Antonio Urbano

Enantiopure sulfoxides: recent applications in asymmetric synthesis

Sulfoxides are nowadays recognised as powerful chiral auxiliaries that may participate in a wide range of asymmetric reactions. Their high configurational stability, the existence of several efficient methods allowing the access to both configurations as well as their synthetic versatility are characteristic features offering a tremendous potential to develop new applications. Significant recent advances leading to high asymmetric inductions in carbon-carbon and carbon-oxygen bond forming reactions, and applications of homochiral sulfoxides to atroposelective synthesis and asymmetric catalysis are discussed. New uses of sulfoxides in the design of chiroptical switches are also shown.

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.

Efficient asymmetric synthesis of [7]helicene bisquinones

The efficient one-pot six-step domino process which occurs when (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone (1) reacts with 3,6-divinyl-1,2,7,8-tetrahydrophenanthrenes 2a-c allowed enantioselective access to [7]helicene bisquinones 3a-c with excellent optical purities (96 to > 99% ee).

Synthesis and asymmetric diels-alder reactions of (S)-2-p-tolylsulfinyl-1,4-benzoquinone

Abstract Optically pure (S)-2- p -tolylsulfinyl-1,4-benzoquinone ( 5 ) is readily obtained by deketalization of the corresponding quinone bisketal 4 , synthesized by Andersens type synthesis on 2-bromo-1,4-dimethoxybenzene ( 1 ) followed by anodic oxidation of the resulting sulfoxide. The Diels-Alder reaction of cyclopentadiene with 5 took place on C 5 -C 6 dienophilic double bond showing high facial selectivity, which can be inverted by using different Lewis acids, and total endo selectivity.

Enantioselective Diels‐Alder Approach to C‐3‐Oxygenated Angucyclinones from (SS)‐2‐(p‐Tolylsulfinyl)‐1,4‐naphthoquinone

Chiral racemic vinylcyclohexenes 2, bearing oxygenated substituents and/or a methyl group at the C-5 position of the cyclohexene ring, were submitted to Diels-Alder reactions with enantiomerically pure (SS)-(2-p-tolylsulfinyl)-1,4-naphthoquinone [(+)-1]. The domino cycloaddition/pyrolytic sulfoxide elimination process led to the formation of enantiomerically enriched angularly tetracyclic quinones anti-6 and syn-7, which were obtained from the kinetic resolution of the racemic diene. In all cases, (SS)-(2-p-tolylsulfinyl)-1,4-naphthoquinone reacted from the less hindered face of the more reactive s-cis conformation, to form products in good enantiomeric excesses. Steric effects and torsional interactions in the corresponding approaches account for the observed pi-facial diastereoselectivities at both partners. The usefulness of this methodology is illustrated with the four-step totally asymmetric synthesis of the C-3-oxygenated angucyclinone derivative (-)-8-deoxytetrangomycin 10 in 26% overall yield and with 50% enantiomeric purity.

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.

Concise Enantioselective Synthesis of the Ten-Membered Lactone Cephalosporolide G and Its C-3 Epimer

Among the naturally occurring lactones of ring sizes in the range of eight to eleven, the ten-membered lactones, also called decanolides, are the most abundant and biologically active. This family of natural products displays a wide range of biological properties, such as antibacterial and antifungal activity and the inhibition of cholesterol biosynthesis. Besides the macrolactone core, they share a methyl group at C-9, but differ in the number and nature of oxygen functionalities and the degree of unsaturation (Scheme 1).

The Effect of Sulfoxides on the Stereoselective Construction of Tetrahydrofurans: Total Synthesis of (+)-Goniothalesdiol

Good to excellent stereoselectivities were achieved in the reductive cyclization (with Et(3)SiH/trimethylsilyl trifluoromethanesulfonate (TMSOTf)) of enantiopure hydroxy sulfinyl ketones en route to 2,5-cis-disubstituted tetrahydrofuran skeletons. Electrostatic effects of the exocyclic sulfoxide, which stabilized the reactive intermediate oxocarbenium conformations, were responsible for the observed stereocontrol. A model is proposed to explain the results. The use of this reaction and the asymmetric β-ketosulfoxide reduction as key steps facilitated the total enantioselective synthesis of the natural β-C-aryl glycoside (+)-goniothalesdiol.

Improved Synthesis of 1,4-Phenanthrenequinones from Diels-Alder Cycloadditions of 2-(p-Tolylsulfinyl)-1,4-benzoquinone

Abstract A wide range of substituted 1,4-phenanthrenequinones 5a–g and benz[c]- and benz[a]-1,4-phenanthrenequinones (5h) and (5i) were synthezised in one step through Diels-Alder cycloadditions of 2-(p-tolylsulfinyl)-1,4-benzoquinone 2 and vinylaromatic derivatives 1a–i under thermal and high pressure conditions in moderate to good yields (33–80%).

General synthesis of chiral 2-p-tolylsulfinylquinones.

Abstract Optically pure (S)-p-tolylsulfinyl substituted quinones were synthesized by deketalization of the corresponding quinone bisketals obtained by Andersens type synthesis starting from 2-bromo-1,4-dimethoxy aromatic derivatives, followed by anodic oxidation of the resulting sulfoxide.