The silylalkyne-Prins cyclization: a novel synthesis of 4-iododihydropyrans

The silylated secondary homopropargylic alcohols undergo smooth coupling with aldehydes in the presence of molecular iodine under mild reaction conditions to produce 4-iododihydropyrans in good yields. This method is highly stereoselective, affording cis-dihydropyrans exclusively.     

Heteroarenium salts in synthesis. Highly functionalized tetra- and pentasubstituted pyridines

Activation of chloropyridines by heteroarenium substituents allows sequential substitutions by O-, N-, and S-nucleophiles. Reaction of 2,3,5,6-tetrachloropyridine and 4-ethylsulfanyl-2,3,5,6-tetrachloropyridine with 4-(dimethylamino)pyridine, 4-(pyrrolidin-1-yl)pyridine, or 4-aminopyridine results in the formation of 2,6-bis-heteroarenium substituted 3,5-dichloropyridines. On nucleophilic displacement of the heteroarenium substituents by O-, N-, or S-nucleophiles highly functionalized 3,5-dichloropyridines form which possess N²,S⁴,N⁶-, O²,S⁴,O⁶-, O²,O⁶-, N²,N⁶-, and S²,S⁶-substitution patterns.     

New multicomponent cyclization: domino synthesis of pentasubstituted pyridines under solvent-free conditions

An efficient methodology for the synthesis of highly functionalized pyridine derivatives starting from readily available common reactants has been developed under microwave irradiation and solvent-free conditions. The new domino reaction enables successful assembly of five new σ bonds including two C-N bonds in a one-pot operation. A new mechanism has been proposed, which involves a novel reaction and sequence consisting of deprotonation-imine formation-anionic carbonyl addition.     

Regio- and stereoselective synthesis of isoindolin-1-ones via electrophilic cyclization

[reaction: see text] A variety of substituted isoindolin-1-ones are readily prepared in good to excellent yields under very mild reaction conditions by the reaction of o-(1-alkynyl)benzamides with ICl, I(2), and NBS. In a few cases, substituted isoquinolin-1-ones were obtained as the major product instead. This methodology accommodates various alkynyl amides and functional groups and has been successfully extended to heterocyclic starting materials. This chemistry has been successfully applied to the synthesis of a biologically interesting alkaloid, cepharanone B.     

Expedient stereoselective synthesis of coronafacic acid through intramolecular Diels-Alder cyclization

A stereoselective synthesis of coronafacic acid, a natural component of the phytotoxin coronatin, was achieved using an intramolecular Diels-Alder reaction as the key step. The triene precursor bearing a substituted diene and a vinylketone as dienophile was synthesized and then tested in the thermal intramolecular cyclization. We have devised a new strategy to assemble the E,Z-diene through the stereoselective aldol reaction of an ester enolate followed by a stereoselective dehydration. Following the thermal cyclization, the corresponding hydrindanone thereby obtained with the desired relative stereochemistry could easily be converted into the natural product. The synthesis of the coronafacic acid was accomplished in six steps in 29% overall yield.     

Highly regio- and stereoselective synthesis of indene derivatives via electrophilic cyclization

[reaction: see text] Indene or naphthalene derivatives are readily prepared in moderate to excellent yields with high regio- and stereoselectivity under very mild reaction conditions by the reaction of acetylenic malonates and ketones with I2, ICl, or NIS. The resulting iodides can be further elaborated using palladium-catalyzed coupling reactions.     

Regulation of cyclization for the stereoselective synthesis of substituted tetrahydrofurans and tetrahydrooxepines

Dramatic solvent effect is observed during the cyclization of 1. Synthesis of 2 is achieved from the reaction of 1 with a hexamethylditin-catalyzed palladium complex followed by aldehydes in the presence of TMSOTf in THF, whereas 3 is formed in CH2Cl2. The method described herein is successful with various substrates 1 in good yields and high levels of diastereoselectivity.     

PTSA-catalyzed tandem cyclization protocol for the stereoselective total synthesis of obolactone

Stereoselective total synthesis of obolactone by the Brønsted acid (PTSA) mediated tandem cyclization of the appropriately substituted diketone in one-pot in a highly selective and efficient manner is reported.     

Practical and convenient synthesis of N-heterocycles: stereoselective cyclization of N-alkenylamides with t-BuOI under neutral conditions

[Structure: see text] tert-Butyl hypoiodite (t-BuOI) was found to be a powerful reagent for the cyclization of N-alkenylamides leading to a variety of N-heterocycles under extremely mild conditions. When N-alkenylsulfonamides were employed in the reaction, three- to six-membered saturated N-heterocycles were obtained in good to excellent yields with complete stereoselectivity. The method was applicable to the cyclization of alkenylbenzamide derivatives to afford N-, O- or N-, S-heterocycles.     

Highly stereoselective synthesis of 2,5-disubstituted 3-vinylidene tetetrahydrofurans via Prins-type cyclization

[reaction: see text]. A novel synthetic methodology for 2,5-disubstituted tetrahydrofurans having an allenyl group at the 3-position via Prins-type cyclization was developed. The reaction led to excellent selectivity and moderate to high yields.     

CAN mediated cyclization of epoxypropyl cinnamyl ethers: a facile stereoselective synthesis of tetrahydropyran derivatives

Cerium(IV) ammonium nitrate in substoichiometric amounts, promotes the intramolecular cyclization of epoxypropyl cinnamyl ethers to the corresponding 3,4,5-trisubstituted tetrahydropyran derivatives in moderate to good yields.     

吲哚并喹嗪衍生物的立体选择性合成

用锂铝氢四还原卟啉得到卟啉醇,它与甲乙酮反应得相应的羟甲基氨基酮,在相转移条件下,它能被转化成光学纯吲哚并喹嗪衍生物.列出了环化机理的反应流程.     

Catalytic stereoselective synthesis of highly substituted indanones via tandem Nazarov cyclization and electrophilic fluorination trapping

A new catalytic stereoselective tandem transformation via Nazarov cyclization/electrophilic fluorination has been accomplished. This sequence is efficiently catalyzed by a Cu(II) complex to afford fluorine-containing 1-indanone derivatives with two new stereocenters with high diastereoselectivity (trans/cis up to 49/1). Three examples of catalytic enantioselective tandem transformation are presented.     

An efficient approach to the stereoselective synthesis of 2,6-disubstituted dihydropyrans via stannyl-Prins cyclization

A general method has been developed for the stereoselective construction of 2,6-disubstituted dihydropyrans based on the Lewis acid-catalyzed intramolecular reactions of oxocarbenium ions with vinylstannanes. This novel methodology was applied to the enantioselective total synthesis of (−)-centrolobine.     

A Samarium(II)-mediated, stereoselective cyclization for the synthesis of azaspirocycles

Unsaturated keto-lactams undergo sequential conjugate reduction-aldol cyclization on treatment with SmI 2 to give syn-spirocyclic pyrrolidinones and piperidinones containing vicinal, fully substituted stereocenters with complete diastereocontrol. The substituent on nitrogen and the lactam ring size have a marked impact on the efficiency of the spirocyclization.     

6-Exo-spiro (alkoxycarbonylamino)methyl radical cyclization: highly regio- and stereoselective synthesis of (-)-sibirine

[reaction: see text] The (methoxycarbonylamino)methyl radical can be readily generated from its PhSe precursor and undergoes preferential 6-exo-spiro cyclization when PhSO(2) is attached at the distal alkene carbon. This property was applied to the synthesis of the racemic and optically active spirocyclic alkaloid sibirine.     

One-pot regio- and stereoselective cyclization of 1,2,n-triols

A simple and efficient process to cyclize triols containing a 1,2-diol functionality with a pendant hydroxyl group is presented. The one-pot procedure converts the 1,2-diol into an ortho ester in situ, which upon treatment with a Lewis acid generates a cyclic acetoxonium intermediate. This intermediate is subsequently trapped by the pendant hydroxyl group to generate a cyclic ether. The stereochemistry of the 1,2-diol is transferred to the product with complete fidelity (inversion at the site of cyclization), and the reaction proceeds with high regioselectivity. The process is akin to the Lewis acid-catalyzed intramolecular ring-opening of epoxides with hydroxyl groups yielding cyclic ethers of various sizes with regio- and stereochemical control.     

Enantioselective organocatalytic Michael-Wittig-Michael-Michael reaction: dichotomous construction of pentasubstituted cyclopentanecarbaldehydes and pentasubstituted cyclohexanecarbaldehydes

Michael addition of carbethoxymethylenetriphenylphosphorane (a Wittig reagent) to nitroalkenes, followed by a reaction with ethyl formylformate and cinnamaldehydes, or formaldehyde and cinnamaldehydes, provided the respective pentasubstituted cyclopentanecarbaldehydes bearing a quaternary carbon center and pentasubstituted cyclohexanecarbaldehydes having five contiguous stereocenters with excellent enantioselectivities (up to >99% ee).