A. M. Martín-Castro

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.

Stereodivergent Quaternization of 2‐Alkyl‐2‐p‐tolylsulfinylacetonitriles: NMR Spectroscopic Evidence of Planar and Pyramidal Benzylic Carbanions

Enantiomerically enriched alpha,alpha-disubstituted phenylacetonitriles have been readily prepared by stereoselective quaternization of 2-alkyl-2-[2-(p-tolylsulfinyl)phenyl]acetonitriles with different alkylating electrophiles in the presence of bases. The use of potassium hexamethyldisilazane (KHMDS)/[18]crown-6 ether and NHMDS with alkyl halides afforded S,S(S) and R,S(S) diastereoisomers, respectively, in high enantiomeric purities, thus providing stereodivergent processes for synthesizing both isomers. The dependence of the stereochemical course of the reactions on the experimental conditions (mainly on the counterion) has been rationalized by assuming a planar or pyramidal structure for the benzylic carbanions. This hypothesis has been supported by NMR spectroscopic studies, which permit one to assign a chelated pyramidal structure to the sodium benzylic carbanions and an almost planar naked carbanionic structure to the potassium benzylic carbanions generated in the presence of [18]crown-6 ether.

Asymmetric synthesis of benzylic quaternary difunctionalized carbons mediated by a remote sulfinyl group.

Enantiomerically enriched α-aryl α-cyanoacetates and α-aryl α-acylacetonitriles bearing a benzylic quaternary stereocenter have been readily synthesized by stereoselective reaction of 2-alkyl-2-[2-(p-tolylsulfinyl)phenyl]acetonitriles with different acylating and alkoxycarbonylating reagents under basic conditions. The stereoselectivity of the reactions proved closely dependent on the nature of the intermediate carbanionic species, the evolution of which was effectively controlled by a sulfinyl group as a remote chiral auxiliary.

Synthesis of enantiomerically pure anti-1,2-diaryl and syn-1,2-alkylaryl vic-selenoamines.

Phenylselenyl benzylcarbanion stabilized by an (S)-2-p-tolylsulfinyl group evolves in a highly stereoselective way in the reactions with (S)-N-(p-tolylsulfinyl)imines at -98 °C affording diastereomerically pure 1,2-selenoamino derivatives in good yields. The syn or anti relationship of the obtained compounds depends on the alkyl or aryl character of the imine. They are easily transformed into enantiomerically pure (1R,2S)-1-aryl[or (1S,2S)-1-alkyl]-2-(phenylseleno)-2-phenylethylamines by reaction with t-BuLi and subsequent methanolysis of the generated sulfinamide derivatives with TFA.

Asymmetric intramolecular Pauson-Khand reaction mediated by a remote sulfenyl or sulfinyl group.

In this work, we report the use of the asymmetric intramolecular Pauson-Khand reactions of 4-aryl-4-cyano-1,6-enynes for obtaining enantiomerically enriched bicyclo[3.3.0]octenones, and the influence of both the quaternary stereocenter and the sulfur functions located at ortho-position of the aryl group, on their stereoselectivity and reactivity. The sulfenyl derivatives bearing substituted or unsubstituted triple bonds and mono- and disubstituted alkene moieties afford bicyclo[3.3.0]octenones in high yields with complete diastereocontrol. These results are explained by assuming the association of the lone electron pair at sulfur to the Co-alkyne complexes.

Use of Lithiated Chiral o-Sulfinylbenzyl Carbanions for the One-Pot Building of Linear Fragments Containing up to Four Connected Stereocenters

The reaction of o-sulfinylbenzyl carbanions with prochiral Michael acceptors, such as differently sized cycloalkenones, proceeded with high levels of stereoselectivity, generating molecules containing up to three asymmetric carbon centers in just one synthetic step. All these reactions involved the use of either a proton or an acylating reagent as the final electrophile. Furthermore, the trapping of the enolate resulting from Michael addition with prochiral electrophiles, such as aldehydes or N-sulfonylimines, allowed the highly stereoselective synthesis of densely functionalized compounds containing four chiral centers in just a one-pot sequence, the stereochemical outcome of the sequence being controlled by the sulfinyl auxiliary.

Synthesis of Enantiomerically Pure 1,2-Disubstituted 2-Selenoamines

Abstract Optically pure phenylseleno-(S)-2-p-tolylsulfinylbenzylcarbanions react with (S)-N-2-p-tolylsulfinylimines derived from aliphatic and aromatic aldehydes in a highly stereoselective manner affording bis-sulfinylselenoamines, easily transformed into 1-phenyl, 2-aryl (or alkyl)-2-phenylseleno ethylamines by subsequent reactions, which were treatment reactions with t-BuLi and TFA. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Stereoselective Michael additions of lithiated ortho-sulfinylbenzyl carbanions derived from α-amino nitriles

Enantiomerically pure α -substituted α -amino ortho-sulfinylphenylacetonitriles have been readily prepared by the reaction of diastereoisomeric mixtures of α -amino phenylacetonitriles with differently sized cycloalkenones and 2-methyl cyclopentenone in the presence of lithium bases. The reactions proceeded with high levels of stereoselectivity, generating molecules containing up to three asymmetric carbon centers in just one synthetic step. GRAPHICAL ABSTRACT