with amines, alcohols or thiols to yield the products of a formal X-H bond insertion (X N, O, S). Unlike the insertion of carbene complexes into aliphatic C-H bonds, insertion into X-H bonds can proceed via intermediate formation of ylides (Figure 4.7). 

In the course of studies of the insertion of carbenes, generated in the photolysis of spirocyclic diazarines, 528, into OH bonds (equation 314) it has been observed641 that formation of ethers from carbene 527 and ROH(D) is associated with partial rearrangement (equation 315). 

Stepwise, but heterolytic, mechanisms have been suggested in the insertion of carbenes into oxygen-hydrogen bonds. The reactivity of water and halide ions towards dihalomethylenes parallels their reactivity in Sn2 displacements (Hine and Dowell, 1954), suggesting that an electrophilic carbene attacks water initially by way of the non-bonded electron pair on oxygen giving an ylid (equation 21). An analogous mechanism could be followed in the insertion of carbenes into the... 

This is known as the linear approach, in which the carbene, with its two substituents already lined up where they will be in the product, comes straight down into the middle of the double bond. The two sulfur dioxide reactions above, 6.127 and 6.128, are also linear approaches, but these are both allowed, the former because the total number of electrons (6) is a (An I 2) number, and the latter because the triene is flexible enough to take up the role of antarafacial component. The alternative for a carbene is a nonlinear approach 6.130, in which the carbene approaches the double bond on its side, and then has the two substituents tilt upwards as the reaction proceeds, in order to arrive in their proper orientation in the product 6.131. The carbene is effectively able to take up the role of the antarafacial component as with ketenes, it is possible to connect up the orthogonal orbitals, as in 6.132 (dashed line), to make the nonlinear approach classifiably pericyclic and allowed. This avoids any problem there might be with reactions like 6.127 and 6.128 being pericyclic and the clearly related reaction 6.130—>6.131 seeming not to be. Similar considerations apply to the insertion of carbenes into cr bonds. 

Immobilized box-Cu complexes were shown to efficiently catalyze the insertion of carbenes into the G-H bond of tetrahydrofuran with enantioselectivity of up to 88% ee. The use of immobilized catalysts allows their recovery and reuse. As can be seen in Equation (186), the major j -isomer was shown to be of 2R,aS absolute configuration by comparing its sign of optical rotation with that of an authentic sample <20070L731>. 

Caibene reagents also functionalize alkanes. Triplet CH2 adds unselecdvely to alkane C—bonds. The product mixture obtained from n-pentane was found to be 48% n-hexane, 3S% 2-methylpentane and 17% 3-methylpentane, so that addition to a primary C—bond appears to be favored. Monochloro-methylcarbene, CHCl, is less reactive and more electrophilic and so the normal tertiary > secondary > primary selectivity pattern was observed. Ethoxycarbonylcarbene, formed on fdiotolysis of the corresponding diazo compound, inserts rather unselectively in to alkane C—H bonds to give the ethoxycarbo-nylmethyl derivatives in ca. 50% yield. Transition metals, such as copper(II) or rhodium(I). also usefully catalyze the insertion of carbenes into alkane C—bonds. 

Why are these reactions considered to be that peculiar The insertion of carbene into a non-activated C-H bond of a saturated hydrocarbon is a well-known but not a very efficient process in the absence of catalysts. The fact that the insertion of carbene (both inter- and intramolecular) at the C-H bond of dodecahedrane frameworks proceeds with such an amazing ease has to be taken as a strong evidence for suggesting the operation of previously unknown and little-understood activating factors in this system. 

Addition reactions to olefins can be used both for the construction and for the functionalization of molecules. Accordingly, chiral catalysts have been developed for many different types of reactions, often with very high enantioselectiv-ity. Unfortunately, most either have a narrow synthetic scope or are not yet developed for immediate industrial application due to insufficient activities and/ or productivities. These reactions include hydrocarbonylation [Ilf], hydrosilyla-tion [12 i], hydroboration [12j], hydrocyanation [12 k], Michael addition [11 g, 121, 12 m], Diels-Alder reaction [11 h, 12n] and the insertion of carbenes in C-H bonds [Hi, 12p, 12q, 38], Cyclopropanation [Hi, 12p, 12q] and the isomerization of allylamines [12 s] are already used commercially for the manufacture of Cilastatin (one of the first industrial processes) [12 r], and citronellol and menthol (presently the second largest enantioselective process) [12t] respectively. 

Somewhat similar considerations apply to the insertion of carbenes into a bonds, except that in this case the reaction can only involve four electrons, and there is no 6-electron alternative.739 We shall return to the carbene insertion reactions later when we discuss periselectivity why carbenes choose to react with a double bond by the nonlinear approach even with dienes, which would make a 6-electron linear approach analogous to the sulfur dioxide reaction 6.158 allowed. 

The insertion of carbenes into N-H bonds has been reported for (i) the insertion of singlet CH2, CHF, and CF2 carbenes into polar N-H bonds of primary amines... 

A second functionalization approach was based on the insertion of carbenes into the C-H bond (Scheme 3). The reaction of different polyolefins, such as high density polyethylene (HDPE), atactic polypropylene (aPP), isotactic polypropylene (iPP), ethylene-propylene copolymers (EP) and polyisobutene (iPBu) with diazoesters at 210T in bulk has been shown to give a product containing the carboxylate functionality attached to the polymer backbone. The presence of the functional groups in the polymer was inferred by IR spectroscopy (carbonyl stretching band at 1740 cm "1 and in case of chloroethyldiazoacetate... 

A novel method related to the insertion of carbenes into N-H bonds has been reported. It involves the reductive coupling of A-tosylhydrazones under mild basic conditions to afford the corresponding A-alkylated hydrazones in moderate to good yields The procedure benefits from the well-known ability of A-tosylhydrazones to generate carbenes in situ, the so-formed carbene finally undergoing insertion into the N-H bond of the second equivalent of A-tosylhydrazones. 

The chemistry of alkenyl- and alkyl-substituted cyclopropylidenes has been explored. They were generated from a. gm-dihalide by lithium-halogen exchange, and were shown to give both allenes and 1,5-CH bond insertion reactions. A new mechanism for the insertion of carbenes into OH bonds was proposed on the basis of a computational study. A cyclic five-membered transition state, composed of the car-bene and two hydroxyl-containing molecules, was shown to be lower in energy than proton transfer or direct insertion into an OH bond. ... 

Two novel methods related to the insertion of carbenes into N-H bonds have been reported. First, urea proved to be an efficient organocatalyst with which to activate... 

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