Sulfinyl-Mediated Stereoselective Functionalization of Acyclic Conjugated Dienes.

The chemo- and stereocontrolled functionalization of conjugated sulfinyl dienes in a cascade process that involves a conjugate addition, diastereoselective protonation and a [2,3]-sigmatropic rearrangement is reported. Enantioenriched 1,4-diol and 1,4-aminoalcohol derivatives are obtained in a very straightforward manner. Further functionalization of these structures, including highly stereoselective epoxidation, dihydroxylation and the stereodivergent synthesis of several polyols in a controlled fashion is described.

Synthesis of Enantiopure 3-Hydroxypiperidines from Sulfinyl Dienyl Amines by Diastereoselective Intramolecular Cyclization and [2,3]-Sigmatropic Rearrangement.

The highly diastereoselective base-promoted intramolecular cyclization of a variety of enantiopure sulfinyl dienyl amines provides novel sulfinyl tetrahydropyridines that are readily converted to 3-hydroxy tetrahydropyridines via sigmatropic rearrangement. The influence of N- and C- substituents on the process has been studied. Procedures to shorten the sequence such as the tandem cyclization followed by [2,3]-sigmatropic rearrangement, as well as cyclization of the free amine, under Boc- or ArSO- deprotection conditions have been examined. Good to excellent levels of selectivity are generally observed for the reported transformations (dr: 75/25 to >98/2). A novel protocol to access substituted amino dienyl sulfoxides is also reported.

An approach to the stereoselective synthesis of enantiopure dihydropyrroles and aziridines from a common sulfinyl-sulfinamide intermediate.

The diastereoselective addition of lithiated vinyl sulfoxides to enantiopure sulfinimines provides direct access to a wide assortment of allylic sulfinamides in good yields and excellent selectivities. These adducts are key precursors to differently functionalized cis- and trans-dihydropyrroles. Modulation of the protecting group on nitrogen prior to cyclization has a significant impact on the stereochemical outcome, allowing for the selective preparation of 2,5-cis- or 2,5-trans-3-sulfinyl disubstituted dihydropyrroles from a common sulfinamide intermediate. Further research on halocyclization conditions has also yielded a stereoselective synthesis of trisubstituted vinyl aziridines from these chiral sulfinamides, simply by changing the halogenating agent.

Applications of 1-alkenyl-1,1-heterobimetallics in the stereoselective synthesis of cyclopropylboronate esters, trisubstituted cyclopropanols and 2,3-disubstituted cyclobutanones.

1-Alkenyl-1,1-heterobimetallics are potentially very useful in stereoselective organic synthesis but are relatively unexplored. Introduced herein is a practical application of 1-alkenyl-1,1-heterobimetallic intermediates in the synthesis of versatile cyclopropyl alcohol boronate esters, which are valuable building blocks. Thus, hydroboration of 1-alkynyl-1-boronate esters with dicyclohexylborane generates 1-alkenyl-1,1-diboro species. In situ transmetalation with dialkylzinc reagents furnishes 1-alkenyl-1,1-borozinc heterobimetallic intermediates. Addition of the more reactive ZnC bond to aldehydes generates the key B(pin) substituted allylic alkoxide intermediates. An in situ alkoxide directed cyclopropanation proceeds with the formation of two more CC bonds, affording cyclopropyl alcohol boronate esters with three new stereocenters in 58-89% isolated yields and excellent diastereoselectivities (>15:1 dr). Oxidation of the BC bond provides trisubstituted alpha-hydroxycyclopropyl carbinols as single diastereomers in good to excellent yields (75-93%). Facile pinacol-type rearrangement of the alpha-hydroxycyclopropyl carbinols provides access to both cis- and trans-2,3-disubstituted cyclobutanones with high stereoselectivity (>17:1 dr in most cases) from a common starting material. This methodology has been applied in the synthesis of quercus lactones A and B.

Enantiopure 1,4-diols and 1,4-aminoalcohols via stereoselective acyclic sulfoxide-sulfenate rearrangement.

Treatment of acyclic α-hydroxy and α-tosylamino sulfinyl dienes with amines affords enantiopure 1,4-diol or 1,4-hydroxysulfonamide derivatives in good yields and diastereoselectivities. This one-pot procedure entails a conjugate addition that triggers a diastereoselective sulfoxide-sulfenate [2,3]-sigmatropic rearrangement.

Highly diastereoselective addition of lithio vinyl sulfoxides to N-sulfinimines: an entry to enantiopure 3-sulfinyl-2,5-cis-dihydropyrroles.

The addition of enantiopure alpha-metalated vinyl and dienyl sulfoxides to enantiomerically pure N-sulfinimines takes place with high diastereoselectivity primarily directed by the N-sulfinimine sulfur. The resulting allylic amines have been further transformed into highly functionalized 3-sulfinyl and 3-sulfonyl 2,5- cis-dihydropyrroles by reaction with electrophiles.

Reductive cleavage of tetrahydrofuryl sulfur-substituted oxiranes: application to the formal synthesis of Kumausyne and Kumausallene.

[reactions: see text] Readily available sulfinyl and sulfonyl tetrahydrofuran methanol derivatives have been transformed efficiently into a variety of substituted tetrahydrofuryl alcohols by treatment with (PhSe)2 in the presence of an excess of NaBH4. Alternatively, oxirane cleavage with MgI2 produces the related ketones, amenable to stereocontrolled reduction. This reductive cleavage methodology has been applied to short formal syntheses of trans-Kumausyne and Kumausallene.