Herstellung von Dihydro-, Tetrahydro- und Hexahydrochelidamsäure-Derivaten

Preparation of dihydro-, tetrahydro- and hexahydro-chelidamic-acid derivatives. Three methods for the preparation of 4-oxo-2,6-piperidine-dicarboxylic acid ( 3 ) and derivatives, required as a synthon for betalaine pigments, were explored. The best method was found to be the catalytic hydrogenation of chclidamic acid ( 1 ) with 5% Rh/Alox in water under 2.7 atm. H₂ for 33 h at 70° and subsequent esterification with methanol which gave 42% of cis, cis-4-hydroxy-2,6-piperidine- ( 7 ) and 10% of 2,6-cis-piperidine-dicarboxylic acid dimethyl ester ( 8 ), readily separable by chromatography. Oxidation of 7 with dimethylsulfoxide and a carbodiimide attached to a polymer afforded 90% of 4-oxo-2,6-cis-piperidine-dicarboxylic acid dimethyl ester ( 19 ). Other methods of oxydizing 7 to 19 were less successful. The electrochemical reduction of 1 followed by esterification with methanol led in a low yield to a mixture of 4-oxo-0-2,6-trans-piperidine-dicarboxylic acid dimethylester ( 24 ), its dimethyl acetal 25 and presumably trans-4-hydroxy-r-2, cis-6-piperidine-dicarboxylic acid dimethyl ester ( 26 ). Reaction of 4-oxo-hepta-2E, 5E-dienoic acid ( 35 ) with aqueous ammonia gave a 98% yield of a 3 : 2 mixture of cis- and trans-ammonium-4-oxo-2, 6-piperidine-dicarboxylate ( 39 and 40 ). The above mentioned catalytic hydrogenation method was also applied to N-ethyl-chelidamic acid ( 16 ) to give a 4:6 mixture of the N-ethyl derivatives 17 and 18 . Furthermore, a number of functional derivatives of 5 , of 19 , of 39 and of 40 were prepared. Oxidation of the hydroxy-diester 7 with dimethylsulfoxide and a carbodiimidc derivative in the presence of trifluoroacetic acid afforded 4-oxo-1,2,3,4-tetrahydro-2, 6-pyridine-dicarboxylic acid dimethyl ester ( 50 ). This ester was also obtained under the same conditions from thc keto-diester 19 .     

Triaziridine. 9. Mitteilung. Ringöffnungen von Triaziridinen

Triaziridines. Ring Openings of Triaziridines Eleven triaziridine derivatives were heated at 60° in CDCl₃ to obtain information on the tendency towards, resp. the resistance to, ring opening of the N₃-homocycle by thermolysis. Among these triaziridines, there are three which contain, as one of the substituents, a methoxycarbonyl group (ester derivatives 1 , 5 and 16 ), three a methyl group (methyl derivatives 18 , 24 , and 26 ), three an H-atom ( 14 , 27 , and 30 ), and two a negative charge ( 31 and 32 ). The other two substituents in each of these four classes of triaziridines are trans-located i-Pr groups ( 1 , 18 , 27 , and 31 ), cis-located i-Pr groups ( 5 , 24 , 14 , and 32 ), and a 1,3-cis-cyclopentylidene group ( 16 , 26 , and 30 ). As major products these mild thermolyses, we isolated : from the trans-ester 1 and from the annellated ester derivative 16 , the 1-acyl-azimines 2 and 17 , respectively, from the cis-ester 5 , the 3-acyl-triazene 4 , from the trans-methyl derivative 18 , the (E)-diazene 19 , and hexamine 21 , from the cis-methyl derivative 24 the 2-methylazimine 25 , both from the trans- and cis-H-derivatives 27 , and 14 , respectively, the H- triazene 13 and, finally, both from the trans-and cis-anion 31 and 32 , respectively – after protonation the H-triazene 13 and – after methylation – the methyl-triazene 33 . The same thermolysis of the annellated methyl and H-derivatives 26 and 30 , respestively, resulted only in decomposition. These results can be uniformly interpreted with a primary opening of the triaziridine ring by rupture of one of the two types of N? N bonds lending to azimines or triazenide anions. Some of the azimines were isolable, namely 2 , 17 , and 25 , and one was spectroscopically observable as an intermediate, namely 11 on the way to the triazene 4 . The other azimines are plausible intermediates to the isolated products, namely 15 on the way to 13 , and 22 on the way to 19 and 21 . The triazenide anion 28 is the evident intermediate on the way to 13 or to 33 . The annellated azimines are assumed not be formed from 26 and 30 , or then to be be decomposed under the conditions of their formation. We conclude that the triaziridine derivatives 1, 16 , and 18 underwent thermal ring opening between N(1) and N(2), while the derivatives 5 , 14 , 24 , 27 , 31 , and 32 were ruptured between N(2) and N(3); no conclusion was possible on the ring opening of the derivatives 26 and 30 . The predominant formation of the (Z)-azimine 2 from the trans-triaziridine 1 , and of the (E)-isomer 3 – among the two azimines – from the cis-triaziridine 5 suggests a stereospecificity in the triaziridine ring openings. This would, however, not be expected to be observable in the products from the other triaziridines, since both N? N bonds of the azimine 25 and of the anion 28 probably rotate rapidly and since the secondary trans formations of the other primary products are not able to retain configurational information.     

Methyl (<Emphasis Type="Italic">Z</Emphasis>)-3-bromo-3-(4-methylbenzenesulfonyl)prop-2-enoate: Synthesis and reactions with dimethyl malonate and methyl acetoacetate

Bromination–dehydrobromination of methyl (E)-3-(4-methylbenzenesulfonyl)prop-2-enoate gave methyl (Z)-3-bromo-3-(4-methylbenzenesulfonyl)prop-2-enoate whose structure was determined by X-ray analysis. Methyl (Z)-3-bromo-3-(4-methylbenzenesulfonyl)prop-2-enoate behaved as a synthetic equivalent of methyl 3-(4-methylbenzenesulfonyl)prop-2-ynoate in reactions with dimethyl malonate and methyl acetoacetate, which afforded the corresponding Michael adducts, trimethyl 3-(4-methylbenzenesulfonyl)prop-1-ene-1,1,2-tricarboxylate and dimethyl (Z)-2-acetyl-3-(4-methylbenzenesulfonyl)but-2-enedioate, respectively, via nucleophilic attack on the β-position with respect to the sulfonyl group.     

Synthesen von 2-Pyronen aus α, β-ungesättigten Säurechloriden und tertiären Aminen

A new synthesis of 2-pyrones has been developed. Two molecules of α, β-unsaturated acid chlorides ( 8 , 12 and 18 ) condense, with loss of two molecules hydrogen chloride, to pairs of substituted 2-pyrones ( 9 and 10 , 13 and 14 , 19 and 20 ) when treated with triethyl amine in chloroform or methylene chloride at room temperature. In the case of 18 , two additional products were obtained, namely the resorcinol derivative 21 and traces of the 1, 3-cyclobutanedione derivative 22 . Under the same conditions the α, β-unsaturated acid chlorides 8 , 15 , 18 and 41 were condensed with trichloroacetyl chloride to give 6-trichloromethyl-2-pyrones ( 42 , 43 , 44 and 46 ). These 2-pyrones are valuable intermediates for the synthesis of 6-carboxy-2-pyrones and 6-methyl-2-pyrones. A methyl group in β-position of the α, β-unsaturated acid chloride appears to be essential for the described condensations, for the acid chlorides 16 and 17 did not yield defined products and the acid chloride 40 reacted with trichloroacetyl chloride in a very low yield. It is considered that the described reactions proceed via the 1, 4-addition of an acid chloride to a vinyl ketene or through the acylation of an intermediate anion by an acyl derivative as outlined in reaction scheme 1. The structures of the 2-pyrones were confirmed by their spectroscopic properties, summarized in table 3, and by some of their chemical transformations.     

Reactions of Zinc Enolates Formed from 1-Aryl-2-bromo-2-phenylethanone or 2-Bromoindanone and Zinc,with Dimethyl 2-(1-Arylmethylene)malonates

Zinc enolates formed from 1-aryl-2-bromo-2-phenylethanones and zinc react with dimethyl 2-(1-arylmethylene)malonates to afford dimethyl 2-(1,3-diaryl-3-oxo-2-phenylpropyl)malonates. The latter react with cyclohexylamine, piperidine, or morpholine to give the corresponding monosubstituted amides. The zinc enolate derived from 2-bromoindanone and zinc reacts with dimethyl 2-(4-bromobenzylidene)malonate, yielding dimethyl 2-[(4-bromophenyl)(1-oxoindan-2-yl)methyl]malonate. The final products largely form as a single diastereomer.     

Photochemical Reactions. Part 67. photochemistry of saturated aliphatic and cyclic β-keto sulfoxides (Cα?S)- and α-cleavage – A new case of photostereomutation

The photochemical behaviour of saturated aliphatic ( 2, 4 , and 5 ) and bicyclic ( 18 and 19 ) β-keto sulfoxides has been studied. Photostereomutation of the sulfoxide group was observed on irradiation of 4a, 4b, 18 , and 19 . Most likely an internal energy transfer from the excited carbonyl to the sulfoxide group is operating on direct irradiation of such compounds. Prolonged photolysis of an aliphatic β-keto sulfoxide, which is nonalkylated a t the α-carbon ( 2 ), yielded a product due to preferential (C_α-S)-cleavage ( 24 ). Mono- ( 4 ) and dialkylated- ( 5 , 6 , and 8 )analogues primarily afforded products due to α-cleavage ( 26–31 and 32 ). The carboxylic acid S-methylesters ( 26–31 ) were exclusively formed by an intermolecular path. Prolonged irradiation of the bicyclic β-keto sulfoxides 18 and 19 favored the formation of a desulfurized compound 34 due to initial ( C_α-S )-cleavage.     

Desoxy-nitrozucker. 3. Mitteilung. Synthese von Ketosen durch Kettenverlängerung von 1-Desoxy-1-nitro-aldosen. Nucleophile Additionen und Solvolyse von Nitroaethern

Synthesis of Ketoses by Chain Elongation of 1-Deoxy-1-nitroaldoses. Nucleophilic Additions and Solvolysis of Nitro Ethers A method for the preparation of chain elongated uloses based upon the base-catalyzed addition of 1-deoxy-1-nitroaldoses to aldehydes and Michael acceptors and subsequent solvolytic replacement of the nitro group by a hydroxy group is described. Thus, addition of 1 , 3 and 9 to formaldehyde, followed by solvolysis gave the chain elongated ulose derivatives 2 , 8 and 10 (63–76%), respectively. The configuration at the anomeric center of the addition products was deduced from ¹³ C – NMR . spectra and mutarotation. In the case of 3 , the primary addition products 4 and 6 were isolated and acetylated to 5 and 7 . The nitro derivatives 4 – 7 do not follow Hudson's rule of isorotation. Addition of 1 to benzaldehyde (44%) and to nonanal (74%) preceded with a small degree of diastereoselectivity to give 15a / 15b , and 11 / 12 , respectively. The configuration of the secondary hydroxyl group of 12 was determined by correlation with methyl 2-hydroxydecanoate ( 14 ). Addition of 1 to the galacroaldehyde 16 gave a single compound 17 (78%). The structure of this dodecosulose was determined by X-ray crystallography. Solvolysis of the acetylation product 18 in formamide gave the hemiacetal 19 (69%). Michael addition of 1 to acrylonitrile, methyl vinyl ketone and cyclohexenone under solvolytic conditions gave the hemiacetals 27 , 30 and 31a , b (49%, 71% and 76%, respectively). Under non-solvolytic conditions (Bu₄NF), 1 reacted with acrylonitrile, and crotononitrile to give the anomeric nitro ethers 23 and 24 (67%) and 25 and 26 (84%). respectively. Similarly. 3 added to acrylonitrile to give 28 and 29 (55%, 4:1). This reaction appears to proceed under kinetic control. Addition of 1 to ethyl propiolate and solvolysis yielded the unsaturated spirolactone 32 (50%) and the hemiacetal 33 (17%). Hydrogenation of 32 gave the saturated spirolactone 34 (100%) which was also obtained from 1 and methyl acrylate (63%). Addition of 1 to dimethylmaleate gave the unsaturated ester 35 (48%).     

Die Wohl-Ziegler-Bromierung von Tiglin- und Angelika-säureestern

The Wohl-Ziegler bromination (with N-bromo-succinimide = NBS) of methyl tiglate ( 1b ) gave a 2:1 mixture of methyl γ-bromotiglate ( 3b ) and methyl β′-bromotiglate ( 5b ). This ratio of γ- to β′-bromination was unaffected by changes of solvent, catalyst or size of the ester alkoxy group. The same products were obtained from the NBS treatment of methyl angelate ( 2b ). This NBS-bromination appears to be thermodynamically controlled, since both angelic and tiglic acid as well as their methyl esters were brought into equilibrium ( 1 ? 2 = > 9:1) with catalytic amounts of NBS.     

Doppelt und dreifach funktionalisierte,enantiomerenreine C4-Synthesebausteine aus β-Hydroxybuttersäure, Äpfelsäure und Weinsäure

Enantiomerically Pure Synthetic Building Blocks with Four C-Atoms and Two or Three Functional Groups from β-Hydroxy-butanoic, Malic, and Tartaric Acid The pool of chiral, non-racemic electrophilic building blocks, which are available from simple natural products in both enantiomeric forms is enlarged by the epoxides 3, 5 , and 10 , by the tosylate 12a , and by the aldehydes 18 (cf. symbols A-D , 14 , and Scheme 1). Key steps of the conversions leading from hydroxyacids to the building blocks are: epoxide-opening by triethylborohydride ( 1 → 2a ) and tosylate reduction ( 12a → 12b ); the Mitsunobu inversion ( 2a → 4a ); the reduction of (R, R)-tartaric ester to (R)-malic ester by NBS (N-bromosuccinimide) opening of the benzaldehyde acetal 8 and tin hydride reduction ( 6c → 7c ); the enantiomer enrichment of optically active ethyl β-hydroxy-butanoate through the crystalline dinitrobenzoate 21b . Detailed procedures are given for large scale preparations of the key intermediates. The enantiomeric purities of the building blocks are secured by correlations.     

Oxidative Addition of Dimethyl Malonate to Styrenes Mediated by Cerium(Iv) Ammonium Nitrate: Some Novel Observations

The oxidative addition of dimethyl malonate to ring substituted styrenes leads to the formation of substituted dimethyl (2-oxo-2-phenylethyl) malonate and methyl 2-oxo-5-phenyltetrahydrofuran-3-carboxylate along with small amounts of substituted dimethyl [2-(nitrooxy)-2-phenylethyl] malonate and dimethyl 2-methoxy-2-phenylethyl) malonate. A tentative mechanism which supports the formation of these products is also presented.     

Über die Strukturaufklärung von (Hydroxy-oxo-cyclopentenyl)alkansäuren,den Aldolkondensationsprodukten von Dioxoencarbonsäuren aus Rinderleber

Structure Elucidation of (Hydroxy-oxo-cyclopentenyl)alkanoic Acids, the Aldol-Condensation Products of Dioxoene Acids from Cattle Liver During homogenization of cattle liver the highly instable dioxoene acids 13a , 13b , and 13c are formed. These acids cyclize in alkaline solution to yield pairs of stable (hydroxy-oxo-cyclopentenyl)alkanoic acids, which were isolated as methyl esters 4a / 5a , 4b / 5b , and 4c / 5c . The structures of these compounds were deduced from an enriched 3-mg mixture sample by microchemical reactions combined with a GC/MS analysis of the reaction products. Compound 13a was obtained as methyl ester by oxidation of the methyl ester of the corresponding F-acid with NaOCl. It was not possible to isolate 13a in pure form due to its high sensitivity. Instead of the methyl ester of 13a , 4a and 5a were isolated, of which the structures were established.     

Synthesis of 5,6-dihydroxy-2-phenyl-4-pyrimidinecarboxylic acid,methyl ester,a corrected structure

Pyrolysis of the adduct of benzamide oxime and dimethyl acetylenedicarboxylate leads to 5,6-dihydroxy-2-phenyl-4-pyrimidinecarboxylic acid methyl ester ( 4a ) rather than 4,5-dihydro-α,4-dioxo-2-phenyl-1H-imidazole-5-acetic acid, methyl ester ( 1 ).     

Reactions of hydro(pero)xy derivatives of polyunsaturated fatty acids/esters with nitrite ions under acidic conditions. Unusual nitrosative breakdown of methyl 13-hydro(pero)xyoctadeca-9,11-dienoate to a novel 4-nitro-2-oximinoalk-3-enal product

13(S)-hydroperoxy- and 13(S)-hydroxyoctadeca-9,11-dienoic acids (1a/b), 15(S)-hydroperoxy- and 15(S)-hydroxyeicosa-5,8,11,13-tetraenoic acids (2a/b), and their methyl esters reacted smoothly with NO2- in phosphate buffer at pH 3-5.5 and at 37 degrees C to afford mixtures of products. 1b methyl ester gave mainly the 9-nitro derivative 3b methyl ester (11% yield) and a peculiar breakdown product identified as the novel 4-nitro-2-oximinoalk-3-enal derivative 4 methyl ester (15% yield). By GC-MS hexanal was also detected among the products. Structures 3b and 4 methyl esters were secured by 15N NMR analysis of the products prepared from 1b methyl ester upon reaction with Na15NO2. 4 methyl ester (14% yield) was also obtained from 1a methyl ester along with the nitrated hydroperoxy derivative 3a methyl ester (10% yield). Under the same conditions, 2a/b methyl esters gave mainly the corresponding nitrated derivatives 5a/b, with no detectable breakdown products, whereas the model compound (E,E)-2,4-hexadienol (6) afforded two main nitrated derivatives identified as 7 and 8. A reaction pathway for 1a/b methyl esters was proposed involving conversion of nitronitrosooxyhydro(pero)xy intermediates which would partition between two competing routes, viz., loss of HNO2, to give 3a/b methyl esters, and a remarkably facile fission leading to 4 methyl ester and hexanal.     

Differences in the crystal structures of two dialkyl diester triphenyl­phospho­nium ylids

Hydrogen bonding and crystal packing play major roles in determining the conformations of ethyl methyl 2‐(triphenyl­phospho­ranyl­idene)malonate, Ph₃P=C(CO₂CH₃)CO₂CH₂CH₃ or C₂₄H₂₃O₄P, (I), and dimethyl 2‐(triphenyl­phosphor­anyl­idene)malonate, Ph₃P=C(CO₂CH₃)₂ or C₂₃H₂₁O₄P, (II). In (I), the acyl O atom of the ethyl ester group is anti to the P atom, while the O atom of the methyl ester group is syn. In (II), the dimethyl diester is a 1:1 mixture of anti–anti and syn–anti conformers.     

5‐Unsubstituted Pyrido[3,2,1‐jk]carbazol‐6‐ones: Syntheses,Substitution, and Cyclization Reactions

The synthesis of the 5‐unsubstituted pyrido[3,2,1‐jk]carbazol‐6‐one 4 can be achieved by the reaction of carbazole ( 1 ) and malonate derivatives, either in a three‐step synthesis via 5‐acetyl‐pyridocarbazolone 3 or in a one‐step reaction from 1 and malonic acid/phosphoryl chloride. The 5‐acetyl derivative 5 can be transformed via a tosylate intermediate to 4‐azido‐pyridocarbazolone 11 , which cyclizes by thermal decomposition to the isoxazolo‐pyrido[3,2,1‐jk]carbazolone 12 . The thermolysis conditions were investigated by DSC. Nitration of pyridocarbazolone 4 and subsequent introduction of azide leads to azido derivative 23 , which cyclizes on thermolysis to furazan‐oxide derivative 24 . Again, the thermolysis conditions were investigated by DSC. 5‐Chloro‐5‐nitro‐pyrido[3,2,1‐jk]carbazole‐4,6‐dione, obtained from 4 by subsequent nitration and chlorination, forms by exchange of both 5‐substituents 5,5‐dihydroxy‐pyridocarbazoledione 17 , which acylates phenol to give 5‐hydroxy‐5‐(p‐hydroxyphenyl)‐pyridocarbazoledione 20 . Acid‐catalyzed cyclodehydration of 20 forms a highly fused benzofuro‐pyridocarbazole 21 . Another C–C coupling at position 5 starts from 4‐chloro‐5‐nitro‐pyridocarbazolone 22 and diethyl malonate 2a , which forms the diethyl (nitrocarbazolyl)malonate 25 . With dimethyl malonate 2c , the intermediate dimethyl (nitrocarbazolyl)malonate gives on thermolysis the (nitrocarbazolyl)acetate 27 by loss of one ester group.     

Ozonolyse von Olefinen,III: Säurekatalysierte Ozonolyse von 3-Hexen-1,6-und 2-Penten-1,5-dicarbonylderivaten

Summary The ozonolysis of mono-unsaturated compounds containing the structural element =CH-CH₂-R [R=COOH, COOCH₃, CH(OCH₃)₂] was investigated. Reductive ozonolysis of (E)-3-hexene-1,6-dioic acid gives methyl 3,3-dimethoxypropanoate (2), whereas ozonolysis of dimethyl (E)-3-hexene-1,6-dioate (1a) and (Z)-1,1,6,6-tetramethoxy-3-hexene (1b) in a methanolic solution of HCl leads to a mixture of2, dimethyl malonate (3 a) and 1,1,3,3-tetramethoxypropane (3 b). The homologuos derivatives, dimethyl glutaconate (4 a) and 1,1,5,5-tetramethoxy-2-pentene (4 b), were ozonized to give mixtures of2, 3, dimethyl oxalate (5), methyl 2,2-dimethoxyacetate (6 a), and 1,1,2,2-tetramethoxyethane (6 b). The ratios of the various reaction products were determined by gas chromatography. In each case the formation of the bifunctional derivatives2 and6 a was favoured.

     

Zur Photochemie von 3,5-Diaryl-2-isoxazolinen. 30. Mitteilung über Photoreaktionen

Irradiation of 3,5-diphenyl- or 3-(p-tolyl)-5-phenyl-2-isoxazoline ( 12 and 13 , respectively) in benzene with a high-pressure mercury lamp yields 4,5-diphenyl- or 4-(p-tolyl)-5-phenyl-3-oxazoline ( 17 and 19 , respectively) and the β-amino-chalcones 18 or 20 in addition to benzaldehyde, benzonitrile and p-tolunitrile, respectively (scheme 6 and ‘Anmerkg.’ p. 2600). The 3-oxazolines 17 and 19 are formed by route a (scheme 8) via 3-phenyl- or 3-(p-tolyl)-2H-azirine ( 23 , R = H and CH₃, respectively) and their photochemically rearranged successors, the nitrile methylides 24 , as intermediates. The discovery of this reaction has served as a basis for the quickly developing photochemistry of 3-aryl-2H-azirines [2] [24]. Photolysis of the 2-isoxazoline 13 in methanol leads to the formation of a mixture of syn/anti-p-tolyl trans-styryl ketoximes (syn/anti, trans- 30 ) and anti, cis- 30 , 2-(p-tolyl)-quinoline ( 29 ), the 4-hydroxymethylated derivative 32 of the latter (in small amounts), besides the β-aminochalcone 20 , benzaldehyde, p-tolualdehyde and p-tolunitrile (scheme 9). It could be shown that the stereoisomeric ketoximes 30 are photochemically interconvertible (scheme 12) and that at least one mechanism of formation of 2-(p-tolyl)-quinoline ( 29 ) is the photo-induced cyclisation of p-tolyl-cis-styryl ketoximes (cis- 30 ) (scheme 13). A tentative mechanism for the formation of p-tolual-dehyde is given in scheme 10; the crucial step is the protonation of p-tolunitrile methylide ( 24 , R = CH₃) by methanol at the nitrile carbon atom, after which hydrolysis yields the aldehyde.     

Ester dienolate [2,3]-Wittig rearrangement in natural product synthesis: diastereoselective total synthesis of the triester of viridiofungin A, A2, and A4

[structure: see text] An ester dienolate [2,3]-Wittig rearrangement was utilized to access the alkylated citric acid skeleton 6 that is characteristic for the viridiofungins and other members of the alkyl citrate family of secondary natural products. The [2,3]-sigmatropic rearrangement of (Z,Z)-15 provided the rearrangement product (+/-)-syn-16 in moderate yield and with very good diastereoselectivity. A Julia-Kocienski olefination efficiently served to connect the polar head (+/-)-syn-26 with the lipophilic tail (32a-c) of the viridiofungins. Amide formation between the racemic viridiofungin precursors 35a-c and the enantiomerically pure amino acid L-tyrosine methyl ester followed by preparative reversed-phase HPLC provided the isopropyl dimethyl ester of viridiofungin A ((+)-39a), A2 ((+)-39b), and A4 ((+)-39c) as well as the nonnatural diastereomers (-)-38a-c.     

Reaction of cyclic imidates with α,β‐unsaturated esters: Synthesis of new pyrrolo[2,1‐b]‐1,3‐oxazine and pyrido[2,1‐b]‐1,3‐oxazine derivatives

The cycloaddition reaction of cyclic imidates, 2‐benzyl‐5,6‐dihydro‐4H‐1,3‐oxazines 1a , 1b , 1c , 1d , 1e , 1f , with dimethyl acetylenedicarboxylate 2 , trimethyl ethylenetricarboxylate 4 , or dimethyl 2‐(methoxymethylene)malonate 6 afforded new fused heterocyclic compounds, such as methyl (6‐oxo‐3,4‐dihydro‐2H‐pyrrolo[2,1‐b]‐1,3‐oxazin‐7‐ylidene)acetates 3a , 3b , 3c , 3d , 3e , 3f (71–79%), dimethyl 2‐(6‐oxo‐3,4,6,7‐tetrahydro‐2H‐pyrrolo[2,1‐b]‐1,3‐oxazin‐7‐yl)malonates 5b , 5c , 5d , 5e , 5f (43–71%), or methyl 6‐oxo‐3,4‐dihydro‐2H,6H‐pyrido[2,1‐b]‐1,3‐oxazine‐7‐carboxylates 7a , 7b , 7c , 7d , 7e , 7f (32–59%), respectively. In these reactions, 1a , 1b , 1c , 1d , 1e , 1f (cyclic imidates, iminoethers) functioned as their N,C‐tautomers (enaminoethers) 2 to α,β‐unsaturated esters 2 , 4, and 6 to give annulation products 3 , 5 , and 7 following to the elimination of methanol, respectively. J. Heterocyclic Chem., (2011).     

Palladium-catalyzed asymmetric alkylation of 2-azaallyl acetates for the synthesis of β-carboxyaspartic acid derivatives

Palladium-catalyzed asymmetric alkylation of 2-azaallyl acetate, N-(diphenylmethylene)acetoxyglycine ester with a sodium salt of malonate ester was successfully carried out. High enantioselectivities were achieved using sodium dimethyl methylmalonate (98%ee) or sodium dimethyl malonate (93%ee) as a nucleophile with t-butyl ester of 2-azaallyl acetate in the presence of (S)-BINAP in acetonitrile.