First stereoselective total synthesis of (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one

A stereoselective total synthesis of (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one is reported. The strategy utilizes an iterative Jacobsen hydrolytic kinetic resolution, ring opening with a chiral propargylic synthon and a preferential (Z)-Wittig olefination reaction and lactonization as the key steps.     

Stereoselective synthesis of (1′S,3R,4R)-4-acetoxy-3-(2′-fluoro-1′-trimethylsilyloxyethyl)-2-azetidinone

A stereoselective synthesis of (1′S,3R,4R)-4-acetoxy-3-(2′-fluoro-1′-trimethylsilyloxyethyl)-2-azetidinone as a new fluorine-containing intermediate towards β-lactams, is described. The synthetic key step relies upon the dynamic kinetic resolution (DKR) of ethyl 2-benzamidomethyl-4-fluoro-3-oxo-butanoate via asymmetric transfer hydrogenation catalyzed by [Ru(η⁶-arene)(S,S)-R₂NSO₂DPEN].     

Efficient synthesis of the cyclopentanone fragrances (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone and Magnolione

This paper describes the selective syntheses of two cis-isomer-enriched cyclopentanone fragrances: (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone (four steps, 62% overall yield, 67% cis) and Magnolione^® (five steps, 60% overall yield, 55% cis). In addition, the asymmetric synthesis of (3aR,7aS)-5-methyl-2,3,3a,4,7,7a-hexahydro-1H-inden-1-one as well as (3a′R,7a′S)-5′-methyl-2′,3′,3a′,4′,7′,7a′-hexahydrospiro[[1,3]dioxolane-2,1′-indene] has been realized by an efficient kinetic resolution, which enables the selective synthesis of the 2S,3R-isomer-enriched 3 and 4.     

Enantioselective synthesis of (−)-(1R,2R)-1,2-dihydrochrysene-1,2-diol

A general chiral building block containing the 1R,2R-trans-diol moiety was constructed utilizing the stereoselective Shi-epoxidation reaction on a tetralone scaffold assembled by a Negishi cross-coupling on N,N-diethylbenzamide. Further elaboration of this chiral building block into polycyclic aromatic compounds was demonstrated with the total synthesis of the precursor for the most carcinogenic metabolite of chrysene, (−)-(1R,2R)-1,2-dihydrochrysene-1,2-diol in 87% ee.     

A concise synthesis of protected (2S,4R)-4-hydroxyornithine

A short synthesis of the nonproteinogenic amino acid, (2S,4R)-4-hydroxyornithine is described. Starting from racemic benzyl glycidol, the scaffold of the target compound was constructed in high enantio- and diastereoselectivity using Jacobsen’s hydrolytic kinetic resolution (HKR) and regioselective opening of an epoxide as key steps.     

Practical synthesis of (E)- and (Z)-2-silyl-3-penten-1-ols with high enantiopurity

Practical methods for the synthesis of the optically active (E)- and (Z)-2-silyl-3-pentene-1-ols are described. The optically pure (E)-allylsilane was synthesized from commercially available (R)-3-butyn-2-ol in five steps involving hydrozirconation followed by alkylation of the resulting alkenylmetal with BnOCH₂Cl. On the other hand, both enantiomers of the corresponding (Z)-allylsilane were prepared from commercially available dimethylphenylvinylsilane through epoxidation, the regioselective epoxide-opening reaction with 1-propynylmagnesium bromide, and the subsequent optical resolution using a lipase.     

Aza variant of intramolecular nucleophile-catalyzed aldol lactonization (NCAL): formal synthesis of (3S,4R) and (3R,4S) 4-(hydroxymethyl)pyrrolidin-3-ol

Aza variant of intramolecular catalytic, asymmetric nucleophile-catalyzed, aldol lactonization (NCAL) reaction has been explored to synthesize β-lactone fused nitrogen heterocycles as aza sugars’ precursors by employing achiral amino acids. The utility of these bicyclic β-lactones is presented by the formal synthesis of aza sugars, (3S,4R) and (3R,4S) 4-(hydroxymethyl)pyrrolidin-3-ol.     

Stereoselective synthesis of (1R,2S)- and (1S,2R)-1-amino-cis-3-azabicyclo[4.4.0]decan-2,4-dione hydrochlorides: bicyclic glutamic acid derivatives

Asymmetric synthesis of (1R,2S)- and (1S,2R)-1-amino-cis-3-azabicyclo[4.4.0]decan-2,4-diones has been achieved. The underlying second generation asymmetric synthesis proceeds via a Strecker reaction with commercially available (R)-1-phenylethylamine (1-PEA) as chiral auxiliary, TMSCN as cyanide source and racemic ethyl 2-(2-oxocyclohex-1-yl)ethanoate. A ring closure addition-elimination reaction between an amide nitrogen and the ester functionality leads to the 1-amino-3-azabicyclo[4.4.0]decan-2,4-diones. The absolute configurations of the title compounds have been assigned based on detailed NMR-spectroscopic analysis and X-ray data.     

First total syntheses and absolute configuration of rugulactone and 6(R)-(4′-oxopent-2′-enyl)-5,6-dihydro-2H-pyran-2-one

The first efficient total syntheses of rugulactone and 6(R)-(4′-oxopent-2′-enyl)-5,6-dihydro-2H-pyran-2-one have been achieved in six steps with 51% and 48% overall yield, respectively. The key steps are Jacobsen’s hydrolytic kinetic resolution (HKR), Horner-Wadsworth-Emmons (HWE) homologation, and ring-closing metathesis reaction.     

Desymmetrisation of (4R,5S)-4,5-diphenylimidazolidine-2-thione using pentafluorophenyl active esters

(4R,5S)-4,5-Diphenylimidazolidine-2-thione is efficiently desymmetrised by stereorandom deprotonation with NaHMDS, followed by kinetic resolution of the resulting racemic intermediate with an enantiomerically pure pentafluorophenyl active ester. The levels of diastereocontrol were found to be excellent (86-92% de at ∼30% conversion). This desymmetrisation reaction is an example of a masked resolution.     

Radical mediated stereoselective synthesis of (4R,8R)-4,8-dimethyldecanal, an aggregation pheromone of Tribolium flour beetles

(4R,8R)-4,8-Dimethyldecanal, a common aggregation pheromone of Tribolium flour beetles, has been synthesized from (R)-2,3-O-isopropylideneglyceraldehyde in 11 steps and 7% overall yield. The key step in the synthesis is the highly diastereoselective chelation-controlled radical reaction of ethyl (4S,5R)-4-benzyloxy-5,6-(isopropylidenedioxy)-2-methylenehexanoate with ethyl (R)-5-iodo-3-methylpentanoate performed in the presence of 7 equiv of MgBr₂·OEt₂.     

Synthesis of (+)-(1S,2R) and (−)-(1R,2S)-2-aminocyclobutane-1-carboxylic acids

(+)-(1S,2R) and (−)-(1R,2S)-2-aminocyclobutane-1-carboxylic acids have been prepared in >97% ee and in 33% and 20% overall yields starting from a single, chiral, bicyclic compound perceived as a chiral uracil equivalent. Construction of the cyclobutane ring is achieved via a [2+2] photocycloaddition reaction of this chiral precursor with ethylene.     

Efficient synthesis of (R)- and (S)-3-octanol, (R)-2-dodecanol, (R)-2-methyl-4-heptanol and (R)-2-methyl-4-octanol: the pheromones of Myrmica scabrinodis, Crematogaster castanea, C. liengmei, C. auberti and Metamasius hemipterus

A simple and efficient synthesis of optically active insect pheromones, such as (R)- and (S)-3-octanol, (R)-2-dodecanol, (R)-2-methyl-4-heptanol and (R)-2-methyl-4-octanol starting from non-racemic β-hydroxy sulfides has been established.     

A convenient and new approach to the synthesis of ω-heterocyclic amino acids from carboxy lactams through ring-chain-transformation. Part 2: Synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid

Making use of amide activation, a convenient and short path synthesis of optically pure ω-heterocyclic-β-amino acids has been achieved from (1R,3R)- and (1R,3S)-5-oxo-1-(1-phenyl-ethyl)-pyrrolidine-3-carboxylic acid methyl ester. The key step of the synthesis involves a regiospecific ring-chain-transformation of the enaminones when subjected to 1,2-binucleophilic attacks. The method is illustrated by the synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid.     

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.     

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.     

An efficient synthesis of optically active (2R,3R)-2-methyl-3-[(1R)-1-methylprop-2-enyl]cyclopentanone, a useful chiral building block for synthesis of vitamin D and steroids

An efficient synthesis of optically active (2R,3R)-2-methyl-3-[(1R)-1-methylprop-2-enyl]cyclopentanone, a useful chiral building block for synthesis of vitamin D and steroids, has been developed starting from readily accessible optically active secondary propargyl phosphate (R)-2, where the asymmetric Michael addition of a chiral allenyltitanium to alkylidenemalonate 3 is a key reaction.     

Introduction of a planar chirality onto steroid substrates: synthesis of (S) and (R)-2′-formylcymantrenyl-17α-ethynylestradiols using (S) and (R)-1-formyl-2-iodo-cymantrenes

We report the synthesis and characterisation of (S) and (R)-2′-formylcymantrenyl-17α-ethynylestradiol synthesized using the Sonogashira cross-coupling reaction between optically pure (S) and (R) 1-formyl-2-iodo cymantrenes and ethynylestradiol. (S) and (R) 1-formyl-2-iodo cymantrenes were obtained from the same precursor: (2R,4R)-4-(methoxymethyl)-2-cymantrenyl-1,3-dioxane.     

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.     

Stereoselective synthesis of (R)-(+)-1-methoxyspirobrassinin, (2R,3R)-(−)-1-methoxyspirobrassinol methyl ether and their enantiomers or diastereoisomers

Stereoselective synthesis of cruciferous indole phytoalexin (R)-(+)-1-methoxyspirobrassinin and its unnatural (S)-(−)-enantiomer was achieved by spirocyclization of 1-methoxybrassinin in the presence of (+)- and (−)-menthol and subsequent oxidation of the obtained menthyl ethers. Methanolysis of menthyl ethers in the presence of TFA afforded (2R,3R)-(−)-1-methoxyspirobrassinol methyl ether as well its unnatural (2S,3S)-, (2R,3S)-, and (2S,3R)-isomers.