Carbon-Heteroatom C-X Bond Formations

CARBON-HETEROATOM (C-X) BOND FORMATIONS 23.3.1 C-B Bond Formations... 

An example of C—Si bond formation concludes this overview of carbon heteroatom bond formation. Reflux of bromide 62 in benzene and in the presence of small amounts of (TMS)3SiH and AIBN afforded the silabicycle 63 in 88 % yield (Reaction 7.64) [76]. The key step for this transformation is the intramolecular homolytic substitution at the central silicon atom, which occurred with a rate constant of 2.4 x 10 s at 80 °C (see also Section 6.4). The reaction has also been extended to the analogous vinyl bromide (Reaction 7.65) [49]. 

A weak C—X bond is required to facilitate the initiation step, but the success of the reaction depends on the subsequently formed C-heteroatom bond being stronger than the one broken in the initial reactant. In other words, to ensure the chain process, the initially generated radical should be more stable than the one formed after the addition. It is also critical that the halogen atom-transfer step be suffi-ciendy rapid to propagate the chain. The usual processes in ATR reactions involve a-carbonyl radicals leading to the formation of lactones, lactams, or cycloalkanones, which embody a new carbon-halogen bond after the transfer step. 

Besides carbon — carbon multiple bonds, carbon —heteroatom double bonds (C = 0 C = NR) are also capable of undergoing metal-catalyzed [3 4- 2] cycloadditions. However, the simplest class of substrates, i.e. ketones and imines, respectively, could so far only be employed when 2-(trimethylsilylmethyl)prop-2-enyl acetate (1) was used as a TMM synthon. These reactions, which additionally require the presence of cocatalysts such as tin or indium compounds when ketones are used as substrates, lead to the selective formation of 3-methylenetetrahydrofurans and 3-methylenepyrrolidines (3, X = O, N), respectively. ... 

Initial imine or iminium generation from amines can be used to allow C-X (X = heteroatom) or C-C bond formation. Thus, anilines substituted in the orf/zo-position with X-H functionalities (X = 0, NMe, S) have been dehy-drogenatively condensed with benzylamines under mpg-CN photocatalysis to yield the corresponding benzofused heterocycles [122]. Via iminium intermediates, AI-aryl-l,2,3,4-tetrahydroisoquinolines could be dehydrogenatively coupled photocatalytically by mpg-CN to various carbon nucleophiles derived from nitroalkanes, malonates, and 2-alkanones, and the latter via tandem organocatalysis with proline [124]. 

In the aromatic Claisen rearrangement (65), the ether-phenol transformation occurs at about 2(X)° S-C allyl shifts are more difficult to achieve (66). As the formation of the dienone intermediates is rate-determining, the analysis of perturbance around the heteroatoms (X) leading to the intermediates should provide clues to the relative rates, for changes are the same elsewhere. Thus, the crux of the problem involves only the net change of a -X to a Qpi -X bond. Such a change is favored with X = O rather than that with X = S because trigonal carbon is harder. 

The design of this new class of trifluoromethylation reagents led to the development of a vast number of specific methodologies addressing a broad array of organic nucleophilic substrates. These cover heteroatom-centered nucleophiles such as thiols, phosphines, alcohols, and azoles, as well as carbon-centered nucleophiles in their virtually unlimited diversity. The formation of the new X-CF3 or C-CF3 bond relies on several different strategies as discussed below, in what is intended to be a brief overview. A more exhaustive account has recently appeared in the form of a comprehensive review article [2]. 

---