Intramolecular, addition carbene insertion

The intramolecular addition of acylcarbene complexes to alkynes is a general method for the generation of electrophilic vinylcarbene complexes. These reactive intermediates can undergo inter- or intramolecular cyclopropanation reactions [1066 -1068], C-H bond insertions [1061,1068-1070], sulfonium and oxonium ylide formation [1071], carbonyl ylide formation [1067,1069,1071], carbene dimerization [1066], and other reactions characteristic of electrophilic carbene complexes. 

Use of Rh2(OAc)4 suggested that there was no inherent selectivity attributable to the coordinated carbene or to rhodium(ll). However, modification of dirhodium(ll) ligands to imidazolidinones provided exceptional diastereocontrol, obtained by influencing the conformational energies of the intermediate metal carbene [19, 23], as well as high enantiocontrol. Representative examples of products from these highly selective intramolecular C-H insertion reactions with cyclic systems is given in Scheme 15.6. Additional examples of effective insertions in systems from which diastereomeric products can result are illustrated in processes of the synthesis of 2-deoxyxylolactone (Scheme 15.7) [64, 65]. Here the conformation of the reactant metal carbene that is responsible for product formation is 32 rather than 33. Other examples in non-heteroatom-bound systems (for example, as in Eq. 15) confirm this preference. 

Many of the limitations of C—C bond formation by C —H insertion outlined for intermolecular reactions (Section 1.2.1.) can be overcome by making the reaction intramolecular. Thus, hydrogen atom abstraction followed by intramolecular radical-radical coupling or radical addition to an alkene are increasingly popular processes. Two-electron carbene insertions, either thermal or transition metal catalyzed, have also been used extensively. In either case, ring construction involves net C—C bond formation at a previously unactivated C-H site. 

Intramolecular carbene insertion (e.g. 1 —> 3) has long been a useful method for ring construction. Masahisa Nakada of Waseda University in Tokyo now reports (J. Am. Chem. Soc. 125 2860, 2003) that with the addition of the ligand 2 this process can be made highly enantioselective. As the starting diazo ketone 1 is easily prepared by diazo transfer to the sulfonyl ketone, this should allow facile entry to enantioenriched cyclopentanones and cyclohexanones. 

In addition, a proline- or phenylalanine-based Rh(II) can catalyze intramolecular asymmetric carbene reactions such as aromatic ring expansion and C—H insertion with moderate selectivity (Scheme 95) (229). Rh(II) carboxamides are also effective catalysts for asymmetric C—H or N—H insertion (228c). 

Analysis of the product distributions arising from both sensitized and non-sensitized irradiation of 2-allyloxyphenyldiazo species (8) showed that the C—H insertion product and much of the cyclopropanation arise from the triplet carbene.16 For the singlet carbene, intermolecular 0—H insertion with methanol is about 50 tunes faster than intramolecular addition to the double bond, hi this system, intramolecular reactions and intersystem crossing of the triplet carbene proceed at similar rates, hi the closely related indanyl system (9), the smaller RCR angle stabilizes the singlet state relative to the triplet and the intramolecular reactivity is dominated by the singlet state.17... 

The rearrangements of silylenes, like those of carbenes, can involve H shifts and the shifts of C—C bonds (intramolecular insertion and ring expansion) or cyclization by intramolecular addition to C=C jr-bonds5. The mechanism discovered by Barton for... 

In addition to the preparations of ethanoadamantane via Lewis acid catalyzed rearrangement of various polycyclic hydrocarbons described above (Section II. A.1), a ring closure reaction of a substituted adamantane has also been developed. Treatment of 2-adamantyl diazoketone with copper results in the intramolecular carbene insertion illustrated in Eq. (48) 14°1. 

Reactions of alkynyliodonium salts 119 with nucleophiles proceed via an addition-elimination mechanism involving alkylidenecarbenes 120 as key intermediates. Depending on the structure of the alkynyliodonium salt, specific reaction conditions, and the nucleophile employed, this process can lead to a substituted alkyne 121 due to the carbene rearrangement, or to a cyclic product 122 via intramolecular 1,5-carbene insertion (Scheme 50). Both of these reaction pathways have been widely utilized as a synthetic tool for the formation of new C-C bonds. In addition, the transition metal mediated cross-coupling reactions of alkynyliodonium salts are increasingly used in organic synthesis. 

Whether carbene, germylene, and silylene are justifiable terms for stabilized versions of the reactive species is a very debatable question [28], However, for synthetic chemists, the most important issue is to know whether these stable species feature the reactivity of transient carbenes. Formation of azaphospholidines upon thermolysis (intramolecular carbene insertion into a carbon-hydrogen bond), cyclopropanation reactions, and [l + l]-addition to isocyanides giving keteneimines... 

The first approach is realizable via a variety of typical carbene reactions. Cyclizations not involving a heteroatom include formation of a new C—C bond as a result of an intramolecular C—H insertion of a carbene (Scheme 1) or its addition onto multiple carbon-carbon bonds [intramolec-... 

The sixth example in Table 6.6, carbene insertion into an adjacent C-H sigma (a) bond, is representative of the gas-phase reaction of carbenes. Indeed, since this intramolecular reaction effectively competes with the intermolecular addition of carbenes to alkenes seen earlier, the intermolecular process (Scheme 6.47) is best examined when no a-hydrogens are available in the carbene. 

In addition to their thermodynamic propensity to dimerize [16], free acyclic car-benes containing alkyl groups are prone to decomposition via intramolecular C—H insertion reactions that lead to net elimination of an alkene (Scheme 16.3a) [35]. Loss of two alkene equivalents has been observed to occur from an Alder-type ADC bound to W or Mo tetracarbonyl fragments, resulting in conversion to an amidine ligand (Scheme 16.3b) [36]. This process appears to be limited to zerovalent metal complexes and may be facihtated by the unusual -(C,N) binding mode of the carbene. 

Carbenes can react either (1) intramolecularly or (2) intermolecularly. The basic reactions are addition and insertion. Triplet carbenes can also react via an abstraction mechanism. As typical examples, the intra- and intermolecular reactions with a double bond are shown in Schemes 4 and 5, respectively. 

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