Fluorinated alkynes synthesis

One of the very few examples of a four-membered heterocycle with sulfur atoms substituted 1,2 was reported by Dupont workers (60JA1515,61JA3434). Its synthesis involves the high temperature reaction of fluorinated alkynes and elemental sulfur, probably via a diradical intermediate (Scheme 102). The chemistry of these 1,2-dithietenes has been reviewed (76RCR639). As discussed later, these dithietenes form complexes with a number of transition metals. 

Under flash vacuum thermolysis (FVT) the 1,2,3-triazine (32) was readily thermolyzed to an alkyne, a nitrile, and nitrogen in high yields. For unsymmetrically substituted 1,2,3-triazines as FVT substrates, fragmentation proceeded selectively a bulky substituent at C-4(6) made the adjacent C—N bond break more easily than the opposite C—N bond. The FVT method was applied to the synthesis of the fluorinated alkynes, perfluoro-3-methyl-l-butyne and difluoroethyne [(33), R = (CF3)2CF, F] (Equation (1)) (89CC1657, 91CC456). It has been claimed, however, that tris(dimethylamino)-1,2,3-triazine forms the monocyclic azete. 

The FVT method can be applied for the synthesis of the fluorinated alkynes, perfluoro-3-methyl-l-butyne and difluoroethyne 40 (R = (CF3)2CF, F) (Scheme 3) <1989CC1657, 1991CC456>. It has been claimed, however, that tris (dimethylamino)-l,2,3-triazine forms the monocyclic azete. 

Kawamoto, A.M., and Campbell, M.M., A new method for the synthesis of a phosphonic acid analogue of phosphoserine via a novel 1,1-difluorophosphonate intermediate, J. Fluorine Chem.. 81, 181, 1997. Burton, D.J., Naae. D.G., Flynn, R.M., Smart, B.E., and Brittelli, D.R.. Phosphine- and phosphite-mediated difluorocarbene exchange reactions of (bromodifluoromethyl)phosphonium salts. Evidence for facile dissociation of (difluoromethylene)triphenylphosphorane. J. Org. Chem.. 48. 3616, 1983. Li, A.-R., and Chen. Q.-Y., Diethyl iododifluoromethylphosphonate. A new synthetic method and its reaction with alkynes. Synthesis, 606, 1996. 

CoF is used for the replacement of hydrogen with fluorine in halocarbons (5) for fluorination of xylylalkanes, used in vapor-phase soldering fluxes (6) formation of dibutyl decalins (7) fluorination of alkynes (8) synthesis of unsaturated or partially fluorinated compounds (9—11) and conversion of aromatic compounds to perfluorocycHc compounds (see Fluorine compounds, organic). CoF rarely causes polymerization of hydrocarbons. CoF is also used for the conversion of metal oxides to higher valency metal fluorides, eg, in the assay of uranium ore (12). It is also used in the manufacture of nitrogen fluoride, NF, from ammonia (13). 

Fluorinated alkenes and alkynes are highly activated toward nucleophilic attack and reaction with bifunctional nucleophiles is a fruitful area for the synthesis of heterocycles. A review on perfluoroalkyl(aryl)acety-lenes contains many examples (91RCR501). 

These critical aspects of the classical fluorous biphasic catalysis led in recent works to the development of protocols for the conversions with modified catalyst systems in non-fluorinated hydrocarbons as solvents. As part of the BMBE lighthouse project, Gladyzs and coworkers appHed this concept to C - C coupHng reactions (Suzuki reaction) and other metal-catalyzed addition reactions (hydrosilylation, selective alcoholysis of alkynes), which have direct relevance for the synthesis of fine chemicals and specialties [74]. 

A variety of fluorinated alkenyl zinc reagents such as CF2=CFZnCl, CF2=CHZnCl, E and Z-RCF = CFZnCl have been prepared by the first method (Scheme 54). In the presence of palladium catalyst, these fluorinated alkenyl zinc reagents undergo cross-coupling reactions with aryl iodides, vinyl iodides, acid chlorides and 1-iodo-l-alkynes to give the corresponding fluorinated alkenyl derivatives [127, 146-153], which have been utilized in the synthesis of fluorinated codlemones [154]. Typical examples are outlined below (Scheme 55). 

Elimination of two halogen atoms is a frequently used process in the synthesis of alkenes and alkynes, using a variety of conditions, and examples will be given later (see Chapter 7). Normally, fluorine is not easily removed by this process, although there are a number of cases where defluorination has been achieved, for instance in the preparation of fluoroaromatic compounds (Chapter 9). 

Chae, J., Konno, T., Ishihara, T., Yamanaka, H. A facile synthesis of various fluorine-containing indole derivatives via palladium-catalyzed annulation of internal alkynes. Chem. Lett. 2004, 33, 314-315. 

Scheme 1 Synthesis of Fluorinated Indoles from Nitrones and Alkynes...

Cycloaddition of alkynes is an easy and efficient approach towards the synthesis of benzene derivatives [21]. However, fluorine-containing alkynes are rarely shown to undergo such reaction [22]. [RUj(CO)32], with phosphine or some phosphine derivative as additive, is able to cyclotrimer-ize the trifluoromethyl group substituted internal alkynes [23]. Particularly, when 2-(diphenylphosphino)benzonitrile (2-DPPBN) is used, the cyclotrimerized unsymmetrical benzene derivative forms in 77-92% yield with more than 98% regioselectivity depending upon the substituent in Ar... 

Konno T, Chae J, Ishihara T, Yamanaka H (2004) A first regioselective synthesis of 3-fluoroalkylated benzofurans via palladium-catalyzed annulation of fluorine-containing internal alkynes with variously substituted 2-iodophenol. Tetrahedron 60 11695-11700... 

In the last decade, metal-catalyzed intramolecular nitrogen addition to alkynes has been introduced as a new methodology for the preparation of pyrazole derivatives. Liu, Xu and co-workers [29] have developed a mild and efficient protocol for the synthesis of 4-fluorinated pyrazoles via gold(l)-catalyzed tandem aminofluorination of alkynes 53 in the presence of Selectfluor (Scheme 16). In all cases (except for R-=H), mixtures of 4-fluorinated 54 and nonfluorinated pyrazoles 55 (54 55=2.1 1... 

Qian J, Liu Y, Zhu J, Jiang B, Xu Z (2011) A novel synthesis of fluorinated pyrazoles via gold(I)-catalyzed tanem aminofluorination of alkynes in the presence of selectfluor. Oig Lett 13 4220-4223... 

Rama Rao WVNS, Lingaiah BPV, Yadla R, Shanthan Rao P, Ravikumar K, Swamy GYSK, Narsimuluc K (2006) Synthesis of fluorine containing N-benzyl-1,2,3-triazoles and N-methyl-pyrazoles from conjugated alkynes. J Heterocycl Chem 43 673-679... 

Xie H, Zhu J, Chen Z, Li S, Wu Y (2010) Synthesis of 2-trifluoromethyl quinoline by the reaction of fluorinated imine with alkyne cattdyzed by indium(III) triflate. Synlett 2010(17) 2659-2663... 

Amii H, Kishikawa Y, Uneyama K (2001) Rh(I)-catalyzed coupling cycUzation of N-aryl trifluoroacetimidoyl chlorides with alkynes one-pot synthesis of fluorinated quinoUnes. Org Lett 3 1109-1112... 

An unusual approach to the synthesis of chain-fluorinated diazines relies on the inverse-electron-demand hetero-Zretro-Diels - Alder ihDA/rDA) sequence. The background of this method for the preparation of nitrogen-containing heterocycles in general has been reviewed recently [674], Typical dienes used for the synthesis of chain-fluorinated diazines are given in Fig. 29. Since electron-deficient dienes are necessary for the first step of the sequence - inverse-electron-danand hetero-Diels -Alder reaction, fluoroalkyl substituents of tri- and tetrazines 1111-1112 are favorable for the process. Typical electron-rich dienophiles for the reactions with 1111-1112 are enamines (including amino heterocycles) and alkynes, although other examples are also known. 

Besset T, Poisson T, Pannecoucke X (2015) Direct vicinal difunctionalization of alkynes an efficient approach towards the synthesis of highly functionalized fluorinated alkenes. Eur J Org Chem 13 2765-2789... 

Abstract Recent developments in the stereoselective synthesis of fluoroalkenes, which include hydrofluorination of alkyne, fluorination of alkenylmetal, condensation methods, dehydrofluorination of cm-difluoro compounds, and a cross-coupling reaction using fluorohaloalkenes or fluoroalkenylmetal, are described in this chapter. 

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