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The high reactivity of 1,2,4,5-tetrazines 1 relative to donor-substituted C N multiple bondsci1 such as in the hydrazones 2 or cyanamides 3 makes amine-substituted triazines 4 and 5 respectively, surprisingly readily accessible by Diels-Alder addition with inverse electron demandl2]. We have found that the C=N functionality in isocyanides 6 behaves differently: the reaction of la-c with benzyl isocyanide 6 is the first example of a synthesis in which five-membered heterocycles result from a [4 + I]cycloaddition and subsequent [4+ 2]cycloreversion. as 9c (m.p. = 180-181 "C, carbon tetrachloride, yield 75%) are obtained after concentration; crystals of 9b (m. p. = 220°C, ethyl acetate, yield 70%) precipitate out after a short time. lla, b: 9a is completely hydrolyzed to l l a (m. p. = 185 C, ethyl acetate, yield 95%) by addition of water. 9b is hydrolyzed by heating for a short time in conc. hydrochloric acid. Treatment of the hydrochloride with an aqueous solution of potassium carbonate led quantitatively to l l b (m.p.=208"C, ethanol).-9 and 11 gave correct C,H,N analysis results and appropriate spectra (MS, In the initial step, the previously only rarely achieved[31 [4+ l]cycloaddition of 6 to 1, in which the azine system is s-cis-fixed, should dominate over a [4 + 2lcycloaddition.The non-isolable tetraazanorbornadienimine derivative 7, whose high angular strain causes elimination of nitrogen via a [4 + 2]cy~loreversion[~~ in a rapid subsequent reaction, is formed; the resulting energy-rich diazacyclopentadienonimine derivative 8 rapidly tautomerizes to the aromatic pyrazole 9. Hydrolysis of 9a-c leads quantitatively to the pharmacologically interesting aminopyrazoles lla-c. The structures of l l a and l l b were confirmed by independent synthesi~'~]. Hence, e.g., condensation of 12a and 13a also led, after transesterification to l l a , although in considerably lower yield. Procedure 9a-c: la-c (5 mmol) is dissolved in 20 mL of anhydrous dichloromethane, and a solution of 6 (5 mmol) in 10 mL of dichloromethane added dropwise at ca. 0°C; the mixture is left to react until the red color of 1 has disappeared. 9a (m. p. = 161 " C , ethyl acetate, yield 65%) as well A Novel Anionic Five-Coordinate Tris(trichlorostannato)platinum(n) Complex**By Albert0 A fbinati, Ralph Nageli. Heinz Riiegger. and Paul S . Pregosin* Trichlorostannato complexes of platinum(i1) are recognized as useful hydrogenation and hydroformylation catalysts"'. Although the exact composition of the active species is not clear, it is known that the catalyst functions optimally when the ratio Sn : Pt exceeds five, and therefore poly(trich1orostannato) derivatives may be important intermediates. We have recently shown that mono-and bis(trichlorostannato)platinum(lr) complexes containing either tertiary phosphane or arsane ligands are stable in soI~t i o n~~.~] , and now report the synthesis and characterization of the anion

As part of our program aimed at optimizing therapeutic effects over toxic effects (as observed in the naturally occurring nicotinic acetylcholine receptor modulators (-)-nicotine, (-)-epibatidine, (-)-ferruginine, and (+)-anatoxin-a), we investigated the bioisosteric potential of diazines in the field of (+)-anatoxin-a-type structures. In the series of diazine analogues of deschloro-UB-165 (DUB-165, 6), bioisosteric replacement of the 3-pyridyl pharmacophoric element by a 4-pyridazinyl, 5-pyrimidinyl, or 2-pyrazinyl moiety resulted in novel nAChR ligands 7, 8, and 9. A palladium-catalyzed Suzuki cross-coupling of the 3-diethylboranylpyridine (14) and a Stille cross-coupling of the corresponding tributylstannyl diazines 15-17 with the vinyl triflate 13 of the N-protected 9-azabicyclo[4.2.1]nonan-2-one 12 constitute the key steps in the syntheses of these enantiopure anatoxinoids 6-9. Studies of the in vitro affinity for (alpha4)(2)(beta2)(3), alpha3(beta)4, and alpha7 nAChR subtypes by radioligand binding assays demonstrated that the diazine analogues 7-9 can be considered as pharmacologically attractive bioisosteres of DUB-165 (6) but with different effects on the binding affinity with regard to the diazine moiety. The pyrimidine-containing bioisostere 8 turned out to be the most active diazine analogue, which interacts potently (K(i) = 0.14 nM) with the (alpha4)(2)(beta2)(3) subtype and differentiates significantly among the nAChR subtypes investigated. The nitrogens in this anatoxinoid 8 show by far the most negative atomic charges (calculated using the AM1 Hamiltonian). This qualitatively correlates with the highest binding affinity observed for 8 for all subtypes under consideration.

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