Base-Induced Sulfoxide-Sulfenate Rearrangement of 2-Sulfinyl Dienes for the Regio- and Stereoselective Synthesis of Enantioenriched Dienyl Diols.

The base-induced [2,3]-sigmatropic rearrangement of a series of enantiopure 2-sulfinyl dienes has been examined and optimized using a combination of NaH and iPrOH. The reaction takes place by allylic deprotonation of the 2-sulfinyl diene to give a bis-allylic sulfoxide anion intermediate that after protonation undergoes sulfoxide-sulfenate rearrangement. Different substitution at the starting 2-sulfinyl dienes has allowed us to study the rearrangement finding that a terminal allylic alcohol is determinant to achieve complete regioselectivity and high enantioselectivities (90:10-95:5) with the sulfoxide as the only element of stereocontrol. Density functional theory (DFT) calculations provide an interpretation of these results.

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.

From Allylic Sulfoxides to Allylic Sulfenates: Fifty Years of a Never-Ending [2,3]-Sigmatropic Rearrangement.

The [2,3]-sigmatropic rearrangement of allylic sulfoxides to allylic sulfenates is a reversible process, generally shifted toward the sulfoxide. In the presence of thiophiles, the sulfenate is trapped, and allylic alcohols are obtained under mild conditions. In most cases, a good transfer of stereochemical information through an ordered transition state is obtained. Furthermore, the ease of coupling this process with other versatile, stereocontrolled reactions has enhanced the usefulness of this protocol. This review aims to provide a comprehensive survey of this rearrangement and its application in the synthesis of natural and bioactive products.

Gold(I)-Catalyzed Cycloisomerization-Dimerization Cascade of Benzene-Tethered 1,6-Enynes.

An unprecedented stereoselective domino reaction of 1,6-enynes with an aryl ring at C3-C4 in the presence of gold(I) catalysts at low temperature is described. This process involves a novel 5-exo-dig cycloisomerization-dimerization sequence to afford formal Diels-Alder adducts that undergo a smooth gold-catalyzed double bond migration at room temperature. In addition, the first examples of the gold mesoionic carbene mediated [2+2+2] cycloaddition of these enynes with benzaldehyde are reported.

Sulfur Groups Improve the Performance of Triazole- and Triazolium-Based Interaction Units in Anion Binding.

An NMR comparative study of 1,2,3-triazole and triazolium anion recognition units containing sulfoxide, sulfone, and sulfoximine groups at C4 unveils an enhancement in binding ability up to ≈1 kcal/mol in acetone-d6 correlated with a theoretical increase of H5 acidity. DFT calculations provide insight into binding modes in line with experimental data for these receptors.

Sulfinyl-Mediated Stereoselective Overman Rearrangements and Diels-Alder Cycloadditions.

Sulfinyl trichloroacetamides are readily obtained in excellent yields through a highly stereoselective Overman rearrangement. Related bis-allylic substrates lead to amido 2-sulfinyl butadiene derivatives in excellent yields, with total chemo- and diastereoselectivity. These amido dienyl sulfoxides undergo highly selective Diels-Alder cycloadditions with N-phenylmaleimide with remarkable stereocontrol by the sulfoxide moiety.

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.

Enantioselective Suzuki cross-coupling of 1,2-diboryl cyclopropanes.

Herein, we describe the catalytic enantioselective cross-coupling of 1,2-bisboronic esters. Prior work on group specific cross coupling is limited to the use of geminal bis-boronates. This desymmetrization provides a novel approach to prepare enantioenriched cyclopropyl boronates with three contiguous stereocenters, that could be further derivatized through selective functionalization of the carbon-boron bond. Our results suggest that transmetallation, which is the enantiodetermining step, takes place with retention of stereochemistry at carbon.

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.

Diastereodivergent Synthesis of 2-Ene-1,4-hydroxy Sulfides from 2-Sulfinyl Dienes via Tandem Sulfa-Michael/Sulfoxide-Sulfenate Rearrangement.

The highly diastereoselective sulfa-Michael addition of thiolates to enantiopure 2-sulfinyl dienes leads to anti or syn 2-ene-1,4-hydroxy sulfides in good yields and selectivities dependent on the reaction conditions in a diastereodivergent process. Synthetic applications of these enantiopure hydroxy sulfides by subsequent sigmatropic rearrangements have been outlined.

Sulfoxide-directed intramolecular [4 + 2] cycloadditions between 2-sulfinyl butadienes and unactivated alkynes.

Sulfinyl dienynes undergo thermal and catalyzed IMDA cycloadditions, often at room temperature, to produce cyclohexa-1,4-dienes with good yields and high selectivities. Additionally, the products preserve a synthetically useful vinyl sulfoxide functionality. The selective manipulation of the double bonds in the cycloadducts has also been examined in this work.

Asymmetric Claisen rearrangements on chiral vinyl sulfoxides.

Highly diastereoselective Claisen rearrangements of acyclic allyl vinyl ethers bearing a chiral sulfoxide at C-5 provide gamma-delta-unsaturated aldehydes or ketones with up to two consecutive asymmetric centers in the molecule whilst preserving a useful vinyl sulfoxide. The reactivity of related vinyl sulfides and sulfones has also been examined in this work.

Highly diastereoselective Katsuki-Jacobsen oxidation-epoxidation of alpha-silyloxy sulfinyl dienes: synthetic applications.

Katsuki-Jacobsen oxidation-epoxidation of acyclic alpha-silyloxy sulfinyl dienes, followed by acid-promoted cyclization, leads to 2,5-trans-sulfonyl dihydrofurans with good selectivities. As an application, the formal syntheses of (6S,7S,9R,10R)- and (6S,7S,9S,10S)-6,9-epoxynonadec-18-ene-7,10-diols is reported.

[2,3]-Sigmatropic rearrangements of 3-sulfinyl dihydropyrans: application to the syntheses of the cores of ent-dysiherbaine and deoxymalayamicin A.

The [2,3]-sigmatropic rearrangement of a variety of configurationally stable diastereomeric allylic sulfinyl dihydropyrans, produced by base-promoted cyclization of sulfinyl dienols, has been studied. In some cases, the efficient transformation of these substrates into dihydropyranols required an in-depth study of reaction conditions, with the preferred protocol relying on the use of DABCO in warm toluene. This methodology has been applied to the syntheses of the cores of ent-dysiherbaine and deoxymalayamicin A by means of efficient tethered aminohydroxylations.

Sulfur-directed enantioselective synthesis of functionalized dihydropyrans.

The highly selective base-promoted cyclization of enantiopure sulfinyl dienols affords allylic sulfinyl dihydropyrans. The scope of this methodology, including the preparation of seven-membered rings, has been studied in depth. The reactivity of our sulfinyl dihydropyrans toward oxidation, imination, and dihydroxylation has been explored, and thus several routes to densely functionalized pyran derivatives have been outlined. The reactivity of allylic dihydropyranyl sulfones and sulfoximines in S(N)2' processes with organocuprates has been examined. The displacement products were obtained with good regio- and stereoselectivity and fair to good yields. The reactivity of these products to dihydroxylation opens new possibilities to access enantiopure polyhydroxylated tetrahydropyrans that could be of interest for the synthesis of natural products.

Desulfinylation of Ag(I) Sulfinyl Mesoionic Carbenes: Preparation of C-Unsubstituted Au(I)-1,2,3-Triazole Carbene Complexes.

New and well-characterized Ag-bis(1,2,3-triazolylidene) complexes having enantiopure (S)-sulfoxides upon sequential treatment with alcohols and Au(I) form separable mixtures of regioisomeric C-unsubstituted Au-1,2,3-triazolylidene complexes. Mechanistic studies and DFT calculations support a desulfinylation process for in situ generated free triazolylidene salts.

Gold Sulfinyl Mesoionic Carbenes: Synthesis, Structure, and Catalytic Activity.

Gold mesoionic carbenes having a chiral sulfoxide group attached to the C4 position of the five membered ring have been prepared and tested as catalysts in the cycloisomerization of enynes. These new catalysts are very efficient, with the sulfoxide moiety playing a key role in their activity and the N1-substituent in control of the regioselectivity of these processes.

Sulfoxide-directed enantioselective synthesis of functionalized dihydropyrans.

[reaction: see text] The highly selective base-promoted cyclization of enantiopure sulfinyl dienols affords allylic sulfinyl dihydropyrans.

Sulfinyl-mediated chirality transfer in diastereoselective Claisen rearrangements.

[reaction: see text] The highly selective Claisen rearrangements of substrates bearing a sulfinyl moiety at C-5 allow for creation of up to two asymmetric centers and preserve a useful vinyl sulfoxide.