Nucleophilic carbenes bond formations

Etherification using a metal vinylidene has also been combined with G-G bond formation through the reaction of an alkynyl tungsten complex with benzaldehyde (Scheme 14). The addition of an internal alcohol to the incipient /3,/Udialkylvinylidene that is generated leads to dehydration and the formation of a Fischer-type alkylidene complex. Further reactions of this carbene with a range of nucleophiles have provided access to various furan derivatives.374,375... 

The intrinsic rate constants for thiolate ion addition to 76-Cr and 76-W are substantially larger than those for alkoxide ion addition. This is similar to the previously mentioned higher intrinsic reactivity of thiolate ions compared to amine nucleophiles for the addition to a-nitrostilbene and p-nitrostyrene. It can be understood in terms of the soft-soft interaction of the thiolate ion with the carbene complex which is more advanced than C S bond formation at the transition state.184... 

Enders D (1993) Enzymemimetic C-C and C-N bond formations. In Stereoselective synthesis. Springer-Verlag, Berlin Heidelberg New York, p 63 Enders D, Balensiefer T (2004) Nucleophilic carbenes in asymmetric organo-catalysis. Acc Chem Res 37 534—541... 

The strained bicyclic carbapenem framework of thienamycin is the host of three contiguous stereocenters and several heteroatoms (Scheme 1). Removal of the cysteamine side chain affixed to C-2 furnishes /J-keto ester 2 as a possible precursor. The intermolecular attack upon the keto function in 2 by a suitable thiol nucleophile could result in the formation of the natural product after dehydration of the initial tetrahedral adduct. In a most interesting and productive retrosynthetic maneuver, intermediate 2 could be traced in one step to a-diazo keto ester 4. It is important to recognize that diazo compounds, such as 4, are viable precursors to electron-deficient carbenes. In the synthetic direction, transition metal catalyzed decomposition of diazo keto ester 4 could conceivably furnish electron-deficient carbene 3 the intermediacy of 3 is expected to be brief, for it should readily insert into the proximal N-H bond to... 

The Lewis acid-Lewis base interaction outlined in Scheme 43 also explains the formation of alkylrhodium complexes 414 from iodorhodium(III) meso-tetraphenyl-porphyrin 409 and various diazo compounds (Scheme 42)398), It seems reasonable to assume that intermediates 418 or 419 (corresponding to 415 and 417 in Scheme 43) are trapped by an added nucleophile in the reaction with ethyl diazoacetate, and that similar intermediates, by proton loss, give rise to vinylrhodium complexes from ethyl 2-diazopropionate or dimethyl diazosuccinate. As the rhodium porphyrin 409 is also an efficient catalyst for cyclopropanation of olefins with ethyl diazoacetate 87,1°°), stj bene formation from aryl diazomethanes 358 and carbene insertion into aliphatic C—H bonds 287, intermediates 418 or 419 are likely to be part of the mechanistic scheme of these reactions, too. 

Azolium systems with C-H bonds can be deprotonated to give rise to an internal azolium ylide or an isoelectronic stable azole carbene system, whereas fully substituted heterocycles such as 142 can evolve in a more complex manner under basic conditions or with nucleophiles. Thus, in the presence of cyanide ion, the formation of adduct 143 could be evidenced by NMR spectroscopy. This intermediate, when stirred at ambient temperature for 48 h in the presence of dimethylacetylene azodicarboxylate (DMAD), led to the adduct 146 (28%) along with products 148 (40%) and 149 (12%) (Scheme 14) <1997JP12919>. 

Ylide formation, and hence X-H bond insertion, generally proceeds faster than C-H bond insertion or cyclopropanation [1176], 1,2-C-H insertion can, however, compete efficiently with X-H bond insertion [1177]. One problem occasionally encountered in transition metal-catalyzed X-H bond insertion is the deactivation of the (electrophilic) catalyst L M by the substrate RXH. The formation of the intermediate carbene complex requires nucleophilic addition of a carbene precursor (e.g. a diazocarbonyl compound) to the complex Lj,M. Other nucleophiles present in the reaction mixture can compete efficiently with the carbene precursor, or even lead to stable, catalytically inactive adducts L M-XR. For this reason carbene X-H bond insertion with substrates which might form a stable complex with the catalyst (e.g. amines, imidazole derivatives, thiols) often require larger amounts of catalyst and high reaction temperatures. 

The established activity of ethereal a-C-H bonds toward carbene and nitrene insertion has evoked new applications for sulfamate oxidation [76-78] In principle, a C-H center to which an alkoxy group is attached should be a preferred site for amination irrespec-hve of the addihonal functionality on the sulfamate ester backbone (Scheme 17.20). Such a group can thus be used to control the regiochemistry of product formation. The N,0-acetal products generated are iminium ion surrogates, which may be coupled to nucleophiles under Lewis acid-promoted conditions [79]. This strategy makes available substituted oxathiazinanes that are otherwise difficult to prepare in acceptable yields through direct C-H amination methods [80]. 

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