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New heterotricyclic systems, 6,10a,11,11a-tetrahydro-5H-bis[1,2,4]oxadiazolo[4,5-d:5′,4′-g][1,4]diazepines 6,7,9-11 and 5,6,10,10a,11,11a-hexahydro-1H-bis[1,2,4]triazolo[4,3-d:3′,4′-g][1,4]diazepines 8,12 have been obtained by double site- and regie-specific 1,3-dipolar cycloaddition of mesitylnitrile oxide (1) or diphenylnitrile imine (2) to 5,7-disubstituted 2,3-dihydro-1H-1,4-diazepines 3-5. The structure of the synthesized bis-adducts 6-12 shows that the hetero double bonds are much more reactive than the olefinic ones in the dipolarophiles under study. No evidence for the formation of mono-adducts was obtained.

This review (56 references) provides a comprehensive survey of the literature on sulfenic acid chemistry from 1990 through June 2006, focusing the attention on salient aspects of their structures and involvement in organic processes. Even if the majority of known sulfenic acids cannot be isolated, some stable ones have been obtained, and their study helped dramatically the comprehension of chemical and physical properties of all sulfenic acids and indirectly of the role that Cys-SOHs play in protein biochemistry. Many papers have been published in the last fifteen years about the sulfenic acid intermediacy in organic chemistry. Once generated, they can be involved in intraand intermolecular additions to unsaturated molecules. Few examples of sulfenic acid addition to double bonds have been recently described and most of them are intramolecular processes, whereas the addition of enantiopure sulfenic acids onto carbon-carbon triple bonds has been widely exploited in the synthesis of vinyl sulfoxides to be used in many stereoselective transformations. The thermic -elimination from sulfinyl precursors is a way to generate sulfenic acids but it has been also used for removing the sulfinyl moiety from organic molecules and forming double bonds with controlled stereochemistry. Some significant applications of extrusion processes are also described in the present review.

[reaction: see text] l-Cysteine is a stimulating starting product for the generation of transient sulfenic acids, such as 4, 6, 9, and 15, which add to suitable acceptors, allowing formation of sulfoxides showing a biologically active residue. These sulfoxides are easily isolated in enantiomerically pure form. For instance, N-(tert-butoxycarbonyl)-l-cysteine methyl ester (1a) furnished in few steps sulfenic acid 9a, which was readily converted into (R,S(S))-(2-tert-butoxycarbonylamino-2-methoxycarbonyl-ethylsulfinyl)ethene (22), the methyl ester of Boc-protected nor-alliin. Moreover, the addition of 9a to 2-methyl-1-buten-3-yne has led to a sulfur epimeric and separable mixture of (R)-2-(2-tert-butoxycarbonylamino-2-methoxycarbonyl-ethylsulfinyl)-3-methyl-buta-1,3-dienes 10a and 11a, still possessing a "masked" sulfenic acid function, producible from their cysteine moieties once the dienes have been converted into the desired derivatives.

This account is intended to provide a brief survey on our contribution in the field of enantiopure sulfinyl homo and hetero dienes which we are able to obtain via enantiopure sulfenic acids. The chemistry of these sulfinyl-dienes was mainly developed taking into account the practical importance of stereoselective homo and hetero Diels-Alder cycloadditions, able to supply useful intermediates in the synthesis of target molecules.

A mild, efficient and seemingly general method for converting α,β-unsaturated sulfoxides into carbonyl compounds by means of trimethylsilyl iodide (TMSI) is described. Experiments on different substrates and trimethylsilyl halides lead to the conclusion that the oxidation state of the sulfur atom, on one hand, and halogen kind in TMSX on the other, assume a determining role in the progression of the reaction. The ease of experimental procedure, the possibility of 1H NMR monitoring, and good yields of final products constitute advantages of the TMSI-promoted conversion of α,β-unsaturated sulfoxides into carbonyl compounds.

The addition of enantiopure sulfenic acids to oxoalkynes constitutes a new and efficient methodology for the synthesis of β-sulfinyl α,β-unsaturated carbonyl compounds. Sulfenic acids 3 and 4 were generated by thermolysis of suitable precursors and trapped in situ by oxoalkynes 5, affording (RS,E)- and (SS,E)-3-alkylsulfinyl-1-phenyl-2-propen-1-ones, 4-alkylsulfinyl-3-buten-2-ones, and 3-[(1S)-isoborneol-10-sulfinyl]-2-propenoates 6 and 7 in good yields and in enantiomerically pure form after simple column chromathography. (RS,E)-3-[(1S)-isoborneol-10-sulfinyl]-1-phenyl-2-propen-1-one (6Ra) was involved as a heterodiene in inverse-electron-demanding Diels−Alder reactions with readily available electron-rich dienophiles 14 and 15, corroborating in each case the sulfinyl auxiliary capability in controlling the stereochemical outcome of these cycloadditions. Furthermore, the addition of methylmagnesium iodide to the carbonyl moiety of 6Ra demonstrated that the chiral sulfur atom exerts a remote stereocontrol...

LiClO 4 catalyzed cycloaddition of (R S ,E)-3-[(1S)-isoborneol-10-sulfinyl]-1-methoxybuta-1,3-diene 1 with ethyl glyoxalate occurred with good endo and facial diastereoselectivities to give (2R,6S,R S )-6-ethoxycarbonyl-4-[(1S)-isoborneol-10-sulfinyl]-2-methoxy-5,6-dihydro-2H-pyran 2 as the main product, easily isolated as crystalline material in high yield.

Simple syntheses of enantiopure (E)- and (Z)-3-(alkylsulfinyl)-1-methoxy-1,3-butadienes 2 and 3 were provided by the addition of (1S)-isoborneol-10-sulfenic and (S)-phenyl-2-hydroxyethanesulfenic acids 8 to (E)- and (Z)-1-methoxybut-1-en-3-ynes (9) and (10). These additions proceeded with asymmetric induction, the extent of which depended upon the nature of the chiral hydroxyalkyl group. Cycloadditions of methyl acrylate to the enantiopure dienes proceeded with complete regioselectivity and very high stereoselectivity when catalyzed by lithium perchlorate or zinc chloride in dichloromethane. The chirality at sulfur controlled the diastereofacial selectivity in these Diels−Alder cycloadditions.

The title compound, C24H34O6S, (I), is an enantiopure sulfinyl adduct, prepared via stereocontrolled Diels–Alder cyclo­addition. The solid-state structure of (I) has been determined at room temperature by single-crystal X-ray diffraction. It is chemically similar to other cited structures; however, it presents a peculiar packing arrangement. Ab initio, density-functional theory (DFT) and semi-empirical (AM1, PM3 and PM5) full-geometry optimizations were carried out for (I). Calculated values of the structural parameters have been compared with those obtained by X-ray crystallography.

Enantiopure 1-methoxy-3-(1-phenyl- and 2-phenyl-2-hydroxyethylsulfinyl)-1,3-butadienes were prepared from ethyl mandelate. Diels-Alder reactions with methyl acrylate proceeded with complete regioselectivity and high diastereoselectivity.

Cycloadditions of methyl acrylate to (R S )- and (S S )-(E)-3-[(1S)-isobornyl-10-sulfinyl]-1-methoxy-buta-1,3-dienes in dichloromethane, catalysed by lithium perchlorate or zinc chloride, proceeded with complete regioselectivity and high stereoselectivity. Chirality at sulfur controlled diastereofacial selectivity.

Uncatalyzed cycloadditions of (RS,E)-1 and (RS,Z)-3-[(1S)-isoborneol-10-sulfinyl]-1-methoxybuta-1,3-diene 2 with maleimide and N-phenylmaleimide occurred with complete endo and very high facial diastereoselectivities. The effects of Lewis acid catalysis on these Diels–Alder reactions have been evaluated. LiClO4 catalyzed cycloaddition of 1 with dimethyl maleate gave cyclohexene 13 as the unique product with complete control of endo and π-facial diastereoselectivities exerted by the sulfinyl group. A significant improvement in diastereoselectivity was also observed in the LiClO4 catalyzed cycloaddition of 1 with dimethyl fumarate.

Uncatalyzed cycloadditions of enantiopure [(1 S )-isoborneol-10-sulfinyl]- and [(1 S - exo )-2-bornylsulfinyl]vinylcyclohexenes with N -phenylmaleimide occur with good facial diastereoselectivity, controlled by the sulfur configuration, even if the extent of this stereoselection appears influenced by the structural features of the terpene residue directly linked to the sulfoxide moiety. Complete endo diastereoselectivity is observed in LiClO 4 catalyzed cycloadditions of ( R S )-1-{1-[(1 S )-isoborneol-10-sulfinyl]- and ( S S )-1-{1-[(1 S-exo )-2-bornylsulfinyl]vinyl}cyclohexenes 4 and 5 , respectively. The Diels–Alder reactivity of 5 and ( S S , E )-1-{2-[(1 S-exo )-2-bornylsulfinyl]vinyl}cyclohexene 7 , with the chiral auxiliary being in a different position with respect to the diene moiety, is also compared, and the results obtained comfirm that 1-sulfinyldienes are less reactive than 2-sulfinyldienes. SnCl 4 catalyzed cycloaddition of 7 with N -methylmaleimide is also performed.

Uncatalyzed and LiClO4 catalyzed cycloadditions of (RS)-1-{1-[(1S)-isoborneol-10-sulfinyl]vinyl}cyclohexene 1 and (RS,E)-3-[(1S)-isoborneol-10-sulfinyl]-1-methoxybuta-1,3-diene 2 with di(p-tolyl)- and di(p-anisyl)thioketones 3 and 4 occur with complete regioselectivity. The lack of facial diastereoselectivity, observed in the cycloadditions of 1 with 3 or 4, appears to be a consequence of the sterical features of both diene and dienophile which, in the transition states, make the topological differentiation induced by the presence of the alkylsulfinyl group as chiral auxiliary uninfluential. No significant improvement in diastereoselectivity is observed in the LiClO4 catalyzed reactions, but the obtained enantiopure cycloadducts are easily separated by column chromatography and isolated in high yields. © 1999 Elsevier Science Ltd. All rights reserved.

The unexpected and previously unknown TMSI-promoted conversion of a,b-unsaturated sulfoxides into carbonyl compounds and disulfides is described. It occurs in good yields under mild conditions. The examples provided support the generality and eAciency of this procedure which acts as a good method for removing the sulfinyl group with the advantage of transforming the vinyl sulfoxides into carbonyl compounds. # 2000 Elsevier Science Ltd. All rights reserved.

Simple syntheses of homochiral (Z)- and (E)-1-methoxy-3-alkylsulfinyl-1,3-butadienes were provided by the cycloaddition of (1S)-d-isobornyl-10-sulfenic acid to (Z)- and (E)-1-methoxybut-1-en-3-yne. Asymmetric induction pertained for such cycloadditions, which also provided homochiral dienes from 1-ethynylcyclohex-1-ene.

The study of the molecular geometry of 1,5-bis(3,5-dimethyl-2-hydroxybenzyl)-1,5-diazocan-2,6-dione (2) as determined by X-ray analysis is reported and compared with that of cyclodi-β-alanyl (3). Interestingly there are 1.5 molecules of (2) in the asymmetric unit, showing the two conformations (1 twist-boat- and 0-5 chair-type) with two parallel aromatic rings (from alternate twist-boat conformers) sandwiching the eight-membered ring of the centrosymmetric chair-type conformation. The twist-boat is shown by pmr spectroscopy to be the only significantly populated conformer at low temperature in deuteriodichloromethane solution

This review (56 references) provides a comprehensive survey of the literature on sulfenic acid chemistry from 1990 through June 2006, focusing the attention on salient aspects of their structures and involvement in organic processes. Even if the majority of known sulfenic acids cannot be isolated, some stable ones have been obtained, and their study helped dramatically the comprehension of chemical and physical properties of all sulfenic acids and indirectly of the role that Cys-SOHs play in protein biochemistry. Many papers have been published in the last fifteen years about the sulfenic acid intermediacy in organic chemistry. Once generated, they can be involved in intraand intermolecular additions to unsaturated molecules. Few examples of sulfenic acid addition to double bonds have been recently described and most of them are intramolecular processes, whereas the addition of enantiopure sulfenic acids onto carbon-carbon triple bonds has been widely exploited in the synthesis of vinyl sulfoxides to be used in many stereoselective transformations. The thermic -elimination from sulfinyl precursors is a way to generate sulfenic acids but it has been also used for removing the sulfinyl moiety from organic molecules and forming double bonds with controlled stereochemistry. Some significant applications of extrusion processes are also described in the present review.

[reaction: see text] Both anomers of O-protected 1-thio-D-gluco- and -D-mannopyranoses were selected to provide the substrates for developing a smooth and general methodology that gives access to anomeric glycosulfoxides. The behavior of the corresponding beta-D-galactopyran derivatives was also investigated. 2-[1-[(2,3,4,6-Tetra-O-acetyl-beta-D-glucopyranosyl)sulfinyl](1-methyl)ethyl]malonic acid diethyl esters 4 were thermolyzed in refluxing dichloromethane for generating 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranose-1-sulfenic acid (8), in the presence of 2-propynyl beta-d-glucopyranoside tetraacetate (32). The syn-addition of transient 8 onto the triple bond of 32 furnished 2-[(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)sulfonyl]-2-propenyl beta-d-glucopyranoside tetraacetate (34), after m-CPBA oxidation of the corresponding sulfinyl epimeric mixture 33. This synthetic pathway appears particularly attractive since it represents an example of a mild and versatile approach to thiodisaccharides of foreseeably significant biological behavior. Various carbohydrate-derived sulfenic acids, different in glycosyl moiety and sulfenic function positioning, and various alkynylated carbohydrates can be adopted as combining units in the synthesis of alkene-linked multivalent thiosaccharides.

Two different synthetic pathways are presented that provide access to enantiopure sulfinyl hydrazones; in both addition of sulfenic acid/unsaturation represents the crucial step of the procedure. The obtained results are discussed in terms of regioselectivity in the formation of α- and/or β-sulfinyl α,β-unsaturated products when sulfenic acids are reacted with substrates showing carbonyl conjugated triple bonds, and/or their derivatives. Despite its structural limitations, (R S ,E,E)-2-[(1S)-isoborneol-10-sulfinyl]-2-butenal dimethylhydrazone (6) behaves as 1-azabuta-1,3-diene in hetero Diels-Alder reaction with N-methylmaleimide, giving a unique cycloadduct with complete endo and facial selectivities.

The synthesis of enantiopure 4-[1-(alkylsulfinyl)vinyl]-1,2-dihydronaphthalenes and their Diels–Alder reactions are described. Cycloadditions with N -phenylmaleimide occur under thermal conditions, very slowly but with notable stereoselection, giving in each case just one of the two endo adducts in high yield. The obtained 16-azasteroid derivatives undergo chiral auxiliary removal in the presence of TMSI.

The unexpected and previously unknown TMSI-promoted conversion of a,b-unsaturated sulfoxides into carbonyl compounds and disulfides is described. It occurs in good yields under mild conditions. The examples provided support the generality and eAciency of this procedure which acts as a good method for removing the sulfinyl group with the advantage of transforming the vinyl sulfoxides into carbonyl compounds. # 2000 Elsevier Science Ltd. All rights reserved.

Uncatalyzed and LiClO4 catalyzed cycloadditions of (RS)-1-{1-[(1S)-isoborneol-10-sulfinyl]vinyl}cyclohexene 1 and (RS,E)-3-[(1S)-isoborneol-10-sulfinyl]-1-methoxybuta-1,3-diene 2 with di(p-tolyl)- and di(p-anisyl)thioketones 3 and 4 occur with complete regioselectivity. The lack of facial diastereoselectivity, observed in the cycloadditions of 1 with 3 or 4, appears to be a consequence of the sterical features of both diene and dienophile which, in the transition states, make the topological differentiation induced by the presence of the alkylsulfinyl group as chiral auxiliary uninfluential. No significant improvement in diastereoselectivity is observed in the LiClO4 catalyzed reactions, but the obtained enantiopure cycloadducts are easily separated by column chromatography and isolated in high yields. © 1999 Elsevier Science Ltd. All rights reserved.

Uncatalyzed cycloadditions of enantiopure [(1 S )-isoborneol-10-sulfinyl]- and [(1 S - exo )-2-bornylsulfinyl]vinylcyclohexenes with N -phenylmaleimide occur with good facial diastereoselectivity, controlled by the sulfur configuration, even if the extent of this stereoselection appears influenced by the structural features of the terpene residue directly linked to the sulfoxide moiety. Complete endo diastereoselectivity is observed in LiClO 4 catalyzed cycloadditions of ( R S )-1-{1-[(1 S )-isoborneol-10-sulfinyl]- and ( S S )-1-{1-[(1 S-exo )-2-bornylsulfinyl]vinyl}cyclohexenes 4 and 5 , respectively. The Diels–Alder reactivity of 5 and ( S S , E )-1-{2-[(1 S-exo )-2-bornylsulfinyl]vinyl}cyclohexene 7 , with the chiral auxiliary being in a different position with respect to the diene moiety, is also compared, and the results obtained comfirm that 1-sulfinyldienes are less reactive than 2-sulfinyldienes. SnCl 4 catalyzed cycloaddition of 7 with N -methylmaleimide is also performed.

The high degree of stereochemical control exerted by the sulfinyl group in Diels-Alder reactions of enantiopure diene sulfoxides is well stated[1] and points out the useful role that these diene systems may fulfil in enantioselective synthesis.[2]

In the search for platinum complexes of secondary dithiooxamides (RNHCS) 2 (termed as R 2 H 2 DTO), showing metallomesogenic properties, several [Pt(R 2 HDTO) 2 ] were synthesised starting from cis -[Pt(Me 2 SO) 2 Cl 2 ]. The paper is mainly devoted to the co-ordination chemistry of long chain dithiooxamides which in some cases show a different behaviour with respect to R 2 H 2 DTO bearing small substituents on nitrogen atoms. The observed reactivity appears related only in part to the lower basicity of amide nitrogen atoms in diaryl- with respect to dialkyl-dithiooxamides, and differently populated conformations of the complexes seem to play an important role. Mesophase formation for [Pt(R 2 HDTO) 2 ] with R = 3,4-[CH 3 (CH 2 ) 9 O] 2 C 6 H 3 and 3,4-[CH 3 (CH 2 ) 11 O] 2 C 6 H 3 is suggested by polarising optical microscopy and differential scanning calorimetry. The synthesis of analogous bis-chelates, but with two different dithiooxamide ligands, is also described.

New heterotricyclic systems, 6,10a,11,11a-tetrahydro-5H-bis[1,2,4]oxadiazolo[4,5-d:5′,4′-g][1,4]diazepines 6,7,9-11 and 5,6,10,10a,11,11a-hexahydro-1H-bis[1,2,4]triazolo[4,3-d:3′,4′-g][1,4]diazepines 8,12 have been obtained by double site- and regie-specific 1,3-dipolar cycloaddition of mesitylnitrile oxide (1) or diphenylnitrile imine (2) to 5,7-disubstituted 2,3-dihydro-1H-1,4-diazepines 3-5. The structure of the synthesized bis-adducts 6-12 shows that the hetero double bonds are much more reactive than the olefinic ones in the dipolarophiles under study. No evidence for the formation of mono-adducts was obtained.

The title compound (systematic name (3aR,3bS,11aS,RS)-3a,3b,4,5,11,11a-hexa­hydro-10-{[[(1S,2R,4R)-2-hydr­oxy-7,7-dimethyl­bicyclo­[2.2.1]hept-1-yl]meth­yl]sulfin­yl}-7-meth­oxy-2-phenyl-1H-naphth[2,1-e]isoindole-1,3(2H)-dione), C33H37NO5S, is an enanti­opure sulfinyl adduct which represents a 16-aza­steroid analogue and displays an estrone-like skeleton. The structure exhibits a strong intra­molecular hydrogen bond and a C—H⋯π inter­molecular inter­action.

The natural abundance 13C-nmr spectra of a series of 2,3,4,5-tetrahydro-1-methyl-1H-1,5-benzodiazepine-2,4-diones have been recorded: two of these compounds, clobazam and triflubazam, are clinically used as psychotherapeutic agents. The assignments of the various resonances have been made by chemical shift arguments, by the analysis of the fine splittings caused by one bond and long range couplings, and also by comparison with model compounds.

A variable temperature 200 MHz 1 H NMR investigation of some N-acylsubstituted 11, 12-dihydrodibenz[b, f][1, 5]oxazocin-6-ones showed the presence at room temperature of at least two conformationally restricted diastereomers (and their enantiomers) which molecular mechanics calculations strongly suggested to be a boat-like structure (major conformer) and a pseudo-chair and/or twistboat-like structure (minor conformer). The diastereomersinterconvert through a bond rotation mechanism just above room temperature (51-54°C, depending upon the nature of the N-acyl substituent), and the boat enantiomers interconvert at higher temperatures (75-95°C, depending upon the nature of the N-acyl substituent and the substitution pattern of the aromatic rings) via a ring inversion process. The N-acyl groups exocyclic to the eight-membered ring are shown to wholly exist - probably as a result of severe dipole: dipole interactions - in the sterically disfavoured conformation where the alkyl substituent bonded to the exocyclic carbonyl carbon atom is trans to the benzylic methylene group. Corresponding N-unsubstituted derivatives exhibit rapid ring inversion on the NMR time scale at room temperature.

The unimolecular processes of some methylenoxazolidinones bombarded in the gas phase by electrons have been investigated by MIKE analysis, precise mass measurements and isotopic labelling studies. The overall delocalisation effect of the substitution on the nitrogen contained has been ascertained through the study of the reaction mechanism and of the possible reacting ionic structures.

The n.m.r. spectra of triterpenoids related to 12-ursene have been examined using the shift reagent Eu(fod)3. The assignment of all the methyl resonances has been achieved for ursolic acid derivatives and the corresponding compounds of the 3-epi series, which have not been investigated previously. The additive shielding effects of various substituents on the methyl resonance frequencies have been deduced from the results.

By observing the shifts of the 1H NMR signals of 1,4-benzoquinones induced by Eu(fod)3, and simulating them with the aid of a novel computer program TWOCEN, it has been shown that the two carbonyl groups of 1,4-toluquinone and 2,6-dimethyl-1,4-benzoquinone compete in the Eu coordination. The metal binds at two sites on both the carbonyl groups, with 4-CO having a greater complexing ability with respect to 1-CO, in line with steric and electronic considerations.

The behaviour of substituted 1,3-oxazolidin-2-ones (1) and 1,3-oxazolin-2-ones (2) on treatment with acid is reported. Electrophylic addition of iminium cations to 1,3-oxazolin-2-onic monomers occurs, yielding the kinetically preferred dimers (3). The elimination pathway to 3 is in direct competition with the formation of the cyclodimerisation products resulting from a thermodynamically controlled process. The stereochemistry of the cyclodimers is discussed on the basis of X-ray analysis. Qualitative energetic considerations on the overall reaction and NMR characteristics are discussed using deuterium labelling experiments.

The synthesis of 11-acyl-11,12-dihydrodibenz[bf][1,5]oxazocin-6-ones 9-13 is reported by reaction of N-(2-hydroxybenzyl)anthranilic acids 1 with acetic, isobutyric, 2-ethylbutyric anhydrides. The structures of the obtained 6,8,6 products are proved with the use of ir, mass spectrometry, 1H and 13C nmr spectra, homo-and heteronuclear two-dimensional nmr experiments. The formation of 9-13 is discussed in relation to the obtainment of 12H-quino[2,1-b][1,3]benzoxazin-5-ones 2-8 and 6a,12-dihydro[3,1]benzoxazino[2,1-b][1,3]-benzoxazin-5-ones 14-19 from the same starting products 1 with suitable anhydrides under controlled reaction conditions.

A new triterpenoid, calaminthadiol, 3,4-seco-4(23),12-ursadien-3,28-diol, was isolated from the leaves of Satureia calamintha and Satureia graeca . Its structure was elucidated by spectroscopic methods and partial synthesis. The natural occurrence of this compound can be conclusive for the chemotaxonomic characterization of the genus because of the rarity of the 3,4-fission in the α- and β-amyrin skeletons. A biogenetic mechanism for its formation is proposed. Sitosterol, stigmasterol and campesterol were also isolated.

Four representatives of the new ring system [3,1]benzoxazino[2,1-b][1,3]benzoxazine, as determined by X-ray crystallography, were prepared by reaction of N-(2-hydroxybenzyl)anthranilic acids with trifluoroacetic anhydride.