C3‐symmetric trialkyl phosphites as starting compounds of asymmetric synthesis

Chiral C₃‐symmetric trialkyl phosphites, derivatives, of (−)‐(1R,2S,5R)‐menthol, and (−)‐di‐O‐isopropylidene‐1,2:5,6‐α‐D ‐glucofuranose, have been studied as starting reagents for the preparation of chiral organophosphorus compounds. The reactions involve induction at the α‐carbon atom of substituted α‐alkylphosphonates. The stereoselectivity of the reaction depends on the structure of the starting compounds and the reaction conditions. The configurations of the alkylphosphonates were defined by means of NMR spectroscopy and by transformation into corresponding alkylphosphonic acids. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:138–143, 2000     

Asymmetric Friedel–Crafts alkylation using chiral α-acyl-α-chloromethylsulphides

Lewis acid catalysed stereoselective Friedel–Crafts alkylation of aromatic compounds with α-(−)-menthyloxycarbonyl-α-(phenylthio)methyl chloride and α-(−)-8-phenylmenthyloxycarbonyl-α-(phenylthio)methyl chloride is described.     

Total Syntheses of (−)-Strictosidine and Related Indole Alkaloid Glycosides

A collective synthesis of glycosylated monoterpenoid indole alkaloids is reported. A highly diastereoselective Pictet–Spengler reaction with α-cyanotryptamine and secologanin tetraacetate as substrates, followed by a reductive decyanation reaction, was developed for the synthesis of (−)-strictosidine, which is an important intermediate in biosynthesis. This two-step chemical method was established as an alternative to the biosynthetically employed strictosidine synthase. Furthermore, after carrying out chemical and computational studies, a transition state for induction of diastereoselectivity in our newly discovered Pictet–Spengler reaction is proposed. Having achieved the first enantioselective total synthesis of (−)-strictosidine in just 10 steps, subsequent bioinspired transformations resulted in the concise total syntheses of (−)-strictosamide, (−)-neonaucleoside A, (−)-cymoside, and (−)-3α-dihydrocadambine.     

One Pot Synthesis of Some New Heteroylselenoglycolic Acids and Their Biological Activity

Abstract

A convenient one pot three-stage synthesis was used for obtaining new heteroylselenoglycolic and di-heteroylselenoglycolic acids by nucleophilic substitution reaction of the starting compounds pyridineselenol, pyridazineselenol, and quinolineselenol with α-chloro- or α,α-dichloroacetic acids for 1-h stirring. The newly synthesized compounds were screened biologically for anti-microbial and anti-oxidant activities. The structure of all new compounds was confirmed by ¹H NMR, ¹³C NMR, Mass, and IR spectroscopy and elemental analyses.     

Total Synthesis of (−)‐Bauhinin

The total synthesis of the naturally occurring cyanoglucoside (−)‐bauhinin ( 1 ) was achieved starting from the optically pure oxatrinorbornenone 2 in 12 steps and 8% overall yield. The aglycone of (−)‐bauhinin was easily obtained from the optically pure oxatrinorbornenone derivative 6 by a Wittig‐Horner reaction followed by the opening of the oxa bridge. Glycosidation with tetra‐O‐isobutyryl‐D ‐glucosyl bromide 9 as the reagent in the Koenigs‐Knorr reaction afforded glucoside 10 in 58% yield, which, after photoisomerization and deprotection, gave (−)‐bauhinin ( 1 ).     

Stereoselective synthesis of α-substituted serines from protected erythrulose oximes

The additions of organolithium reagents to the CN bond of several chiral oxime ethers derived from erythrulose afforded protected amino polyols with high diastereoselectivity. Four of the latter compounds have been converted into the α,α-disubstituted α-amino acids (R)-2-(−)-methylserine, (S)-2-(+)-methylserine, (R)-(+)-2-phenylserine and (R)-(−)-2-n-butylserine.     

Total Synthesis of (−)-Rotundone and (−)-epi-Rotundone from Monoterpene Precursors

The first total synthesis of (−)-rotundone has been accomplished from (+)-(R)-limonene and therefore for the first time from an unrelated monoterpene instead of modifying structurally closely related sesquiterpene precursors such as α-guaiene. Challenges such as intermediates with stereocenters prone to epimerization by enolization were overcome by designing a β-methyl-keto route starting from (+)-(R)-limonene which finally gave (−)-rotundone by Nazarov cyclization of a precursor 13a . Diastereomer (−)-epi-rotundone was separated from (−)-rotundone chromatographically. An alternative route from rac-citronellal provided a diastereomer mixture of racemic Nazarov precursor 13 through a TRIP-catalyzed intramolecular aldolization, thus indicating that the Nazarov cyclization precursor 13a is in principle accessible from (−)-(S)-citronellal. The 11-step synthesis from (+)-(R)-limonene with ca. 1 % overall yield confirmed the absolute configuration of (−)-rotundone and provided samples of good olfactory quality.     

An effective new synthesis of 2-aminopyrrole-4-carboxylates

Efficient syntheses of 2-aminopyrroles are presented starting from β-dicarbonyl compounds, bromoacetonitrile, and amines. Alkylation of β-dicarbonyl compounds with bromoacetonitrile furnished α-cyanomethyl-β-dicarbonyl compounds. The condensation reaction of α-cyanomethyl-β-dicarbonyl compounds with amines catalyzed by p-TsOH affords the corresponding enamines in good yields. Base catalyzed cyclization via the addition of an amine moiety to the carbon-nitrogen triple bond of nitrile furnished 2-aminopyrroles in high yields.     

Synthesis of Aristotelia‐Type Alkaloids,Part XVI

Two independent total syntheses of the Aristotelia alkaloid (−)‐serratenone ((−)‐ 1 ) are disclosed, one starting with (−)‐α‐pinene, the other one with (S)‐α‐terpineol. These correlations led to a revision of the originally proposed absolute configuration of the natural product. In the course of systematic investigations of the behavior of the indole alkaloids (+)‐makomakine ((+)‐ 18 ) and (−)‐hobartine ((−)‐ 22 ) towards oxidizing reagents, it was found that treatment with I₂ leads to no less than five different products. Depending on the exact reaction conditions, each of them can be obtained as the major component in yields between 40 and 60%. One of these compounds was shown to be identical with the natural product (+)‐11,12‐didehydromakonin‐10‐one ((+)‐ 28 ).     

Tetrahydrofurane und Lactone,I. Synthese und Reaktionen chiraler 2,5-überbrückter Tetrahydrofurane – ein neuer Weg zu optisch aktiven γ-Lactonen und γ-Bislactonen

Tetrahydrofurans and Lactones, I. - Synthesis and Reactions of Chiral 2,5-Bridged Tetrahydrofurans - A New Approach to Optically Active γ-Lactones and γ-Bislactones Diels-Alder reaction of 3,4-hexamethylenefuran with acrylic acid gives the carboxylic acid 1a with high endo selectivity. 1a was separated into the enantiomers via the α-phenylethylammonium salts. Comparison of the CD spectra of (−)- 1a and (−)- 3 and the X-ray structural analysis of the camphanoyl derivative (−)- 4b lead to the 1R,2S,4S configuration of (−)- 1a as well. The 2,5-bridged tetrahydrofuran (−)- 5 with all-cis and RSS configuration is obtained by ozonolysis of the ester (−)- 1b . (−)- 5 can be oxidized to the γ-lactone (2R,3S)-(−)- 6 with sodium metaperiodate/potassium permanganate in 22% yield. Hydride reduction of (−)- 6 under various conditions leads to the γ-bislactones (−)- 8 and (−)- 9 or to the bislactol (−)- 10 . (−)- 8 has the same absolute configuration as the naturally occuring (−)-canadensolide.     

Synthesis of 2-fluorotetralones by oxidative radical cyclization of α-fluoroacetophenones and olefins

The oxidative radical cyclization of α-fluoroacetophenones in the presence of olefins offers an efficient access to 2-fluorotetralones. Fluorinated starting materials can be prepared from α-bromoacetophenones. The reaction was optimized with respect to a future application in the synthesis of 18-fluorine labeled compounds, where reaction times are a critical aspect.     

Expedient synthesis of highly substituted α-pyrones from Baylis-Hillman adducts and their conversion to poly-substituted aromatics

An efficient synthetic protocol of fully substituted α-pyrones has been developed starting from the Baylis-Hillman adducts. Subsequent Diels-Alder reaction of the α-pyrones and DMAD produced poly-substituted aromatic compounds in high yields.     

Diastereoselective α-iminoamine rearrangement: asymmetric synthesis of (R)-(−)- and (S)-(+)-2-benzyl-2-hydroxycyclohexanone

A convenient asymmetric synthesis of both (R)-(−)- and (S)-(+)-2-benzyl-2-hydroxycyclohexanones starting from racemic 2-benzyloxycyclohexanone and the chiral auxiliary 1-phenylethylamine is reported. The route involves a [1,3]-sigmatropic shift and a new diastereoselective α-iminoamine rearrangement of a 2-benzyl-2-iminocyclohexanamine substrate.     

Chiral trans-carboxylic trifluoromethyl 2-imidazolines by a Ag2O-catalyzed Mannich-type reaction

Trifluoromethyl aldimines derived from α-amino esters have proven to be very good starting materials to obtain the title compounds. A Ag₂O-catalyzed Mannich-type/cyclization cascade reaction starting from suitable α-isocyano acetates leads to enantiopure valuable trans-carboxylic trifluoromethyl substituted 2-imidazolines by a highly stereoselective addition without the need to add organocatalysts.     

Über En-Synthesen mit Singulett-Sauerstoff Die Farbstoff-sensibilisierte Photooxygenierung von (−)-Caryophyllen und (−)-iso-Caryophyllen und die Stereochemie der dargestellten Caryophylladienole

The dye-sensitized photooxygenation leads in the case of (−)-caryophyllene ( 1 ) to 4 allylhydroperoxides, and with (−)-iso-caryophyllene ( 2 ) additionally to 2 tertiary compounds of this kind. The stereochemistry of the isolated 6 caryophylladienols derivatives 6 – 11 is elucidated. By that way an interpretation of the reaction mechanism is possible.     

An efficient stereocontrolled synthesis of (−)-10-epi-5β,11-dihydroxyeudesmane and (−)-4,10-epi-5β,11-dihydroxyeudesmane

A concise and efficient synthesis of (−)-10-epi-5β,11-dihydroxyeudesmane 1 and (−)-4,10-epi-5β,11-dihydroxyeudesmane 2, via (−)-10-epi-γ-eudesmol 5, was accomplished starting from (+)-dihydrocarvone. The salient feature of our synthesis is the utilization of substrate-directable epoxidation and homogeneous hydrogenation to control the stereochemistry at the C-4 and C-5 positions of the title compounds.     

The use of (S)-(−)-1-(1-naphthyl)ethylamine as a resolving agent for α-methoxy fatty acids

A general method was developed for the diastereoselective resolution of α-methoxy fatty acids utilizing (S)-(−)-1-(1-naphthyl)ethylamine as resolving agent. The diastereomeric amides can be easily separated by silica gel column chromatography and/or capillary gas chromatography, thus allowing for a preparative and analytical method for determining the enantiomeric purity of naturally occurring and/or synthetic α-methoxy fatty acids. The first synthesis of the naturally occurring (R)-2-methoxyhexadecanoic acid was also accomplished in four steps starting from commercially available (±)-2-hydroxyhexadecanoic acid.     

Enantiodivergent syntheses of cycloheptenone intermediates for guaiane sesquiterpenes

The syntheses of enantiomeric 6-isopropenyl-3-methyl-2-cycloheptenones 16 and 22 have been effected starting from (R)-(−)-carvone. In the synthesis of 16, (R)-(−)-carvone was reduced and the resulting dihydrocarvone transformed regioselectively into silyl enol ethers. Cyclopropanation with dibromocarbene and in situ rearrangement gave an α-bromo-cycloheptenone which was reduced to the (R)-(+)-cycloheptenone 16. In the synthesis of 22, (R)-(−)-carvone was cyclopropanated with a sulfur ylide, followed by reduction with LiAlH₄ and acid-catalyzed cyclopropylcarbinyl rearrangement to afford a cycloheptenol. Oxidation and double bond conjugation led to the (S)-(−)-cycloheptenone 22 in a partially racemized form. Four cycloheptenones have been obtained and are suitable intermediates for the enantiodivergent syntheses of guaiane sesquiterpenes.     

Stereocontrolled total synthesis of the macrocyclic lactone (−)-aspicilin

The essential features of the enantiocontrolled total synthesis of (−)-aspicilin are the strategic use of the photochemical rearrangement of α,β-epoxy diazomethyl ketones to 4-hydroxyalkenoates (Scheme 1) and the stereochemical control of the Sharpless epoxidation, α,ω functionalization of an alkynol using potassium 3-aminopropylamine (KAPA) as acetylene zipper, coupling between C₇ and C₈ by means of a Wittig reaction and lactonization by using 2,6-dichlorobenzoyl chloride.     

Synthesis and Odor of Chiral Partial Structures of Khusimone. Part 3. Short communication

Khusimone ( 1 ), one of the main odor-donating compounds of vetiver oil, is subject of the following study on structure/odor relationship. The omittance of the methano bridge of the tricyclic khusimone should lead to the bicyclic partial structure (−)- 2 . Unexpectedly, (−)- 2 could not be obtained since epimerization favored (−)- 16 . The stereochemical key step of the synthesis of the hydrazulene nucleus is based on a highly diastereoselective conjugate addition to a chiral oxocyclopent-1-ene-1-carboxylate.