Redox Reaction of the Pd0 Complex Bearing the Trost Ligand with meso‐Cycloalkene‐1,4‐biscarbonates Leading to a Diamidato PdII Complex and 1,3‐Cycloalkadienes: Enantioselective Desymmetrization Versus Catalyst Deactivation

The Pd⁰ complex 1 that bears the Trost ligand 2 undergoes a facile redox reaction with 1,4‐biscarbonates 5 b – d and rac‐ 22 under formation of the diamidato–Pd^II complex 7 and the corresponding 1,3‐cycloalkadienes 8 b – d . The redox deactivation of complex 1 was the dominating pathway in the reaction of 5 b – d with HCO₃^? at room temperature. However, at 0 °C the six‐membered biscarbonate 5 b , catalytic amounts of complex 1 , and HCO₃^? mainly reacted in an allylic alkylation, which led to a highly selective desymmetrization of the substrate and gave alcohol 6 b with ≥99 % ee in 66 % yield. An increase of the catalyst loading in the reaction of 5 b with 1 and HCO₃^? afforded the bicyclic carbonate 12 b (96 % ee, 92 %). Formation of carbonate 12 b involves two consecutive inter‐ and intramolecular substitution reactions of the π‐allyl–Pd^II complexes 16 b and 18 b , respectively, with O‐nucleophiles and presumably proceeds through the hydrogen carbonate 17 b as key intermediate. The intermediate formation of 17 b is also indicated by the conversion of alcohol rac‐ 6 b to carbonate 12 b upon treatment with HCO₃^? and 1 . The Pd⁰‐catalyzed desymmetrization of 5 b with formation of 12 b and its hydrolysis allow an efficient enantioselective synthesis of diol 13 b . The reaction of the seven‐membered biscarbonate 5 c with ent‐ 1 and HCO₃^? afforded carbonate ent‐ 12 c (99 % ee, 39 %). The Pd⁰ complex 1 is stable in solution and suffers no intramolecular redox reaction with formation of complex 7 and dihydrogen as recently claimed for the similar Pd⁰ complex 9 . Instead, complex 1 is rapidly oxidized by dioxygen to give the stable Pd^II complex 7 . Thus, formation of the Pd^II complex 10 from 9 was most likely due to an oxidation by dioxygen. Oxidative workup (air) of the reaction mixture stemming from the desymmetrization of 5 c catalyzed by 1 gave the Pd^II complex 7 in high yield besides carbonate 12 c .     

Synthesis of N'-substituted amidines through the cleavage an oxadiazolone heterocycle by weakly basic nucleophiles. Effect of the nature of the nucleophile and of the nucleophile/substrate molar ratio

The reaction of 1-ethoxycarbonylmethyl-5,5,7,7-tetramethyl-2-oxo-tetrahydroimidazo[1,5-b]oxadiazol-6-oxyl with the weakly basic nucleophiles NaN₃, NaCN, KF, KBr, KCl and NaNO₂ has been studied. It was shown for the first time that, as in the case of NaOH and MeONa, the reaction occurs with opening of the oxadiazolone ring to form exo-N-substituted amidines. It was shown that the weakly basic nucleophiles readily react with substrates which contain a substituent sensitive to attack by such nucleophiles as NaOH or MeONa. The effect of the nature of the nucleophiles on the reaction course for opening of the oxadiazolone ring was also studied. It was found that the reactivity of the nucleophiles in DMSO changes in the series F⁻ > CN⁻ > N₃^– >NO₂⁻ > Cl⁻ > Br⁻ and qualitatively correlates with their basicities in this solvent. Examination of the effect of the ratio of the reagents on the degree of conversion of the starting oxadiazolone has shown that a quantity of nucleophiles less than one equivalent also allowed the cleavage reaction of the oxadiazolone heterocycle to go to completion through just increasing the reaction time. The experimental data obtained lends support to the proposed reaction scheme. Dedicated to Academician B. A. Trofimov in his 70^th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 71–78, January, 2009.     

Reactions of 2,2,4,4-tetramethyl-1,3-cyclobutanedione with amines and other nucleophiles. II

The reaction of 2,2,4,4-tetramethyl-1,3-cyclobutanedione with various nucleophiles has been demonstrated to be dependent on the reaction conditions, steric factors and the nucleophilicity of the attacking species. In the reaction with primary amines the intermediate has been established as the N-substituted imine which is hydrolyzed to the corresponding amide in the presence of water. The reaction of diamines with the dione has been shown to be a method of synthesizing 2-substituted imidazolines and 1 H-4,5-dihydropyrimidines.     

Ring‐Opening Reactions of 3‐Aryl‐1‐benzylaziridine‐2‐carboxylates and Application to the Asymmetric Synthesis of an Amphetamine‐Type Compound

Nucleophilic ring‐opening reactions of 3‐aryl‐1‐benzylaziridine‐2‐carboxylates were examined by using O‐nucleophiles and aromatic C‐nucleophiles. The stereospecificity was found to depend on substrates and conditions used. Configuration inversion at C(3) was observed with O‐nucleophiles as a major reaction path in the ring‐opening reactions of aziridines carrying an electron‐poor aromatic moiety, whereas mixtures containing preferentially the syn‐diastereoisomer were generally obtained when electron‐rich aziridines were used (Tables 1–3). In the reactions of electron‐rich aziridines with C‐nucleophiles, S_N2 reactions yielding anti‐type products were observed (Table 4). Reductive ring‐opening reaction by catalytic hydrogenation of (+)‐trans‐(2S,3R)‐3‐(1,3‐benzodioxol‐5‐yl)aziridine‐2‐carboxylate (+)‐trans‐ 3c afforded the corresponding α‐amino acid derivative, which was smoothly transformed into (+)‐tert‐butyl [(1R)‐2‐(1,3‐benzodioxol‐5‐yl)‐1‐methylethyl]carbamate((+)‐ 14 ) with high retention of optical purity (Scheme 6).     

Reactions of Di(tert‐butyl)diazomethane with Acceptor‐Substituted Ethylenes

Di(tert‐butyl)diazomethane ( 4 ) is a nucleophilic 1,3‐dipole with strong steric hindrance at one terminus. In its reaction with 2,3‐bis(trifluoromethyl)fumaronitrile ((E)‐ BTE ), a highly electrophilic tetra‐acceptor‐substituted ethene, an imino‐substituted cyclopentene 9 is formed as a 1 : 2 product. The open‐chain zwitterion 10 , assumed as intermediate, adds the second molecule of (E)‐ BTE . The ¹⁹F‐ and ¹³C‐NMR spectra allow the structural assignment of two diastereoisomers, 9A and 9B . The zwitterion 10 can also be intercepted by dimethyl 2,3‐dicyanofumarate ( 11 ) and furnishes diastereoisomeric cyclopentenes 12A and 12B ; an X‐ray‐analysis of 12B confirms the ‘mixed’ 1 : 1 : 1 product. Competing is an (E)‐ BTE ‐catalyzed decomposition of 4 to give 2,3,4,4‐tetramethylpent‐1‐ene ( 7 )+N₂; the reaction of (E)‐ BTE with a trace of water appears to be responsible for the chain initiation. The H₂SO₄‐catalyzed decomposition of diazoalkane 4 , indeed, produced the alkene 7 in high yield. The attack on the hindered diazoalkane 4 by 11 is slower than that by (E)‐ BTE ; the zwitterionic intermediate 21 undergoes cyclization and furnishes the tetrasubstituted furan 22 . In fumaronitrile, electrophilicity and steric demand are diminished, and a 1,3‐cycloaddition produces the 4,5‐dihydro‐1H‐pyrazole derivative 25 . The reaction of 4 with dimethyl acetylenedicarboxylate leads to pyrazole 29 +isobutene.     

Substitution in the hydantoin ring. Part IX. N-cyanohydantoins

The N₁-and N₃-cyanohydantoins, a new series of derivatives, were prepared by reaction of the parent hydantoin with a base and a cyanogen halide. Analysis of ir, pmr, and mass spectral data allowed the assignment of ring position-3 to the cyano group in derivatives IIa,b of 1,3-unsubstituted hydantoins. 3-Cyanohydantoins can transfer the cyano substituent to strong nucleophiles via an addition-elimination process.     

Simple Procedure for the Synthesis of 5,7-Diarylpyrido[2,3-d]pyrimidine Derivatives catalyzed by KF-Alumina

A simple KF/Al₂O₃-catalyzed reaction of 1,3-diaryl-2-propen-1-one and 2,6-diamino-4-hydroxylpyrimidine in ethyl alcohol gave aromatized 5,7-diarylpyrido[2,3-d]pyrimidine derivative by air oxidation. On the other hand, the unaromatized intermediate products were isolated under dry nitrogen successfully. A possible reaction mechanism with two pathways to lose water was proposed based on the further experimental results; one of them was confirmed by ¹H NMR spectra of isolated intermediate product.     

Nucleophilic Addition Reactions of Tricarbonyl [η5−1-(Phenylsulfonyl)cyclohexadienyl]iron(I) Complex

Hydride abstraction of tricarbonyl[η⁴-1-(phenylsulfonyl)-1,3-cyclohexadiene]iron(0) complex 2 with Ph₃C⁺PF₆^? regiospecifically provided the title compound 3 in excellent yield. Cationic complex 3 could react with a variety of nucleophiles in good yields. Soft nucleophiles prefer to attack at the C-5 position, whereas hard nucleophiles such as methyllithium and the enolate of ethyl acetate gave the C-5 as well as the C-2 addition products. Some synthetic applications of the addition products were also studied.     

Fast and Cysteine-Specific Modification of Peptides,Proteins and Bacteriophage Using Chlorooximes

This work reports a novel chlorooxime mediated modification of native peptides and proteins under physiologic conditions. This method features fast reaction kinetics (apparent k₂=306±4 M⁻¹s⁻¹ for GSH) and exquisite selectivity for cysteine residues. This cysteine conjugation reaction can be carried out with just single-digit micromolar concentrations of the labeling reagent. The conjugates show high stability towards acid, base, and external thiol nucleophiles. A nitrile oxide species generated in situ is likely involved as the key intermediate. Furthermore, a bis-chlorooxime reagent is synthesized to enable facile Cys-Cys stapling in native peptides and proteins. This highly efficient cysteine conjugation and stapling was further implemented on bacteriophage to construct chemically modified phage libraries.     

Synthesis of Peptides by Silver‐Promoted Coupling of Carboxylates and Thioamides: Mechanistic Insight from Computational Studies

The mechanism of the recently described N→C direction peptide synthesis through silver‐promoted coupling of N‐protected amino acids with thioacetylated amino esters was explored by using density functional theory. Calculation of the potential energy surfaces for various pathways revealed that the reaction proceeds through silver‐assisted addition of the carboxylate to the thioamide, which is followed by deprotonation and silver‐mediated extrusion of sulfur as Ag₂S. The resulting isoimide is the key intermediate, which subsequently rearranges to an imide through a concerted pericyclic [1,3]‐acyl shift (O–sp²N 1,3‐acyl migration). The proposed mechanism clearly emphasises the requirement of two equivalents of Ag^I and basic reaction conditions, which is in full agreement with the experimental findings. Alternative rearrangement pathways involving only one equivalent of Ag^I or through O–sp³N 1,3‐acyl migration can be excluded. The computations further revealed that peptide couplings involving thioformamides require significant conformational changes in the intermediate isoformimide, which slow down the rearrangement process.     

Dehydrotropylium-Co2(CO)6 ion: generation, reactivity and evaluation of cation stability

The dehydrotropylium–Co₂(CO)₆ ion was generated by the action of HBF₄ or BF₃ ? OEt₂ on the corresponding cycloheptadienynol complex, which in turn has been prepared in four steps from a known diacetoxycycloheptenyne complex. The reaction of the cycloheptadienynol complex via the dehydrotropylium–Co₂(CO)₆ ion with several nucleophiles results in substitution reactions with reactive nucleophiles (N>1) under normal conditions, and a radical dimerisation reaction in the presence of less reactive nucleophiles. Competitive reactions of the cycloheptadienynol complex with an acyclic trienynol complex show no preference for generation of the dehydrotropylium–Co₂(CO)₆ ion over an acyclic cation. DFT studies on the dehydrotropylium–Co₂(CO)₆ ion, specifically evaluation of its harmonic oscillator model of aromaticity (HOMA) value (+0.95), its homodesmotic‐reaction‐based stabilisation energy (≈2.8 kcal mol^?1) and its NICS(1) value (?2.9), taken together with the experimental studies suggest that the dehydrotropylium–Co₂(CO)₆ ion is weakly aromatic.     

Hydrogen rearrangement in molecular ions of alkyl benzenes: Mechanism and time dependence of hydrogen migrations in molecular ions of 1, 3-diphenylpropane and deuterated analogues

Hydrogen migrations in the molecular ions of 1,3-diphenylpropane, preceding the fragmentations to [C₇H₇]⁺ and [C₇H₈]⁺ ions, have been investigated by use of deuterated derivatives. By comparing the distribution of deuterium labels in the [C₇(H, D)₈]⁺ products from metastable molecular ions with the distribution patterns calculated for various exchange models, it is shown that the H migrations occur by two processes linked by a common intermediate: (i) exchange between hydrogen isotopes at the γ-methylene group and at the ortho positions of the phenyl group: (ii) exchange between hydrogen isotopes at the ortho and orthó positions in the intermediate. In these mechanisms the eight hydrogen isotopes at both benzylic positions and both the ortho and orthó positions of 1,3-diphenylpropane participate in a mutual exchange. A statistical equipartition of the hydrogen isotopes at these eight positions is not reached in metastable molecular ions, however. The distribution pattern of [C₇(H, D)₈]⁺ ions from the deuterium labelled compounds as a function of the mean number n of exchange cycles has been calculated according to this reaction model and compared with experimental results for unstable molecular ions, generated by 70 eV and 12 eV electrons, respectively, and metastable molecular ions. Good agreement is obtained for all compounds and n = 0.4–0.8 for unstable molecular ions and n = 5–8 for metastable ions. Therefore, the hydrogen exchange in the molecular ion of 1,3-diphenylpropane is a rather slow process. These results firmly establish the isomerization reaction involving the conversion of the molecular ion of 1,3-diphenylmethane to the intermediate and hence to the molecular ion of 7-(2-phenylethyl)-5-methylene cyclohexa-1,3-diene and preceding the fragmentations. The postulated intermediate is a true one which corresponds to a s?-complex type ion and which fragments to [C₇H₈]⁺ ions. Surprisingly, no isomerizations of the intermediate by hydrogen shifts within the protonated aromatic system (‘ring walks’) are observed.     

Dérivés C-glycosyliques. VII. Synthèse et réactions de nitrones dérivées de sucres. Communication préliminaire

The syntheses of three types of sugar nitrones (aldonitrone, ketonitrone and α-β unsaturated aldonitrone) are described. On 1,3-dipolar cycloaddition with phenylacetylene, the aldonitrone gave two Δ₄-isoxazolines epimeric at the new asymetric carbon, while the same reaction on the ketonitrone led to a spiro-Δ₄-isoxazoline. The reaction of these nitrones with carbon nucleophiles like phenylethynylmagnesium bromide constitutes a novel chain-extension reaction in carbohydrate chemistry.     

Unkatalysierte sigmatrope 1,5-Wanderung von Acylgruppen bei der Thermolyse von 5-Acyl-5-methyl-1,3-cyclohexadienen

Uncatalyzed Sigmatropic 1,5-Shift of Acyl Groups in the Thermolysis of 5-Acyl-5-methyl-1,3-cyclohexadienes Four different 5-acyl-5-methyl-1,3-cyclohexadienes 1a–d (R = COOCH₃, COCH₃, COC₆H₅, CHO) have been shown to yield mixtures of 1,3-disubstituted cyclohexadienes 2–7 and 1,3-disubstituted aromatic product 8 upon thermolysis at 150–300° in solution and at 350–500° in the gas phase in a flow system. Two reaction pathways (A and B in Scheme 2) are considered for the rearrangement of the C-Skeleton. For the ester 1a ¹³C-isotopic substitution shows that products arise to 75–86% through a 1,5-sigmatropic shift of the methoxycarbonyl group ( A in Scheme 2) and to 14–25% through a sequence of reaction steps involving a 1,7-H-shift reaction in an acyclic intermediate ( B in Scheme 2). For the more reactive compounds 1b–d isomerization is assumed to follow the 1,5-sigmatropic pathway exclusively ( A in Scheme 2). A kinetic study yields the following sequence for the migration tendency of acyl groups toward sigmatropic 1,5-shift: COOCH₃ < COCH₃ < COC₆H₅ < CHO.     

Rhodium(I)-NHC Complexes Bearing Bidentate Bis-Heteroatomic Acidato Ligands as gem-Selective Catalysts for Alkyne Dimerization

A series of Rh(κ²-BHetA)(η²-coe)(IPr) complexes bearing 1,3-bis-hetereoatomic acidato ligands (BHetA) including carboxylato (O,O), thioacetato (O,S), amidato (O,N), thioamidato (N,S), and amidinato (N,N), have been prepared by reaction of the dinuclear precursor [Rh(μ-Cl)(IPr)(η²-coe)]₂ with the corresponding anionic BHetA species. The Rh^I-NHC-BHetA compounds catalyze the dimerization of aryl alkynes, showing excellent selectivity for the head-to-tail enynes. Among them, the acetanilidato-based catalyst has shown an outstanding catalytic performance reaching unprecedented TOF levels of 2500 h⁻¹ with complete selectivity for the gem-isomer. Investigation of the reaction mechanism supports a non-oxidative pathway in which the BHetA ligand behaves as proton shuttle through intermediate κ¹-HBHetA species. However, in the presence of pyridine as additive, the identification of the common Rh^IIIH(C≡CPh)₂(IPr)(py)₂ intermediate gives support for an alternative oxidative route.     

Reactions of Nucleophiles with Reactive Intermediates in the 3,4,6‐Tri‐O‐benzyl‐d‐glucal–TfOH–n‐Bu4NI Reaction System

The unique reactive intermediate formed in the 3,4,6‐tri‐O‐benzyl‐d‐glucal–TfOH (triflic acid)–n‐Bu₄NI reaction system (in dichloromethane) reacted with nucleophiles in a regio‐ and stereoselective manner. These selectivities resulted in hitherto unknown compounds, such as benzyl 4,6‐di‐O‐benzyl‐2,3‐dideoxy‐3‐iodo‐α‐glucopyranoside, which was obtained in the presence of an iodide ion as a nucleophile. The corresponding 2‐deoxy α‐glycosides were obtained exclusively in the corresponding reaction with hydroxylic nucleophiles.     

Exploring the Border between Concerted and Two‐Step Pathways of 1,3‐Dipolar Cycloadditions of Organic Azides to Cyclic Ketene N,X‐Acetals. – Synthesis and 15N‐NMR Spectra of Zwitterions and Spirocyclic Cycloadducts

Cyclic ketene N,X‐acetals 1 are electron‐rich dipolarophiles that undergo 1,3‐dipolar cycloaddition reactions with organic azides 2 ranging from alkyl to strongly electron‐deficient azides, e.g., picryl azide ( 2L ; R¹=2,4,6‐(NO₂)₃C₆H₂) and sulfonyl azides 2M – O (R¹=XSO₂; cf. Scheme 1). Reactions of the latter with the most‐nucleophilic ketene N,N‐acetals 1A provided the first examples for two‐step HOMO(dipolarophile)–LUMO(1,3‐dipole)‐controlled 1,3‐dipolar cycloadditions via intermediate zwitterions 3 . To set the stage for an exploration of the frontier between concerted and two‐step 1,3‐dipolar cycloadditions of this type, we first describe the scope and limitations of concerted cycloadditions of 2 to 1 and delineate a number of zwitterions 3 . Alkyl azides 2A – C add exclusively to ketene N,N‐acetals that are derived from 1H‐tetrazole (see 1A ) and 1H‐imidazole (see 1B , C ), while almost all aryl azides yield cycloadducts 4 with the ketene N,X‐acetals (X=NR, O, S) employed, except for the case of extreme steric hindrance of the 1,3‐dipole (see 2E ; R¹=2,4,6‐(^tBu)₃C₆H₂). The most electron‐deficient paradigm, 2L , affords zwitterions 16D , E in the reactions with 1A , while ketene N,O‐ and N,S‐acetals furnish products of unstable intermediate cycloadducts. By tuning the electronic and steric demands of aryl azides to those of ketene N,N‐acetals 1A , we discovered new borderlines between concerted and two‐step 1,3‐dipolar cycloadditions that involve similar pairs of dipoles and dipolarophiles: 4‐Nitrophenyl azide ( 2G ) and the 2,2‐dimethylpropylidene dipolarophile 1A (R, R=H, ^tBu) gave a cycloadduct 13 H , while 2‐nitrophenyl azide ( 2 H ) and the same dipolarophile afforded a zwitterion 16A . Isopropylidene dipolarophile 1A (R=Me) reacted with both 2G and 2 H to afford cycloadducts 13G , J ) but furnished a zwitterion 16B with 2,4‐dinitrophenyl azide ( 2I) . Likewise, 1A (R=Me) reacted with the isomeric encumbered nitrophenyl azides 2J and 2K to yield a cycloadduct 13L and a zwitterion 16C , respectively. These examples suggest that, in principle, a host of such borderlines exist which can be crossed by means of small structural variations of the reactants. Eventually, we use ¹⁵N‐NMR spectroscopy for the first time to characterize spirocyclic cycloadducts 10 – 14 and 17 (Table 6), and zwitterions 16 (Table 7).     

Influence of Cu(II) Ions on the Mechanism of the Ring Transformation of S‐(2‐Oxotetrahydrofuran‐3‐yl)‐N‐(4‐methoxyphenyl)isothiouronium Bromide

The effect of additional Cu(II) ions on the rate of transformation of S‐(2‐oxotetrahydrofuran‐3‐yl)‐N‐(4‐methoxyphenyl)isothiouronium bromide ( 1 ) into 5‐(2‐hydroxyethyl)‐2‐[(4‐methoxyphenyl)imino]‐1,3‐thiazolidin‐4‐one ( 2 ) has been studied in aqueous buffer solutions. The reaction acceleration in acetate buffers is caused by the formation of a relatively weakly bonded complex (K_c = 600 L·mol^?1) of substrate with copper(II) acetate in which the Cu(II) ion acts as a Lewis acid coordinating the carbonyl oxygen and facilitating the intramolecular attack, leading to the formation of intermediate T^±. The formation of the complex of copper(II) acetate with free isothiourea in the fast preequilibrium (K_c) is followed by the rate‐limiting transformation (k_Cu) of this complex. At the high concentrations of the acetate anions, the reaction is retarded by the competitive reaction of these ions with copper(II) acetate to give an unreactive complex [Cu(OAc)₄]^2?_. The influence of Cu(II) ions on the stability of reaction intermediates and the leaving group ability of the alkoxide‐leaving group compared to the Cu(II)‐uncatalyzed reaction is also discussed.     

Carbon-phosphorus bond formation and transformation in the reaction of 1,2-diaza-1,3-butadienes with alkyl phenylphosphonites

The reaction of 1,2-diaza-1,3-butadienes with dialkyl phenylphosphonites under solvent-free conditions proceeds via zwitterionic intermediate and gives, by precipitation, the stable ylidic α-phosphanylidene-hydrazones that, in turn, can be transformed into the corresponding 3-phenyl-2H-1,2,3λ⁵-diazaphospholes. The latter compounds are converted by hydrolytic cleavage in methanol-water (95:5) into E-hydrazonophosphonates that are useful for the preparation of the corresponding β-ketophosphonates and 4-[alkoxy(phenyl)phosphoryl]-1,2-diaza-1,3-butadienes. These peculiar 1,2-diaza-1,3-butadienes, bearing an alkoxy(phenyl)phosphoryl group on the carbon atom in position 4 are also able to add different nucleophiles, such as methanol or thiourea, giving 2-[alkoxy(phenyl)phosphoryl]-2-methoxyhydrazones and 5-phosphinate-substituted thiazol-4-ones, respectively.     

Umsetzung von Diazoessigsäure-ethylester mit 1,3-Thiazol-5(4H)-thionen

Reaction of Ethyl Diazoacetate with 1,3-Thiazole-5(4H)-thiones Reaction of ethyl diazoacetate ( 2a ) and 1,3-thiazole-5(4H)-thiones 1a,b in Et₂O at room temperature leads to a complex mixture of the products 5–9 (Scheme 2). Without solvent, 1a and 2a react to give 10a in addition to 5a–9a . In Et₂O in the presence of aniline, reaction of 1a,b with 2a affords the ethyl 1,3,4-thiadiazole-2-carboxylate 10a and 10b , respectively, as major products. The structures of the unexpected products 6a, 7a , and 10a have been established by X-ray crystallography. Ethyl 4H-1,3-thiazine-carboxylate 8b was transformed into ethyl 7H-thieno[2,3-e][1,3]thiazine-carboxylate 11 (Scheme 3) by treatment with aqueous NaOH or during chromatography. The structure of the latter has also been established by X-ray crystallography. In the presence of thiols and alcohols, the reaction of 1a and 2a yields mainly adducts of type 12 (Scheme 4), compounds 5a,7a , and 9a being by-products (Table 1). Reaction mechanisms for the formation of the isolated products are delineated in Schemes 4–7: the primary cycloadduct 3 of the diazo compound and the C?S bond of 1 undergoes a base-catalyzed ring opening of the 1,3-thiazole-ring to give 10 . In the absence of a base, elimination of N₂ yields the thiocarbonyl ylide A ′, which is trapped by nucleophiles to give 12 . Trapping of A ′, by H₂O yields 1,3-thiazole-5(4H)-one 9 and ethyl mercaptoacetate, which is also a trapping agent for A ′, yielding the diester 7 . The formation of products 6 and 8 can be explained again via trapping of thiocarbonyl ylide A ′, either by thiirane C (Scheme 6) or by 2a (Scheme 7). The latter adduct F yields 8 via a Demjanoff-Tiffeneau-type ring expansion of a 1,3-thiazole to give the 1,3-thiazine.