(E)-Cycloalkenes and (E,E)-cycloalkadienes by ring closing diyne- or enyne-yne metathesis/semi-reduction

A concise, practical and stereoselective entry into macrocyclic (E)-alkenes is outlined comprising a sequence of ring closing alkyne metathesis (RCAM), trans-selective hydrosilylation of the resulting cycloalkynes catalyzed by [Cp^∗Ru(MeCN)₃]PF₆, and a protodesilylation of the ensuing vinylsilanes with AgF in aq. THF/MeOH. Moreover, the first examples of intramolecular enyne-yne metathesis reactions catalyzed by the Schrock alkylidyne complex (tBuO)₃WCCMe₃ are reported; the resulting cyclic enynes can be converted along similar lines into the corresponding (E,E)-configured 1,3-dienes in good overall yields. Cycloalkyne 4 and the (E)-configured cyclic olefins 6 and 21 were characterized by X-ray crystallography.     

Stereoselective synthesis of protected (2S,3S)-N-methyl-5-hydroxyisoleucine, a component of halipeptins

The stereocontrolled synthesis of the protected (2S,3S)-N-methyl-5-hydroxyisoleucine, a component of halipeptins A and B with potent anti-inflammatory activity, has been achieved. The key steps include (i) installation of a double bond to bicyclic lactam 4 using N-tert-butyl phenylsulfinimidoyl chloride, (ii) highly exo-selective Michael reaction with lithium dimethylcuprate in the presence of chlorotrimethylsilane, and (iii) Ru-catalyzed oxidative deprotection of N,O-benzylidene acetal to the acid anhydride.     

Stereoselective synthesis of either (E)- or (Z)-silyl enol ether from the same acyclic α,β-unsaturated ketone using cationic rhodium complex-catalyzed 1,4-hydrosilylation

The stereoselective synthesis of either (E)- or (Z)-silyl enol ether from the same acyclic α,β-unsaturated ketone is reported. Highly (Z)-selective conditions were the use of [Rh(cod)₂]BF₄/DPPE at room temperature with no solvent, whereas (E)-selective conditions were the use of [Rh(cod)₂]BF₄/P(1-Nap)₃ (1-Nap = 1-naphthyl) under refluxing dichloromethane.     

Alkynes to (E)-enolates using tandem catalysis: stereoselective anti-aldol and syn-[3,3]-rearrangement reactions

A new tandem catalysis strategy that transforms alkyne derivatives to (E)-enol-equivalents followed by stereoselective anti-selective aldol coupling or syn-selective [3,3]-rearrangement transformations is reported. The mechanism is thought to proceed through an interchanging series of Lewis acid and Brønsted acid catalyzed reactions via the intermediacy of a ketiminum ion species.     

Stereospecific synthesis of conjugated (1E,3E)- and (1Z,3Z)-1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes from 2-chloro-1-(n-N,N-dimethylaminophenyl)ethenes: fluorescence properties

The conjugated 1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes (n=o-, m-, p-) were efficiently synthesised by homocoupling of the appropriate 2-chloro-1-(n-N,N-dimethylaminophenyl)ethene (n=o-, m-, p-) with stoichiometric amounts of zerovalent nickel complexes. The 1,3-butadienes were obtained as a mixture of stereoisomers, with independence of the starting E or Z chlorovinyl isomer. Moreover, the stereospecific (Z,Z) stereoisomer was obtained by partial hydrogenation of the corresponding 1,3-butadiyne, while the stereospecific (E,E) stereoisomer was obtained by exposure to the sunlight radiation of the (Z,Z) or the (Z,E) compound in ethanol.     

Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin

A convergent synthesis of (4R,15R,16R,21S)-rollicosin (1) and (4R,15S,16S,21S)-rollicosin (2) was accomplished. Hydroxy lactone 6a and/or 6b were synthesized from 4-pentyn-1-ol, and α,β-unsaturated lactone 7 was synthesized from γ-lactone 8 and 5-hexen-1-ol. Inhibitory activity of these compounds was examined with bovine heart mitochondrial complex I.     

(6Z,9Z,12Z)-6,9,12-Octadecatriene and (3Z,6Z,9Z,12Z)-3,6,9,12-icosatetraene, the novel sex pheromones produced by emerald moths

(6Z,9Z,12Z)-6,9,12-Octadecatriene and (3Z,6Z,9Z,12Z)-3,6,9,12-icosatetraene, hydrocarbons unsaturated more highly than usual lepidopteran Type II pheromones, were identified from geometrid females of Hemithea tritonaria and Thalassodes immissaria intaminata, respectively. The triene was synthesized by a double Wittig reaction between hexanal and an ylide derived from (Z)-1,6-diiodo-3-hexene, and the tetraene was synthesized by a coupling between (Z)-3-undecenal and an ylide derived from (3Z,6Z)-1-iodo-3,6-nonadiene. Each synthetic compound attracted males of the corresponding emerald moths in a field.     

Stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucines

A stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucine is disclosed. The key step of the reaction sequence involves, stereo- and regioselective bromohydration of 7, using a brominating agent derived in situ from N-bromosuccinimide and 2,6-lutidine, via intramolecular sulfinyl group participation.     

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of common cutworm (Spodoptera litura)

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of Spodoptera litura was carried out. Substrate was converted to three new terpenoids, (+)-(1R,2S)-10-hydroxyfenchol, (+)-(1R,2R,3S)-8-hydroxyfenchol and (−)-(1S,2S,6S)-6-exo-hydroxyfenchol, and one known terpenoid, (−)-(1R,2R,3R)-9-hydroxyfenchol. These structures were established by NMR, IR, specific rotation and mass spectral studies.     

Synthesis of 12-aza analogs of epothilones and (E)-9,10-dehydroepothilones

N-Boc-12-aza-epothilone analog (azathilone) 1 is a potent inhibitor of human cancer cell growth and represents a structurally new class of natural product-derived microtubule-stabilizing agents. Compound 1 has been prepared employing a convergent strategy that is based on the consecutive assembly of building blocks 3, 4, and 19 into diene 20 and subsequent RCM-mediated macrocycle formation. The aldol reaction between aldehyde 3 and ketone 4 delivered the required 6R,7S diastereoisomer 5 with good selectivity and provided a reliable entry into the stereoselective synthesis of carboxylic acid 12. RCM with diene 20 was highly E-selective, thus giving efficient access to (E)-9,10-dehydro-1 (2). The latter is a key analog in SAR studies with 1.     

The stereoselective synthesis of (E)-octafluoro-1,3,5-hexatriene and (3E,5E,7E)-dodecafluoro-1,3,5,7,9-decapentaene

(E)-(1,2-Difluoro-1,2-ethenediyl)bis[tributylstannane], 3, readily undergoes a Pd(PPh₃)₄/CuI-catalyzed cross-coupling reaction with iodotrifluoroethene to yield (E)-octafluoro-1,3,5-hexatriene, 4, in high isomeric purity. (1Z,3E,5Z)-(1,2,3,4,5,6-Hexafluoro-1,3,5-hexenetriyl)bis[tributylstannane], 7, was sequentially prepared from (1Z,3E,5Z)-(1,2,3,4,5,6-hexafluoro-1,3,5-hexenetriyl)bis[triethylsilane], 5, which was prepared via a Pd(PPh₃)₄/CuI-catalyzed cross-coupling reaction of 3 with (E)-1,2-difluoro-1-iodo-2-triethylsilylethene, 6. Pd(PPh₃)₄/CuI cross-coupling of 7 with iodotrifluoroethene gave (3E,5E,7E)-dodecafluoro-1,3,5,7,9-decapentaene, 8.     

Enantioselective synthesis of (1S,2S)-1,2-di-tert-butyl and (1R,2R)-1,2-di-(1-adamantyl)ethylenediamines

An enantioselective synthesis of sterically congested 1,2-di-tert-butyl and 1,2-di-(1-adamantyl)ethylenediamines has been developed. Thus, diastereomerically pure trans-1-apocamphanecarbonyl-4,5-dimethoxy-2-imidazolidinones 6 and 7 were successfully prepared by optical resolution of (±)-trans-4,5-dimethoxy-2-imidazolidinone using apocamphanecarbonyl chloride (MAC-Cl) followed by stereospecific and stepwise substitution of the dimethoxyl groups using tert-butyl or 1-adamantyl cuprates to provide (4S,5S)-4,5-di-tert-butyl and (4R,5R)-4,5-di-(1-adamantyl)-2-imidazolidinones 12 and 15, respectively. Furthermore, N-acetyl 4,5-di-tert-butyl and 4,5-di-(1-adamantyl)-2-imidazolidinones 16a,b were enantioselectively deacetylated using a catalytic oxazaborolidine system to provide enantiopure 1-p-tolylsulfonyl-4,5-di-tert-butyl-2-imidazolidinones 12 and 19 and 1-p-tolylsulfonyl-4,5-di-(1-adamantyl)-2-imidazolidinones 18 and 20, respectively. Finally, N-p-tolylsulfonyl-2-imidazolidinones 12 and 15 were treated with 30 equiv of Ba(OH)₂·8H₂O to achieve ring cleavage and to provide (1S,2S)-1,2-di-tert-butylethylenediamine 3 and (1R,2R)-1,2-di-(1-adamantyl)ethylenediamine 4.     

Concise and practical synthesis of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6-iminosugars

The syntheses of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6 iminosugars 1a and 1b, respectively, from d-glucose are described. The key transformations in this reaction sequence include regio-selective epoxide ring opening with N-benzylamine followed by intramolecular reductive amination of amino-aldehyde.     

Stereospecific preparation of (1E,3E,5E)-3.4-difluoro-1,6-diphenylhexatriene and (2E,4E,6E)-diethyl-4,5-difluoroocta-2,4,6-trienedioate

Palladium(0) catalyzed coupling of β-bromostyrene (E/Z = 89/11) with (E)-(1,2-difluoro-1,2-ethenediyl)bis[tributylstannane], 1, in DMF at room temperature stereospecifically gave only (1E,3E,5E)-3,4-difluoro-1,6-diphenylhexatriene. Similarly, palladium(0) catalyzed coupling of (E)-ethyl 3-bromoacrylate as the vinyl halide precursor stereospecifically gave (2E,4E,6E)-diethyl-4,5-difluoroocta-2,4,6-trienedioate. This work demonstrates that a non-fluorine-containing vinyl bromide will selectively undergo coupling with 1 and enable the stereospecific preparation of a mixed polyene system. The (E)-ethyl 3-bromoacrylate coupling with 1 illustrates that mixed functionalized hexatriene systems can be easily accessed via this methodology. The X-ray structure of (2E,4E,6E)-diethyl-4,5-difluoroocta-2,4,6-trienedioate confirmed its structure.     

Domino pericyclic reactions of acyclic conjugated (E,Z,E,E)-tetraenes

Acyclic conjugated (E,Z,E,E)-tetraenes, upon thermolysis, undergo a domino pericyclic process involving 6π electrocyclisation of the (E,Z,E)-triene moiety to give the corresponding cis-disubstituted 5-vinyl-1,3-cyclohexadienes, followed by an intramolecular Diels-Alder reaction with the vinyl side chain to give tricyclo[3.2.1.0^2,7]oct-3-enes.     

Synthesis of (+)-(3S,7S,10S)- and (+)-(3S,7S,10R)-3,7,10-trimethylboratrane. Amplification of enantiomeric purity in the reacti

The synthesis is described of the two enantiomerically pure isomers (+)-(3S,7S,10S)- and (+)-(3S,7S,10R)-3,7,10-trimethylboratr The structures were determined by ¹H- and ¹³C-NMR spectroscopy. A method for increasing the enantiomeric purity by trimerization reactions of partially-resolved (S) propylene oxide is proposed. The reaction was studied from the kinetic viewpoint and interpreted according to a binomial probability scheme. The experimental findings point to a rapid growth in enantiomeric purity for the (SSS) trimer compared with the starting material, whilst no increase was found for the (SSR) trimer.     

Chemoenzymatic synthesis and HPLC analysis of the stereoisomers of miyakosyne A [(4E,24E)-14-methyloctacosa-4,24-diene-1,27-diyne-3,26-diol], a cytotoxic metabolite of a marine sponge Petrosia sp., to determine the absolute configuration of its major component as 3R,14R,26R

Six samples [(3R,14R,26R)-, (3R,14S,26R)-, (3S,14R,26S)-, and (3S,14S,26S)-1, a mixture of (3R,14R,26S)- and (3S,14R,26R)-1, and a mixture of (3R,14S,26S)- and (3S,14S,26R)-1] of miyakosyne A [1, (4E,24E)-14-methyloctacosa-4,24-diene-1,27-diyne-3,26-diol] were synthesized starting from the enantiomers of citronellal (2), employing olefin cross metathesis and R-selective asymmetric acetylation of a stereoisomeric mixture of acetylenic alcohols with vinyl acetate and lipase PS as key reactions. Separation of the eight stereoisomer of 1 by reversed phase HPLC at −56 °C was achieved after their esterification with (1R,2R)-2-(anthracene-2,3-dicarboximido)cyclohexanecarboxylic acid (16), and the natural miyakosyne A was found to be a mixture of 95.7% of (3R,14R,26R)-1 and 4.3% of (3R,14S,26R)-1. This is different from the (3R,14S,26R)-configuration of 1 as tentatively assigned by X-ray analysis.     

(N,N) vs. (N,S) chelation of palladium in asymmetric allylic substitution using bis(thiazoline) ligands: A theoretical and experimental study

New thiazoline-containing ligands including non-symmetric bis(thiazolines) and oxazoline-thiazolines were synthesized and then compared to C₂-symmetric bis(thiazolines) in the palladium-catalyzed allylic substitution. The experimental results obtained in this study support the hypothesis of a competition between the (N,N) and the (N,S) palladium chelation, when sterically hindered bis(thiazolines) are used as ligands. A quantum chemical study performed on the Pd-complexes derived from three selected ligands, two C₂-symmetric bis(thiazolines) and one oxazoline-thiazoline, also supports this hypothesis.     

An acyclic,dansyl based colorimetric and fluorescent chemosensor for Hg(II) via twisted intramolecular charge transfer (TICT)

An efficient fluorescent chemosensor for Hg²⁺ ion, based on 5-(dimethylamino)-N-(2-mercaptophenyl)naphthalene-1-sulfonamide, has been developed. It exhibits Hg²⁺-selective on–off fluorescence quenching behavior via twisted intramolecular charge transfer (TICT) mechanism, which is rationalized by time dependent density functional theory (TD-DFT) calculations. The system exhibits visible color change from colorless to gray upon Hg²⁺ binding with very high selectivity and sensitivity (as low as 5.0 × 10⁻¹⁰ mol L⁻¹) over other metal ions such as K⁺, Na⁺, Ag⁺, Mn²⁺, Ca²⁺, Ba²⁺, Fe²⁺, Zn²⁺, Pb²⁺, Cu²⁺, Sn²⁺, Cd²⁺, Ni²⁺ and Co²⁺. The present sensing system is also successfully applied for the detection of Hg²⁺ ion in real samples.     

Synthesis and absolute configuration of two diastereoisomeric (1R,2S,3R)-and (1S,2S,3R)-2-amino-1-(2-furyl)-1,3-butandiols

The synthesis of (1R, 2S, 3R) and (1S, 2S, 3R)-2-(N-benzoylamino)-1-(2-furyl)-1, 3-butandiols (15) and (16) from D-threonine is described. The assignment of absolute configuration of the newly formed asymmetric center at C-1 was based on the ¹H-NMR spectra of O-isopropylidene derivatives 17 and 18.