JoséL. García Ruano

ASYMMETRIC AZIRIDINATION BY REACTION OF CHIRAL N-SULFINYLIMINES WITH SULFUR YLIDES : STEREOSELECTIVITY IMPROVEMENT BY USE OF TERT-BUTYLSULFINYL GROUP AS CHIRAL AUXILIARY

Abstract Chiral tert -butylsulfinyl group has been shown to be the chiral auxiliary of choice for the asymmetric aziridination of N-sulfinyliminas. Moreover, the sense of the asymmetric induction can be tuned in two ways: the chirality at the tert -butylsulfinyl Sulfur, or the nature of the methylene transfer reagent used. Thus, both aziridines 10( S s , S ) and 10( R s , R ), epimeric at C-2, were obtained in enantiomerically pure form by a single crystallisation (75% yield).

Mild and regiospecific nuclear iodination of methoxybenzenes and naphthalenes with N-iodosuccinimide in acetonitrile

Abstract A wide range of methoxy substituted benzenes and naphthalenes were regiospecifically iodinated at para position with N -iodosuccinimide in acetonitrile under mild conditions in excellent yields. Methylanisoles afforded only nuclear iodination products.

On the reaction of chiral sulfinimines with sulfur ylides: a novel route to the asymmetric aziridination

Abstract The reaction of optically pure N-sulfinyl phenylimine with dimethyloxosulfonium methylide ( A ) and dimethylsulfonium methylide ( B ) yields a mixture of N-sulfinylaziridines, epimers at C-2, which are easily separated. The stereochemical outcome of this aziridination was shown to be dependent on the nature of the methylene transfer reagent. The elimination of the sulfinyl group occurs under mild conditions, leading to optically pure phenyl aziridines.

Asymmetric synthesis of orsellinic acid type macrolides: The example of lasiodiplodin

Abstract The asymmetric synthesis of both enantiomers of methyl lasiodiplodin is described. The chiral centers were created in the very last steps of the synthesis by asymmetric induction of a chiral sulfoxide group.

ortho-Directed metallation in the regiocontrolled synthesis of enantiopure 2- and/or 3-substituted (S)S-(p-tolylsulfinyl)-1,4-benzoquinones

Abstract Enantiomerically pure (S) S -( p -tolylsulfinyl)-1,4-benzoquinones with alkyl and methoxy substituents at C-2 and/or C-3 are synthesized by CAN oxidation of adequately substituted (S) S -( p -tolylsulfinyl)-1,4-dimethoxyaromatic precursors 2 or 3 . These compounds were obtained by ortho -directed metallation or bromo-metal exchange from the corresponding p -methoxyanisoles in a highly regiocontrolled manner.

Stereoselective functionalisation of N-Boc pyroaminoadipic acid: Synthesis of 5-substituted aminoadipic and pipecolic acids

Abstract 5-Alkylsubstituted aminoadipic and pipecolic acids were diastereoselectively synthetized from methyl N-Boc pyroaminoadipate.

Short enantioselective approach to substituted triazolopyridazines from [(S)R]-1-(1E, 3E)-1-p-tolylsulfinyl-1,3-pentadiene

Abstract Enantiomerically pure hydroxy substituted triazolopyridazine 5a was obtained in one pot under mild conditions by reaction of (+)-( R )-(1 E ,3 E )-1-( p -tolylsulfinyl)-1,3-pentadiene and 4-methyl-1,2,4-triazoline-3,5-dione in the presence of P(OMe) 3 . The process involved a tandem Diels-Alder cycloaddition/sulfoxide-sulfenate rearrangement and trapping of the intermediate sulfenate.

Asymmetric Diels-Alder reaction of (S)-α-p-tolylsulfinyl α,β-unsaturated esters: the role of the sulfinyl group in asymmetric Diels-Alder reactions of vinylsulfoxides

Abstract The mechanistic models so far proposed to explain the behavior of vinylsulfoxides as dienophiles in asymmetric Diels-Alder reactions are revised on the basis of the results obtained in the reactions of (S)-benzyl 2-p-tolylsulfinylacrylate 3 with cyclopentadiene, Danes diene and furan under different conditions, as well as other results previously reported, concerning sulfinylacrylates, sulfinylmaleates and trialkoxycarbonyl sulfinyl ethenes. The moderate reactivity of sulfinylacrylates and the scarce influence that the incorporation of additional alkoxycarbonyl groups exerts on their reactivity is explained by assuming a variable electronic influence of the sulfinyl group on the double bond, acting as withdrawing and donating electron group depending on the substitution at the double bond. In the reactions with cyclopentadiene, both reactivity and stereoselectivity raised in the presence of ZnX2 as catalysts (ZnX2>ZnBr2>ZnCl2), but TiCl4 was found to be the most efficient catalyst allowing the reactions to take place at low temperatures. With cyclopentadiene and furan, steric and electronic interactions between the CH2 and O, respectively, and the substituent at sulfur on the s-cis conformation of the vinylsulfoxide must be considered to predict the favored stereochemical course.

(S,S)-1,1-bis-ethoxycarbonyl-2,2-bis-p-tolylsulfinyl ethene: a highly stereoselective but unexpectedly unreactive dienophile in asymmetric diels-alder reactions

Abstract The synthesis and dienophilic behaviour of ( S , S )-1,1-bis-ethoxycarbonyl-2,2-bis- p -tolysulfinyl ethene with cyclic and acyclic dienes is reported. The stereoselectivity is high with cyclopentadiene and complete with acyclic dienes, but its reactivity is unexpectedly low, requiring high pressures (13 Kbar) to evolve into the corresponding adducts or their pyrolytic sulfinyl elimination products.

DIELS-ALDER REACTIONS OF (S)R-(1E,3E)-1-P -TOLYLSULFINYL-1,3-PENTADIENE WITH MONOSUBSTITUTED ETHYLENES

Abstract Diels-Alder reactions of [(S)R]-(1E,3E)-1-p-tolylsulfinyl-1,3-pentadiene with 1-pyrrolidinyl-1-cyclohexene and methyl acrylate evidenced: i) low reactivity of the diene regardless of the electronic character of the dienophile (high pressures were always required); ii) a complete regio- and endo-selectivity (both controlled by the sulfoxide), but a low π-facial diastereoselectivity in the cycloaddition with enamine; iii) diastereoselectivity (facial and endo exo ) for the reaction with methyl acrylate is dependent on the regiochemistry (mainly controlled by the methyl substituent).