Base-catalyzed reaction between isatins and N-Boc-3-pyrrolin-2-one

The base-catalyzed reaction between isatins and N-Boc-3-pyrrolin-2-one yields Morita–Baylis–Hillman (MBH) adducts instead of the expected aldol products in good to high yields (up to 97%). Various organic and inorganic bases are efficient catalysts for this reaction. Our study excluded the Morita–Baylis–Hillman mechanism for the formation of the MBH-type products. The MBH products are most likely formed as a result of the subsequent isomerization of the original aldol products between isatins and N-Boc-3-pyrrolin-2-one.     

Synthesis of N-acyl-N,O-acetals from N-aryl amides and acetals in the presence of TMSOTf

Secondary amides undergo in situ silyl imidate formation mediated by TMSOTf and an amine base, followed by addition to acetal acceptors to provide N-acyl-N,O-acetals in good yields. An analogous, high-yielding reaction is observed with 2-mercaptothiazoline as the silyl imidate precursor. Competing reduction of the acetal to the corresponding methyl ether via transfer hydrogenation can be circumvented by the replacement of CY₂NMe with 2,6-lutidine under otherwise identical reaction conditions.     

An efficient synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenyl piperidine and N-Boc-safingol

An efficient strategy has been developed for the stereo selective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenyl piperidine and N-Boc-safingol from benzaldehyde and N-Boc-imine.     

Synthesis of eight-membered iminocyclitols from d-glucose

The Baylis-Hillman reaction of 3-O-benzyl-α-d-xylo-pentodialdo-1,4-furanose 2 afforded a diastereomeric mixture of l-ido- and d-gluco-configurated α-methylene-β-hydroxy esters 3a and 3b, respectively, in 1:1 ratio. Conjugate addition of benzyl amine on 3a gave adduct 4a as a major product while, addition of benzyl amine to 3b gave only one diastereomer 4b. Reduction of ester functionality in 4a/4b, opening of 1,2-acetonide functionality followed by reductive amino-cyclization under hydrogenation condition afforded azocanes 1c/1d in good yield.     

Synthesis of 3-acetonyl- and 3-(2-oxoethyl)glutarates

Several synthetic routes to 3-acetonyl- and 3-(2-oxoethyl)glutarates 1-5 have been explored. The most advantageous involves, as the key steps, the conjugate addition of an appropriately substituted vinylmagnesium bromide to an alkylidenemalonic ester, a bis-homologation of the resulting diester and, finally, the reductive ozonolysis of the carbon-carbon double bond. The synthesis can be satisfactorily conducted in good overall yield on a multigram scale.     

Tributylphosphine, excellent organocatalyst for conjugate additions of non-nucleophilic N-containing compounds

Conjugate additions of non-nucleophilic N-containing compounds such as amides, thioamides, sulfonamides, and electron-poor anilines with different Michael acceptors can be promoted through the use of tributylphosphine. The range of useful pK_a's of nucleophiles has been established (pK_a<25) and new insights into the mechanism proposed.     

Conjugate addition of amines to chiral 3-aziridin-2-yl-acrylates

Conjugate addition of benzylamine to chiral methyl cis-3-aziridin-2-yl-acrylates was successfully proceeded to yield 3-aziridin-2-yl-3-benzylaminopropionates in high yield with high stereoselectivity. The addition products were used for the asymmetric synthesis of vicinal diamine derivatives including 4-amino-5-methylpyrrolidin-2-one, 3,4-diaminopentanoate, and 5-chloromethyl-4-alkoxycarbonylmethylimidazolidin-2-one.     

RAFT/MADIX copolymerization of vinyl acetate and 5,6‐benzo‐2‐methylene‐1,3‐dioxepane

The synthesis of well‐defined degradable poly(vinyl acetate) analogues is achieved by RAFT copolymerization of 5,6‐benzo‐2‐methylene‐1,3‐dioxepane (BMDO) and vinyl acetate (VAc) using methyl (ethoxycarbonothioyl)sulfanyl acetate (MEA) as controlling agent. Several monomer mixtures with low BMDO contents (<30 mol %) are employed to prepare different copolymers. In all the cases, the evolution of molar masses and the dispersity values (<1.26) confirm the controlled feature of the polymerization. The livingness of the obtained chains is demonstrated by successful chain extension experiments with VAc, although the presence of dead chains is also shown. The introduction of ester groups into the main chain of these P(VAc‐co‐BMDO) copolymers allows their degradation when treated with a mixture of KOH/MeOH in reflux during 2.5 h. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 104–111     

Synthesis and highly selective Diels-Alder cycloadditions of the new dienes N-substituted 2,3,5,6-tetrahydrobenzoxazol-2-ones

The synthesis of the new dienes N-substituted 2,3,4,5-tetrahydrobenzoxazol-2-ones 8a-8c is described, through a one-step convergent process from 1,2-cyclohexanedione (7a) and the corresponding isocyanates 2a-2c. The presence of electron-donor substituents in the aryl ring of the isocyanate gave rise to the exclusive formation of the captodative olefins 10. Diene 8a proved to be reactive and stereoselective in Diels-Alder additions with a cyclic olefin. The reaction with acetylenic dienophiles yielded the 2,3-dihydrobenzoxazol-2-ones 21 and 24, as the products of sequential [4+2] cycloaddition and retro-Diels-Alder reactions. Methyl vinyl ketone (22) underwent regio- and stereoselective tandem Diels-Alder and Michael additions to give propellane 29a. Evidence of an endo π-pyramidalization of the central double bond of adduct 19 would rationalize the exo stereoselection in the formation of 29a. The regioselectivity in these reactions has been rationalized in terms of FMO theory by ab initio calculations.     

Stereochemical course of the reductive spiroannulations of N-Boc and N-benzyl 2-cyanopiperidines

The stereochemical outcome of spiroannulations of N-protected 2-lithiopiperidines (generated by lithium di-tert-butyl biphenylide (LiDBB) mediated reductive lithiation of 2-cyanopiperidines) was investigated using deuterium labeled side-chains containing phosphate leaving groups. High stereoselectivity was observed when benzyl (Bn) protected 2-cyanopiperidines were employed, while tert-butoxycarbonyl (Boc) protected 2-cyanopiperidines afforded lower selectivity. Models are proposed to rationalize the results of this study.     

Synthesis of 3-(2-nitroalkyl) indoles by reaction of 3-(1-arylsulfonylalkyl) indoles with nitroalkanes

Sulfonyl indoles act as effective precursors of vinylogous imino derivatives in the reaction with nitroalkanes under basic conditions leading to the corresponding nitro indoles in good yield. This procedure represents an effective option to the classical conjugate addition of indoles to nitroalkenes.     

Studies in multidrug resistance reversal: a rapid and stereoselective synthesis of the dihydroagarofuran ring system

Several dihydroagarofuran esters have been reported to be effective multidrug resistance (MDR) reversing agents for both cancer cells and bacteria. We report a rapid synthesis of the dihydroagarofuran ring system from carvone in a sequence that is highlighted by a sequential conjugate addition/aldol sequence, a ring closing metathesis reaction, and a diastereoselective alkene reduction to provide an axial methyl group. The synthesis allows for differential esterification reactions as required to study the roles of these groups in MDR reversal.     

Efficient synthesis of 5-substituted thiazolidin-2-ones from xanthates and tert-butyl N-allylcarbamates

A series of 5-substituted thiazolidin-2-ones with various functional groups was synthesized efficiently via a radical addition of xanthates and tert-butyl N-allylcarbamates and subsequent 88% HCO₂H-catalyzed cyclization. The mechanism of the acid-catalyzed cyclization was proposed as well.     

Synthesis of unsaturated silyl nitronates via the silylation of conjugated nitroalkenes

A new method for the synthesis of conjugated silyl nitronates from nitroalkenes is described. The procedure has wide substrate scope and is compatible with in situ generation of the substrates from 2-nitroalcohols or 2-chloro-nitroalkanes. A cascade transformation to give 3,4,5,6-tetrahydropyridine N-oxide derivatives was disclosed.     

Direct synthesis of N-substituted, functionalized aspartic acids using alkali maleates and amines

A practical and general one-pot synthesis of mono-N-substituted, functionalized aspartic acids has been developed. The N-substituted aspartic acids are formed directly from alkali maleates and primary amines in hot DMSO. Products from several different primary amines can be prepared chemoselectively in moderate to good yields.     

Surprisingly great difference in reactivity depending upon the ring size: solvolysis and molecular structure study of some N-trimethylsilylated cyclic ureas

The molecular structure of N-trimethylsilylated five- (1a-c), six- (2a,b) and seven-membered (3) cyclic ureas was studied by single crystal X-ray diffraction method and quantum chemical calculations. Solvolysis rate constants of compounds in n-octanol/tetrahydrofuran mixtures were determined by gas chromatography. An alternative sampling method eliminating the effect of the hot injector was also developed in the rate measurement of 2a. The half-lives of the five-membered rings (1a,b) were found to be at least three orders of magnitude higher than those of the six- (2a,b) and seven- (3) membered ones. Relationship between the reactivity and the extent of the pseudo-pentacoordination around the silicon centre in reactants was found. The results are in correlation to our simple static (structure-based) predictive model established previously.     

New synthetic method for 2,3-trans-2-methyl-tetrahydropyran-3-ol and oxepan-3-ol by unique insertion of a methyl group

Treatment of tetrahydropyran-3-ol and oxepan-3-ol derivatives, which have a 1′-mesyloxy group at the C-2 side chain, with Me₃Al effected removal of the mesyloxy group, 1,2-hydride shift, and stereoselective insertion of a methyl group into the resulting oxonium ion, giving 2,3-trans-2-methyl-tetrahydropyran-3-ol and oxepan-3-ol derivatives, respectively.     

One-Pot Synthesis of 4-Hydroxy-3-phenyl-2H-pyrano[3,2-b]benzofuran-2-one Derivatives

Novel 4-hydroxy-3-phenyl-2H-pyrano[3,2-b]benzofuran-2-ones (15a–d), were synthesized in a one-step procedure by the reaction of substituted benzofuran-3-ones 12a–d and (chlorocarbonyl)phenyl ketene.     

One-pot synthesis of thia-Michael products from thio acids, epoxides, and electron-deficient alkenes promoted by a silica gel/Et3N combined catalyst

An efficient method for the one-pot production of thia-Michael adducts using thio acids, epoxides, and electron-deficient alkenes is described. Epoxides quickly underwent nucleophilic ring-opening with thio acids on the silica gel surface at room temperature under solvent-free conditions to yield β-hydroxy thioester intermediates. After addition of an electron-deficient alkene and a catalytic amount of Et₃N to the reaction mixture, the β-acyloxy mercaptans were generated in situ and subsequently underwent thia-Michael addition reactions to produce the corresponding adducts in good to excellent yields.