Properly designed modular asymmetric synthesis for enantiopure sulfinamide auxiliaries from N-sulfonyl-1,2,3-oxathiazolidine-2-oxide agents

Simple and practical asymmetric synthesis of functionally differentiated aminoindanol based endo-N-sulfonyl 1,2,3-oxathiazolidine-2-oxide as sulfinyl transfer agents are developed. The importance of these new and unique sulfinyl transfer reagents are exemplified by the expedient production of several sulfinamide ligands, including either enantiomer of (R)-tert-butanesulfinamide in excellent yields and enantiopurities.     

Catalytic enantioselective sulfinyl transfer using cinchona alkaloid catalysts

[reaction: see text] Practical reaction conditions for the catalytic enantioselective synthesis of sulfinate esters are reported. Commercially available cinchona alkaloids were found to be superior catalysts for the sulfinyl transfer reaction of tert-butanesulfinyl chloride and a variety of benzyl alcohols. Sulfinyl transfer with 2,4,6-trichlorobenzyl alcohol and 10 mol % of the commercially available, inexpensive catalyst quinidine provided the pure sulfinate ester product in 92% isolated yield and with 90% ee.     

Formal synthesis of ent-dysiherbaine from sulfinyl dihydropyrans by sigmatropic rearrangement and tethered aminohydroxylation

A stereospecific [2,3]-sigmatropic rearrangement of a sulfinyl dihydropyran, followed by a tethered aminohydroxylation reaction, are the key steps of a formal synthesis of ent-dysiherbaine from an enantiopure sulfinyl dienol.     

Stereochemistry of transition metal catalyzed asymmetric intramolecular allyl transfer in chiral α-sulfinyl allylic esters

The stereochemistry of palladium or nickel catalyzed asymmetric intramolecular allyl transfer in chiral α-sulfinyl allylic esters was determined. The participation of the catalyst and the chiral sulfinyl functionality in these transformations, presumably by the coordination of the sulfinyl group to the catalyst, is discussed, and a novel mechanism is proposed for the rationalization of the results obtained.     

The sulfinyl moiety as an internal nucleophile. 2. Stereoselective synthesis of (-)-galantinic acid via 1,3-asymmetric induction

A stereoselective synthesis of (-)-galantinic acid is disclosed. The key steps include hydrolytic kinetic resolution of a racemic epoxide and regio- and stereoselective heterofunctionalization of an olefin, using a pendant sulfinyl group as the nucleophile. The participation of the sulfinyl group was unambiguously proven by conducting the reaction in the presence of H(2)(18)O.     

Studies on proton pump inhibitors. I. Synthesis of 8-[(2-benzimidazolyl)sulfinyl]-5,6,7,8-tetrahydroquinolines and related compounds

Many 8-[(2-benzimidazolyl)sulfinyl]-5,6,7,8-tetrahydroquinolines were synthesized and examined for their (H+ + K+) adenosine triphosphatase ATPase-inhibitory and antisecretory activities. These sulfinyl compounds could be considered to be rigid analogues of the 2-[(2-pyridyl)methylsulfinyl]benzimidazole class of antisecretory agents. All the compounds tested were potent inhibitors of (H+ + K+)ATPase. Most of the compounds also inhibited histamine-induced gastric acid secretion in rats. Among them, 8-[(5-fluoro-2-benzimidazolyl)sulfinyl]-3-methyl-5,6,7,8-tetrahydroqu inoline (XIVm) was found to have the most potent activity. The structure-activity relationships are discussed.     

The sulfinyl moiety as an internal nucleophile. Part 8: Efficient, stereospecific synthesis of (+)-polyoxamic acid

A straightforward and stereospecific synthesis of (+)-polyoxamic acid is disclosed. The key step of the synthesis involves the regio- and stereospecific bromohydration of an olefin via intramolecular participation by the sulfinyl group.     

Synthesis of an advanced intermediate enroute to (−)-clavosolide A

A stereoselective route to an advanced intermediate toward the synthesis of clavosolide A is disclosed. The key steps include Wadsworth-Emmons cyclopropanation, utilization of a sulfinyl moiety as an internal nucleophile to open a cyclopropane ring activated by Hg(II)- to create the C3-C5 stereogenic centers, CC bond formation employing an α-chloro sulfide, asymmetric transfer hydrogenation, regioselective hydrosilylation and Tamao-Fleming oxidation.     

Catalytic enantioselective synthesis of sulfinate esters through the dynamic resolution of tert-butanesulfinyl chloride

Development of a new synthetic route to obtain enantiomerically enriched tert-butanesulfinate esters in excellent yields through catalytic enantioselective sulfinyl transfer is described. As little as 0.5 mol % of chiral amine catalysts was used to couple racemic tert-butanesulfinyl chloride with arylmethyl alcohols to provide sulfinate esters in near quantitative yields and with enantiomeric excesses up to 81%. The method represents the first example of the catalytic dynamic resolution of sulfinyl derivatives.     

Comparative Kinetic Monte Carlo study of the Sulfinyl and Dithiocarbamate Precursor Route toward Highly Regioregular MDMO‐PPV

A comparative kinetic Monte Carlo (kMC) modeling study is presented for the synthesis of poly(2‐methoxy‐5‐(3′,7′‐dimethyloctyloxy)‐1,4‐phenylenevinylene) (MDMO‐PPV) via the sulfinyl and dithiocarbamate (DTC) precursor route. The sulfinyl precursor route allows a much faster polymerization toward highly regioregular and high molar mass MDMO‐PPV starting from non‐equimolar amounts of the isomeric sulfinyl premonomers. In the DTC precursor route, the polymerization can be started from a single dithiocarbamate premonomer and a higher yield can be reached. In contrast, synthesis of highly regioregular MDMO‐PPV via the sulfinyl precursor route requires separation of the isomeric premonomers after their synthesis and before polymerization.

     

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.     

Stereoselective synthesis of (−)-allosedamine and (1R,3R)-HPA-12 from β-p-toluenesulfonamido-γ,δ-unsaturated sulfoxide

A stereoselective synthesis of (−)-allosedamine and HPA-12 is disclosed. The key steps of the synthesis include the diastereoselective synthesis of a β-sulfonamido unsaturated sulfoxide, elaboration of a bromohydrin via intramolecular sulfinyl group participation and a ring-closing metathesis reaction for the construction of the piperidine ring of allosedamine.     

Asymmetric induction by sulfinyl chirality. A total synthesis of (+)-talaromycin A and (−)-talaromycin B

A total synthesis of (+)-talaromycin A and (−)-talaromycin B was accomplished by means of successive asymmetric induction of all chiral centers using a chiral sulfinyl group.     

手性亚砜的合成及其在不对称合成中的应用

本文综述了手性亚砜的合成。由于亚砜结构上的特征以及与金属离子的络合能力,使手性亚砜在不对称合成中具有强烈的诱导作用,使它成为进行不对称合成的一个手段。本文列举了它在不对称合成中的应用情况。     

Diastereoselective synthesis of N-sulfinyl α-aminophosphine sulfides and phosphines

The diastereoselective synthesis of N-sulfinyl α-aminophosphine sulfides and phosphines is reported. These molecules are synthesized by formation of sulfinyl imine followed by diastereoselective addition of a diphenylphosphine sulfide. The product N-sulfinyl α-aminophosphine sulfides can be converted to phosphines through removal of the sulfur by reaction with Raney nickel. Hydrolysis of the sulfinyl group provides an amine that can then be attached to other ligands or structural scaffolds.     

Asymmetric synthesis of aziridine 2-phosphonates from enantiopure sulfinimines (N-sulfinyl imines). Synthesis of alpha-amino phosphonates

An aza-Darzens reaction, involving the addition of chloromethylphosphonate anions to enantiopure sulfinimines, has been developed for the asymmetric synthesis of aziridine 2-phosphonates. Best results involve cyclization of the syn and anti diastereomerically pure alpha-chloro-beta-amino phosphonates to cis- and trans-N-sulfinyl aziridine 2-phosphonates, respectively, with n-BuLi. A transition-state hypothesis is proposed wherein the chloromethylphosphonate anion adds to the C-N bond on the side that is opposite the bulky p-tolyl sulfinyl group. The N-sulfinyl group is easily removed by treatment with MeMgBr or TFA/MeOH, which affords the NH-aziridines in good yield. Using transfer hydrogenation conditions, the NH-aziridines were regioselectively opened to the corresponding enantiopure alpha-amino phosphonates without N-activation and in excellent yield.     

Sulfinyl Chlorides Through the Oxidative Chlorination of Sulfenyl Derivatives with Trimethylsilyl Acetate/Sulfuryl Chloride System

A new and useful procedure for the synthesis of sulfinyl chlorides is described involving a combined action of trimethylsilyl acetate and sulfuryl chloride as a oxidative chlorination system on sulfenyl derivatives.     

Synthesis of enantiopure ethyl deoxymonate B from allylic sulfinyl dihydropyrans

A completely stereoselective dihydroxylation of a dihydropyranol and a cross-metathesis in the presence of a free homoallylic hydroxyl group are the key steps of a synthesis of enantiopure ethyl deoxymonate B from a sulfinyl dienol.     

A formal convergent synthesis of (+)-trans-solamin

A formal convergent synthesis of solamin is disclosed. The synthetic strategy exploits the potential of the sulfinyl group as an auxiliary, nucleophile and in C-C bond formation. The synthetic route can be adapted to the synthesis of stereoisomers of solamin, analogs with variable carbon side chains, and other members of mono-THF acetogenins.     

Sulfinylamine metathesis at oxo metal species--convenient entry into imido metal chemistry

The exchange of terminal metal oxo functionalities by N-organo and N-sulfonylimido functionalities via metathesis with bent, thus very reactive sulfinyl amines R-NSO and sulfinyl sulfonylamides R-SO(2)-NSO is described. It is demonstrated that in many cases sulfinyl amine metathesis offers a more convenient entry into imido complex synthesis than the much better investigated isocyanate metathesis at oxo complexes or condensation reactions with amines and silylated amines. Improved syntheses for some known key compounds and several new complexes of the type [V(NR)Cl(3)] and [M(NR)(2)Cl(2)] (M = Cr, Mo, W) are described. Emphasis is put on the synthesis of formerly unknown base free Lewis acids with electron-withdrawing N-substituents such as haloaryl and sulfonylaryl. Surprisingly, even [CrO(2)Cl(2)] is selectively transformed by sulfinylamines into aryl imido derivatives without any reduction by sulfur dioxide. The molecular structures of novel haloaryl imido complexes [Cr(NAr)(2)Cl(2)] Ar = C(6)F(5) and 2,4,6-Cl(3)C(6)H(2) as determined by X-ray crystallography are reported.