SRN1 reactions-synthesis

In the reaction of 1-naphthoxide ions, a mixture of 2- and 4-aryl-, along with 2,4-diaryl-l-naphthol, is formed. However, substitution occurs only at C4 with the 2-Me-substituted anion (50-70% yields) [1[. On the other hand, 2-naphthoxide ions react with ArX to give substitution only at Cj of the naphthalene ring [32, 33]. The reactivity of the 2-naphthoxide ions allows the synthesis of naphthylpyridines, naphthylquinolines, and naphthylisoquinolines via their coupling reactions with the corresponding halo arenes, in good to excellent yields (50-95%) [33], The photostimulated reaction between 2-naphthoxide ions and l-iodo-2-methoxy-naphthalene was explored in liquid ammonia, as a novel approach to the synthesis of [1,1 ] binaphthalenyl-2,2 -diol (BINOL) derivatives (Scheme 10.23). This procedure has also been applied to the synthesis of BINOL in moderate yield (40%), which represents the first report of an SRN1 reaction in water [34]. 

The reactivity of sulfur-centered nucleophiles such as thiourea anion [46] and thioacetate anion [17] in photoinduced SRN1 reaction has been reported as a one-pot, two-step method for the synthesis of several sulfur-aromatic compounds from moderate to good yields. Without isolation, the ArS ions obtained by the aromatic substitution are quenched with Mel to yield ArSMe in a one-pot procedure, together with Ar2S in variable yields, from an SRN1 between ArS- and aryl radicals (Scheme 10.3). 

The synthesis of indoles by the photoinduced substitution reaction of o-haloanilines (22) with carbanions derived from aliphatic ketones in liquid ammonia is an important example of the SRN1 reaction followed by a spontaneous ring closure in the reaction media in moderate to excellent yield (53%-100%) [1]. Although the enolate anions of aromatic ketones do not react in liquid ammonia with 22, they will cyclize to indoles in DM SO under photoinitiation (Scheme 10.44) [60, 61]. 

The synthesis of 3-substituted isoquinolinones and fused isoquinolinones can be performed by the photoinduced SRN1 reactions in DMSO of o-iodobenzamide with the enolates of acyclic aromatic and aliphatic ketones and cyclic ketones, respectively. These reactions proceed from moderate to good yields (Schemes 10.47 and 10.48) [65],... 

The key step in the synthesis of the azaphenanthrene alkaloid eupoulauramine 27 (56% yield) is an intramolecular SRN1 reaction, followed by in situ stilbene photo-cyclization, and further methylation (Scheme 10.52) [68]. 

Rossi, R.A. and Penenory, A.B. (2006) Strategies in synthetic radical organic chemistry, recent advances on cyclization and SRN1 reactions. Current Organic Synthesis, 3, 121-158. 

Uberman, P.M., Martin, S.E. and Rossi, R.A. (2005) Synthesis of functionalized diaryldimethylstannanes from the Me2Sn2 dianion by SRN1 reactions. 

Photochemical aromatic substitution initiated by a reductive step as in SRN1 reactions can be used for the synthesis of cephalotaxinone (15). The corresponding iodoketone precursor cyclizes in liquid ammonia under photolysis [15]. 

Fluoride ion is not a good leaving group in SRN1 reactions. For instance / - fluoroiodobenzene [66c] and 2-fluoro-3-iodopyridine [67] react with carbanions with retention of fluorine. Synthesis of anti-inflammatory drugs, such as fluorobiprophen 39 can be achieved by reaction of 4-bromo-... 

One of the first reports of an intramolecular SRN1 reaction is the synthesis of cephalotaxinone (43). The iodoketone 42 cyclizes in liquid ammonia under photostimulation affording product 43 in excellent yields (Sch. 45). 

The procedure reported here is based on a reaction discovered by Bunnett and Creary, and was first employed for preparative purposes by Bunnett and Traber.3 It is attractive because of the high yield obtained, the ease of work-up, and the cleanliness of the reaction. The reaction is believed to occur by the SRN1 mechanism, which involves radical and radical anion intermediates.2,4 The SRN1 arylation of other nucleophiles, especially ketone enolate ions,5 ester enolate ions,6 picolyl anions,7 and arenethiolate ions,8 has potential application in synthesis. 

Intramolecular nucleophilic substitution by the anions of o-haloanilides is another viable oxindole synthesis. This is a special example of the category Ic process described in Section 3.06.2.3. The reaction is photo-stimulated and the mechanism is believed to be of the electron-transfer type SRN1 rather than a classical addition-elimination mechanism. The reaction is effective when R = H if 2 equivalents of the base are used to generate the dianion (equation 202) (80JA3646). 

For the chemist practicing polysubstituted aromatic and heteroaromatic synthesis, methods steeped in classical electrophilic (1, Scheme 1) [1] and nucleophilic substitution [2] and SRN1 (2) [3] reactions have been joined and, not infrequently super-ceded, by vicarious substitution (3) [4] and by DoM (4) [5] processes. The Murai ortho CH activation (5) [6] is a recently evolving and potential competitive method to the DoM tactic. The 60 years since its discovery by Wittig and Gilman, and 40 years since its systematic study by the school of Hauser, the DoM reaction has advanced by the contributions of Christensen, Beak, Meyers, and many other... 

The synthesis of 6-substituted uracils in a three-step reaction (SRN1—Stille— hydrolysis) is accomplished in good yields using commercial 6-chloro-2,4-dimethox-ypyrimidine as the starting substrate (Scheme 10.33) [49]. 

Arylboronic acids are readily available via transmetalation between ArSnMe3 and borane in THF. Consequently, a variety of arylpolyboronic acids is achievable from the stannanes previously synthesized by the SRN1 mechanism from ArCl or ArOH in around 80% yields [50, 51]. These arene di- and tri-boronic acids can be used as starting materials for the synthesis of polycyclic aromatic systems via double or triple Suzuki crosscoupling reactions [50, 51], as shown in Scheme 10.34 [51],... 

The SRN1 mechanism represents an excellent alternative to accomplishing the following intramolecular cyclization reaction (Scheme 10.42), which constitutes one of the steps in the synthesis of rugulovasines A and B (20, a-H and P-H), novel structures within the family of ergot alkaloids [58]. 

Baumgartner, M.T., Tempesti, T.C. and Pierini, A.B. (2003) Steric effects in the synthesis of ortho-substituted 1,1 -binaphthalene derivatives by the SRN1 and the Stille reaction. ARKIVOK, X, 420 133. 

Corsico, E.F. and Rossi, R.A. (2000) Synthesis of mono-, di-, and tri-phenyl arenes by sequential photostimulated SRN1 and Pd(0)-catalyzed cross coupling reactions on aryl halides. Synlett, 230-232. 

Barolo, S.M., Rosales, C., Angel Gufo, J.E. and Rossi, R.A. (2006) One pot synthesis of substituted dihydroindeno[l,2-fr]indoles and dihydrobenzo[a]carbazoles by photostimulated reactions of o-iodoaniline with carbanions by the SRN1 mechanism. Journal of Heterocyclic Chemistry, 43, 695-699. 

Dichloropyridine reacts in the dark (88% of disubstitution), whereas 2,6- and 3,5-dichloropyridines require photostimulation to afford ca. 80% yield of disubstitution products [26]. Aryltrialkylstannanes are valuable intermediates in organic synthesis, and the fact that they can be easily synthesized through the SRN1 mechanism, opens up important synthetic routes to different reaction schemes. For over a decade, the Pd(0)-catalyzed cross-coupling of organotin compounds with electrophiles, known as the Stille reaction, has been a very important tool in product design [104]. 

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