Nucleophilic epoxidation of γ-alkoxy dienyl sulfoxide derivatives

(E,E) and (Z,E) γ-alkoxy dienyl sulfones undergo nucleophilic epoxidation with remarkable regio- and stereoselectivity to render syn oxiranes in a process mainly controlled by the alkoxy stereocenter. Upon epoxidation γ-hydroxy dienyl sulfoxides provide sulfinyl and sulfonyl oxiranes along with bis-epoxides formed through a Payne rearrangement that can be prevented by silylation of the OH group. Interestingly, the presence of a γ-silyloxy group can invert the stereochemical trend of the molecule affording mainly an anti epoxidation process.     

Katsuki-Jacobsen oxidation-epoxidation of α-silyloxy sulfinyl dienes: application to the formal synthesis of (6S,7S,9R,10R)-6,9-epoxynonadec-18-ene-7,10-diol

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

Polymer-supported selenium-induced electrophilic cyclization: solid-phase synthesis of poly-substituted dihydrofurans and tetrahydrofurans

Poly-substituted dihydrofurans and tetrahydrofurans have been synthesized through polymer-supported selenium-induced intramolecular electrophilic cyclization, followed by selenoxide syn-elimination or novel nucleophilic substitution cleavage of selenium resin with good yields and purities.     

Nucleophilic epoxidation of alpha'-hydroxy vinyl sulfoxides

The nucleophilic epoxidation of a variety of alpha'-(1-hydroxyalkyl) vinyl sulfones and sulfoxides has been studied. The sulfones give rise to anti oxiranes with modest (E) or excellent (Z) selectivities and in good yields. The (E)-sulfoxides display low reactivity within a reinforcing/nonreinforcing scenario. The use of t-BuOOLi in Et(2)O allows for a highly syn-selective epoxidation-oxidation. The (Z)-sulfoxides display a remarkably high reactivity under these conditions. The reinforcing (S,S(S)) diastereomers (3e-g) yield hydroxy sulfinyl oxiranes with high yields and selectivities. In contrast, the (R,S(S)) diastereomers (4e-g) show diminished reactivities and a very substrate-dependent stereochemical outcome. The structure of these oxiranes has been secured by chemical correlations and an X-ray crystal structure.     

Asymmetric synthesis of cyclopropanes and dihydrofurans based on phosphine oxide chemistry

The asymmetric synthesis of gamma-azido trans-cyclopropyl ketones is accomplished via a short, simple and efficient sequence. The cyclopropanation step is achieved by an intramolecular nucleophilic ring closure, with a diphenylphosphinate leaving group, to give trans-cyclopropane exclusively. beta-Keto-diphenylphosphine oxides cyclise to form optically active dihydrofurans. All possible diastereoisomers of dihydrofurans can be prepared selectively starting from the same olefin.     

Stereoselective synthesis of 2,3-difunctionalised thioesters using nucleophilic epoxidation of 1-arylthio-1-nitroalkenes

Stereoselective nucleophilic epoxidation of protected 3-amino and 3-hydroxy-substituted 1-arylthio-1-nitroalkenes, followed by intramolecular capture involving the amino and hydroxyl protecting groups, has led to the formation of isomeric oxazolidinones 5 and 7, and a cyclic carbonate 11. Together with the oxazolidinone precursor anti-alpha-bromo thioester 15a, the absolute and relative stereochemistry of these compounds has been determined by X-ray crystallography.     

Optically pure trans-2,3-disubstituted N-sulfinyl aziridines. Regio- and stereoselective opening mediated by the sulfinyl group

A new entry to optically pure trans-2,3-disubstituted N-sulfinyl aziridines starting from 1,2-aminosulfides, involving formation of a sulfonium salt intermediate followed by intramolecular nucleophilic attack by the sulfinamide nitrogen atom, is reported. The regio- and stereoselective opening of the aziridine ring can be achieved by anchimeric assistance of the sulfinyl group.     

1,3-Dipolar Addition of Methyl α-Diazoacetoacetate to Enamines： A New Synthetic Route to 5-Amino-4,5-dihydrofurans

The reaction of methyl α-diazoacetoacetate with enamines catalyzed by dirhodium and copper complexes underwent formal 1,3-dipolar addition to give 5-amino-4,5-dihydrofurans in moderate yields. The reaction was suggested to proceed via a nucleophilic addition of enamines to rnetal-carbenes and a subsequent intramolecular cyclization of the resulting zwitterionic intermediates.     

Synthesis of highly substituted enantiopure piperazines and ketopiperazines from vicinal N-sulfinyl diamines

Enantiopure 1-benzyl-2,3-disubstituted piperazines (4) have been synthesized by treatment of N-sulfinyl-N-benzyldiamino alcohols (1) with diethyl oxalate and sodium methoxide followed by reduction with borane. Alternatively, the sulfinamido group was preserved by an N-acylation/cyclization protocol using alpha-chloroacetyl chloride that led to the synthesis of N-sulfinyl ketopiperazines (11). Ensuing elimination of the sulfinyl group with NaH produced imino ketopiperazines (9) that are suitably functionalized for nucleophilic addition to the imino moiety. Stereoselective and high yielding allylation of imino ketopiperazines (9c) was achieved under Barbier conditions using CeCl3.7H2O as the additive.     

Complete stereocontrol in organocatalytic additions of β-ketosulfoxides to conjugated aldehydes

The use of β-ketosulfoxides as nucleophiles in reactions with α,β-unsaturated aldehydes catalyzed by proline derivatives allows complete control of configuration at the two chiral centers that are created during 1,4-addition reactions. The sulfinyl group can be used to create additional chiral centers in the resulting compounds and then removed while preserving the chirality of the carbon joined to the sulfur. The catalyst and the sulfinyl group are mainly responsible for the configurational control of the carbon atoms acting as electrophile and nucleophile, respectively, which allows the preparation of the four possible diastereoisomers in optically pure form. Theoretical calculations of the possible chiral nucleophilic species bearing diastereotopic faces allow us to postulate, for the first time, that enolates, instead of enols, are the active reagents in these reactions.     

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.     

Novel,short, stereospecific synthesis of lyxo-(2R,3R,4R)-phytosphingosine and erythro-(2R,3S)-sphingosine

Lyxo-phytosphingosine and erythro-sphingosine have been elaborated from a common intermediate. The key step in the reaction sequence involves stereo- and regiospecific functionalization of an olefin by intramolecular nucleophilic sulfinyl group participation.     

Theoretical investigation on the chiral diamine-catalyzed epoxidation of cyclic enones: mechanism and effects of cocatalyst

The asymmetric epoxidation of 2-cyclohexen-1-one with aqueous H(2)O(2) as oxidant, 1,2-diaminocyclohexane as catalyst, and a Br?nsted acid trifluoroacetic acid (TFA) as cocatalyst has been studied by performing density functional theory calculations. It is confirmed that the catalyzed epoxidation proceeds via sequential nucleophilic addition and ring-closure processes involving a ketiminium intermediate. Four possible pathways associated with two Z isomers and two E isomers of ketiminium have been explored in detail. Our calculation indicates that these four pathways have high barriers and a small energy gap between two more favorable R and S pathways. We have analyzed the effects of the TFA anion and H(2)O on the activity and enantioselectivity of catalytic epoxidation. It is found that the TFA anion acts as a counterion to stabilize the transition states of the catalytic epoxidation by hydrogen-bond acceptance, leading to decreases in the barriers of the nucleophilic addition and ring-closure processes. The most significant decrease occurred in the ring-closure step of the Z-R-pathway, resulting in H-bond-induced enantioselectivity. Our calculations also show that water cooperates with TFA to further increase the reaction rate significantly.     

Highly enantioselective addition of phenylethynylzinc to aldehydes using aziridine-functionalized tridentate sulfinyl ligands

Diastereomerically pure tridentate heteroorganic ligands containing hydroxyl, sulfinyl and aziridine moieties as nucleophilic centers, capable of binding to various organometallic reagents, have been proven to be highly efficient catalysts in the enantioselective addition of phenylethynylzinc to aldehydes to give the desired products in very high yields (up to 95%) and with ee’s up to 90%. The influence of the stereogenic centers located on the sulfinyl sulfur atom and in the aziridine moiety on the stereochemical course of the reaction is also discussed.     

Asymmetric epoxy cyclohexenyl sulfones: readily accessible progenitors of stereo defined six-carbon arrays

[formula: see text] Enantiopure epoxy vinyl sulfones serve as highly effective substrates for a variety of stereo- and regiospecific oxidation and nucleophilic functionalization reactions. These materials can be easily transformed to cyclic and acyclic six-carbon segments. Nucleophilic epoxidation of 3a,b followed by palladium[0] catalysis enables access to differentially protected arene diols 21 and 22.     

New synthesis of pentacyclic steroids by stereoselective epoxide ring opening

A stereoselective synthesis of pentacyclic steroids has been achieved. Starting from commercially available cholic acid 1, followed by asymmetric epoxidation and by stereoselective epoxide ring opening, employing nucleophilic species, the corresponding products were afforded in good yields. The compounds were being evaluated for their biological activity.     

Intramolecular Substitution Reaction of Alkylidene‐Lithium Carbenoids: Regioselective Synthesis of Indenes

Intramolecular substitution reaction of geminal dibromo alkenes proceeds to afford indenes, dihydronaphthalenes, dihydrofurans, and dihydropyran via in situ generated lithium alkylidene carbenoids, which have a carbon or oxygen nucleophilic moiety. This reaction provides a regioselective method for the preparation of polysubstituted indenes.     

Regio- and stereoselective transfer of p-toluenesulfonamido group from sulfur to carbon: preparation of aminoalcohol derivatives from allylalcohols

A novel methodology for the regio- and stereoselective synthesis of amino alcohol derivatives from allylalcohols/ethers via intramolecular nucleophilic participation by the sulfilimine moiety is disclosed. The sulfilimine moiety is stereospecifically transformed to a sulfinyl moiety with an inverted configuration. The reaction is general and affords highly functionalised products.     

Syntheses of 6-fluoro-7-piperazin-1-yl-9-cyclopropyl-2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-dione and 6-fluoro-7-piperazin-1-yl-9-p-fluorophenyl-2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-dione

The syntheses of 6-fluoro-7-piperazin-1-yl-9-cyclopropyl (or 9-p-fluorophenyl)-2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-diones as well as novel synthesis of isothiazolo-3(2H)-one system are described. Key steps include the regiospecific displacement of a sulfinyl group and the amination of the resultant mercapto derivative followed by an intramolecular nucleophilic displacement cyclization reaction to generate the novel 2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-dione nucleus.     

正十六烷基磺酰氯的合成

正十六烷醇经亚磺酰甩作用转换成1－氯代正十六烷,在相转移催化剂条件下,1－氯代正十六烷和硫脲进行亲核反应,合成正十六烷基异硫脲盐酸盐,并以此为中间体用氯气氧化法制备正十六烷基磺酰氯,纯度大于95％,总收率为67％。