Enantioselektive Synthese von Allyl- und Propargylaminen durch nucleophile 1,2-Addition an chirale Aldimine. Preliminary communication

Enantioselective Synthesis of Allyl- and Propargylamines via Nucleophilic 1,2- Addition to Chiral Aldinines The asymmetric Synthesis of allylamines and propargylamines 5 in high enantiomeric purity (e.e. ? 97%) is described. Key step is the 1,2-addition of organocerium reagents to chiral α,β-unsaturated aldimines 3 to produce secondary animes 4 . The Chiral auxiliary (S,S)- 2 is removed in three steps, affording the title compounds 5 , useful bifunctional building blocks and compounds of pharmaceutical interest.     

Synthesis of chiral azamacrocycles using the bis(α-chloroacetamide)s derived from chiral 1,2-diphenylethylenediamine

Optically active diphenyl-substituted tetraaza-12-crown-4 diamide ( 10 ), tetraaza-15-crown-5 diamide ( 12 ), tetraaza-18-crown-6 diamide ( 11 ), and hexaaza-18-crown-6 diamide ( 9 ) ligands were prepared by treating the appropriate secondary diamines with the (R,R)- and (S,S)- forms of 1,2-bis(N-methyl-α-chloracetamido)-1,2-diphenylethane ( 20 ). Macrocyclic diamides 9 and 10 were reduced to form the optically active diphenyl-substituted hexaaza-18-crown-6 ( 13 ) and tetraaza-12-crown-4 ( 14 ), respectively. Reduction of macrocyclic diamide ligands 11 and 12 gave a complex mixture of products from which the desired tetraaza-15-crown-5 and 18-crown-6 compounds could not be isolated. Dichloride 20 was prepared by treating the chiral forms of 1,2- diphenylethylenediamine with chloroacetic anhydride or chloroacetyl chloride. The crystal structures for the (R,R)-form of dichloride 20 and the (S,S)-forms of macrocycles 10 and 11 are reported.     

Totalsynthese von (+)-D-Homoöstron-3-methyläther

Total Synthesis of (+)-D-Homoestrone 3-methyl ether A novel total synthesis of (+)-D-homoestrone 3-methyl ether ( 21 ) is described starting from (S)-8a-methyl-3,4,8,8a-tetrahydro-2H, 7H-naphthalene-1,6-dione ( 1 ) as a chiral synthon for the rings C and D. The key step involves alkylation of the derived 3 with m-methoxyphenacyl bromide ( 4 ) as an AB-building block to give the dioxo-secosteroid 5 . Hydrogenation of 5 affords the trans-decalone 11 . As by-products the epimeric cis-decalones 12 and 13 were characterized. Cyclization of 11 leads under kinetic control predominantly to the Δ⁹⁽¹¹⁾-tetraene 14 . Catalytic hydrogenation of 14 and subsequent modification in ring D give the title compound 21 . It was found that 14 and also the derived Δ⁸-isomer 15a add hydrogen from the α-face of the molecule to an extent of about 80%. The 8α-D-homoestrone derivatives 20a and 23 as well as the 9β-isomers 19a and 22 were characterized.     

Totalsynthese von (+)-D-Homo-19-nortestosteron

Total Synthesis of (+)-D-Homo-19-nortestosterone A novel total synthesis of (+)-D-homo-19-nortestosterone ( 2 ) is described starting from (4a S, 5S)-5-(t-butoxy)-4a-methyl-4, 4a, 5, 6, 7, 7-hexahydro-3 H-naphthalen-2-one ( 3 ) as a chiral building block for the rings C and D. The key step involves combining of the derived reactive one-carbon atom adducts 5 and 6 with the β-keto ester 16 , a synthon for the rings A and B, to give the Δ⁹-4, 5-secosteroid 21 . 21 was readily transformed to the title compound 2 by hydrogenation and subsequent ring closure. Hydrogenation of the derived 3, 5-dione 22 followed by base-catalyzed cyclization gave the 17a-t-butoxy compound 27 and the 9β, 10α-D-homosteroid 29 as by-product.     

Totalsynthese von Decarboxybetalainen durch photochemische Ringöffnung von 3-(4-Pyridyl)alanin

Total Synthesis of Decarboxybetalaines by Photochemical Ring Opening of 3-(4-Pyridyl)alanine A photochemical approach is presented for the total synthesis of the decarboxybetalaines, which were previously known from the mild decarboxylation of the natural plant colorants, the betalaines: Irradiation of rac-3-(4-pyridyl)alanine ( 1 ) yielded the rac-2-decarboxybetalamic-acid-imine ( 4 , 86%), presumably via a Dewar pyridine 2 , a cyclic aminal 3 and an electrocyclic ring opening. The imine-zwitterion 4 was treated with three amines, namely (S)-cyclodopa ( 6 ), (S)-proline ( 7 ), and indoline ( 8 ), to afford three decarboxybetalaines, namely (2S)-17-decarboxybetanidine ( 9 , red, 34%), (2S)-13-decarboxyindicaxanthine ( 10 , yellow, 56%), and rac-16-decarboxyindobetalaine ( 11 , orange, 78%), respectively. The structures of these coloring matters were confirmed by their electrophoretic behavior and their spectroscopic properties. 17-Decarboxybetanidine 9 was shown to be a ca. 1:1 mixture of two C(15)-epimers 9a and 9b , separable by chromatography. The configuration of 9a was determined as (2S, 15S) and that of 9b as (2S, 15R), by correlating their optical rotations with those of betanidine ( 12a ) and isobetanidine ( 12b ), respectively. The decarboxybetalaines 9 , 10 , and 11 did not show the double-bond isomerism at C(β), (Cγ) of the chromophore which had been found characteristic for the corresponding betalaines 12 , 13 , and 14 .     

Synthesis and Circular Dichroism of Optically Pure (±)-(1S,2S,5S)-5-Methoxy-3,4,6,7-tetramethylidenebicyclo[3.2.1]oct-2-yl Derivatives. Baker's Yeast Reduction of 4-Methoxy-5,6,7,8-tetramethylidenebicyclo[2.2.2]octan-2-one

Baker's yeast reduction of 4-methoxy-5,6,7,8-tetramethylidenebicyclo[2.2.2]octan-2-one ( 11 ) under fermenting conditions afforded (?)-(1S,2S,4R)-4-methoxy-5,6,7,8-tetramethylidenebicyclo[2.2.2]octan-2-ol ((?)- 13 ) in 60% yield with an e.e. > 99.5%. Its methanesulfonate (?)- 14 was hydrolyzed and rearranged with high stereo-selectivity into (+)-(1S,2S,5S)-5-methoxy-3,4,6,7-tetramethylidenebicyclo[3.2.1]octan-2-ol ((+)- 15 ). The absolute configuration of (?)- 13 was deduced from the CD spectrum of its 4-(dimethylamino)benzoate ((+)- 22 ) applying the chiral exciton-coupling method. The CD spectrum of (+)- 15 and of its (tert-butyl)dimethylsilyl ether ((+)- 23 ) showed exciton-split type of Cotton effects attributed to through-space interactions between the s-gauche-buta-diene and s-cis-butadiene chromophores of these systems.     

A practical synthesis of ethyl 1,2,4-triazole-3-carboxylate and its use in the formation of chiral 1′,2′-seco-nucleosides of ribavirin

A practical and efficient synthesis of ethyl 1,2,4-triazole-3-carboxylate ( 6a , R' = H) from ethyl carboethoxyformimidate hydrochloride ( 7 ) is described. Alkylation of this heterocycle with the chloromethyl ethers of 1,3-O-dibenzylbutane-1,2R,3S-triol ( 8a ) and 1,3,4-O-tribenzylbutane-1,2R,3S,4-tetrol ( 8b ), followed by conversion of the ester function to the amide and deprotection, furnished the chiral 1′,2′-seco-nucleosides of ribavirin, 11a and 11b , respectively.     

Synthese von enantiomerenreinem Mimulaxanthin und seiner (9Z,9′Z)- und (15Z)-Isomeren

Synthesis of Enantiomerically Pure Mimulaxanthin and of Its (9Z,9′Z)- and (15Z)Isomers We present the details of a synthesis of optically active, enantiomerically pure stereoisomers of mimulaxanthin (=(3s,5R,6R,3′S,5′R,6′R)-6,7,6′,7′-tetradehydro-5,6,5′,6′-tetrahydro-β,β-carotin-3,5,3′,5′-tetrol) either as free alcohols 1a and 24a or as their crystalline (t-Bu)Me₂Si ethers 1b and 24b . Grasshopper ketone 2a , a presumed synthon, unexpectedly showed a very sluggish reaction with Wittig-Horner reagents. Upon heating with the ylide of ester phosphonates, an addition across the allenic bond occurred. On the contrary, a slow but normal 1,2-addition took place with the ylide from (cyanomethyl)phosphonate but, unexpectedly, with concomitant inversion at the chiral axis. So a mixture of(6R,6S,9E,9Z)-isomers 6 – 9 was produced {(Scheme 1). However, a fast and very clean 1,2-addition occurred with the ethynyl ketone 12 to yield the esters 13 and 14 (Scheme 2). DIBAH reduction of the separated stereoisomers gave the allenic alcohols 15 and 16 in high yield. Mild oxidation to the aldehydes 17 and 18 followed by their condensation with the acetylenic C₁₀-bis-ylide 19 led to the stereoisomeric 15,15′-didehydromimulaxanthins 20 and 22 , respectively (Schemes 3 and 4). Mimulaxanthins 1 and 24 were prepared by partial hydrogenation of 20 and 22 followed by a thermal (Z/E)-isomerization. As expected, the mimulaxanthins exhibit very weak CD curves, obviously caused by the allenic bond that insulates the chiral centers in the end group from the chromophor. On the contrary, some of the C₁₅-allenic synthons showed not only fairly strong CD effects but also a split CD curve which, in our interpretation, results from an exciton coupling between the allene and the C(9)?C(10) bond. We postulate a rotation around the C(8)? C(9) bond, presumably caused by an intramolecular H-bond in 16 or by a dipol interaction between the polarized double bonds in 6 , 7 , 8 , and 17 .     

Synthesis of chiral fused heterocyclic compounds containing 1,2,4‐triazole ring

A series of new chiral (S)‐3‐ary1‐6‐pyrrolidin‐2‐yl‐[1,2,4]triazolo[3,4‐b]thiadiazole (II_1‐5), (S)‐1‐(3‐aryl‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐ethylamine (II_6‐8) and (S)‐1,2‐bis(3‐aryl‐[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐ethylamine (II_9‐11) were prepared by the condensation of 3‐aryl‐4‐amino‐5‐mercapto‐1,2,4‐triazoles with different L‐amino acids in the presence of phosphorus oxychloride and evaluated for their antibacterial activity.     

The Diastereoselective Formation of 1,2,4-Trioxanes and 1,3-Dioxolanes by the reaction of endoperoxides with chiral cyclohexanones

1,4-Diphenyl-2,3-dioxabicyclo[2.2.1]hept-5-ene ( 2 ), on treatment with a catalytic amount of trimethylsilyl trifluoromethanesulfonate (Me₃SiOTf) in CH₂Cl₂ at ?78°, reacts with excess (?)-menthone ( 10 ) to give (1S,2S,4′aS,5R,7′aS)-4′a,7′a-dihydro-2-isopropyl-5-methyl-6′,7′-diphenylspiro[cyclohexane-1,3′-[7′H]cyclopenta-[1,2,4]trioxine] ( 11 ) and its (1R,2S,4′aR,5R,7′aR)-diastereoisomer 12 in a 1:1 ratio and in 21% yield. Repeating the reaction with 1.1 equiv. of Me₃SiOTf with respect to 2 affords 11 , 12 , and (1S,2S,3′a.R,5R,6′aS)-3′a,6′a-dihydro-2-isopropyl-5-methyl-3′a-phenoxy-5′-phenylspiro[cyclohexane-l,2′-[4′H]cyclopenta[1,3]dioxole] ( 13 ) together with its(1R,2S,3′aS,5R,6′aR)-diastereoisomer 14 in a ratio of 3:3:3:1 and in 56% yield. (+)-Nopinone( 15 ) in excess reacts with 2 in the presence of 1.1 equiv. of Me₃SiOTf to give a pair of 1,2,4-trioxanes ( 16 and 17 ) analogous to 11 and 12 , and a pair of 1,3-dioxolanes ( 18 and 19 ) analogous to 13 and 14 , in a ratio of 8:2:3:3 and in 85% yield. (?)-Carvone and racemic 2-(tert-butyl)cyclohexanone under the same conditions behave like 15 and deliver pairs of diastereoisomeric trioxanes and dioxolanes. In general, catalytic amounts of Me₃SiOTf give rise to trioxanes, whereas 1.5 equiv. overwhelmingly engender dioxolanes. Adamantan-2-one combines with 2 giving only (4′aRS,7′aRS)-4′a,7′a-dihydro-6′.7′a-diphenylspiro[adamantane-2,3′-[7′H]cyclopenta[1,2,4]trioxine] in 98% yield regardless of the amount of Me3SiOTf used. The reaction of 1,4-dipheny 1-2,3-dioxabicyclo[2.2.2]oct-5-ene ( 32 ) with 10 and 1.1 equiv. of Me3SiOTf produces only the pair of trioxanes 33 and 34 homologous to 11 and 12 . Treatment of the (S,S)-diastereoisomer 33 with Zn and AcOH furnishes (1S,2S)-1,4-diphenylcyclohex-3-ene-1,2-diol. The crystal structures of 11 – 13 and 16 are obtained by X-ray analysis. The reaction courses of 10 and the other chiral cyclohexanones with prochiral endoperoxides 2 and 32 to give trioxanes are rationalized in terms of the respective enantiomeric silylperoxy cations which are completely differentiated by the si and re faces of the ketone function. The origin of the 1,3-dioxolanes is ascribed to 1,2 rearrangement of the corresponding trioxanes, which occurs with retention of configuration of the angular substituent.     

Povarov Reaction of Glyoxylate Imines Derived from 12-Aminodehydroabietic Acid

Glyoxylate and arylglyoxal imines based on 12-aminodehydroabietic acid undergo hetero-Diels—Alder (Povarov) reaction with ethyl vinyl ether, cyclopentadiene, and indene to give, respectively, methyl (8aR,9R,12aS)-3-aroyl-5-isopropyl–9,12a-dimethyl–7,8,8a,9,10,11,12,12a-octahydronaphtho[1,2-f]quinoline-9-carboxylates, methyl (7R,10aS,10dR,13aS)-1-aroyl–3-isopropyl–7,10a-dimethyl–2,5,6,6a,7,8,9,10,10a,10d,13,13a-dodecahydro-1H-naphtho[1,2-f]cyclopenta[c]quinoline-7-carboxylates, and methyl (6aS,11bS,11eS,15R,15aR)-6-aroyl–4-isopropyl–11e,15-dimethyl–2,5,6,6a,7,11b,11e,12,13,14,15,15a-1H-dodecahydroindeno[2,1-c]-naphtho[1,2-f]quinoline-15-carboxylates.     

Synthesis of nitrogen-containing drimane sesquiterpenoids from 11-dihomodrim-8(9)-en-12-one

Products from the reaction of 11-dihomodriman-8α-ol-12-one with several reagents such as MeSO₃SiMe₃, CF₃SO₃SiMe₃, Sc(CF₃SO₃)₃, conc. H₂SO₄ in EtOH (30% solution), and Amberlist-15 ion-exchange resin were studied. 11-Dihomodrim-8(9)-en-12-one and its oxime were synthesized. The reaction of its oxime with H₃PO₄ (86%) or CF₃CO₂H produced (1S,2S,4aS,8aS)-2,5,5,8a-tetramethyldecahydro-1H-naphtho [1,2-e]-3-methyl-4,5-dihydro-[1,2,6]-oxazine; with p-TsCl in Py, (1S,2S,4aS,8aS)-2,5,5,8a-tetramethyldecahydro-1H-naphtho[1,2-d]-2-methylpyrroline-N-oxide; and with PCl₅ in Et₂O, 11-acetylaminodrim-8(9)-ene and 11-methylaminooxodrim-8(9)-ene.     

α-Alkylation of Amino Acids without Racemization. Preparation of Either (S)- or (R)-α-Methyldopa from (S)-Alanine

Enantiomerically pure cis- and trans-5-alkyl-1-benzoyl-2-(tert-butyl)-3-methylimidazolidin-4-ones ( 1, 2, 11, 15, 16 ) and trans-2-(tert-butyl)-3-methyl-5-phenylimidazolidin-4-one ( 20 ), readily available from (S)-alanine, (S)-valine, (S)-methionine, and (R)-phenylglycine are deprotonated to chiral enolates (cf. 3, 4, 12, 21 ). Diastereoselective alkylation of these enolates to 5,5-dialkyl- or 5-alkyl-5-arylimidazolidinones ( 5, 6, 9, 10, 13a-d, 17, 18, 22 ) and hydrolysis give α-alkyl-α-amino acids such as (R)- and (S)-α-methyldopa ( 7 and 8a , resp.), (S)-α-methylvaline ( 14 ), and (R)-α-methyl-methionine ( 19 ). The configuration of the products is proved by chemical correlation and by NOE ¹H-NMR measurements (see 23, 24 ). In the overall process, a simple, enantiomerically pure α-amino acid can be α-alkylated with retention or with inversion of configuration through pivaladehyde acetal derivatives. Since no chiral auxiliary is required, the process is coined ‘self-reproduction of a center of chirality’. The method is compared with other α-alkylations of amino acids occurring without racemization. The importance of enantiomerically pure, α-branched α-amino acids as synthetic intermediates and for the preparation of biologically active compounds is discussed.     

Photochemisches Verhalten von 1- und 2-alkylierten 1,2-Dihydronaphtalinen

Irradiation of 1-alkyl-substituted 1,2-dihydronaphthalenes ( 10, 11, 12 ) with a lowpressure mercury lamp yields by ring opening ω-vinyl-o-quinodimethanes, which undergo [1, 7] H-shifts to give 1,2-divinyl-benzenes ( 8, 18, 23 ; cf. schemes 2, 3 and 4). In a further photoreaction of the divinylbenzenes, benzobicyclo [3.1.0]hex-2-enes ( 17, 19, 22 ) are formed. 2-Alkyl-substituted 1,2-dihydronaphthalenes ( 13, 14, 15, 16 ) are transformed by irradiation into ω-vinyl-o-quinodimethanes, which show [1, 7] H-shifts to yield in this case 2-(buta-1′, 3′-dienyl)-toluenes ( 9, 25, 26, 27 ; cf. schemes 6 and 7). The irradiation of 1-methyl- ( 10 ) and 1-ethyl-1, 2-dihydronaphthalene ( 11 ) with a high-pressure mercury lamp produces, besides the products of irradiation using the lowpressure lamp, 2-ethyl-allenylbenzene ( 24 ), and (from 11 ) 4-exo-ethyl-benzobicyclo[3.1.0]hex-2-ene (exo- 20 ) and 2-propyl-allenylbenzene ( 21 ), respectively (cf. scheme 5). Obviously, these products arise from a photreaction of the primarily formed ω-vinyl-o-quinodimethanes a .     

Epimeric Isopavine N-Oxides from Roemeria refracta

Roemeria refracta DC. (Papaveraceae) of Turkish origin yielded two novel epimeric N-oxides, (?)-(5R, 11S,14R)-reframidine N-oxide ( = (?)-(5R, 11S,14R)-11,12-dihydro-14-methyl-11,5-(iminomethano)-5H -cyclohepta[1, 2-f: 4, 5-f′]bis[1,3]benzodioxole 14-oxide; 1 ) and (?)-(5R, 11S, 14S)-reframidine N-oxide ( = (?)-(5R, 11S, 14S)-11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxole 14-oxide; 2 ). The isolated (?)-roelactamine ( = (?)-11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-one, 4 ) is the first natural isopavinoid incorporating a lactam group. The epimeric (?)-15-(2-oxopropyl)reframidines ( = (?)-1-[11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-y1]propan-2-ones; 5/6 ) and the epimeric (?)-ethyl (reframidin-15-yl)acetates ( = (?)-ethyl [11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-y1]acetates; 7/8 ) are probably artifacts. (±)-Coclaurine ( 9 ), (±)-N-methylcoclaurine ( 10 ), (?)-roemeridine ( 11 ), and N-feruloyltyramine ( 12 ) are also isolated from R. refracta together with the previously reported bases. Specific ¹³C-NMR assignments are reported for the first time for the isopavines.     

Eine chiral ökonomische Totalsynthese von (R)- und (S)-Muskon via Epoxysulfoncyclofragmentierung

A chiral economic synthesis of (R)- and (S)-muscone using the cyclofragmentation of epoxysulfones Starting with isobutyric acid (2) and using a microbiological oxidation with pseudomonas putida (S)-β-hydroxy-iso-butyric acid (3) has been prepared. From this /pseudosymmetrical: (see text) intermediate the two enantiomeric bromo derivatives 8 (R) and 20 (S) have been synthesized (cf. scheme 4) by altering the sequence of the reactions (cf. scheme 3). A Grignard reaction starting from the two bromo compounds 8 and 20 and from cyclododecanone 1 produced after hydrogenolysis the two enantiomeric dialcohols 9 and 21 (1 + 8 → 9, 1 + 20 → 21 , cf. scheme 5). The subsequent transformations led to the two enantiomeric olefin derivatives 12 and 24 . Oxidation of 12 with peracid produced a mixture of the two epoxy-sulfones 13 and 14 (cf. scheme 6). The olefin-derivative 24 was oxidized to the corresponding mixture of 25 and 26 . A one pot cyclofragmentation (cf. [4] and scheme 6) produced a mixture of (E)- and (Z)-3-methylcyclopentadec-4-en-1-one (13 + 14 → 15 + 16, 25 + 26 → 27 + 28) . The final hydrogenation led to natural (R)- and unnatural (S-muscone (3-methylcyclopentadecanone). The achiral starting material has been transformed to the desired optically active target products without loss of material with undesired absolute configuration. The authors used the notion of chiral economic synthesis to characterize synthetic sequences with the above mentioned features.     

1,3-Oxathiolan-Synthese: Spirocyclische 1,3-Oxathiolane aus der Lewis-Säure-katalysierten Umsetzung von cyclischen Trithiocarbonaten und Oxiranen

1,3-Oxathiolanc Synthesis: Spirocyclic 1,3-Oxathiolanes from the Lewis-Acid-Catalyzed Reaction of Cyclic Trithiocarbonates and Oxiranes The cyclic trithiocarbonates 1.3-dithiolane-2-thione ( 4 ) and 1,3-dithiole-2-thione ( 9 ) in 1,2-dichloroethane and MeCN, respectively, react with alkyl- and phenyl-substituted oxiranes 2 in the presence of Lewis acids to give 1-oxa-4,6,9-trithiaspiro[4.4]nonanes 5 and 6 (Scheme 2) and 1-oxa-4,6,9-trithiaspiro[4.4]non-7-enes 10 and 11 (Scheme 3), respectively. The reactions proceed regioselectively yielding 2-alkyl ( 5 , 10 ) and 3-phenyl derivatives ( 6 , 11 ) as the main products. From the reaction of 4 and 2-phenyloxirane ( 2e ) with TiCl₄, 2-phenyl-1,4,6,9-tetrathia-spiro[4.4]nonane ( 7 ) is isolated as a minor product. The molecular structures of 5a , 6e , and 7 are established by X-ray crystallography.     

Synthesis of Novel Polymers with a Chiral 1,2-Diamine Moiety by Polycondensation and their Application to Catalyst for Asymmetric Hydrogenation of Aromatic Ketones

Summary: Novel polymers with chiral 1,2-diamine moiety were successfully synthesized by polycondensation of N-Boc protected enantiopure 1,2-diamine bearing two phenol groups ( S , S )-4 , bisphenol derivatives, and dibromides, followed by deprotection of N-Boc moiety. Hydrogenation of acetophenone was performed with use of polymeric catalyst system prepared from the polymer-supported chiral 1,2-diamine and RuCl₂/(S)-BINAP. The reaction proceeded smoothly even in 2-propanol to give 1-phenylethanol in quantitative yield with high level of enantioselectivity. Furthermore, various other aromatic ketones could be asymmetrically hydrogenated by the polymeric catalyst system.     

Synthesis and First Applications of a New Chiral Auxiliary (tert-butyl 2-(tert-butyl)-5,5-dimethyl-4-oxoimidazolidine-1-carboxylate)

Both enantiomers of tert-butyl 2-(tert-butyl)-5,5-dimethyl-4-oxoimidazolidine-1-carboxylate ( 11 ; Bbdmoic) were prepared from L -alanine (Schemes 1 and 2). The parent heterocycle, 2-tert-butyl-5,5-dimethylimidazolidin-4-one ( 12 ; from 2-aminoisobutyramide, H-Aib-NH₂, and pivalaldehyde) was also available in both enantiomeric forms by resolution with O,O′-dibenzoyltartaric acid. The compound (R)- or (S)- 11 was used as an auxiliary, but also as a chiral Aib building block in a dipeptide synthesis. The 3-propanoyl derivative 13 of (R)- 11 was used for the preparation of enantiomerically pure 2-methyl-3-phenylpropanoic acid (enantiomer ratio (e.r.) 99.5:0.5), by benzylation of the Zn-enolate (→ 14 ; Scheme 3). Oxidative coupling of the bis-enolate derived from heptanedioic acid and (S)- 11 (→ 23 ) and methanolysis of the auxiliary gave dimethyl trans-cyclopentane-1,2-dicarboxylate ( 26 ) with an e.r. of 93:7 (Scheme 5, Fig. 5). The 3-(Boc-Gly)-Bbdmoic derivative 29 was doubly deprotonated and, after addition of ZnBr₂ alkylated with alkyl, benzyl, or allyl halides to give the higher amino-acid derivatives with excellent selectivities (e.r. > 99.5:0.5, Schemes 6 and 7). Michael additions of cuprates to [(E)-MeCH?CHCO]-Bbdmoic 36 occurred in high yields, but high diastereoselectivities were only observed with aryl cuprates (diastereoisomer ratio (d.r.) 99:1 for R = Ph, Scheme 8). Finally, 3-(Boc-CH₂)-Bbdmoic 17 was alkylated through the ester Li-enolate with primary and secondary alkyl, allyl, and benzyl halides with diastereoselectivities (ds) ranging from 91 to 98%, giving acetals of Boc-Aib-Xxx-O(t-Bu) dipeptides (Scheme 4). The effectiveness of Bbdmoic is compared with that of other chiral auxiliaries previously used for the same types of transformations.     

Samaderin B and C from Samadera indica

Samaderin B, or (1R,2S,5R,5aR,7aS,11S,11aS,11bR,14S)‐1,7,7a,11,11a,11b‐hexa­hydro‐1,11‐di­hydroxy‐8,11a,14‐tri­methyl‐2H‐5a,2,5‐(methan­oxy­metheno)­naphth­[1,2‐d]­oxepine‐4,6,10(5H)‐trione, C₁₉H₂₂O₇, and samaderin C, or (1R,2S,5R,5aR,7aS,10S,11S,11aS,11bR,14S)‐7,7a,10,11,11a,11b‐hexa­hydro‐1,10,11‐tri­hydroxy‐8,11a,14‐tri­methyl‐2H‐5a,2,5‐(methan­oxy­metheno)­naphth­[1,2‐d]­oxepine‐4,6(1H,5H)‐dione, C₁₉H₂₄O₇, were isolated from the seed kernels of Samadera indica and were shown to exhibit antifeedant activity against Spodoptera litura third‐instar larvae. The replacement of the carbonyl group in samaderin B by a hydroxy group in samaderin C causes conformational changes at the substitution site, but the overall conformation is not affected; however, the compounds pack differently in the crystal lattice.