Derivatives of α‐ and β‐S‐thiophosphates of 2‐bromo‐2‐deoxy‐D‐hexopyranose

The first examples of S‐thiophosphate derivatives of 2‐bromo‐2‐deoxy sugars 7–12 were synthesized by reacting alkyl ammonium salts 1–4 of thiophosphoric acids with α‐1,2‐cis (5) or α‐1,2‐trans dibromo sugars (6) and addition of free thiophosphoric acids 1a or 2a to 2‐bromo‐D‐glucal (13). It was observed that the solvent determines formation of either the O‐ or S‐glycosyl compound. β‐Thiophosphates can be transformed to the α‐configuration in the presence of acid in quantitative yield. The structures of the synthesized derivatives of 7–12 were confirmed by spectroscopic methods. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 465–470, 1999     

The preparation of 3‐substituted 1,2‐benzisothiazole 1,1‐dioxides from lithiated intermediates or grignard reagents and methyl 2‐(aminosulfonyl)benzoate

A polylithiated β‐ketoester, β‐diketone, or β‐ketoamide was condensed‐cyclized with lithiated methyl 2‐(aminosulfonyl)benzoate, to afford new 3‐substituted 1,2‐benzisothiazole 1,1‐dioxides. Some Grignard or organolithium reagents were also condensed‐cyclized with methyl 2‐(aminosulfonyl)benzoate to give 3‐substituted 1,2‐benzisothiazole 1,1‐dioxides.     

The preparation of 3‐substituted 1,2‐benzisothiazole‐1,1‐dioxides from the condensation‐cyclization of dilithiated β‐ketoesters with methyl 2‐(aminosulfonyl)benzoate or 1,2‐benzisothiazol‐3(2H)‐one‐1,1‐dioxide

Several β‐ketoesters were dilithiated with an excess of lithium diisopropylamide, followed by condensation with methyl 2‐(aminosulfonyl)benzoate to give intermediates that were not isolated but cyclized to 3‐substituted 1,2‐benzisothiazole‐1,1‐dioxides. In most instances involving the ester‐sulfonamide, a single β‐ketoester tautomer is usually formed after recrystallization from ethanol. The same dilithiated β‐ketoesters generally condense less well with 1,2‐benzisothiazol‐3(2H)‐one‐1,1‐dioxide (saccharin) under the same conditions to afford the same products usually in the same or lower yields. The use of N,N,N',N'‐tetramethylethylenediamine during these syntheses has sometimes resulted in improved yields of products.     

Preparation and cyclization of 4‐chloro‐5,5‐dimethyl‐3‐formyl‐1,2‐oxathiolene 2,2‐dioxide

Chloroformylation of 5,5‐dimethyl‐1,2‐ oxathiolan‐4‐one 2,2‐dioxide 4 with Vilsmeier reagent (DMF/POCl₃) led to the formation of cyclic β‐chloro‐vinylaldehyde (4‐chloro‐5,5‐dimethyl‐3‐formyl‐1,2‐oxathiolene 2,2‐dioxide 5 ). Compound 5 reacted with formamidine, o‐aminophenol, 1,2‐phenylenediamine, aminopyrazole, and aminotetrazole to give the corresponding heterocyclic compounds. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:200–204, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20094     

A novel photoisomerzation of 1,2‐benzothiazine 1,1‐dioxides to 1,3‐benzothiazine 1,1‐dioxides

A novel facile photoconversion of 4‐hydroxy‐1,2‐bezothiazine 1,1‐dioxides ( 3a‐e ) into 4‐oxo‐1,3‐2H‐benzothiazine 1,1‐dioxides ( 4a‐e ) and 4‐hydroxy‐2‐methyl‐N‐(pyridin‐2‐yl)‐2H‐1,2‐benzothiazine‐3‐carboxamide 1,1‐dioxide (PRX) into N‐methyl saccharin ( 2 ) upon 254 nm irradiation in methanol or acetonitrile is reported. The structures of the products have been elucidated by spectroscopic methods and single crystal X‐ray structure determination for 4a and 4d .     

Synthesis of a Six‐Membered‐Ring (2R)‐10a‐Homobornane‐10a,2‐sultam and Structural Comparison with Oppolzer's,Lang's,and King's Sultams

The new six‐membered‐ring (2R)‐10a‐homobornane‐10a,2‐sultam (−)‐ 3a was synthesized and its X‐ray structural analysis was compared with that of the novel structure of the five‐membered‐ring (2R)‐bornane‐10,2‐sultam analogues (−)‐ 1a , b as well as with that already published for the six‐membered‐ring trans‐decalin‐like sultam 4a . Based on DN** density‐function calculations and X‐ray crystallographic studies of the N‐methylated analogues (−)‐ 1e and 4b and by comparing with the conformation of the N‐fluoro derivatives (−)‐ 1c and (+)‐ 1d , the anomeric stabilization was estimated to be smaller than the 2.0–2.5 kcal/mol earlier suggested. The direction of pyramidalization is rationalized in terms of H‐bond and steric and electronic interactions and extended to the known toluenesultam derivatives 10a – c .     

Diastereo‐ and Enantioselective Synthesis of β‐Aminoboronate Esters by Copper(I)‐Catalyzed 1,2‐Addition of 1,1‐Bis[(pinacolato)boryl]alkanes to Imines

Reported herein is an efficient copper(I)‐catalytic system for the diastereo‐ and enantioselective 1,2‐addition of 1,1‐bis[(pinacolato)boryl]alkanes to protected imines to afford synthetically valuable enantioenriched β‐aminoboron compounds bearing contiguous stereogenic centers. The reaction exhibits a broad scope with respect to protected imines and 1,1‐bis[(pinacolato)boryl]alkanes, thus providing β‐aminoboronate esters with excellent diastereo‐ and enantioselectivity. The synthetic utility of the obtained β‐aminoboronate ester was also demonstrated.     

On the chemistry of 5‐aryl‐2‐hydrazino‐benzo[6,7]cyclohepta[1,2‐b]pyrido[2,3‐e] pyrimidin‐4‐one

Several pyrido[2,3‐e]pyrimidine fused with other rings have been prepared by intramolecular cyclization of 5‐(4‐chlorophenyl)‐2‐hydrazino‐benzo [6,7]cyclohepta‐[1,2‐b]pyrido[2,3‐e]pyrimidine‐4‐one ( 1 ) with acids, carbon disulfide to form triazole derivatives ( 2,4 ), halo‐ketones to give triazine derivative ( 5 ), β‐ketoesters, β‐cyanoesters, and β‐diketones to yield 2‐(1‐pyrazolyl) derivatives ( 7,9,10 ), and aldehydes to form arylhydrazone derivatives ( 11a,b ) which cyclized to form triazoles ( 12a,b ). Also, acyclic N‐nucleosides are prepared by heating under reflux 2‐hydrazino‐benzo[6,7]cyclohepta[1,2‐b]pyrido[2,3‐e] pyrimidin‐4‐one ( 1 ) with xylose and glucose to give the corresponding acyclic N‐nucleosides ( 13a,b ) which are cyclized to afford the corresponding protected tetra and penta–O‐acetate C‐nucleosides ( 14a,b ). Deacetylating of the latter nucleosides afforded the free acyclic C‐nucleosides ( 15a,b ). © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:34–43, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20248     

Fused 1,2‐Dithioles. Part VII

The 1,2‐dithiolosultam derivative 14 was obtained from the (α‐bromoalkylidene)propenesultam derivative 9 (Scheme 1). Regioselective cleavage of the two ester groups (→ 1b or 2b ) allowed the preparation of derivatives with different substituents at C(3) in the dithiole ring (see 27 and 28 ) as well as at C(6) in the isothiazole ring (see 17 – 21 ; Scheme 2). Curtius rearrangement of the 6‐carbonyl azide 21 in Ac₂O afforded the 6‐acetamide 22 , and saponification and decarboxylation of the latter yielded ‘sulfothiolutin’ ( 30 ). Hydride reductions of two of the bicyclic sultams resulted in ring opening of the sultam ring and loss of the sulfonyl group. Thus the reduction of the dithiolosultam derivative 14 yielded the alkylidenethiotetronic acid derivative 33 (tetronic acid=furan‐2,4(3H,4H)‐dione), and the lactam‐sultam derivative 10 gave the alkylidenetetramic acid derivative 35 (tetramic acid=1,5‐dihydro‐4‐hydroxy‐2H‐pyrrol‐2‐one) (Scheme 3). Some of the new compounds ( 14, 22, 26 , and 30 ) exhibited antimycobacterial activity. The oxidative addition of 1 equiv. of [Pt(η²‐C₂H₄)L₂] ( 36a , L=PPh₃; 36b , L=1/2 dppf; 36c , L=1/2 (R,R)‐diop) into the S? S bond of 14 led to the cis‐(dithiolato)platinum(II) complexes 37a – c . (dppf=1,1′‐bis(diphenylphosphino)ferrocene; (R,R)‐diop={[(4R,5R)‐2,2‐demithyl‐1,3‐dioxolane‐4,5‐diyl]bis(methylene)}bis[diphenylphosphine]).     

Studies with Heterocyclic β‐Enaminoniriles: A Simple Route for the Synthesis of Polyfunctionally Substituted Thiophene,Imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene and Thieno[3,2‐d]pyrimidine Derivatives

Reaction of 3,5‐diaminothiophene‐2‐carbonitrile derivatives 3a‐c with ethoxycarbonylmethyl isothiocyanate and/or N‐[bis(methylthio)methylene]glycine ethyl ester led to formation of 7‐substituted‐8‐amino‐5‐thioxo‐6H‐imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene‐2(3H)‐one derivatives 6a‐c and 7‐substituted‐8‐amino‐5‐(methylthio)imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene‐2(3H)‐one 7a‐c , respectively. Also, the synthetic potential of the β‐enaminonitrile moiety in 3a‐c has been explored; it proved to be a promising candiate for the synthesis of 1,6‐disubstituted‐2,4‐diamino‐7,8‐dihydro‐8‐oxopyrrolo[1,2‐a]thieno[2,3‐e]pyrimidine derivatives 10a‐f and pyrido[2′,3′:6,5]pyrimido[3,4‐a]benzimidazole derivatives 12a,b .     

Catalyst‐Controlled 1,2‐ and 1,1‐Arylboration of α‐Alkyl Alkenyl Arenes

Two methods are reported for the 1,2‐ and 1,1‐arylboration of α‐methyl vinyl arenes. In the case of 1,2‐arylboration, the formation of a quaternary center occurred through a rare cross‐coupling reaction of a tertiary organometallic complex. 1,1‐Arylboration was enabled by catalyst optimization and occurred through a β‐hydride elimination/reinsertion cascade. Enantioselective variants of both processes are presented as well as mechanistic investigations.     

Synthesis of 5‐Amino‐3,3‐dimethyl‐7‐phenyl‐3H‐[1,2]oxathiolo[4,3‐b]pyridine‐6‐carbonitrile 1,1‐Dioxides

The reaction of 4‐amino‐5,5‐dimethyl‐5H‐1,2‐oxathiole 2,2‐dioxide ( 1 ) with 2‐(arylidene)malononitriles 2 in ethanol, at reflux, using piperidine as catalyst, afforded 5‐amino‐3,3‐dimethyl‐7‐aryl‐3H‐[1,2]oxathiolo[4,3‐b]pyridine‐6‐carbonitrile 1,1‐dioxides ( 3 ) in moderate chemical yields.     

The behavior of 2‐thioxo‐4‐thiazolidinones toward organophosphorus reagents

The reaction of 2‐thioxo‐4‐thiazolidinone ( 1a ) with phosphorus ylides 2a and 2b afforded compounds 5 and 6. On the other hand, formylmethylenetriphenylphosphorane (2c) reacts with 1a and its N‐methyl derivative 1b to give the new complicated phosphonium ylides 7a,b, respectively. Reactions of 1b with ylides 2a and 2d gave rise to the olefinic compound 8 and the new phosphorane product 9. Moreover, dialkyl phosphites 3a,b and trialkyl phosphites 4a–c react with 1a to give both the alkylated products 10a–c and the dimeric compounds 11,12. A mechanism is proposed to explain the formation of the new products.© 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 337–341, 1999     

Synthesis of glycosyl esters from phosphoroates derivatives of 2‐bromosugars

This work presents the synthesis of glycosyl esters of 2‐bromo‐2‐deoxy‐D ‐hexopyranose, having the α‐D ‐manno ( 10a–cα ), β‐D ‐gluco ( 11a–dβ ) and α‐D ‐gluco ( 11a,bα ) configuration, by a stereoselective reaction between phosphoroates 3–8 and carboxylic acids 9a–d. Derivatives of 10a–c and 11a–d are formed in an overall quantitative yield, in an aprotic solvent in the presence of silver salts as a leaving group activator. The phosphoroselenoate of 3 was obtained by the condensation reaction of the triethylammonium salt of phosphoroseleno acid 2 with α‐1,2‐D ‐manno‐pyranosyl dibromide 1 with high stereoselectivity. The structures of the compounds 3,10a–c and 11a–d were established by ¹H and ¹³C NMR spectra and by elemental analyses. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:292–298, 2000     

N‐(X‐Chlorophenyl)‐4‐hydroxy‐2‐methyl‐2H‐1,2‐benzothiazine‐3‐carboxamide 1,1‐dioxide (with X = 2 and 4)

The structures of N‐(2‐chlorophenyl)‐4‐hydroxy‐2‐methyl‐2H‐1,2‐benzothiazine‐3‐carboxamide 1,1‐dioxide and N‐(4‐chlorophenyl)‐4‐hydroxy‐2‐methyl‐2H‐1,2‐benzothiazine‐3‐carboxamide 1,1‐dioxide, both C₁₆H₁₃ClN₂O₄S, are stabilized by extensive intramolecular hydrogen bonds. The 4‐chloro derivative forms dimeric pairs of molecules lying about inversion centres as a result of intermolecular N—H...O hydrogen bonds, forming 14‐membered rings representing an R₂²(14) motif; the 2‐chloro derivative is devoid of any such intermolecular hydrogen bonds. The heterocyclic thiazine rings in both structures adopt half‐chair conformations.     

An expedient synthesis of 2,3‐dihydro‐5,6‐dimethoxy‐3‐methylsulfonamido‐1,2‐benzisothiazole‐1,1‐dioxide via intramolecular sulfamoyl michael addition

A simple method of introducing a sulfamoylmethyl group on carbon‐3 in 1,2‐benzisothiazole‐1,1‐dioxide is described.     

Reactions of a,ß‐unsaturated N‐benzenesulfonyl Imine – N‐[(2E)‐3‐phenyl‐2‐propen‐1‐ylidene]benzenesulfonamide with Methyllithium

α,β‐Unsaturated N‐benzenesulfonyl imine 1 was treated with 1.1 eq methyllithium to afford 1,2‐addition adduct as a sole product. However, when compound 1 was treated with 2 eq MeLi, 1,2‐addition product, benzenesulfonamide derivative 3 and 2H‐1,2‐benzothiazine 1,1‐dioxide derivatives 4 and 5 were isolated.     

A Simple and One‐Pot Synthesis of β‐Sultams by Using the Vilsmeier Reagent

Mild and efficient one‐pot synthesis of β‐sultams with the Vilsmeier reagent proceeded in good to excellent yield. [2 + 2] Cycloaddition of imines with sulfenes (prepared in situ) afforded the corresponding cis‐β‐sultams. Optimization of solvents, molar ratio of reagents,and temperature was performed. Toxic and corrosive compounds have been avoided in this novel method.     

Kinetics of the hydrogen abstraction reactions of 1,1‐ and 1,2‐difluoroethane with hydroxyl radical: an ab initio study

The hydrogen abstraction reactions of 1,1‐ and 1,2‐difluoroethane with the OH radical have been investigated by the ab initio molecular orbital theory. The geometries of the reactants, products, and transition states have been optimized at the (U)MP2=full level of theory in conjunction with 6‐311G(d,p) basis functions. Single‐point (U)MP2=full with larger basis set, such as 6‐311G(3d,2p), and QCISD(T)=full/6‐311G(d,p) calculations have also been carried out to observe the effects of basis sets utilized and higher order electron correlation. Three and four reaction channels have been identified for 1,1‐ and 1,2‐difluoroethane, respectively. In the case of 1,1‐difluoroethane, hydrogen abstraction from the α‐carbon has been found to be easier than that from the β‐carbon. The barriers of the four reaction channels for 1,2‐difluoroethane are close to each other. Weak hydrogen bonding interactions have been observed between hydroxyl hydrogen and a fluorine atom in the transition states. Rate constants for the reactions of 1,1‐ and 1,2‐difluoroethane with the OH radical have been calculated using the standard transition state theory and found to be in good agreement with the experimental results. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1305–1318, 2000     

Asymmetric Catalysis with a Phosphoramidite Derived from (−)‐(aR)‐ [1,1′‐Binaphthalene]‐8,8′‐diol

Treatment of (aR)‐[1,1′binaphthalene]‐8,8′‐diol ((−)‐ 1 ) with hexamethylphosphorous triamide afforded the N,N‐dimethylphosphoramidite (−)‐ 3 (Scheme 1). The synthesis of the analogous N,N‐diisopropylphosphoramidite 4 failed, however, and afforded the acyclic phosphonamidate (−)‐ 5 . The application of the cyclic phosphoramidite (−)‐ 3 towards asymmetric catalysis was investigated. The borane reduction of acetophenone ( 6 ) to (R)‐1‐phenylethanol ( 7 ) in the presence of (−)‐ 3 proceeded with 96% ee (Scheme 2). The use of (−)‐ 3 as ligand in several Cu‐catalyzed addition and substitution reactions resulted in enantioselectivities ranging from 0 to 50% (Schemes 3 and 4).