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A novel strategy to N-Boc-N-methyl-tryptophans (abrine derivatives) was developed that relies on the palladium-catalyzed annulation of ortho-iodoanilines 12 with either N-Boc-N-methyl-propargylglycine 16 or aldehyde 11. Both 11 and 16 can be prepared from D-serine. An alternative route to propargylglycine 16 utilizes an enantioselective propargylation reaction of glycine imine 17.

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...

The first total synthesis of the natural herbicide MBH-001 (1) is reported. Structurally it is a 2-methyloxazol-5(2H)-one with a (1-hydroxyethyl) substituent at the 2-position. By relying on cyclic nitrones, a flexible route to MBH-001 and relevant analogues was developed. Key steps include the reaction of a 2-hydroxyimino ester with an aldehyde to form a 5-oxo-2,5dihydrooxazole 3-oxide. In an aldol-type reaction, the anion of these cyclic nitrones reacted with an aldehyde at the 2-position.[a] Scheme 1. Retrosynthetic considerations for MBH-001 (1) and the issue of regioselectivity in reactions of oxazolones with electrophiles. Results and DiscussionInitial studies were performed on oxazolone 4b, obtained by the Steglich method from acylated amino acid [6] 10 using water soluble carbodiimide [7] 11 (Scheme 2). Reaction of aromatic aldehydes 12a-c with oxazolone 4b (isomer of 4a) in the presence of triethylamine or diisopropylethylamine (Hünig′s base) provided the desired addition products with the carbinol connected to C2 (Scheme 2). However, preliminary tests showed that these aryl analogues 13a-13c of MBH-001 have no significant herbicidal activity.Unfortunately, the reaction of oxazolone 4b with acetaldehyde under identical conditions took a different course (Scheme 3). Thus, it seems hydroxyalkylation takes places at C4 to form intermediate A. This intermediate could not be isolated since it reacted with another acetaldehyde molecule to intermediate B followed by opening of the oxazolone ring and formation of 1,3-dioxanone 14, whose structure was confirmed by a single-crystal X-ray diffraction. We cannot rule out that other stereoisomers are formed in this transformation. The aldol-like reaction between 4b and acetaldehyde might be diastereo-Eur.

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