Highly practical and general synthesis of monodisperse linear pi-conjugated oligoenynes and oligoenediynes with either trans- or cis-olefin configuration

Efficient and practical synthesis of a variety of 1-iodo-4-(trimethylsilyl)but-1-en-3-yne derivatives 1 and 2 with trans- and cis-olefin configuration was described. Their repeated use as building blocks allowed the facile synthesis of trans- and cis-oligoenynes, respectively. Development of a highly practical method for preparing monodisperse trans- and cis-oligoenediynes having the effective conjugation length was also accomplished by using 5 and 4, which can be readily prepared from 1 and 2, respectively.     

A concise synthesis of a very late antigen-4 antagonist trans-4-[1-[[2,5-dichloro-4-(1-methyl-3-indolylcarboxyamide)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid via reductive etherification

This contribution describes a concise synthesis to ethyl trans-[(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate (2b) as a key intermediate of very late antigen-4 (VLA-4) antagonist trans-4-[1-[[2,5-dichloro-4-(1-methyl-3-indolylcarboxyamide)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid (1). The synthesis employs a reductive etherification as a key reaction using (2S,4S)-1-benzyloxycarbonyl-4-methoxypyrrolidine-2-carboxyaldehyde (12) and trans-4-triethylsilyloxycyclohexanecarboxilic acid ethyl ester (13b). This synthesis provides 2b in 6 steps with 38% overall yield from commercially available starting material.     

Synthesis of 5-n-alkyl-2-(trans-4-n-alkylcyclohexyl)pyridines

The cyclization of trans-1-acrylyl-4-n-alkylcyclohexanes with trans-1-N-piperidino-1-alkenes was used to synthesize 3-n-alkyl-6-(trans-4-n-alkyl-cyclohexyl)-3,4-dihydro-2-N-piperidino-2H-pyrans, which were converted under the influence of hydroxylamine to 5-n-alkyl-2-(trans-4-n-alkylcyclohexyl)-pyridines. Problems in the stereochemistry of the cyclohexane derivatives in the investigated scheme of synthesis were examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 643–647, May, 1984.     

Tether-directed selective synthesis of fulleropyrrolidine bisadducts

Selective synthesis of C60 bisadducts has been achieved by using the Prato 1,3-dipolar cycloaddition of tethered bis-azomethine ylides. New bis(benzaldehydes) 1-4 tethered by a rigid linker were prepared and used to direct the second cycloaddition of azomethine ylide to C60. Equatorial, trans-4, trans-3, trans-2, and trans-1 bisadducts have been selectively prepared with this approach. However, the introduction of chiral centers in the pyrrolidine rings in the course of the reaction complicated the chemistry, as a number of stereoisomers theoretically could be formed. The structure determination of the isomeric bisadducts was made based on spectroscopic data and theoretical calculations. To our best knowledge, this represents the first example of a systematic study on tether-directed selective synthesis of C60 fulleropyrrolidine bisadducts.     

Isomerization of trans-[Ru(PTA)4Cl2] to cis-[Ru(PTA)4Cl2] in water and organic solvent: revisiting the chemistry of [Ru(PTA)4Cl2

trans-[Ru(PTA)4Cl2] (trans-1), (PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane) has been isolated and structurally characterized by X-ray crystallography. The structure reveals ruthenium in a slightly distorted-octahedral environment bound to two axial chlorides and four equatorial PTA ligands. In organic solvents, trans-1 undergoes a relatively clean isomerization to cis-1. In aqueous environments, trans-1 undergoes a more complicated transformation involving isomerization, protonation, and ligand substitution affording cis-1 and a series of structurally related molecules. From these results, we conclude that the synthesis of [Ru(PTA)4Cl2] (1) affords trans-1, not cis-1, as earlier reports suggest. The water-soluble hydride cis-[Ru(PTA)4H2] (2) has also been synthesized from the reaction of trans-[Ru(PTA)4Cl2] with excess sodium formate. Compound 2 is stable in deoxygenated water and undergoes H/D exchange with D2O (t1/2 approximately equal to 120 min, at 25 degrees C). The solid-state structures of both trans-1 and 2 are described.     

Catalytic enantioselective aziridoarylation of aryl cinnamyl ethers toward synthesis of trans-3-amino-4-arylchromans

Catalytic enantioselective one-pot aziridoarylation reaction of aryl cinnamyl ethers has been demonstrated in detail. Combination of suitable copper catalyst and chiral bis-oxazoline ligand was found to be very efficient for asymmetric aziridination followed by intramolecular arylation (Friedel-Crafts) reaction to provide a general and direct method for the synthesis of trans-3-amino-4-arylchromans with high regio-, diastereo- (dr > 99:1), and enantioselectivity (up to 95% ee) with moderate yield. trans-3-Amino-4-arylchroman is an advanced intermediate for the synthesis of chromenoisoquinoline compounds such as doxanthrine, a potent and selective full agonist for the dopamine-D(1) receptor.     

A novel synthetic approach to very late antigen-4 antagonist trans-4-[1-[[2,5-dichloro-4-(1-methyl-3-indolylcarboxyamide)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid via tert-butyl trans-[(4S)-Methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate as a key intermediate

This contribution describes a novel synthetic approach to very late antigen-4 (VLA-4) antagonist trans-4-[1-[[2,5-dichloro-4-(1-methyl-3-indolylcarboxyamide)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid (1) via tert-butyl trans-[(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate (2b) as a key intermediate. The synthesis, which includes n-Bu?NSO?H that catalyzed basic etherification of 12 and iodine-mediated cyclization to provide the 2,4-disubstituted pyrrolidine frame of 2b, is designed to utilize trans-4-hydroxycyclohexanecarboxylic acid (9) as a commercially available starting material.     

LC diketones: synthesis, transformations and mesomorphic properties

The synthesis and chemical transformations of various diketones into liquid crystalline compounds are discussed. The diketones were prepared by the interaction of cyclohexene with acid chlorides and benzene in the presence of aluminium chloride (Nenitzescu method) or by Friedel Crafts reaction of trans-4-alkanoyl-1-phenylcyclohexanes or trans-2-alkyl-5-phenylcyclohexanones with acid chlorides, or by the condensation of corresponding Mannich salts with 2-substituted acetoacetates or acetylacetone.     

Beta-hydroxy-gamma-lactones as chiral building blocks for the enantioselective synthesis of marine natural products

The enantioselective synthesis of trans-(+)-laurediol, (2S,3S,5R)-5-[(1R)-1-hydroxy-9-decenyl]-2-pentyltetrahydro-3-furanol, and (2S,3S,5S)-5-[(1S)-1-hydroxy-9-decenyl]-2-pentyltetrahydro-3-furanol are described. In addition, a formal synthesis of trans-(-)-kumausyne is also developed. All the synthetic procedures have in common the use of enantiomerically enriched beta-hydroxy-gamma-lactones, easily available by Sharpless asymmetric dihydroxylation (AD) from the suitable beta,gamma-unsaturated ester. The use of Katsuki-Sharpless asymmetric epoxidation (AE) as an additional enantioselective reaction provides cyclic compounds of high enantiomeric purity.     

The synthesis of trans-8-methyl-5-(p-methoxyphenyl)hydrindan-1-one

Summary We have carried out the synthesis of trans-8-methyl-5-(p-rnethoxyphenyl)hydrindan-1-one, a structural analog of estrone.     

Use of enantiomerically pure 7-azabicyclo[2.2.1]heptan-2-ol as a chiral template for the synthesis of aminocyclitols

Using enantiopure 7-azabicyclo[2.2.1]heptane-2-ol, the synthesis of cis- as well as trans-2-aminocyclohexanols, dihydroconduramine E-1, and ent-conduramine F-1 has been described.     

LC diketones: synthesis,transformations and mesomorphic properties

The synthesis and chemical transformations of various diketones into liquid crystalline compounds are discussed. The diketones were prepared by the interaction of cyclohexene with acid chlorides and benzene in the presence of aluminium chloride (Nenitzescu method) or by Friedel Crafts reaction of trans-4-alkanoyl-1-phenylcyclohexanes or trans-2-alkyl-5-phenylcyclohexanones with acid chlorides, or by the condensation of corresponding Mannich salts with 2-substituted acetoacetates or acetylacetone.     

α-Phosphoryl Cyclopentanones as Possible Intermediates in the Total Synthesis of Sarkomycin

Abstract

In an effort to synthesize sarkomycin 1 trans-2-diphenylphosphinoyl-3-tris (methylthio) methyl-cyclopentanone 7 and trans-2-diphenylphosphinoyl-3-carbo-methoxy-cyclopentanone 8 were prepared. The Horner-Wittig reaction of the latter with formaldehyde failed. (±)-Sarkonycin 1 was prepared by a sequence of reactions starting from diethyl 2-oxopropanephosphonate. The key steps in this synthesis involve the intramolecular carbenoid cyclization of 1-diazo-2-oxopropanephosphonate 10 and the Horner-Wittig reaction of 2-diethoxyphosphoryl-3-carboxy-cyclopentanone 12 with formaldehyde.     

Facile route to 3,5-disubstituted morpholines: enantioselective synthesis of O-protected trans-3,5-bis(hydroxymethyl)morpholines

[reaction: see text] (3R,5R)-1 R1 & R2 = TBDPS, (3S,5R)-2 R1 = Bn,R2 = TBDPS, (3S,5S)-3 R2 & R2 = Bn. trans-3,5-Bis(benzyl/tert-butyldiphenylsilyloxymethyl)morpholines, promising candidates for the C(2)-symmetric class of chiral reagents, were prepared with excellent optical purity. A key step in the synthesis is the coupling of a serinol derivative with 2,3-O-isopropylideneglycerol triflate or its equivalent. This methodology was extended to the synthesis of chiral trans-3-(benzyloxymethyl)-5-(tert-butyldiphenylsilyloxymethyl)morpholine, a potentially useful chiral building block.     

Regio- and stereocontrolled synthesis of novel 3-sulfonamido-2,3,4,5-tetrahydro-1,5-benzothiazepines from 2-(bromomethyl)- or 2-(sulfonyloxymethyl)aziridines

2-(Bromomethyl)-1-sulfonylaziridines were converted into novel 3-sulfonamido-2,3,4,5-tetrahydro-1,5-benzothiazepines upon treatment with 2-aminothiophenol in THF in the presence of K2CO3. Starting from 3-substituted 2-(sulfonyloxymethyl)aziridines, a regio- and stereocontrolled synthesis of trans-2-phenyl- and trans-4-(phenyl or propyl)-3-sulfonamido-2,3,4,5-tetrahydro-1,5-benzothiazepines was developed in good yields via two different reaction pathways, depending on the nature of the sulfonyloxy group.     

Synthesis of enantiopure trans-3,4-disubstituted piperidines. An enantiodivergent synthesis of (+)- and (-)-paroxetine

Reaction of (R)-phenylglycinol with methyl 5-oxopentanoate gave either bicyclic lactam cis-1 (the kinetic product) or its isomer trans-1 (under equilibrating conditions) as the major products, which were converted to the corresponding (cis or trans) unsaturated lactams 4 and 5. On treatment with lithium alkyl (or aryl) cyanocuprates, these chiral building blocks undergo conjugate addition to give enantiopure trans-3,4-substituted 2-piperidone derivatives in high yield and stereoselectivity. The synthetic potential of this transformation is illustrated by the synthesis of (+)-femoxetine and the two enantiomers of the known antidepressant paroxetine.     

Total synthesis of (+)-7-deoxypancratistatin from furan

A new total synthesis of (+)-7-deoxypancratistatin 1 has been accomplished in 19 steps (8% overall yield) from two readly available compounds, furan and trans-1,2-bis(phenylsulfonyl)ethylene.     

DBU-promoted cyclization of ortho-(3-hydroxy-1-alkynyl)benzamide: synthesis of trans-3,4-dihydroisoquinolin-1(2H)-ones and (E)-4-(1-alkenyl)isoquinolin-1(2H)-ones

DBU-promoted cyclization of ortho-(3-hydroxy-1-alkynyl)benzamide is presented, providing an efficient method for the synthesis of trans-3,4-dihydroisoquinolin-1(2H)-ones and (E)-4-(1-alkenyl)isoquinolin-1(2H)-ones under mild conditions.     

Synthesis of (+)-polyoxamic acid and D-sorbitol from simple achiral allylic halides employing (S,S)-hydrobenzoin as a chiral source

Coupling of cis-1-bromo-2-pentene and (S,S)-hydrobenzoin stannylene acetal followed by regio- and stereoselective transformations of the resulting allylic ether gave (+)-polyoxamic acid and a similar procedure was applied to the synthesis of D-sorbitol from trans-1-iodo-2-hexene.     

The synthesis of dicationic extended bis-benzimidazoles

The synthesis of extended dicationic bis-benzimidazoles starting from trans-1,2-bis(4-cyanophenyl)ethene and trans-1,2-bis(4-cyanophenyl)cyclopropane is reported. The target diamidines show significant in vitro activity against B. subtilis.