M. Rosario Martín

Abnormal Behaviour of Allenylsulfones under Lu’s Reaction Conditions: Synthesis of Enantiopure Polyfunctionalised Cyclopentenes

Formal [3+2] cycloadditions of 5-alkoxyfuran-2(5H)-ones 1 and 2 with allenylsulfones 3-5, promoted by different nucleophiles, afford 3-alkoxy-5-arylsulfonyl-3,3 a,6,6 a-tetrahydro-1H-cyclopenta[c]furan-1-ones in good yields with complete control of both regio- and pi-facial selectivity. The incorporation of a sulfinyl group on the furanone ring enhances the reactivity of the furanones and allows the synthesis of optically pure, bicyclic adducts in good yields. Allenylsulfones evolve through a different mechanism to that proposed for allenoates (Lus reaction) and afford bicyclic adducts in which the sulfonyl group is joined to C-5. This has advantages on the stereochemical control of further reactions leading to enantiomerically pure polyfunctionalised cyclopentenes and cyclopentanes.

Totally Regio-and Stereoselective Behavior of Mono-and Diactivated Cyclic Alkenes in the Lu Reaction : Synthesis of Enantiopure Functionalized Cyclopentanes

5-Alkoxyfuran-2(5H)-ones and their optically pure 3-p-tolylsulfinyl derivatives, synthetic equivalents of the acyclic esters, react with dipoles generated from allenoates and PPh(3) (Lu reaction), in a completely regioselective, pi-facial selective and endo-selective manner, yielding bicyclic adducts, which are easily converted into optically pure highly substituted cyclopentane derivatives.

(Ss)-5-ethoxy-3-p-tolylsulfinylfuran-2(5H)-ones as chiral dipolarophiles: First asymmetric cycloaddition of diazomethane to vinyl sulfoxides

Abstract Cycloadditions of diazomethane to (S s )-5-ethoxy-3- p -tolylsulfinylfuran-2(5 H )-ones 1a–b and their corresponding 4-methyl derivatives 3a–b , proceeds in quantitative yields, to give enantiomerically pure 3 H ,6 H ,3a,6a-dihydrofuro[3,4-c]pyrazol-4-ones 2a–b and 4a–b , respectively. The sulfinyl group at C-3 strongly increases both the reactivity and the π-facial selectivity. The dipole approach mode is determined by the configuration at the sulfinyl group. Pyrolysis of pyrazolines 2a or 2b gives the methyl derivatives 3a or 3b in excellent yield.

Asymmetric Synthesis of Pyrrolo[2,1-a]isoquinoline Derivatives by 1,3-Dipolar Cycloadditions of Stabilized Isoquinolinium N-Ylides with Sulfinyl Dipolarophiles

Enantiomerically pure pyrrolo[2,1-a]isoquinoline derivatives are obtained by 1,3-dipolar reactions of isoquinolinium azomethine ylides with enantiopure 3-p-tolylsulfinylacrylonitriles, tert-butyl (2E)-4,4-diethoxy-2-p-tolylsulfinylbut-2-enoate, and 5-ethoxy-3-p-tolylsulfinylfuran-2(5H)-ones. Reactions evolve through the anti conformation of the ylide with complete regioselectivity. The facial selectivity is completely controlled by the configuration of the sulfinyl sulfur for acyclic dipolarophiles, whereas it is high (dr 83/17 or 89/11) but controlled by the C-5 configuration for sulfinylfuranones. Complete endo selectivity is observed with cyclic dipolarophiles and substituted acrylonitriles, but it is low with butenoate. The sulfinyl group also exerts a positive influence on the dipolarophilic reactivity toward these ylides.

1,3-cycloaddition of nitrile oxides to cyclic and open-chain 4-oxo-2-sulfinylbut-2-enoic acid derivatives

Abstract The reactions of tert-butyl (E)-4,4-diethoxy-2-p-tolylsulfinylbut-2-enoate with benzonitrile, acetonitrile, and bromoformonitrile oxides yield isoxazoles. However, (S5,SS)- and (R5,SS)-5-ethoxy-3-p-tolylsulfinylfuranones with benzonitrile oxide afford isoxazolines. The reactivity of the double bond as a dipolarophile is strongly increased by the sulfinyl group. This is also the case of the regioselectivity, which usually is opposite to that exhibited by dipolarophiles lacking the sulfinyl group. Electrostatic interactions seemingly explain this behaviour. The π-facial selectivity of the reactions with the cyclic dipolarophiles is dependent on steric effects, but some role seems to be exerted by electrostatic attraction.

Pseudoesters and derivatives. XXIII Reaction of 3-bromo-5-methoxyfuran-2(5H)-one with nucleophiles. Formation of cyclopropane derivatives

Abstract The reactions of 3-bromo-5-methoxyfuran-2 (5 H )-one ( 1 ) with nucleophiles in acetonitrile, in the presence of potassium carbonate and tetrabutylammonium bromide as a catalyst, are reported. The bromofuranone 1 reacts, with several carbon and oxygen nucleophiles to give the cyclopropane bis-lactones 7 , 8 , 11 or 12 . When 1 is reacted with diethylamine or propane-2-thiol in a 2:1 ratio, similar cyclopropane bis-lactones 16 or 21 , respectively, are formed. This behaviour is explained on the basis of a mechanism involving a double Michael addition, followed by ring closure via internal nucleophilic substitution of the halogen.

Pyrrolo[2,1-b]thiazole Derivatives by Asymmetric 1,3-Dipolar Reactions of Thiazolium Azomethine Ylides to Activated Vinyl Sulfoxides

1,3-Dipolar reactions of thiazolium azomethine ylides to enantiopure cyclic and acyclic vinyl sulfoxides provide an efficient access to polyfunctionalized pyrrolo[2,1-b][1,3]thiazoles in a highly regio- and stereoselective manner. Regioselectivity can be inverted by modifying the position of the sulfinyl group at the double bond of the sulfinylfuranones. The sulfoxide is the main controller of the endo selectivity of these processes as well as of the pi-facial selectivity in reactions of (Z)-3-p-tolylsulfinylacrylonitriles. In contrast, the pi-facial selectivity in reactions of 5-alkoxy-3-p-tolylsulfinyl furan-2(5H)-ones is mainly controlled by the configuration at C-5, affording the anti adducts with respect to the alkoxy group as the major or exclusive adducts.

Stereoselectivity control in Diels–Alder reactions of 4-thiosubstituted 5-alkoxyfuranones: synthesis and reactivity of enantiopure 4-sulfinyl and sulfonyl 5-(l-menthyloxy)furan-2(5H)-ones

Abstract The synthesis of enantiomerically pure (S)-4-phenylsulfinyl- and 4-phenylsulfonyl-(5S)-5-(l-menthyloxy)furan-2(5H)-ones 5a and 6 and (5R)-5-(l-menthyloxy)-4-phenylsulfonylfuran-2(5H)-one 8 and the study of their reactions with cyclopentadiene are described. The sulfur substituents at C-4 modify (sulfone 8, anti/syn=78/22) and invert (sulfoxide 5a and sulfone 6, anti/syn≈27/73) the trend imposed by C-5 on the π-facial selectivity and the syn-adducts become the favoured ones. The endo or exo approach mode is favoured for anti (endo/exo ratio ranging between 26 and 5) or syn (exo/endo ratio ranging between 4.5 and 2.3) attack, respectively.

1,3-Dipolar Cycloaddition of Diazoalkanes to (S)-(+)-3-[(4-Methylphenyl)sulfinyl]-5,6-dihydropyran-2-one. Synthesis of Optically Pure Cyclopropanes by Denitrogenation of Sulfinyl and Sulfonyl Pyrazolines

The addition of diazomethane and diazoethane to enantiopure (S)-(+)-3-[(4-methylphenyl)sulfinyl]-5,6-dihydropyran-2-one (3) afforded the corresponding pyrazolines 4 and 6-exo in good yields and with almost complete pi-facial selectivity. When the reaction is effected in the presence of Yb(OTf)(3), the facial selectivity is inverted to give the pyrazolines 5 and 7-exo. The denitrogenation of optically pure sulfinyl pyrazolines 4-7-exo into the corresponding cyclopropanes with Yb(OTf)(3) occurred with complete retention of configuration but moderate chemoselectivity and yields. These results were significantly improved starting from sulfonyl pyrazolines, which afforded optically pure 3-oxabicyclo[4.1.0]heptan-2-ones with yields ranging between 65% (17 and ent-17) and > or = 95% (16 and ent-16).

Asymmetric 1,3-dipolar cycloadditions of diazoalkanes to (5S,SS)-5-[(1R)-menthyloxy]-4-phenylsulfinyl (and phenylsulfonyl)furan-2(5H)-ones ☆

Abstract The behavior of the title compounds in their reactions with diazomethane and diazoethane is reported. The reactivity of the 5-alkoxyfuran-2(5 H )-ones as dipolarophiles is dramatically enhanced by the presence of sulfur functionalities at C-4. The regioselectivity of the cycloadditions of diazomethane is opposite to that observed with diazoethane, due to control by the carbonyl group in the first case and by the sulfur function in the second case, with the sulfonyl group exhibiting a higher regio-orientating ability than the sulfinyl one. The π-facial selectivity is moderate, being controlled mainly by steric factors in the reactions involving the formation of N dipole C(4) furanone bonds, whereas the predominant role of electronic factors, modulated by the polarity of the solvent, leads to high stereoselectivities in processes involving the formation of N dipole C(3) furanone bonds. Finally, the endo / exo ratios from reactions with diazoethane can be rationalized on steric grounds.