A Sommelet-Hauser rearrangement

An effective method of hexahydrothieno[3,2-c]- and [2,3-c]azocines 146 and 148 syntheses involving a Sommelet-Hauser rearrangement of l,l-dimethyl-2-(2- or 3-thienyl)pyrrolidine salts 145 and 147 under the action of NaNH2 in liquid ammonia has been described (87SC935 Scheme 40). 

Based on a previous study by Miller,289 a series of iV-benzyl-MSMA chlorides or bromides have been treated with a base and/or a nucleophile. For example, in the presence of the amide anion, the trimethylsilyl derivative yields iV,/V-dimethyl-2-methyl-a-(trimethylsilyl)benzylamine (a Sommelet-Hauser rearrangement product) as the main... 

Similar rearrangements also occur in the case of sulfur analogs. Since the product of a Sommelet-Hauser rearrangement is a benzylic tertiary amine (or sulfide), just as the starting material was a benzylic amine (or sulfide), the process can be repeated and is a unique method to move substituents around the periphery of aromatic rings (Scheme 109). 

Tertiary amines are aminated to give unstable hydrazinium compounds, for example (54), is suggested by the formation of hydrazine (55) via a Sommelet-Hauser rearrangement on reaction of (51) with iV,jV-dimethylallyl amine (Scheme 11) <91S327>. 

A Sommelet-Hauser rearrangement of the initially formed sulfonium ylide 13 is a key reaction step. This brings about the required ortho-linkdigQ with the arene, which results in the formation of the o-aminobenzyl carbonyl compound 14. 

In the course of this synthesis, the anilinosulfonium salts 53 are deprotonated by Et3N to give sulfonium ylides, which undergo a Sommelet-Hauser rearrangement (situation 54) to the (o-aminobenzyl) ketones 57. Subsequent (spontaneous) cyclization to 3-thiomethyhndoles 56 and reductive desulfurization lead to the 2- (or 1,2-) substituted indoles 55. 

Exposure of l,l-dimethyl-2-vinylpiperidinium chloride (239) to sodamide gave a 94% yield of l-methylazacyclonon-4-ene (240) by a Sommelet-Hauser rearrangement. The catalytic co-oligomerization of ketazines and aldazines with butadienes... 

Aggarwal s group studied a variety of sulfides as catalysts for cyclopropanations. They observed that thianes (six-membered-ring sulfides) are better catalysts compared to the thiolanes (five-membered-rings). The slower reaction of the ylide form of the latter ones with enones provides time for an alternative reaction. Ylide anion equilibration eventually enables a Sommelet-Hauser rearrangement (Scheme 7.44) [169]. The propensity for this alternate reaction is lower in six-membered-ring ylides. 

Another indole/oxindole synthesis achieves the critical ortho-substitution by Sommelet-Hauser rearrangement of an anilinosiilfonium ion intermediate. Use of P-thioketones (G = R, an alkyl group) generates 2-substituted indoles, whereas P-thioesters (G = OR) lead to oxindoles. In each case, a 3-thio substituent must be removed by desulfuri2ation. 

The mechanism of the indolization of aniline 5 with methylthio-2-propanone 6 is illustrated below. Aniline 5 reacts with f-BuOCl to provide A-chloroaniline 9. This chloroaniline 9 reacts with sulfide 6 to yield azasulfonium salt 10. Deprotonation of the carbon atom adjacent to the sulfur provides the ylide 11. Intramolecular attack of the nucleophilic portion of the ylide 11 in a Sommelet-Hauser type rearrangement produces 12. Proton transfer and re-aromatization leads to 13 after which intramolecular addition of the amine to the carbonyl function generates the carbinolamine 14. Dehydration of 14 by prototropic rearrangement eventually furnishes the indole 8. 

The Sommelet-Hauser rearrangement competes when Z is an aryl group (see 3-26). Hofmann elimination competes when one of the R groups contains a 0 hydrogen atom (7-6 and 7-7). 

The chlorosulfonium compounds can also be used for the synthesis of oxindoles, the stable tautomeric form of 2-hydroxyindoles. The a -methylthio ketone is replaced by ethyl methylthioacetate and the products of the Sommelet-Hauser rearrangement are cyclized to 3-methylthiooxindoles. The methylthiooxindoles are reductively desulfurized with Raney nickel (equation 102) (74JA5508). 

We have mentioned previously as a stable ylide dimethyl sulfonium fluorenide (see Section 2.9). It yielded the first example (1938) of a [2,3] sigmatropic rearrangement of a sulfur ylide [505, 506] (Sommelet-Hauser rearrangement). 

In a base-catalyzed ring expansion route to 1,2-diazocines, Sommelet-Hauser rearrangement of the A-amino derivative of nicotine (22) using sodium in ammonia afforded pyrido-l,2-diazocine 23. The reaction was regiospecific, i.e., no isomeric 24 was detected (82H1595). 

The presence of an alkyl group or not on the benzylic carbon atom has little influence on the result (example 2). The Sommelet-Hauser rearrangement product is not obtained as its exo-1 -alkylidene-cyclohexadi-2,4-ene precursor is stable (allowed typical cyclohexadiene chemistry) and isolable as a 1 5 mixture (35% yield) of the two stereoisomers. Styrene is also obtained as the major product (50%) whereas the Stevens product is formed in trace amounts. Triene A is converted quantitatively into 2-ethylbenzylamine under treatment with diluted KOH at 60 °C for 0.5 h in ethanol.368... 

An illustration of the Sommelet-Hauser rearrangement is the synthesis of 2-methyl-2,3,4,5,6,7-hexahydro-lH-2-benzazonine from 2-phenyl-l-[(trimethylsilyl)methyl]-piperidine in good yield, where a stable trienic intermediate aromatized only after treatment with base for 24 h at room temperature.369... 

Otter et al. (89JHC1851) obtained the thienopyrimidine 253 in 50% yield by heating 5-(2-propynylthio)pyrimidine 248 in DMSO at 145°C. The reaction proceeds via a Claisen rearrangement of 248 in the allene 249, which then cyclizes to the product 253. An 18% yield of the thiomethyl compound 252 was also isolated. This was explained by a mechanism involving solvent incorporation into allene 249 to give intermediate 250 this intermediate then undergoes a Sommelet-Hauser type of rearrangement to afford 251, which cyclizes to the product 252. 

The Sommelet-Hauser rearrangement formally involves the conversion of a benzyl ammonium salt such as 76 into a benzyl amine (e.g., 79). 

The Sommelet-Hauser rearrangement has rarely been used as a tool in organic synthesis and then only for very special systems [54], The reason is undoubtedly that the Hofmann elimination and the dealkylation reaction of quaternary nitrogen atoms are in direct competition with the ring expansion reactions of these substrates. 

Lactams participate in a number of ring enlargement reactions of different types. Because of the classification in this review they are described at other places too e.g. Sommelet-Hauser rearrangement (Chapter V3). 

Benzylic quaternary ammonium salts, when treated with aUcali-metal amides, undergo a rearrangement called the Sommelet-Hauser rearrangement Since the product is a benzylic tertiary amine, it can be further alkylated and the product again subjected to the rearrangement. This process can be continued aroimd the ring until an ortho position is blocked. ... 

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