Smiles rearrangement process

In a transition metal-ffee one-pot regioselective Smiles rearrangement process at ambient temperature, 2-mercaptonicotin(benz)amides 151 reacted with 1,2-dihalobenzenes 152 to afford fused l,4-thiazepin-5(4Jl) ones 153 in good-to-excellent yields (14JOC8040). 

An unprecedented domino radical cyclization/Smiles rearrangement process of 175 to give 3-(2-aryl-N-methylacetamido)indolin-2-ones 178 or 180 was reported by Gerard, Sapi, et al. [63] (Scheme 5.38). The reaction proceeds via a 5-exo-trig cyclization followed by radical substitution. The radical intermediate 177, formed via the radicals A and 176, could undergo either a normal termination of a radical to form product 178 in 11-66% yields or an additional amidyl radical cyclization, giving the product 180 in up to 40% yield depending on the reaction conditions. 

Scheme 5.38 Domino radical cyclization/Smiles rearrangement process.

Both cis- and rrans-l-arylsulfonyl-2-arylsulfenyl propenes (56) underwent a Smiles rearrangement under electron impact at 20 and 70 eV and formed a diarylsulfide ion [M — 104]+ (equation 27a)39 through a process where a bond between the R C H group and the sulfide sulfur is formed and a rearomatization occurs by a loss of the neutral thiirene dioxide or a simultaneous expulsion of SOz and propyne. The ion m/z 148 was also obtained from all of the sulfonyl-sulfides, 56 (equation 27b) and here the loss of R2 seemed to be related to the bond strength39. In addition to the above compounds 56 exhibited some simple cleavages before and after sulfone-sulfinate rearrangements. 

The increased resonance effect due to the presence of two nitro groups at both ortho positions and combined resonance and inductive effects enforced by one nitro and one halogen atom activate the Smiles rearrangement as well as the ring closure to such an extent that both processes take place instantaneously. However, the resonance elfect in 2,4-dinitrochlorobenzene is not so pronounced and its reaction with 2-aminobenzenethiol does not go in one step (88MI1). 

Scheme 18.73 Propargylic disulfide casradp rearrangement/cyclizatinn process.— CHAPTER 19 SMILES REARRANGEMENTS Scheme 19.1 Smiles rearrangements. 

One of the most commonly encountered applications of Smiles rearrangements in synthesis is to prepare fused aromatic systems via three-step cascades displaying two nucleophilic substitutions with a Smiles rearrangement in between. These sequences have been adapted into more conplex three-conponent couplings such as the benzothiazine synthesis shown in Scheme 19.9. hi this process, 19 reacts first with acyl chloride 18 leading to 20 after substitution with 17. Heating the mixture under microwave conditions tri ers the Smiles rearrangement and the final Sj Ar toward 21. 

One advantage of the U-4CR lies in its ability to efficiently generate substances of significant molecular complexity from simple starting materials. As a result, the products of these reactions are often well suited for further transformations via tandem processes. Smiles rearrangements, ... 

In a transition metal-free, one-pot, and regioselective process, 2-halo-benzenethiols 195 or 3-chloro-5-(trifluoromethyl)pyridine-2-thiol 196 reacted with N-substituted nitrobenzamides 197 to afford a library of dibenzo[I>,/][l,4]thiazepin-ll(10id)-ones 198 or pyridobenzothiazepines 199, respectively, via a Smiles rearrangement (13ACO130). 

Ito and coworkers discovered a nniqne Trnce-Smiles rearrangement of the substituted anilide intermediate 16 upon exposure to LDA. When 16 was subjected to an oxidative process (LDA, THE, Oj, -70°C), the rearranged product 17 was obtained in 75% yield instead of the desired oxidation product. Their proposed transition state geometry (18) is depicted in the box in Figure 18.2 [11]. 

Although the mechanism of this process was not studied, a plausible mechanistic hypothesis is invoked by the authors (Scheme 8.4). On the latter, the nitrophenol 16 is assumed to act as acid surrogate activating the aldehyde to promote the further isocyanide addition. The resulting nitrilium 17 is trapped by the nucleophilic phenoxide generating imidate intermediate 18, which undergoes a final Smiles rearrangement [15,16] to provide the more stable a-aryloxy amide 15 (Scheme 8.4). 

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