Reactivity ring expansion

Ring expansion of activated aziridines (43) with sulfur ylides also provides a synthesis of azetidines (75JOC2990, 58BSF345, 81CC417). The highly reactive sulfonium methylide (44 R = R = H) undergoes further reaction with the azetidines (46), but the reaction is satisfactory for substituted methylides. The less reactive sulfoxonium methylide (45 R = R = H)... 

The highly reactive species methylene inserts into C—H bonds,both aliphatic and aromatic,though with aromatic compounds ring expansion is also possible (see 15-62). This version of the reaction is useless for synthetic purposes because of its nonselectivity (see p. 248). This contrasts with the metal carbene insertion reaction, which can be highly selective, and is very useful in synthesis. Alkylcarbenes usually rearrange rather than give insertion (p. 249), but, when this is impossible. 

Carbenes are so reactive that they add to the double bonds of aromatic rings. The products are usually not stable and rearrange to give ring expansion. Carbene reacts with benzene to give cycloheptatriene ... 

The highly strained and reactive 2iT-azirines have been extensively studied for various synthetic purposes, such as ring expansion reactions, cycloaddition reactions, preparation of functionalized amines and substituted aziridines. The older literature on azirines in synthesis has extensively been reviewed [69]. Concerning azirines with defined chirality only scarce information is available. Practically all reactions of azirines take place at the activated imine bond. Reduction with sodium borohydride leads to cz5-substituted aziridines as is shown in Scheme 48 [26,28]. 

Figure 4.21 BASED can react with molecules after photoactivation to form crosslinks with nucleophilic groups, primarily amines. Exposure of its phenyl azide groups to UV light causes nitrene formation and ring expansion to the dehydroazepine intermediate. This group is highly reactive with amines. The cross-bridge of BASED is cleavable using a disulfide reducing agent.

Figure 5.31 ASIB can react with sulfhydryl-containing molecules through its iodoacetate group to form thioether linkages. Subsequent exposure to UV light causes a ring-expansion process to occur, creating a highly reactive dehydroazepine intermediate that can couple to amine-containing molecules.

Photolyzing with UV light may result in immediate reaction of the nitrene intermediate with a target molecule within Van der Waals distance, or may result in ring expansion to the nucleophile-reactive dehydroazepine. The ring-expanded product is reactive primarily with amine groups (Figure 5.31). 

Figure 11.14 Photobiotin can be made to couple spontaneously with nucleophiles by exposure to UV light. The phenyl azide ring undergoes ring expansion to a highly reactive dehydroazepine intermediate, which can react with amines.

In this chapter we describe experimental studies on the ring expansion reactions of phenylcarbene and phenylnitrene and the calculations that have been performed in order to try to explain the experimental results. Our aim is to show how theory can rationalize these observations and can also serve to stimulate additional experiments by predicting their outcome. We will attempt to demonstrate that an understanding of the fundamental differences between the electronic structures of phenylcarbene and phenylnitrene can explain the many differences in the chemistry of these reactive intermediates. 

The high reactivity of the cobalt-complexed propargylic systems has also allowed for ether oxygens to serve as nucleophiles, which has led to the fashioning of medium-sized ring ethers via ring expansion (Equation (60)), and also... 

For another example of the strong dnality in the chemical behavior of distonic cation-radicals, see Moraes and Eberlin (1998). In the gaseons phase, m- and /7-dehydrobenzoyl cation-radicals ( CgH4C =0) react selectively either as free radicals or as acylium ions, depending on the choice of the reacting partner. Transacetalization with 2-methyl-l,3-dioxolane, ketalization with 2-methoxy-ethanol and epoxide ring expansion with epichlorohydrin demonstrate their acylium reactivity. 

Biscarbene 34 was characterized by IR and UV/vis spectroscopy [49], The analysis of the experimental data showed that these are compatible with the presence of two phenylchlorocarbene (6) subunits in 34. This interpretation was further supported by the reactivity behavior of 34, which, like 6, is unreactive toward oxygen under conditions where triplet carbenes react fast. In contrast to its para isomer (22), 34 appears to undergo photochemical ring expansion analogous to that of 6[105]. In addition, the computed [RHF/6-31G(d)] IR spectrum of 34, which is in good agreement with the observed one, is based on the wave function for the singlet (cr /cr ) biscarbene (54 of Fig. 9). 

Galbraith, J. M. Caspar, P. P Borden, W. T. What Accounts for the Difference between Singlet Phenylphosphinidene and Singlet Phenylnitrene in Reactivity toward Ring Expansion J. Am. Chem. Soc. 2002, 124, 11669-11674. 

A further advantage of this protocol is that it allows the azidohydrin intermediate to be isolated. This will facilitate important mechanistic work to clarify the nature of the reactive species responsible for the ring expansion. Although only the preparation of azepin-2-... 

The difference between the reactivities of la and lb toward ring expansion is nicely explained by the difference between the electronic structures of their lowest... 

Without the calculations that showed that there is a fundamental difference between the lowest singlet states of la and lb, ° and that this difference is responsible for the difference between their reactivities, it is not clear how the correct explanation for the much faster ring expansion of lb than of la would ever have been found. 

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