Carbenoid center

Base-induced rearrangement of bicyclo[2.2.2]octane oxide 67 gives predominantly bicyclo[2.2.2]octanone 68 (Scheme 5.15), which once again indicates that close proximity between the carbenoid center and the C-H bond into which it may insert is important if such an insertion is to occur [30]. In comparison, the sense of product distribution is reversed for the related substrate bicyclo[2.2.2]octadiene oxide 70 on treatment with LDA [15, 22], alcohol 72 being the favored product. 

VAPOL ligand, chiral 25 f. carbenoid center 153 carbenoids 146... 

Enantioselective carbenoid cyclopropanation can be expected to occur when either an olefin bearing a chiral substituent, or such a diazo compound or a chiral catalyst is present. Only the latter alternative has been widely applied in practice. All efficient chiral catalysts which are known at present are copper or cobalt(II) chelates, whereas palladium complexes 86) proved to be uneflective. The carbenoid reactions between alkyl diazoacetates and styrene or 1,1 -diphenylethylene (Scheme 27) are usually chosen to test the efficiency of a chiral catalyst. As will be seen in the following, the extent to which optical induction is brought about by enantioselection either at a prochiral olefin or at a prochiral carbenoid center, varies widely with the chiral catalyst used. 

By contrast, Con(salen) (100), which has the same ligand as (93), catalyzes cyclopropanation with excellent cis- and enantioselectivity (Scheme IT) 1, 274 The addition of NMI also improves stereoselectivity. It is noteworthy, however, that the sense of enantioselection by (100) is opposite to that by (93). Reversal of the enantioselectivity has been attributed to differences in the substrate s approach to the carbenoid centers.274... 

As demonstrated in the preceding Section III.A, configurations of not only the C-H bond of the alkoxide to be inserted but also the carbenoid center present is evidence for the insertion mechanism. In this regard, norcaranylidene carbenoid30 has an unsymmetrical stereochemical environment similar to those of alkylidenemethylene carbenes (Scheme 20) and, therefore, it is expected to be informative of the insertion mechanism. 

Intramolecular alkylation of phenol with diazoketone [14] can be analyzed as the following The carbenoid center acts first as an acceptor and then a donor. Since the resulting cyclopropane derivative is vicinally substituted with an acceptor (C=0) and a donor (enol), fragmentation follows instantaneously (vide infra). 

Finally, analogous to the epoxides, aziridines can also be prepared by the addition of carbenoid centers to a carbon-nitrogen double bond. In this arena, Aggarwal and co-workers have reported a highly diastereoselective aziridination of imines with trimethylsilyldiazo-methane (TMSD). Thus, tosylimine 146 was converted to the cis aziridine 147 in 65% yield <02JOC2335>. 

The synthetic applications of halocarbenoids are mainly determined by the framework bearing the carbenoid center. This article describes the different kinds of synthetic transformations that can be achieved by the use of alkylidene, a-heterosubstituted, cyclopropylidene, vinylidene, and allylidene lithium halocarbenoids. Their particuliar value in organic synthesis results from various rearrangement reactions of the primary adducts formed by reaction of the carbenoid with the electrophile. 

Some characteristics of their chemistry are still not well enough understood, as for example the nucleophilic substitution on the carbenoid center and its possible application in synthesis. Another still unsolved problem is the question of the structure of halo carbenoids. More insight into this difficult problem is expected from physical measurements and theoretical calculations 69,70). 

Unlike the insertion of 2-monosubstituted alkenyl carbenoids (69, 70, and 73), the reaction of 2,2-disubstituted alkenyl carbenoids with alkenyl zirconocene chlorides afforded the expected products as a mixture of stereoisomers. Thus, when 77, derived from the deprotonation of the stereodefined E-l-chloro-2-methyl-l-octene 76, was reacted with -l-hexenylzirconocene chloride 78 at low temperature, a partial inversion of configuration at the alkenyl carbenoid center occurred before or during the rearrangement to afford the expected metalated diene 79 with an E Z isomeric ratio of 58 42 after hydrolysis (see 80, Scheme 27) [53]. The poor stereocontrol was attributed to the metal-assisted ionization [58-60], which promotes the interconversion of the E- to the Z-alkenyl carbenoids 77. The latter occurs at a rate comparable with that of the insertion into organozirconocene chloride, and hence this is responsible for the loss of stereochemistry. 

The absolute configuration of the products It + Ic, trans and cis isomers, is explained by the coimection between the prochiral face of styrene to the prochiral face of the intermediate carbenoid center (Scheme 7.3). The re-face of styrene attacks... 

Thietanium ylide intermediates, obtained by the action of carbenoid centers with a 7-divalent sulfur atom, undergo the Stevens rearrangement as shown for... 

Intramolecular cyclopropanation of olefinic a-diazo ketones and a-diazo esters has been widely used in organic synthesis. When a carbenoid center and the double bond are separated by a chain of three atoms, one of which is oxygen, a five-membered O-containing heterocycle is formed. Intermolecular cyclopropanations of olefins are known to allow stereospecific formation of desired products. Thus, decomposition of substituted allyl diazomalonates 265 in the presence of copper salts gives rise to bicyclic... 

Reaction of carbonylcarbenes with a triple bond results in either 1,1-cycloaddition product 326 or 1,3-cycloaddition product 327. Substituted furans 327 are also accessible through photolysis, thermolysis, or catalytic rearrangement of carbonylcyclopropenes 326. However, furan formation can be imagined as a cyclization of 6ir-electron system 328, incorporating a singlet carbene or carbenoid center and a conjugated heteroatomic diene... 

For the control of intramolecular cyclopropanation versus 1,2-hydride shift to the carbenoid center, see ref 338. 

Unlike intermolecular cyclopropanation reactions, the intramolecular version is stereo-specific with respect to the configuration of both, the C-C double bond and (due to steric constraints) the carbenoid center. This fact can be used for the directed synthesis of cis-1,2-disubstituted, all-ci. -l,2,3-trisubstituted or d. , ra . -l,2,3-trisubstituted cyclopropanes. For example, a-diazo esters (a-diazocarboxamides) with an unsaturated ester (amide) residue yield bicyclic lactones (lactams) stereospecifically which can be ring opened to give the monocyclic cyclopropanes mentioned with defined stereochemistry. Some possibilities are illustrated by the examples, 20 -+ 22 -> 23, and 24 25. ... 

Although the formation of three-membered rings by cyclopropanation of olefins with metal carbenoids is commonplace, the construction of such systems via intramolecular C-H insertion is quite rare. This is because 1,2 migration of any hydride atoms a to the carbenoid center is typically very facile, rendering it inactive toward further transformations [56], It was found, however, that [i-tosyl a-diazo carbonyl compounds 37 are suitable substrates for intramolecular 1,3 C-H insertion reactions catalyzed by achiral rhodium carboxylates 25 (Scheme 6) [57],... 

Employing a [4+l]cycloaddition that unites a conjugated carbonyl unit with the carbenoid center of a Cr-complex paves way to a novel approach to furans/... 

Experience has shown that cyclopentadiene annulatlon of 2,3-dimethylenebicyclo[2.2.2]octanes can be efficiently realized by means of the Skattebtfl procedure.7 However, the added strain in 2,3-dimethylenenorbornanes reroutes the rearrangement instead into vinylallene formation. This phenomenon has been attributed to an inability on the part of the torsionally-constrained empty carbene p orbital to interact with the flanking double bond. This structural inhibition 1s entirely alleviated by positioning the cyclopropyl carbene completely external to the norbornene ring as in the present example. The heightened conformational maneuverability of the carbenoid center 1s conducive to exclusive cyclopentadiene ring formation. 

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