Smiles rearrangement intramolecular rearrangements

Smiles rearrangement Intramolecular nucleophilic aromatic rearrangement of activated aromatic substrates. 416... 

Smiles rearrangement. Intramolecular nucleophilic aromatic substitution in alkaline solution resulting in the migration of an aromatic system from one heteroatom to another. 

Intramolecular cyclization can yield fluorinated phenoxazines by a Smiles rearrangement (86IZV1855) and 2,3-dihydro-l,4-benzodioxins by a base-induced reaction [81JFC(18)483]. 

The 2-(2,4,6-triiodophenoxy)acetamide 399 on treatment with NaOMe underwent Smiles rearrangement to 400, which cyclized intramolecularly to the 2,3,5,6-tetrahydro-3-oxo-[l,4]oxazino[4,3,2-. 

Excited-state intramolecular nucleophilic aromatic substitutions are known as photo-Smiles rearrangements. Ealier, these were reported for 2,4-dinitrophenyl ethers and. v-lriazinyl ethers32. The exploratory33 and mechanistic34 studies on photo-Smiles rearrangements of p-(nitrophenoxy)- >-anilinoalkanes were carried out (equation 28). 

Buncel et a/.215 found that at a higher temperature, or in the presence of an excess of nucleophile, subsequent transformation of 173 irreversibly leads to new products (Scheme 12). A proton transfer occurs first from thes/ 3 carbon atom to the N-oxide group. The resulting intermediate 175 changes by two routes, leading to 176, presumably by an intramolecular shift of the oxide substituent similar to a Smiles rearrangement, and to anion 167 by loss of OH and subsequent MeO attachment. 

The cine substitution of phenyl 3-nitro-4-thienyl sulfone has been discussed in Section 3.14.3.5. An intramolecular example of cine substitution by an AEa mechanism is provided by the Truce-Smiles rearrangement of the sulfone (459) to (460) (78JOC101). PhS02 as a leaving group has a higher steric requirement than Br in nucleophilic substitution reactions. In order to give a unified picture, details are deferred to Section 3.14.3.8. 

The photoaddition to aromatic ring is simply classified in Table 13. Direct attack of nucleophiles such as cyanide anion and carbanion to aromatic rings in the excited species has been recognized by SRN2 reactions [Eq. (4)], which were discussed in the past three decades [27,28], We will discuss briefly some examples in this section, including intramolecular photocyclization such as photo-Smiles rearrangement. 

Intramolecular cyclisation of the azides (79) by refluxing in toluene has produced the [ 1,2,3]triazolo[ 1,5-u][ 1,4]diazepines (80) <95S647>. Removal of the Boc protecting group in the benzodiazepine derivative (81), prepared in three steps from 2-fluoro-5-nitro-benzoic acid, results in ring expansion to (82) via a Smiles rearrangement <95SL539>. 

The carbanion generated from the dinitrile 24 causes a Smiles-type nucleophilic rearrangement to produce new anions 25 and 26. The tandem intramolecular cyclization of the latter affords dihydrothiophene 27. Thieno[2,3-3][l,6]naphthyridine 28 is derived from 27 in four steps (Scheme 6) <1995H(41)1307>. 

Historically, the possibihty of obtaining intramolecular rearrangement came from the tautomeric irreversible rearrangements observed by Chapman (Scheme 2) [4,5]. In his early work. Chapman was able to demonstrate that the reaction undertakes an intramolecular pathway, i.e. via a spirocyclic intermediate. Not much later Smiles foimd another reaction causing the 1,3 shift of the substituent in the aromatic ring, involving a similar intermediate [6,7]. 

As regards solvent effects, it seems likely that in nonpolar solvents, rotation around the central bond in the Smiles rearrangement product will be retarded by intramolecular bounding of the lithium cation by SO2 and the benzothiazolyl group. 

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