Über die Dicyanierung der 1,4-Diaminoanthrachinone und die Reaktivität der 1,4-Diamino-9,10-dihydroanthracen-2,3-dicarbonitrile gegenüber nucleophilen Reagenzien 3. Mitteilung über Arylierungen und Heterocyclisierungen von Anthrachinonsystemen

The Dicyanation of 1,4-Diaminoanthraquinones and the Reactivity of 1,4-Diamino-9,10-dioxo-9,10-dihydroanthracene-2,3-dicarbonitriles towards Nucleophilic Reagents The reaction of 1-amino-9, 10-dioxo-4-phenylamino-9,10-dihydroanthracene-2-sulfonic acid ( 1 , R?C₆H₅) with cyanide in water yields a mixture of 1-amino-9,10-dioxo-4-phenylamino-9,10-dihydroanthracene-2-carbonitrile ( 3 , R ? C₆H₅) and 1-amino-4-(phenylamino)anthraquinone ( 4 , R ? C₆H₅) under the usual reaction conditions (Scheme 1). In dimethylsulfoxide, however, a second cyano group is introduced, and 1-amino-9,10-dioxo-4-phenylamino-9,10-dihydroanthracene-2,3-dicarbonitrile (7) is formed (Scheme 2). The cyano groups are very reactive towards nucleophiles. The cyano group in 2-position can be substituted by hydroxide and aliphatic amines (Schemes 5 and 6). The cyano group in 3-position can be eliminated by aliphatic amines and hydrazine (Scheme 7). Nucleophilic attack at the cyano C-atom of the 2-cyano group by suitable reagents leads to ring formation, yielding e.g. 2-(Δ²-1, 3-oxazolin-2-yl)-, 2-(benz[d]imidazol-2-yl)- and 2-(1H-tetrazol-5-yl)anthraquinones (Schemes 8 and 10).     

Synthese von 4(5)-acyl-5(4)-alkylimidazolen aus symmetrischen 1,3-dicarbonylverbindungen

Synthesis of 4(5)-Acyl-5(4)-alkylimidazoles from Symmetrical 1,3-Diones A new synthesis of 4(5)-acyl-5(4)-alkylimidazoles 1 is described. The symmetrical 1,3-diones 5a and 5b were reacted with N₂O₄ to give the nitro compounds 7a and 7b , respectively; 5c was treated with NaNO₂ to give the nitroso compound 7c (Scheme 2). Hydrogenation of 7a , 7b and 7c over Pd/C in acetic acid/acetic formic anhydride yielded the formamides 9a , 9b and 9c , whose cyclization in formamide/formic acid afforded the 4(5)-acyl-5(4)-alkylimidazoles 1a, 1b and 1c , respectively. Oxazoles 11a and 11b were obtained from the corresponding formamides 9a and 9b with methanesulfonic acid/P₂O₅.     

Herstellung enantiomerenreiner Derivate von 3-Amino- und 3-Mercaptobuttersäure durch SN2-Ringöffnung des β-Lactons und eines 1,3-Dixoanons aus der 3-Hydroxybuttersä ure

Preparation of Enantiomerically Pure Derivatives of 3-Amino- and 3-Mercaptobutanoic Acid by S_N2 Ring Opening of the β-Lactone and a 1,3-Dioxanone Derived from 3-Hydroxybutanoic Acid From (S)-4-methyloxetan-2-one ( 1 ), the β-butyrolactone readily available from the biopolymer ( R )-polyhydroxybutyrate (PHB) and various C, N, O and S nucleophiles, the following compounds are prepared:(s)-2-hydroxy-4-octanone ( 3 ), (R)-3-aminobutanoic acid ( 7 ) and its N-benzyl derivative 5 , (R)-3-azidobutanoic acid ( 6 ) (R)-3-mercaptobutanoic acid ( 10 ), (R)-3-(phenylthio)butanoic acid ( 8 ) and its sulfoxide 9 . The (6R)-2,6-dimethyl-2-ethoxy-1,3-dioxan-4-one ( 4 ) from (R)-3-hydroxybutanoic acid undergoes S^N2 ring opening with benzylamine to give the N-benzyl derivative (ent- 5 ) of (S)-3-aminobutanoic acid in 30?40% yield.     

Reactions of Chiral 2-(tert-Butyl)-2H,4H-1,3-dioxin-4-ones Bearing Functional Groups in the 6-Position and Diastereoselective Catalytic Hydrogenation to cis-2,6-Disubstituted 1,3-Dioxan-4-ones

(R)-5-Bromo-6-(bromomethyl)-2-(tert-butyl)-2H,4H-1,3-dioxin-4-one ( 2 ) derived from (R)-3-hydroxybutanoic acid is used for substitutions and chain elongations at the side-chain C-atom in the 6-position of the heterocycle (→ 3–6 , 10–13 ). Subsequent simultaneous reductive debromination and double-bond hydrogenation (Pd/C,H₂)occurs with essentially complete diastereoselectivity (>98% ds), with H transfer from the face opposite to the t-Bu group (→ 15–20 , Table 1). Hydrolytic cleavages of the dioxanones then lead to enantiomerically pure β-hydroxy-acid derivatives (overall self-reproduction of the stereogenic center of 3-hydroxybutanoic acid or alkylation in the 4-position of this acid with preservation of configuration).     

Bemerkungen zur Synthese von 3-Aminotoluol-5-sulfonsäure und 2-Aminotoluol-3-sulfonsäure

Some comments on the synthesis of 3-aminotoluene-5-sulfonic acid and 2-aminotoluene-3-sulfonic acid. Sulfonation of 3-nitrotoluene ( 5 ) yields predominantly the unsymetrical isomer 5-nitrotoluene-2-sulfonic acid ( 7 ), and lesser amounts of 5-nitrotoluene-3-sulfonic acid ( 6 ), previously reported as the major product. The desired 5-aminotoluene-3-sulfonic acid ( 3 ) was synthesized in preparative amounts from 6-aminotoluene-3-sulfonic acid (4) via the following sequence of reactions: diazotation and Sandmeyer replacement of 6-chlorotoluene-3-sulfonic acid ( 13 ), nitration of the sulfonyl chloride 14 under suitable conditions to give isomer free 6-chloro-5-nitrotoluene-3-sulfonyl chloride ( 15 ), hydrolysis to the sulfonic acid 16 and finally, simultaneous hydrogenolysis and reduction to 3 . The isomeric 7 was unequivocally prepared from 2-amino-5-nitrotoluene ( 9 ) via two routes: (1) diazotation, Sandmeyer thiocyanatation to 5-nitro-2-thiocyanatotoluene ( 10 ), Na₂S reduction to the di(2-methyl-4-nitro-phenyl)-disulfide ( 11 ), treatment with nitric acid and chlorine to give 5-nitrotoluene-2-sulfonyl chloride ( 12 ) and finally alkaline hydrolysis to 7 ; (2) Meerwein's SO₂ treatment of the diazonium salt derived from 9 leads directly to 12 and thence to 7 . 2-Aminotoluene-3-sulfonic acid ( 1 ) was prepared from the key intermediate 3-amino-2-nitrotoluene ( 18 ) via the same two routes used to prepare 7 from 9 . Both reaction sequences provided 2-nitrotoluene-3-sulfonly chloride, the hydrolysis product of which was reduced to 1 . Intermediate 18 was prepared in the following four steps from m-toluic acid ( 19 ): nitration to the 2-nitroderivative ( 20 ), whose acid chloride ( 21 ) was converted to 2-nitro-m-toluamide ( 22 ), and Hoffmann rearrangement to 18 .     

2, 3-Alkadiensäureester als Dienophile; Anwendung bei der Synthese von (+)-(R)-Lasiodiplodin

2,3-Alkadienoates as Dienophiles, Application in the Synthesis of (+)-(R)-Lasiodiplodin Methyl 2, 3-alkadienoates 2 are shown to react at 80° with l, 1-dimethoxy-3trimethylsilyloxy-l, 3-butadiene (1) to give the adducts 3 in good yields. Rearrangement of 3 , catalyzed by p-toluenesulfonic acid or by sodium methoxide, affords the 6-substituted methyl 4-hydroxy-2-methoxybenzoates 4 (R ? H, CH₃, C₆H₅). An analogous reaction sequence starting with (-)-(11 R)-dodeca-2, 3-dien-11-olide ((-) -6 ) and 1 leads, via the adduct (R)-7 , to (+)-( R )-lasiodiplodin ((+) ?8 ) with properties identical to those of the natural product. The allene lactone (-) -6 was prepared by an intramolecular Wittig condensation of (R) ?5 , produced from (–)-(R)-9-hydroxydecanoic acid.     

Neue Derivate der 7-Amino-cephalosporansäure. Über die Substitution der Acetoxygruppe durch aromatische Reste. Modifikationen von Antibiotica, 11. Mitteilung [1]

7-Phenylacetamido-3-trifluoroacetoxymethyl-ceph-2-em-4-carboxlic acid ( 7 ), which is easily produced from the iso-cephalosporanic acid derivatives 4 or 6 by treatment with trifluoroacetic acid, reacts smoothly with ‘C-nucleophiles’ to give derivatives of type 5 (Schema 1 and 2). Compounds 5 are converted into microbiologically active cephalosporins of type 8 (Table) by previously described methods.     

Bestimmung des Chiralitätssinns der enantiomeren 2,6-Adamantandiole

Determination of the Chirality Sense of the Enantiomeric 2,6-Adamantanediols The enantiomers of 2,6-adamantanediol ( 1 ) are resolved via the diastereoisomeric camphanoates. The (2R,6R)-chirality sense for (?)- 1 and (2S,6S) for (+)- 1 was determined by chemical correlation with (?)-(1R,5R)-bicyclo[3.3.1]nonan-2,6-dion ((1R,5R)- 3 ) of known absolute configuration in the following way: alkylation of the bis(pyrrolidine enamine) of (?)-(1R,5R)- 3 with CD₂I₂ and hydrolysis of the product gives the enantiomer 4 of (4,4-D₂)-2,6-adamantanedione. Reduction of 4 with LiAlH₄ leads to one enantiomer (Scheme 2) of each of the three diols 5 – 7 of known absolute configuration. The three diols are themselves configurational isomers due to the presence of the CD₂ group, but correspond otherwise entirely to the enantiomeric diols 1 . Accordingly, they can also be separated by means of their diastereoisomeric camphanoates to give the diols 5 / 6 and 7 . These samples are easily distinguished and identified by their characteristic ¹H-NMR spectra (cf. Fig. 2). This allows to identify the (2R,6R)- and (2S,6S)-enantiomer of 1 on the basis of their behavior in the resolution experiment analogous to that of the diols 5 / 6 and 7 , respectively. The diol (?)- 1 must have the (2R,6R)-configuration because it forms, like the diols 5 / 6 , with (?)-camphanic acid the diastereoisomeric ester less soluble in benzene. The diol (+)- 1 has (2S,6S)-configuration, because it forms, like 7 , with (+)-camphanic acid the diastereoisomeric ester less soluble in benzene. The bis(4-methoxybenzoate) of (?)-(2R,6R)- 1 shows chiroptical properties which are in accordance with Nakanishi's rule for two chromophores having coupled electric dipol transition moments arranged with a left-handed torsion angle.     

Reactions of a 4-(trifluoromethyl)thiazole dianion

Treatment of 2-trifluoroacetamido-4-(trifluoromethyl)thiazole with two equivalents of n-butyllithium at -78° produced the thiazole dianion 5 in situ, which reacted preferentially at the 5-position with a variety of electrophiles. These electrophiles include: an aldehyde, ketone, chloroformate, acid chloride, phosphorus oxychloride, silicon chloride, and disulfide. Dianion 5 also combined with dibromodifluoromethane at -98° to give the corresponding 5-(bromodifluoromethyl)thiazole 7 , which is an unusual reaction for an aromatic or heteroaromatic system. Compound 7 was converted to a 4,5-bis-(trifluoromethyl)thiazole 8 using tetrabutylammonium fluoride.     

Herstellung von Dihydro-, Tetrahydro- und Hexahydrochelidamsäure-Derivaten

Preparation of dihydro-, tetrahydro- and hexahydro-chelidamic-acid derivatives. Three methods for the preparation of 4-oxo-2,6-piperidine-dicarboxylic acid ( 3 ) and derivatives, required as a synthon for betalaine pigments, were explored. The best method was found to be the catalytic hydrogenation of chclidamic acid ( 1 ) with 5% Rh/Alox in water under 2.7 atm. H₂ for 33 h at 70° and subsequent esterification with methanol which gave 42% of cis, cis-4-hydroxy-2,6-piperidine- ( 7 ) and 10% of 2,6-cis-piperidine-dicarboxylic acid dimethyl ester ( 8 ), readily separable by chromatography. Oxidation of 7 with dimethylsulfoxide and a carbodiimide attached to a polymer afforded 90% of 4-oxo-2,6-cis-piperidine-dicarboxylic acid dimethyl ester ( 19 ). Other methods of oxydizing 7 to 19 were less successful. The electrochemical reduction of 1 followed by esterification with methanol led in a low yield to a mixture of 4-oxo-0-2,6-trans-piperidine-dicarboxylic acid dimethylester ( 24 ), its dimethyl acetal 25 and presumably trans-4-hydroxy-r-2, cis-6-piperidine-dicarboxylic acid dimethyl ester ( 26 ). Reaction of 4-oxo-hepta-2E, 5E-dienoic acid ( 35 ) with aqueous ammonia gave a 98% yield of a 3 : 2 mixture of cis- and trans-ammonium-4-oxo-2, 6-piperidine-dicarboxylate ( 39 and 40 ). The above mentioned catalytic hydrogenation method was also applied to N-ethyl-chelidamic acid ( 16 ) to give a 4:6 mixture of the N-ethyl derivatives 17 and 18 . Furthermore, a number of functional derivatives of 5 , of 19 , of 39 and of 40 were prepared. Oxidation of the hydroxy-diester 7 with dimethylsulfoxide and a carbodiimidc derivative in the presence of trifluoroacetic acid afforded 4-oxo-1,2,3,4-tetrahydro-2, 6-pyridine-dicarboxylic acid dimethyl ester ( 50 ). This ester was also obtained under the same conditions from thc keto-diester 19 .     

Hydrogen bonding in two ammonium salts of 5‐sulfosalicylic acid: ammonium 3‐carboxy‐4‐hydroxybenzenesulfonate monohydrate and triammonium 3‐carboxy‐4‐hydroxybenzenesulfonate 3‐carboxylato‐4‐hydroxybenzenesulfonate

The structures of two ammonium salts of 3‐carboxy‐4‐hydroxybenzenesulfonic acid (5‐sulfosalicylic acid, 5‐SSA) have been determined at 200 K. In the 1:1 hydrated salt, ammonium 3‐carboxy‐4‐hydroxybenzenesulfonate monohydrate, NH₄⁺·C₇H₅O₆S⁻·H₂O, (I), the 5‐SSA⁻ monoanions give two types of head‐to‐tail laterally linked cyclic hydrogen‐bonding associations, both with graph‐set R₄⁴(20). The first involves both carboxylic acid O—H...O_water and water O—H...O_sulfonate hydrogen bonds at one end, and ammonium N—H...O_sulfonate and N—H...O_carboxy hydrogen bonds at the other. The second association is centrosymmetric, with end linkages through water O—H...O_sulfonate hydrogen bonds. These conjoined units form stacks down c and are extended into a three‐dimensional framework structure through N—H...O and water O—H...O hydrogen bonds to sulfonate O‐atom acceptors. Anhydrous triammonium 3‐carboxy‐4‐hydroxybenzenesulfonate 3‐carboxylato‐4‐hydroxybenzenesulfonate, 3NH₄⁺·C₇H₄O₆S²⁻·C₇H₅O₆S⁻, (II), is unusual, having both dianionic 5‐SSA²⁻ and monoanionic 5‐SSA⁻ species. These are linked by a carboxylic acid O—H...O hydrogen bond and, together with the three ammonium cations (two on general sites and the third comprising two independent half‐cations lying on crystallographic twofold rotation axes), give a pseudo‐centrosymmetric asymmetric unit. Cation–anion hydrogen bonding within this layered unit involves a cyclic R₃³(8) association which, together with extensive peripheral N—H...O hydrogen bonding involving both sulfonate and carboxy/carboxylate acceptors, gives a three‐dimensional framework structure. This work further demonstrates the utility of the 5‐SSA⁻ monoanion for the generation of stable hydrogen‐bonded crystalline materials, and provides the structure of a dianionic 5‐SSA²⁻ species of which there are only a few examples in the crystallographic literature.     

The Light-Induced Oxygenation of the B-Didehydrocorrinoid Vitamin-B12 Derivative ‘Pyrocobester’

The didehydrocorrinoid derivative of vitamin B₁₂, ‘pyrocobester’ 1 (hexamethyl Coα, Cob?-dicyano-7-de (carboxymethyl)-7,8-didehydrocobyrinate), is oxygenated in the presence of visible light and molecular oxygen to give the previously unknown ‘5,6-dioxosecopyrocobester’ 3 (hexamethyl Coα, Cob?-dicyano-5,6-dioxo-7-de(carboxymethyl)-7,8-didehydro-5,6-secocobyrinate) under regioselective cleavage of the macrocycle at the 5,6-position. Efficiency and yield of this reaction involving ‘singlet oxygen’ depend on the solvent used: with CCl₄ a 96% yield of 3 is obtained.     

Über die Herstellung von Äther der enantio-14, 15-Dinorlabdan-Reihe aus Eperusäure

The Conversion of Eperuic Acid into Ethers of the enantio-14, 15-Dinorlabdane Series 5 and 6 are strongly odiferous substances of the ambra-type. Their enantiomers 7 and 8 , hitherto unknown, have been synthesized from eperuic acid (4) and their olfactory properties compared with those of 5 and 6 . 4 was esterified by CH₂N₂ and dehydrogenated with (C₆H₅Se)₂/H₂O₂ to the α,β-unsaturated ester 9 (61%). Oxidation by KMnO₄ in acetone yielded the ketone 3 (60%). Epoxidation followed by treatment with acid converted 3 into the acetals 7 (61%) and 8 (14%). 7 and 8 differ from 5 and 6 in odor intensity, and 6 and 8 show slightly different odor quality.     

CH-Acidität in α-Stellung zum N-Atom in N,N-dialkylamiden mit sterisch geschützter Carbonylgruppe zur nucleophilen minoalkylierung

CH-Acidity in α-position to the N-Atom of N, N -Dialkylamides with Sterically Protected Carbonyl Groups Contribution to the Nucleophilic Amino Alkylation Sterically protected amides 1 such as the 2,4,6-triisopropyl-benzoic acid derivatives 3, 8b and 10 undergo readily H/Li-exchange with s-butyllithium at the CH₃N- or CH₂N-groups. The resulting organolithium compounds (cf. 9, 11 ) are alkylated and hydroxyalkylated with primary haloalkanes, aldehydes, and ketones under chain elongation in the amine position of the amides. The (E/Z)-rotamers of the dialkylamides 7 and 8 are separated by chromatography; the amides 4 – 6 , 12 , and 13 formally derived from β-hydroxyamines are obtained in the (Z)-form only. The configurational (E/Z)-assignments follow from NMR. and IR. data. The erythro and threo configuration of the two diastereomeric amides 12a and 12b are tentatively concluded from Eu(fod)₃-¹H-NMR.-shift experiments. The results strongly suggest that the H/Li-exchange takes place regioselectively at the CH? N group which is in cis-position to the C?O double bond (→ 14 ). The methyl 2,4,6-tri(t-butyl)benzoate ( 18 ) can also be deprotonated to the lithium acyloxymethanide 19 which is trapped by alkylation with 1-iodooctane (→ 20 ). – The steric protection of the carbonyl groups in the products 4 – 8, 10, 12, 13 , and 20 prevents their ready hydrolysis to amines and alcohols, respectively. Therefore, triphenylacetic acid derivatives 21 rather than 2,4,6-triisopropylbenzoic acid derivatives for use in the electrophilic substitution of equation (1) are recommended. The trityl group in 21 may be considered a C-leaving-group (C? C protective group, cf. 22, 23 ). The acetamide 25 reacts readily (→ 26 ) and then with electrophiles to give products 27a – c . As shown in the Table, the amides 27 are cleaved under a variety of conditions with formation of triphenylmethane. LiAlH₄ produces a tertiary amine, CH₃Li a secondary amine, and dissolving alkali metals/naphthalene under aprotic conditions mixtures of secondary amine and its formamide (hydrolysed by acid treatment). Thus the overall process (2) is feasible.     

Enantioselektive α-Alkylierung von Asparagin- und Glutaminsäure über die Dilithium-enolatocarboxylate von 2-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]essigsäure und 3-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]propionsäure

Overall Enantioselective α-Alkylation of Aspartic and Glutamic Acid through Dilithium Enolatocarboxylates of 2- [3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]acetic and 3-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]propionic Acid, respectively The pure methyl esters 10 of the heterocyclic carboxylic acids specified in the title were prepared in several steps by known methods from aspartic and glutamic acid, with overall yields of ca. 20%. The corresponding heterocyclic acids 11 were doubly deprotonated by LiNEt₂/BuLi or LiN(i-Pr)₂/BuLi to give enolatocarboxylates ( 3 ). The latter were reacted with electrophiles (MeOD, Mel, C₆H₅CH₂Br) to give the crystalline products 14 – 21 diastereoselectively. Hydrolysis of the imidazolidinone ring of three such products gave the corresponding α-branched aspartic and glutamic acids 22 – 24 of known absolute configuration, thus establishing the stereochemical course of the overall enantioselective alkylations.     

Umsetzung von Diazoessigsäure-ethylester mit 1,3-Thiazol-5(4H)-thionen

Reaction of Ethyl Diazoacetate with 1,3-Thiazole-5(4H)-thiones Reaction of ethyl diazoacetate ( 2a ) and 1,3-thiazole-5(4H)-thiones 1a,b in Et₂O at room temperature leads to a complex mixture of the products 5–9 (Scheme 2). Without solvent, 1a and 2a react to give 10a in addition to 5a–9a . In Et₂O in the presence of aniline, reaction of 1a,b with 2a affords the ethyl 1,3,4-thiadiazole-2-carboxylate 10a and 10b , respectively, as major products. The structures of the unexpected products 6a, 7a , and 10a have been established by X-ray crystallography. Ethyl 4H-1,3-thiazine-carboxylate 8b was transformed into ethyl 7H-thieno[2,3-e][1,3]thiazine-carboxylate 11 (Scheme 3) by treatment with aqueous NaOH or during chromatography. The structure of the latter has also been established by X-ray crystallography. In the presence of thiols and alcohols, the reaction of 1a and 2a yields mainly adducts of type 12 (Scheme 4), compounds 5a,7a , and 9a being by-products (Table 1). Reaction mechanisms for the formation of the isolated products are delineated in Schemes 4–7: the primary cycloadduct 3 of the diazo compound and the C?S bond of 1 undergoes a base-catalyzed ring opening of the 1,3-thiazole-ring to give 10 . In the absence of a base, elimination of N₂ yields the thiocarbonyl ylide A ′, which is trapped by nucleophiles to give 12 . Trapping of A ′, by H₂O yields 1,3-thiazole-5(4H)-one 9 and ethyl mercaptoacetate, which is also a trapping agent for A ′, yielding the diester 7 . The formation of products 6 and 8 can be explained again via trapping of thiocarbonyl ylide A ′, either by thiirane C (Scheme 6) or by 2a (Scheme 7). The latter adduct F yields 8 via a Demjanoff-Tiffeneau-type ring expansion of a 1,3-thiazole to give the 1,3-thiazine.     

Umwandlung von 6-Methylen-tricyclo[3.2.1.02,7]oct-3-en-8-onen mit Ameisensäure in kernmethylierte Phenylessigsäuren

In a preceding communication [5] it was shown that 1, 5-dimethyl-6-methylene-tricyclo[3.2.1.0^2,7]oct-3-en-8-one ( 2 ) and related tricyclic ketones are converted by strong acids (CF₃COOH, FSO₃H) into polymethylated tropylium salts with loss of carbon monoxide, e.g. the 1, 2, 4-trimethyltropylium ion 4 from 2 (Scheme 1). Under the influence of neat formic acid at 20°, 2 gives rise to ring-methylated phenylacetic acids, i.e. 2, 4, 5-trimethylphenylacetic acid ( 5 , main product) as well as smaller amounts of 2, 4, 6-and 2, 3, 5-trimethylphenylacetic acids ( 6, 7 resp.; Scheme 2). –On rearrangement of 2 in HCOOD, ca. 2 D-atoms are incorporated (formula d₂-5) into the 2, 4, 5-trimethylphenylacetic acid. The tricyclic 15 , containing 3 methyl groups, gives 2, 3, 5, 6-tetramethylphenylacetic acid ( 11 ; Scheme 4) with formic acid; the isomeric tricyclic 16 , 2, 3, 4, 5-tetramethylphenylacetic acid ( 12 ; Scheme 5). From 1, 2, 4, 5-tetramethyl-6-methylene-tricyclo[3.2.1.0^2,7]oct-3-en-8-one ( 17 ) one obtains pentamethylphenylacetic acid ( 14 ; Scheme 6). Similarly from 18 , a phenylacetic acid derivative, most probably 4-ethyl-2, 5-dimethyl-phenylacetic acid ( 19 ; Scheme 17), has been obtained. –In no case was the formation of α-phenylpropionic acid derivatives observed, not even from the tricyclic 23 containing six methyl groups. From the tricyclic ketone 2 in 70% formic acid a trimethyl-cyclohepta-2, 4, 6-triene-1-carboxyclic acid with partial formula 24 , besides 2, 4, 5-trimethylphenylacetic acid ( 5 ), is formed. 24 remained practically unchanged on standing in neat formic acid and thus does not represent an intermediate product arising by the rearrangement of 2 in that solvent. On standing in methanolic sulfuric acid, tricyclic 2 furnishes the two stereioisomeric methanol-addition products Z- 26 and E- 26 (Scheme 10); these are converted into the phenylacetic acids 5 , 6 and 7 by neat formic acid. The conversion of 2 and related compounds into ring-polymethylated phenylacetic acids, represents a novel and rather complicated reaction. In our opinion the reaction paths represented in Schemes 12 and 18 are responsible for the conversion of 2 into the trimethylphenylacetic acids, compound 40 representing a key intermediate. Analogous reaction paths can be assumed for the other tricyclic ketone transformations. The use of shift reagents in the NMR. spectroscopy and the high-resolution gas-chromatography of the corresponding methyl esters proved particularly important for the analysis of the reaction mixtures. The majority of the polymethylated phenylacetic acids were independently synthesised by means of the Willgerodt-Kindler reaction (chap. 3.2.), whose course is strongly influenced by methyl groups in the ortho-positions of the acetophenone derivatives employed.     

Michael-Addition von Thiocarbonsäureestern Anwendung bei der Synthese von (±)-Jasminketolacton

Michael addition of carbothioates. Application to the synthesis of (±)-jasmine ketolactone It is shown that the lithium enolate of S-t-butyl thioacetate adds to 2-cyclopentenone in the β-position and that fluoride ions catalyze the 1, 4-addition of the trimethylsilyl enol ether of S-t-butyl thioacetate ( 5 ) to 2-cyclopentenone ( 4 ) to give 6 . These novel versions of the Michael addition have been applied to a synthesis of jasmonoid compounds. Cleavage of the trimethylsilyl enol ether in 6 with tetrabutylammonium fluoride produced the corresponding ketone enolate which could be trapped in situ by alkylation with 1-bromo-5-(2′-tetrahydropyranoxy)-2-pentyne ( 7 ) to form 8 . Removal of the alcohol protecting group in 8 , followed by partial hydrogenation of the triple bond over Lindlar palladium and mercury ion promoted hydrolysis of the carbothioate moiety in 9 , led to 5′-hydroxy jasmonic acid ( 10 , Scheme 3). 10 was converted into the S-(2-pyridyl) carbothioate and cyclized in dilute benzene solution under the influence of silver ion to give (±)-jasmine ketolactone ( 1 , Scheme 4), a component of the essential oil of Jasminum grandiflorum, in 72% yield. Similarly, methyljasmonate ( 2 , Scheme 2) was obtained from 6 by the reaction with 1-bromo-2-pentyne and tetrabutylammonium fluoride followed by methanolysis and partial hydrogenation of the triple bond.     

2, 3-Disubstituted γ-Butyrolactams from the Michael-Additions of Doubly Deprotonated,Optically Active β-Hydroxycarboxylates to Nitroolefins. Preliminary Communication

The conjugate addition of the chiral, non-racemic alkoxy-enolates 5 and 6 to nitroolefins furnishes the hydroxynitroesters 7–13 , which are catalytically hydrogenated to give the lactams 14–18 . The configuration of adduct 7 from nitroethylene was elucidated by NMR. analysis of the acetal 20 derived from 7 . The assignment establishes that the reaction follows the stereochemical rule of attack depicted in 21 and previously deduced for other electrophiles, i.e. formation of erythro-products of type 3b and 4b . No stereocontrol was found at the newly formed chiral centers in α- and β-position to the NO₂ group of 8–12 .     

Stabilisierung von ?PC〈-Bindungen durch cyclische Silylhydrazone

Stabilization of ? P?C〈 Bonds by Cyclic Silylhydrazones 1,2-Diaza-3-sila-5-cyclopentenes unsubstituted at the 4-position react after lithiation with halophosphanes and -arsanes to give 1 – 4 . The 4-methylated ring 5 reacts analogously with F₂P? N(SiMe₃)₂ to give 6 , but exchanges the dimethylsilyl group of the ring in reaction with PCl₃, to give 1,2-diaza-3-phospha-3,5-cyclopentadien 7 . The phosphaethenes 8 and 9 are formed from 4-trimethylsilylsubstituted lithiated rings by reaction with difluorophosphanes, F₂PR (R = N(SiMe₃) CMe₃, N(SiMe₃)₂) and elimination of LiF and chlorosilane.