José Luis García Ruano

Efficient synthesis of disulfides by air oxidation of thiols under sonication

Alkyl, aryl and heteroaryl symmetrical disulfides can be easily obtained by heating the corresponding thiols for several hours at 80 °C with Et3N in DMF under atmospheric oxygen. These reactions are markedly accelerated by ultrasounds (few minutes at rt). Aromatic groups bearing electron donating and electron withdrawing groups, heteroaromatic, and alkyl thiols are analogously efficient affording disulfides in almost quantitative yields. Aminothiols and L-cysteine provide the corresponding disulfides without affecting the nitrogen function.

Copper-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes: synthesis of cyclopropylboronates.

A novel Cu-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes to afford nonracemic cyclopropylboronates is described. Trapping the cyclopropylcopper intermediate with electrophilic amines allows for the synthesis of cyclopropylaminoboronic esters and demonstrates the potential of the approach for the synthesis of functionalized cyclopropanes.

Highly chemoselective reduction of N-Boc protected lactams

Abstract N-Boc protected lactams can be reduced chemoselectively in the presence of other groups such as esters, nitriles, carbamates or double bonds by first reducing the amide carbonyl group into the corresponding hemiaminal using lithium triethylborohydride followed by further reduction of the hemiaminal intermediate with triethylsilane/Boron trifluoride etherate. This method preserves the chirality present in the substrate.

A General Aminocatalytic Method for the Synthesis of Aldimines

A general and efficient biomimetic method for the synthesis of aldimines from aldehydes and compounds bearing the NH2 group in the presence of pyrrolidine as a catalyst has been developed. These organocatalytic reactions, based on the application of the concept of nucleophilic catalysis, proceed with outstanding yields in the absence of acids and metals under simple conditions and minimum experimental manipulation. The method has been mainly applied to the synthesis of N-sulfinyl and N-sulfonyl imines, but its general validity has been proven with the preparation of representative N-phosphinoyl, N-alkyl, and N-aryl imines. These unprecedented reactions, which presumably occur via iminium activation without requiring acidic conditions, are an interesting and competitive alternative to the classical methods for preparing aldimines.

Enantioselective aza-Henry reactions of cyclic α-carbonyl ketimines under bifunctional catalysis

The aza-Henry reaction of nitroalkanes with the C=N group of 2-aryl-3H-indol-3-ones catalyzed by thiourea-chincona derivatives takes place with good yield and high ees.

One-Pot Synthesis of Pentasubstituted Cyclohexanes by a Michael Addition Followed by a Tandem Inter–Intra Double Henry Reaction

Michael, Henry, and Henry: A new one-pot reaction of α,β-unsaturated aldehydes and β-dicarbonyls, which involves a Michael reaction catalyzed by diarylprolinol ethers and an inter–intramolecular Henry tandem reaction catalyzed by TBAF (see scheme), has been developed. The reaction proceeds in high enantio- and diastereoselectivity for a wide range of unsaturated aldehydes and β-dicarbonyl reagents.

Asymmetric synthesis of α-alkyl α-selenocarbonyl compounds catalyzed by bifunctional organocatalysts.

A new organocatalytic approach for the synthesis of a variety of α-alkyl, α-phenylselenyl ketones as well as their corresponding esters and amides, by the addition of α-selenocarbonyl derivatives to nitroalkenes catalyzed by thiourea or squaramide cinchona catalysts, is presented. This catalytic system allows the preparation in high yields of enantiomerically enriched selenocarbonyl derivatives bearing two chiral centers with excellent ees and drs by using catalytic loadings of 3 mol%.

Anionic–Anionic Asymmetric Tandem Reactions: One-Pot Synthesis of Optically Pure Fluorinated Indolines from 2-p-Tolylsulfinyl Alkylbenzenes†

The indoline skeleton is a ubiquitous scaffold found in the structures of several alkaloids and other natural products which have diverse biological activity. Indolines are considered to be “privileged structures” which accounts for their widespread use not only as building blocks in the total synthesis of natural products, but also as a common motif in the design of new biologically significant compounds. Indolines have also been successfully employed as chiral auxiliaries in asymmetric synthesis. Consequently, a number of multistep strategies have been developed for synthesizing these compounds. However, no short and efficient methods for the preparation of enantiomerically pure substituted indolines have been developed to date, therefore the search for new methods for synthesizing them remains a challenge. Surprisingly, no examples of fluorinated indolines have been reported despite the fact that the inclusion of fluorinated fragments, such as the trifluoromethyl group, in organic molecules has contributed significantly to the development of new pharmaceuticals. Our research group has recently reported that reactions of 2-(p-tolylsulfinyl) benzylcarbanions with different electrophiles take place with almost complete control of the configuration at the benzylic position, thus providing one of the best methods for creating optically pure benzylic carbon centers. In particular, the use of imines as electrophiles has allowed us to synthesize 2-phenylethyl (and propyl) amines with complete control of the configuration at the two stereogenic centers that are created simultaneously. [9] We hypothesized that amines resulting from nucleophilic addition (AN) could serve as substrates for the synthesis of optically pure indolines—once the optimal reaction conditions for the displacement of the sulfinyl group by the nitrogen center are determined, an intramolecular nucleophilic aromatic substitution (SNAr) could take place (Scheme 1). [10] We also felt that

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.

Asymmetric [4+2] Cycloadditions Mediated by Sulfoxides

Asymmetric [4,2] cycloadditions involving the use of enantiomerically pure sulfoxides as the main controller of stereoselectivity are reviewed. Diels-Alder reactions with sulfinyldienes and sulfinyldienophiles, 1,3-dipolar reactions with vinylsulfoxides, and hetero-Diels-Alder reactions are the main objectives of this review. The influence of the sulfinyl group on the reactivity, regioselectivity, and especially stereoselectivity of these reactions has been mainly considered in order to understand the synthetic scope and limitations of the sulfinyl group acting as a chiral inductor in these reactions. Apparent deficiencies in proposed stereochemical models have been also highlighted.