3.4- Pyridyne generation

Dehydropyridine (pyridyne) generated by dehydrohalogenation of 3- or 4-halopyridine with hard bases in the presence of methanethiol (38) gives equimolar amounts of 3- and 4-methylthiopyridines predominantly. 

The triazolo[4,5-d]pytimidine nucleoside 12 was obtained, albeit in low yield, by cyclization of tri-O-benzoyl-P-D-ribofuranosyl azide with 2-r-butyl-4-pyridyne generated in situ - ... 

The data described above give sound evidence for the existence of 3,4-pyridyne but do not indicate that 2,3-pyridyne occurs as an intermediate. The generation and reactivity of 3,4-pyridyne and some of its derivatives are discussed next. Section II, A, 3 deals with problems concerning 2,3-pyridyne. 

In 57 a bromine migration possibly competes with the generation of 4-ethoxy-2,3-pyridyne (58), induced by the abstraction of a hydrogen ion from C-2 of 57 (cf. the isomerization of 1,2,4-tribromobenzene to... 

Quinolynes are generated and behave analogously to pyridynes. The reaction of 3-bromo-4-chloro- and 3-bromo-2-chloro-quinoline with lithium amalgam in the presence of furan gives phenanthridine (83, 9% yield) and acridine (85, 0.1% yield), respectively, via 3,4-... 

Diels-Alder reaction of the furoindole 544 with 3,4-pyridyne (1193), generated in situ via two different ways, led to a mixture of the two possible cycloadducts 1194 and 1195 in approximately equal amounts. Without purification, the crude adducts 1194 and 1195 were treated with basic sodium borohydride (NaBH4) to afford a separable mixture of ellipticine (228) and isoellipticine (1196) in 23% and 29% yield, respectively (527) (Scheme 5.197). 

Pyridynes are also commonly generated from orf/io-dihalogenopyridines by lithium exchange processes, e.g. Scheme 138, and processes not involving halogenopyridines, e.g. thermal decomposition of pyridinediazonium carboxylates. 

In 1972 Berry and co-worker detected 3,4-pyridyne (101) by MS. Trapping experiments also provided evidence for the existence of this intermediate, although the chemistry of 101 differs considerably from that of o-benzyne. Thus, neither anthracene nor dimethylfulvene form Diels-Alder adducts with 101. Nam and Leroi were able to generate 101 in nitrogen matrices at 13 K and characterized it by IR spectroscopy. Irradiation of 3,4-pyridinedicarboxylic anhydride (103) with 1 > 340 nm results in formation of 101, which upon short wavelength photolysis (k > 210 nm) fragments to buta-l,3-diyne (104) and HCN, and to acetylene (105) and cyanoacetylene (106, Scheme 16.24). The assignment of an intense... 

Similarly, 4-lithiated 3-bromo and 3-chloro pyridines generated from substrates 40, are stable between -60 and -40°C, and lithium halide elimination to 2-fluoro-3,4-pyridyne occurs only upon warming to room temperature, as evidenced by the formation of adduct 41 (Scheme 13) [72CR(C)(275)1439, 72CR(C)(275)1535]. 

Direct formation of aza-anthraquinones 181 has been achieved using in situ generated lithio cyanophthalide 177 (a 1,4-dipole equivalent) and 3,4-pyridyne 178 (Scheme 52) [88H(27)2643]. Thus, addition of 3-bromopyridine derivative to a solution of LDA and 177 at -40°C leads, when warmed to room temperature, to aza-anthraquinones 181 in good yields via intermediates 179 and 180. This type of reaction has also been applied to 4-bromoquinoline to give benzo[rf]-2-azaanthraquinone in 60% yield [88H(27)2643]. 

The scope of this methodology is restricted to the generation of 3,4-pyridyne. To date, analogous formation of 2,3-pyridyne from 2-halopyridines has not been reported. 

May and Moody (52) have reported a full account of their Diels-Alder cycloaddition route to ellipticine (1) and isoellipticine (27) (Scheme 10). Conversion of indole (50) to 3-indole-2-propionic acid (56) with lactic acid was followed by a Plieninger cyclization to the pyranoindole 57. Reaction of 57 with 3,4-pyridyne (59), as generated from triazene 58, afforded equal amounts of ellipticine (1) and isoellipticine (27). Although the overall yield of 1 from indole is only 3%, the sequence involves only three steps. 

Directed lithiation. 2-Arenesulfonyl benzamides are deprotonated in a re-gioselective fashion, furnishing thioxanthen-9-one 10,10-dioxides in good yields (57-96%). 3-Halopyridines, including the iodo compounds, manifest directed o-lithiation and regioselective reaction (at C-4) with electrophiles. It should be noted that 3-chloro-4-iodopyridine generates 3,4-pyridyne on treatment with either BuLi or f-BuLi. Halogen dance is also observed. ... 

The most recent successful method for generating 3-pyridynes uses 4-trialkylsilyl-3-pyridyl triflates as precursors (a similar approach but with a bromine in place of the triflate group is considerably less successful). They were synthesized by o-metallation... 

---