Asymmetric lithiation of 2-alkynyl aryl sulfides—Enantio- and diastereoselective formation of allenyl aryl sulfides and their application in nickel-catalyzed cross-coupling reactions

The enantio- and diastereoselective synthesis of allenyl aryl sulfides by asymmetric lithiation of 2-alkynyl (2-hetero)aryl sulfides is described. A dynamic thermodynamic resolution by selective crystallization of the intermediate lithium complexes derived from deprotonation, applying a bis(oxazoline) ligand, was achieved to give enantioselectivities up to 85% ee. Subsequent stereospecific nickel-catalyzed cross-coupling reactions with arylzinc reagents established a versatile access to threefold carbon-substituted allenes.     

5,6-Trimethylenethiapyrylium and 5,6,7,8-tetrahydrothiochromylium salts

5,6-Trimethylenethiapyrylium salts have been obtained for the first time. 5,6-Trimethyleneγ-thiopyrans (or 5,6,7,8-tetrahydro-γ-thiochromenes), which belong to a previously unknown series of two-ring sulfides, are formed by reaction of the 5,6-trimethylenethiapyrylium salts (or 5,6,7,8-tetrahydrothiochromylium salts) with Grignard reagents and lithium aluminum hydride.     

Transition-Metal-Free Difunctionalization of Sulfur Nucleophiles**

Efficient protocols for accessing iodo-substituted diaryl and aryl(vinyl) sulfides have been developed using iodonium salts as reactive electrophilic arylation and vinylation reagents. The reactions take place under transition-metal-free conditions, employing odorless and convenient sulfur reagents. A wide variety of functional groups are tolerated in the S-diarylation, enabling the regioselective late-stage application of several heterocycles and drug molecules under mild reaction conditions. A novel S-difunctionalization pathway was discovered using vinyliodonium salts, which proceeds under additive-free reaction conditions and grants excellent stereoselectivity in the synthesis of aryl(vinyl) sulfides. A one-pot strategy combining transition-metal-free diarylation and subsequent reduction provided facile access to electron-rich thioanilines and a direct synthesis of a potential drug candidate derivative. The retained iodo group allows a wide array of further synthetic transformations. Mechanistic insights were elucidated by isolating the key intermediate, and the relevant energy profile was substantiated by DFT calculations.     

1,2-联烯基酮的合成与反应

1,2-联烯基酮可以通过2-丙炔基酮异构化反应,相应有机金属试剂中间体与酯、酰氯或酰胺的反应,[2,3]或[3,3]迁移反应,Wittig反应,消除反应,2,3-联烯醇氧化等方法合成。由于联烯酮上含有吸电子基团羰基,它可发生亲核加成、环加成、环化反应。     

Synthesis and reactivity of sulfur and silyl substituted α-alkylidene-β-lactams

Synthetically valuable α-alkylidene-β-lactams are produced from the addition of chlorosulfonyl isocyanate to allenyl sulfides.     

Cu(I)/Chiral Bisoxazoline-Catalyzed Enantioselective Doyle-Kirmse Reaction of Allenyl Sulfides with α-Diazoesters

Herein, a Cu(I)-catalyzed enantioselective Doyle-Kirmse reaction of allenyl sulfides and α-diazoesters is reported, which provides an efficient synthetic route to enantio-enriched chiral tertiary homopropargylic sulfides. This reaction features high enantioselectivities (up to 96 % ee) and good functional group tolerance. The alkyl substituted α-diazoester has also been demonstrated as the efficient substrates in the asymmetric Doyle-Kirmse reaction. Mechanistic studies, including kinetic experiments, were conducted to gain insights into the details of the reaction pathway. The potential synthetic utility of this protocol has also been demonstrated.     

Reaction of arylthiacyclanylsulfonium salts with nitrogen bases

When arylthiacyclanylsulfonium salts are heated with nitrogen bases the C-S bond of the heteroring undergoes quantitative cleavage and the base adds to form a C-N bond. These sulfonium salts react with ammonia or pyridine to give ammonioalkyl sulfides; amino sulfides and secondary amine salts are obtained with excess secondary amines. The described reaction is a new preparative method for the synthesis of amino sulfides and ammonioalkyl aryl sulfides.     

Electrophilic Vinylation of Thiols under Mild and Transition Metal-Free Conditions

The iodine(III) reagents vinylbenziodoxolones (VBX) were employed to vinylate a series of aliphatic and aromatic thiols, providing E-alkenyl sulfides with complete chemo- and regioselectivity, as well as excellent stereoselectivity. The methodology displays high functional group tolerance and proceeds under mild and transition metal-free conditions without the need for excess substrate or reagents. Mercaptothiazoles could be vinylated under modified conditions, resulting in opposite stereoselectivity compared to previous reactions with vinyliodonium salts. Novel VBX reagents with substituted benziodoxolone cores were prepared, and improved reactivity was discovered with a dimethyl-substituted core.     

Oxidation does not (always) kill reactivity of transition metals: solution-phase conversion of nanoscale transition metal oxides to phosphides and sulfides

Unexpected reactivity on the part of oxide nanoparticles that enables their transformation into phosphides or sulfides by solution-phase reaction with trioctylphosphine (TOP) or sulfur, respectively, at temperatures of ≤370 °C is reported. Impressively, single-phase phosphide products are produced, in some cases with controlled anisotropy and narrow polydispersity. The generality of the approach is demonstrated for Ni, Fe, and Co, and while manganese oxides are not sufficiently reactive toward TOP to form phosphides, they do yield MnS upon reaction with sulfur. The reactivity can be attributed to the small size of the precursor particles, since attempts to convert bulk oxides or even particles with sizes approaching 50 nm were unsuccessful. Overall, the use of oxide nanoparticles, which are easily accessed via reaction of inexpensive salts with air, in lieu of organometallic reagents (e.g., metal carbonyls), which may or may not be transformed into metal nanoparticles, greatly simplifies the production of nanoscale phosphides and sulfides. The precursor nanoparticles can easily be produced in large quantities and stored in the solid state without concern that "oxidation" will limit their reactivity.     

Electrophilic Vinylation of Thiols under Mild and Transition Metal‐Free Conditions

The iodine(III) reagents vinylbenziodoxolones (VBX) were employed to vinylate a series of aliphatic and aromatic thiols, providing E‐alkenyl sulfides with complete chemo‐ and regioselectivity, as well as excellent stereoselectivity. The methodology displays high functional group tolerance and proceeds under mild and transition metal‐free conditions without the need for excess substrate or reagents. Mercaptothiazoles could be vinylated under modified conditions, resulting in opposite stereoselectivity compared to previous reactions with vinyliodonium salts. Novel VBX reagents with substituted benziodoxolone cores were prepared, and improved reactivity was discovered with a dimethyl‐substituted core.     

Ab Initio Calculations of the Protonated Forms of Vinyl Methyl and Allenyl Methyl Ethers and Sulfides

The torsion potentials of the protonated forms of vinyl methyl and allenyl methyl ethers and sulfides were calculated by the ab initio HF, MP2, and B3LYP methods. The requirements to calculations of series of these compounds were established. It was confirmed that preferable protonation occurs on the -carbon atom. Proton affinity energies were calculated. For allenyl methyl sulfide, rotamers may be formed in the gas phase under normal conditions.     

Organic synthesis with reagents derived from 3R3SiMgMe and MnCl2

Synthetically useful reactions mediated by reagents derived from 3 equiv. of R₃SiMgMe and MnCl₂ are disclosed. (1) The manganese species reacted with terminal acetylenes to give 1,2-disilylated 1-alkenes. Mono- and bis(trimethylsilyl) acetylenes gave tri- and tetrasilylated ethenes, respectively, in good yields. Highly strained tetrakis(trimethylsilyl) ethene has now become easily accessible by this technique. (2) The reaction of alkenyl halides, alkenyl sulfides, and enol phosphates with the title reagents provides vinylsilanes in good yields. The method is also applicable to the synthesis of allylsilanes from allylic sulfides and ethers. (3) Treatment of 1,3-dienes with the manganese reagents provides silylated allylmanganese compounds which add to the carbonyl moiety with high regio-selectivity.     

One-pot synthesis of α-phenylsulfinyl ketones by reaction of phenyl benzenethiosulfinate with enolate anions,and synthesis of sulfoxides and sulfides by its reaction with Grignard reagents

Phenyl benzenethiosulfinate reacts with enolate anions derived from ketones to give α-phenylsulfinyl ketones directly, together with minor amounts of α-phenylsulfanyl ketones. These are easily separated by forming the water-soluble sodium salts of the sulfinyl compounds. Grignard reagents also react with phenyl benzenethiosulfinate, to give mixtures of sulfoxides and sulfides.     

Palladium pincer complex catalyzed stannyl and silyl transfer to propargylic substrates: synthetic scope and mechanism

Pincer complex catalyzed substitution of various propargylic substrates could be achieved using tin- and silicon-based dimetallic reagents to obtain propargyl- and allenylstannanes and silanes. These reactions involving chloride, mesylate, and epoxide substrates could be carried out under mild conditions, and therefore many functionalities (such as COOEt, OR, OH, NR, and NAc) are tolerated. It was shown that pincer catalysts with electron-supplying ligands, such as NCN, SCS, and SeCSe complexes, display the highest catalytic activity. The catalytic substitution of secondary propargyl chlorides and primary propargyl chlorides with electron-withdrawing substituents proceeds with high regioselectivity providing the allenyl product. Opening of the propargyl epoxides takes place with an excellent stereo- and regioselectivity to give stereodefined allenylstannanes. Silylstannanes as dimetallic reagents undergo an exclusive silyl transfer to the propargylic substrate affording allenylsilanes with high regioselectivity. According to our mechanistic studies, the key intermediate of the reaction is an organostannane (or silane)-coordinated pincer complex, which is formed from the dimetallic reagent and the corresponding pincer complex catalyst. DFT modeling studies have shown that the trimethylstannyl functionality is transferred to the propargylic substrate in a single reaction step with high allenyl selectivity. Inspection of the TS structures reveals that the trimethylstannyl group transfer is initiated by the attack of the palladium-tin sigma-bond electrons on the propargylic substrate. This is a novel mechanism in palladium chemistry, which is based on the unique topology of the pincer complex catalysts.     

Reactions of disubstituted (in the phenyl ring) arylthiolanium and arylthianium salts with amines

The reactions of 2(3)-methyl-4-hydroxy- and 2,4-dihydroxyphenylthiolanium salts with excess secondary amine (piperidine, morpholine) lead to the corresponding aryl aminobutyl sulfides. The amino sulfides formed on the basis of 2,5-dihydroxyphenylthiolanium and -thianium salts are unstable and require rapid treatment with acetic anhydride or HCl. The reaction of 2,4-dihydroxyphenylthiolanium and 2,5-dihydroxyphenylthianium salts with an equimolar amount of amine makes it possible to isolate the intermediate zwitterionic phenoxides.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1552–1558, November, 1988.     

Syntheses and some properties of N-unsubstituted sulfilimines

A variety of S-aminosulfonium mesitylenesulfonates, R¹R²S⁺NH₂·X⁻, were prepared in high yields by the reaction of sulfides with O-mesitylenesulfonylhydroxylamine (MSH). The thermal stability of the derived sulfilimines was examined. Reaction of allyl sulfides with MSH afforded directly the salts of allylamines in good yields, presumably via [2,3]-sigmatropic rearrangement of unisolable allylsulfilimines followed by S---N bond cleavage. The reactions of disulfides and thioketone with MSH are also described.     

The Reaction of Organometallic Reagents with Unsymmetrically Substituted Vinamidinium and Chloropropeniminium Salts

A variety of organometallic reagents have been found to undergo regioselective reaction with 1-aryl-vinamidinium salts and 3-aryl-3-chloropropeniminium salts. The products of such reactions were found to be α,β-unsaturated ketones and chlorovinyl amines, respectively.     

联二烯丁基硫醚衍生物合成呋喃的反应

本文报道以联二烯丁基硫醚为起始物的呋喃衍生物的合成方法.实验结果表明,β-联二烯丁基硫醚醇在氢化钠的作用下以很高的收率环化生成一个苯硫基离去的呋喃产物,β-联二烯丁基硫醚醛与外加亲核试剂作用后能得到多一个取代的类似呋喃产物,而β-联二烯丁基硫醚酮在P2O5的促进下也能环化生成呋喃衍生物.     

Conjugate addition reactions of alpha-aminoalkylcuprates with alpha, beta-alkenyl-, alpha,beta-alkynyl-, alpha,beta-beta,gamma-allenyl-, and alpha,beta-gamma,delta-dienyl carboxylic acid derivatives, nitriles, and sulfoxides

alpha-Aminoalkylcuprates prepared from alpha-lithio carbamates and CuCN.2LiCl participate in 1,4-addition reactions with alpha, beta-unsaturated esters, thiol esters, imides, and nitriles in poor to excellent yields depending upon the electron-withdrawing substituent and the substitution pattern of the unsaturated substrate. These reagents also undergo conjugate addition reactions with alpha,beta-alkynyl esters, sulfoxides, and nitriles and with alpha,beta-beta,gamma-unsaturated allenyl esters. Excellent stereocontrol is achieved in the conjugate additions of alpha-aminoalkylcuprates to the allenyl esters, while poor stereoselectivity results in the conjugate additions to the alkynyl derivatives. Deprotection and cyclization of the alkynyl adducts affords pyrrolin-2-ones, while similar treatment of the allenyl adducts affords 4-alkylidine- pyrrolidin-2-ones and pyrrolizidinones.     

Electronic absorption spectrum of methyl allenyl sulfide

The ultraviolet absorption spectrum of methyl allenyl sulfide CH₃SCHCCH₂ was recorded in solution from 30000–50000 cm^?1 in order to inquire further into the role of sulfur 3d valence-shell and 4s Rydberg-type atomic orbitals for the low-lying excited singlet states in unsaturated organic sulfides. It is shown that sulfur 3d atomic orbitals cannot be neglected for the interpretation of the low-energy excited singlet states of unsaturated organic sulfides.