Análisis de data de Planeamiento

To the best of our knowledge, N- to C sulfonyl migration has not been previously reported in cyclic non-aromatic ring structures. However, related reactions have been reported for both acyclic and and aromatic systems and have been termed 1,3-sulfonyl migration, 1,3-sulfonyl shift and ortho-isomerisation (Scheme 4.6).

Scheme 4.6. General Scheme of N- to C sulfonyl migration in sulfonamides

From the literature, N- to C sulfonyl migration can be promoted by either photochemical or thermal reactions and these approaches are discussed in the following section.

4-1-2-1. Photochemistry

The general term photochemistry is used to describe the use of light to promote chemical reactions by absorption of either ultraviolet (wavelength from 100-400 nm), visible light (400-700 nm) or infrared radiation (700-2500 nm). Compared with thermal chemical reactions, photochemical reactions can help to overcome large activation barriers and can also be used to promote reactions that are inaccessible by thermal processes, for example some [2+2] cycloaddition processes.

N- to C-Sulfonyl Photoisomerisation Reaction

In 1959, Stacey et al. reported a photoisomerisation under UV light at 250 nm to convert vinylsulfonamides 430 into 2-sulfonylvinylamines 431 (Scheme 4.7).157 Aryl sulfonylamides such as SO2Ph and tosyl gave isomerisation products in good yields (68-94%). Unfortunately,

alkyl sulfonylamides only result in 5-10% yields of the photoisomerisation products. Furthermore, the reaction could be inhibited by small amounts of Et3N, 1,2-ethanedithiol,

thiophenol, butyraldehyde or styrene, and is not catalysed by either pyridine or p-toluenesulfonic acid, which all suggest that the isomerisation is not an ionic reaction but is radical in nature.

Scheme 4.7 The photochemical isomerisation of sulfonamides

Photo-Fries Rearrangement

The Fries rearrangement is an ortho, para-selective isomerisation transforming a phenolic ester 432 into a hydroxyl aryl ketone catalysed by a Lewis acid such as AlCl3 under thermal

conditions. The reaction involves an acyl group migration onto an aromatic ring.158 The regioselectivity can be affected by variation in the reaction conditions such as temperature and solvent (Scheme 4.8).

Photo-Fries rearrangements are promoted by light and are thought to proceed by a radical mechanism. Irradiating the N-sulfonyl aniline 437 under UV light generates sulfonyl radical and aniline radical. These two radicals can recombine at the ortho position or para position resulting in two regioisomers 439 and 441 (Scheme 4.9). There are a few literature reports of the photo-Fries rearrangement with N- to C-sulfonyl migration in aromatics such as benzenes,159,160 indoles161 and carbazoles.162

Scheme 4.9 General proposed mechanism of photo-Fries rearrangement

For example, Park and co-workers have demonstrated a photo-Fries rearrangement of N-tosylamides.160 Irradiating N-tosyl amides 442 at 254 nm in acetonitrile resulted in photoisomerisation into anilines 443 and 444. The regioselectivity of the method could be improved by blocking the para position with a substituent (Scheme 4.10). However, the yields were generally low in most cases.

Photo-Fries rearrangement of carbazoles with various sulfonyl groups has been reported by Chakaborty et al.162 The carbazoles 445 were irradiated with UV light at 254 and 365 nm either in methanol or benzene (Scheme 4.11). The wavelength at 365 nm gave shorter reaction times and slightly increased yields. The aryl sulfonyl substituent favoured forming the para-isomer 447 (ortho: para, 3:4), whereas, the mesyl sulfonyl group more favoured the ortho-isomer 446 (ortho: para, 4:3).

Scheme 4.11 Photo-Fries Rearrangement of Carbazoles with Various Sulfonyl Groups

In most cases, photo-Fries rearrangement gives a mixture of two regioisomer of products with low yield and poor regioselectivity. Hence, this reaction procedure is not readily applied in large-scale synthetic procedures.

4-1-2-2. Catalytic 1,3-Sulfonyl Migration

In addition to photo-induced procedures, N- to C-sulfonyl migration can be promoted by organometallic chemistry.163–165 Recently, Chan and co-workers have developed a gold-catalysed domino aminocyclisation/1,3-sulfonyl migration of 1,7-enyne benzoates 448

Scheme 4.12 Gold-Catalysed Cycloisomerisation of 1,7-enyne benzoates

This gold-catalysed cycloisomerisation could involve the activation of 1,7-enyne benzoates by coordinating gold catalyst 450 with the alkyne moiety to give gold(I) intermediate 451, which undergoes the intramolecular aminocyclisation forming complex 452. Then, complex

452 can undergo either dehydration following by 1,3-sulfonyl migration into product 449

(Scheme 4.13, path a) or 1,3-sulfonyl migration then dehydration (path b). A crossover experiment demonstrated that the 1,3-sulfonyl migration is an intramolecular process (Scheme 4.13).

A novel 1,3-sulfonyl migration has also been demonstrated usingLewis base catalysis. Zhan et al. employed DMAP as catalyst for synthesis of mutisubstituted pyrazoles from propargylic hydrazones 453 (Scheme 4.14).166 This method examined various sulfonyl groups and a wide scope providing good to excellent yields (47-95%). A crossover experiment of propargylic amides suggested this 1,3-sulfonyl migration is an intramolecular process. The proposed mechanism starts with isomerisation of the alkyne moiety of propargylic amide 453 into the allenic sulfonamide 454. Nucleophilic addition of DMAP to the terminal sp2 carbon of the allene 456 pushes electron density onto the sulfonylamide to afford intermediate 457, which undergoes 1,3-sulfonyl migration resulting in 458. Elimination of the Lewis base catalyst gives α,β-unsaturated imine 459, which then undergoes intramolecular Michael addition to generate the zwitterionic cyclic intermediate 460. Finally, proton transfer affords the observed pyrazole products 455.

Compared with photoisomerisation, catalytic thermal methodologies not only provide more precise 1,3-sulfonyl migration without regioselectivity issues but also generally provide a wide range of scope and good yields. Hence, the photo-induced N- to C-sulfonyl migration discovered from Smith group is particularly interesting as it provides specific isomerisation products in excellent yield and it is also the first example of N- to C-sulfonyl migration of non-aromatic cyclic substrates containing stereocentres.