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The first example of catalyst-free tandem acetalization/ 5-exo-dig cyclization reactions of 6-phenylethynylpyrimidine-5-carbaldehydes is presented. Efficient novel synthesis of 5,7-dihydrofuro[3,4-d]pyrimidine core is described.Functionally substituted alkynes are versatile intermediates in the synthesis of heterocyclic or carbocyclic compounds. 1 A literature survey revealed that carbonyl group on alkynes could undergo transition-metal-catalyzed or electrophile-induced 5-exo-dig and/or 6-endo-dig cyclization reactions (Scheme 1). Scheme 1 Literature results overview.Several years ago, Yamamoto et al. reported an interesting reaction of acetylenic aldehydes with alcohols catalyzed by palladium. 2 The Pd(II) salt employed was claimed to exhibit a dual role of both as a Lewis acid and a transitionmetal catalyst. In a more recent study, the analogous cyclization of the same acetylenic carbonyl precursors with nucleophiles was achieved in the presence of Cu(I), 3 Cu(II), 3 Ag(I), 4 Au(I), 4 Au(III) 4 salts, bis(pyridine)iodonium tetrafluoroborate (IPy 2 BF 4 ) 5 and HBF 4 . 5 Recently, Prof. Larock's group found that o-(1-alkynyl)-substituted arene carbonyl compounds treated with electrophiles, such as NBS, I 2 , ICl, PhSeBr, 4-NO 2 C 6 H 4 SCl and various alcohols or carbon-based nucleophiles underwent smooth three-component reaction to form highly substituted oxygen heterocycles. 6 It was shown, that electrophiles attacked the triple bond of the starting compounds, therefore nucleophilic attack of neighboring carbonyl oxygen became more favorable.During continuation of our research aimed on the use of 6-arylethynylpyrimidines in the synthesis of fused pyrimidine derivatives 7 we have found that 6-phenylethynylpyrimidine-5-carbaldehydes underwent smooth cyclization reactions during refluxing in alcohols in the presence of bases to form 5-alkoxy-(7Z)-7-benzylidene-5,7-dihydrofuro[3,4-d]pyrimidines in good yields. We were surprised that these reactions took place easily without any transition-metal catalysts or electrophilic initiator, so herein we wish to report our results on the tandem acetalization/5-exo-dig cyclization reactions of the title compounds.Compounds 2a-k were synthesized by the palladium-catalyzed Sonagashira coupling of the corresponding 4-substituted 6-chloropyrimidine-5-carbaldehydes 8 1a-k with phenylacetylene. The best yields of 2a-k were obtained when the reactions were carried out in DMF in presence of triethylamine under argon at 40 °C (Scheme 2).Following our ongoing efforts towards the synthesis of pyrido[4,3-d]pyrimidine derivatives, 7c we were intrigued on finding that, while performing the synthesis of intermediate tert-butylimine by the reaction of 2a with an equivalent of tert-butylamine in boiling methanol, the formation of unexpected colorless product 3a was observed. Neither IR nor 13 C NMR spectra of 3a showed the presence of C≡C or C=O group in the molecule. In the 1 H NMR spectra of the obtained product two new singlets at d = 6.48 and 6.64 ppm along with a singlet of methoxy gro...

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