A ‘One-Pot’ Anellation Method for the Transformation of Heptalene-4,5-dicarboxylates into Benzo[a]heptalenes

It has been found that dimethyl heptalene-4,5-dicarboxylates, when treated with 4 mol-equiv. of lithiated N,N-dialkylamino methyl sulfones or methyl phenyl sulfone, followed by 4 mol-equiv. of BuLi in THF in the temperature range of ?78 to 20°, give rise to the formation of 3-[(N,N-dialkylamino)sulfonyl]- or 3-(phenylsul-fonyl)benzo[a]heptalene-2,4-diols of. (cf. Scheme 4, and Tables 2 and 3). Accompanying products are 2,4-bis{[(N,N-dialkylamino)sulfonyl]methyl}- or 2,4-bis[(phenylsulfonyl)methyl]-4,10a-dihydro-3H-heptaleno[1,10-bc]furan-3-carboxylates as mixtures of diastereoisomers of. cf. Scheme 4, and (Tables 2 and 3) which are the result of a Michael addition reaction of the lithiated methyl sulfones at C(3) of the heptalene-4,5-dicarboxylates, followed by (sulfonyl)methylation of the methoxycarbonyl group at C(5) and cyclization of. (cf. Scheme 5). It is assumed that the benzo[a]heptalene formation is due to (sulfonyl)methylation of both methoxycarbonyl groups of the heptalene-4,5-dicarboxylates of. (cf. Schemes 6 and 8). The resulting bis-enolates 35 are deprotonated further. The thus formed tris-anions 36 can then cyclize to corresponding tris-anions 37 of cyclopenta[d]heptalenes which, after loss of N,N-dialkylamido sulfite or phenyl sulfinate, undergo a ring-enlargement reaction by 1,2-C migration finally leading to the observed benzo[a]heptalenes of. (cf. Schemes 8 and 9). The structures of the new product types have been finally established by X-ray crystal-structure analyses (cf. Figs. 1 and 2 as well as Exper. Part).     

On the Formation of 2‐Sulfonylbenzo[a]heptalene‐1,3‐diols as Precursors for the Synthesis of Colchicinoids

The benzo[a]heptalene formation from 4‐[(R‐sulfonyl)acetyl]heptalene‐5‐carboxylates 15 and 5‐[(R‐sulfonyl)acetyl]heptalene‐4‐carboxylates 16 (R=Ph or morpholino) in the presence of R′SO₂CH₂Li and BuLi has been investigated (Scheme 6). Only the sulfonyl moiety linked to the C?O group at C(4) of the heptalene skeleton is found at C(3) of the formed benzo[a]heptalene‐2,4‐diols 3 in accordance with the general mechanism of their formation (Scheme 3). Intermediates that might rearrange to corresponding 2‐sulfonylbenzo[a]heptalene‐1,3‐diols lose HO^? under the reaction conditions to yield the corresponding cyclopenta[d]heptalenones of type 11 (Schemes 6 and 7). However, the presence of an additional Me group at C(α) of the lithioalkyl sulfones suppresses the loss of HO^?, and 4‐methyl‐2‐sulfonylbenzo[a]heptalene‐1,3‐diols of type 4c have been isolated and characterized for the first time (Schemes 8 and 10). A number of X‐ray crystal‐structure analyses of starting materials and of the new benzo[a]heptalenes have been performed. Finally, benzo[a]heptalene 4c has been transformed into its 1,2,3‐trimethoxy derivative 23 , a benzo[a]heptalene with the colchicinoid substitution pattern at ring A (Scheme 11).     

A Useful Modification of the Evans Auxiliary: 4-Isopropyl-5,5-diphenyloxazolidin-2-one

The 4-isopropyl-5,5-diphenyloxazolidinone ( 1 ) is readily prepared from (R)- or (S)-valine ester, PhMgBr, and ethyl chlorocarbonate. It has a melting point of ca. 250°, a low solubility in most organic solvents, and a C=O group which is sterically protected from nucleophilic attack. Thus, the soluble N-acyl-oxazolidinones ( 7 – 16 ) can be prepared from 1 with BuLi at temperatures around 0° instead of −78° (Scheme 3), their Li enolates can be generated with BuLi, rather than with LDA, and deacylation in the final step of the procedure can be achieved with NaOH at ambient temperatures (Scheme 12), with facile recovery of the precipitating auxiliary 1 (filtering, washing, and drying). The following reactions of N-acyl-oxazolidinones from 1 have been investigated: alkylations (Scheme 4), aminomethylations and hydroxymethylations (Scheme 5), aldol additions (Schemes 6 and 7), Michael additions (Schemes 9 and 10), and a (4+2) cycloaddition (Scheme 11). The well-known features of reactions following the Evans methodology (yield, diastereoselectivity, dependence on conditions, counter ions, additives etc.) prevail in these transformations. Most products, however, have higher melting points and a much more pronounced crystallization tendency than those derived from conventional oxazolidinones, and can thus be purified by recrystallization, avoiding chromatography (Table 1). The disadvantage of 1 having a higher molecular weight (ca. 150 Da) than the non-phenyl-substituted auxiliary is more than compensated by the ease of its application, especially on large scale. A number of crystal structures of oxazolidinones derived from 1 and a TiCl₄ complex of an oxazolidinone are described and discussed in view of the diastereoselective-reaction mechanisms.     

Bortrifluorid-katalysierte Umsetzungen von 3-Amino-2H-azirinen mit Aminosäure-estern und Aminen

Boron-Trifluoride-Catalyzed Reactions of 3-Amino-2H-azirines with Amino-acid Esters and Amines After activation by protonation or complexation with BF₃, 3-amino-2H-azirines 1 react with the amino group of α-amino-acid esters 3 to give 3,6-dihydro-5-aminopyrazin-2(1H)-ones 4 by ring enlargement (Scheme 2, Table 1). The configuration of 3 is retained in the products 4 . With unsymmetrically substituted 1 (R¹ ≠ R²), two diastereoisomers of 4 (cis and trans) are formed in a ratio of 1:1 to 2:1. With β-amino-acid esters 5 and 7 , only openchain α-amino-imidamides 6 and 8 , respectively, are formed, but none of the seven-membered heterocycle (Scheme 3). Primary amines also react with BF₃-complexed 1 to yield α-amino-imidamides of type 9 (Scheme 4, Table 2). Compound 9b is characterized chemically by its transformation into crystalline derivatives 10 and 12 with 4-nitrobenzoyl chloride and phenyl isothiocyanate, respectively (Scheme 5). The structure of 12 is established by X-ray crystallography. Mechanisms for the reaction of activated 1 with amino groups are proposed in Schemes 6 and 7.     

Intramolekulare Inversionssubstitution am Dreiring von 77exo-Brombicyclo[4.1.0]heptan-3endo-ol unter Bildung eines Tetrahydrofuranringes

Intramolecular Substitution under Inversion at the Threemembered Ring of 7exo-Bromobicyclo[4.1.0]heptan-3endo-ol yielding a Tetrahydrofuran Ring The reaction 1a → 2a involving substitution at a cyclopropane carbon atom can be observed only with the bromophilic alkyllithium reagents but not with the bases lithium diisopropyl amide (LDA) (Table 1) or potassium t-butoxide (KTB). The mechanism must be an insertion as outlined in Scheme 1. - The monobromides 1b , 1c and 1d are prepared stereoselectively from the acetal 3a . Again, cyclization of 1b takes only place with LDA in the presence of alkyllithium (Table 2, entries 1--4) suggesting an insertion mechanism (route (a) or (b) in Scheme 2). In contrast, KTB effects the substitution in high yield with no loss (from 1c ) or incorporation of deuterium at the cyclopropane substitution center (Table 2, entries 5--7); the possibility is discussed that this process is an S_N2-type reaction.     

Photosolvolysis of 2-Allylated Anilines to 2-Indanols

It is shown that 2-allylated anilines (cf. Schemes 2–4, 7, and 8) on irradiation in protic solvents such as H₂O. MeOH, and EtOH in the presence of H₂SO₄ undergo a novel photosolvolysis reaction to yield specifically trans-2-hydroxy- and trans-2-alkoxy-1-methylindanes. Intermediates are presumably tricyclo[4.3.0.0^1,8]nona-2,4-dienes formed in an intramolecular [2s + 2s] cycloaddition reaction (cf. Scheme 7). On the other hand, N,N,N-trimethyl-2-(1′-methylallyl)anilinium salts 18 (Scheme 6) and 2-(3′-butenyl)-N,N-dimethylaniline ( 17 ) lose on irradiation in MeOH or H₂SO₄/MeOH the ammonium group reductively to yield (1-methylallyl)benzene ( 19 ) and 1-methylindane ( 20 ), respectively.     

Zur Photochemie von 1H- und 2H-Indazolen in saurer Lösung

On the Photochemistry of 1H- and 2H-Indazoles in Acidic Solution It is shown that 1H- and 2H-indazoles (cf. Scheme 2) on protonation (0, 1N H₂SO₄ in water or alcoholic solution) give analogous indazolium ions (see Fig. 1 and 2) which on irradiation undergo heterolytic cleavage of the N (1), N (2) bond whereby aromatic nitrenium ions in the singlet ground state are formed (cf. Scheme 13). If the para position of these nitrenium ions is not occupied by a substituent (e.g. a methyl group) they are readily trapped by nucleophiles present (e.g. water, alcohols, chloride ions) to yield the corresponding 5-substituted 2-amino-benzaldehydes or acetophenones (cf. Schemes 4–10). Photolysis of indazole ( 4 ) and 3-methyl-indazole ( 5 ) in 0,75N H₂SO₄ in alcoholic solutions gives in addition minor amounts of the corresponding 3-substituted 2-amino-benzaldehydes and acetophenones, respectively (cf. Schemes 6 and 8 and Table 2). Phenylnitrenium ions carrying a methyl group in the para position give in aqueous sulfuric acid mainly the reduction products, i.e. 2-amino-5-methyl-benzaldehydes (cf. Schemes 11 and 12 and Table 3). In methanolic sulfuric acid, in addition to the reduction products, 6-methoxy substituted benzaldehydes are found (cf. Schemes 11 and 12 and Table 3) which are presumably formed by an addition-elimination mechanism (cf. Scheme 18). It is assumed that precursors of the reduction products are the corresponding nitrenium ions in the triplet ground state. Singlet-triplet conversion of the nitrenium ions may become efficient when addition of nucleophiles to the singlet nitrenium ions is reversible (cf. Scheme 22) thus, enhancing the probability of conversion or when conjugation in the singlet nitrenium ions is disturbed by steric effects (cf. Scheme 20) thus, destabilizing the singlet state relative to the triplet state.     

Nucleosides and Oligonucleotides with Diynyl Side Chains: Base Pairing and Functionalization of 2′‐Deoxyuridine Derivatives by the Copper(I)‐Catalyzed Alkyne?Azide ‘Click’ Cycloaddition

Oligonucleotides containing the 5‐substituted 2′‐deoxyuridines 1b or 1d bearing side chains with terminal C?C bonds are described, and their duplex stability is compared with oligonucleotides containing the 5‐alkynyl compounds 1a or 1c with only one nonterminal C?C bond in the side chain. For this, 5‐iodo‐2′‐deoxyuridine ( 3 ) and diynes or alkynes were employed as starting materials in the Sonogashira cross‐coupling reaction (Scheme 1). Phosphoramidites 2b – d were prepared (Scheme 3) and used as building blocks in solid‐phase synthesis. T_m Measurements demonstrated that DNA duplexes containing the octa‐1,7‐diynyl side chain or a diprop‐2‐ynyl ether residue, i.e., containing 1b or 1d , are more stable than those containing only one triple bond, i.e., 1a or 1c (Table 3). The diyne‐modified nucleosides were employed in further functionalization reactions by using the protocol of the Cu^I‐catalyzed Huisgen–Meldal–Sharpless [2+3] cycloaddition (‘click chemistry’) (Scheme 2). An aliphatic azide, i. e., 3′‐azido‐3′‐deoxythymidine (AZT; 4 ), as well as the aromatic azido compound 5 were linked to the terminal alkyne group resulting in 1H‐1,2,3‐triazole‐modified derivatives 6 and 7 , respectively (Scheme 2), of which 6 forms a stable duplex DNA (Table 3). The Husigen–Meldal–Sharpless cycloaddition was also performed with oligonucleotides (Schemes 4 and 5).     

Highly Diastereoselective Aldol Reaction of Bicyclo[3.2.1]oct-6-en-3-ones and 8-Oxabicyclo[3.2.1]oct-6-en-3-ones. (E)-Selective conversion into α-alkylidene ketones

The bicyclic ketones 1–6 entered into diastereoselective (> 95% d.e.) aldol reactions with a variety of aldehydes (Scheme 1 and Table 1). A representative series of aldols was converted (E)-selectively into α,β-unsaturated ketones by (i) spontaneous base-promoted dehydration (Scheme 1 and Table 2) and also by (ii) conversion into brosylate and base-mediated elimination with lithium diisopropylamide/N,N,N′,N′-tetramethylethylenediamine (LDA/TMEDA; Scheme 2). The simple α-methylidene ketones 17a and 18a were obtained via oxidation of the phenylselenides 19 and 20 , respectively (Scheme 4). The tertiary aldol 27 was synthesized best by treatment of 1,3-diketone 26 with Me₄Zr (Table 4). In this fashion, the facile retro-aldol reaction of 27 was suppressed effectively.     

Angular Alkylation of cis-Decalin Epoxides with C-nucleophiles: Mechanism,scope, and limitations of a novel bridgehead functionalisation

The angular alkylation of cis-decalin epoxides like 5 or 7 can be achieved at C(8a)

1 For convenience, the arbitrary numbering given for 5 (Scheme I) is used throughout the General Part; for systematic names, see Exper. Part.

in good yield by using CuI and a large excess of Grignard reagents without an sp³ centre at C(2). The reaction proceeds via a carbenium-ion intermediate which is stabilised by homoconjugative interaction with the adjacent double bond. Due to 1,3-diaxial strain in the alkoxides resulting from alkylation or reduction at C(4a) of the epoxides 5 or 7 , the nucleophile is delivered selectively to C(8a). Grignard reagents possessing H-atoms at C(β), transfer a hydride to the epoxide yielding the trans-decalol 11 (Grignard reduction). The angular alkylation of 5 with allylic and benzylic Grignard reagents proceeds with good yield.     

Chiral Lithiated Phosphoric Triamides: Structure,Reactivity, and Salt Effects

The theoretical structure of a cyclic phosphoric triamide 3 and of its monolithiated isomers 4 – 6 was calculated by ab initio methods (Fig. 1, Tables 1 and 2). The global minimum in 4 consists of a five-membered Li−C−N−P−O chelate. The intermediates 5 and 6 are, relative to 4 , energetically unfavorable by 15 and 18 kcal mol⁻¹, respectively, due to distortion in order to accommodate the N-complexation of the Li⁺ ions. NMR Investigations (¹H, ¹³C, ³¹P, and ⁷Li) of the lithiated bicyclic phosphoric triamide 1 were performed (Tables 3 – 5). The lithium aminomethanide 2 is characterized by a sp³-hybridized anion supporting Li−C contacts. The anions exist in a monomer-dimer equilibrium in solution (Scheme 2). Trapping reactions of rac- 2 with carbonyl compounds generated the corresponding amino-alcohol derivatives with high diastereoselectivities (Scheme 3, Table 6). A rational for the stereochemical outcome is given (Fig. 4). In the presence of LiBr, a P−N bond cleavage occurred on reaction of rac- 2 with aldehydes, which allowed the synthesis of (1-hydroxylalkyl)phosphonic diamides (Scheme 5, Table 7).     

Formation of Heptaleno[1,2-c]furans and Heptaleno[1,2-c]furanones

The dehydrogenation reaction of the heptalene-4,5-dimethanols 4a and 4d , which do not undergo the double-bond-shift (DBS) process at ambient temperature, with basic MnO₂ in CH₂Cl₂ at room temperature, leads to the formation of the corresponding heptaleno[1,2-c]furans 6a and 6d , respectively, as well as to the corresponding heptaleno[1,2-c]furan-3-ones 7a and 7d , respectively (cf. Scheme 2 and 8). The formation of both product types necessarily involves a DBS process (cf. Scheme 7). The dehydrogenation reaction of the DBS isomer of 4a , i.e., 5a , with MnO₂ in CH₂Cl₂ at room temperature results, in addition to 6a and 7a , in the formation of the heptaleno[1,2-c]-furan-1-one 8a and, in small amounts, of the heptalene-4,5-dicarbaldehyde 9a (cf. Scheme 3). The benzo[a]heptalene-6,7-dimethanol 4c with a fixed position of the C?C bonds of the heptalene skeleton, on dehydrogenation with MnO₂ in CH₂Cl₂, gives only the corresponding furanone 11b (Scheme 4). By [²H₂]-labelling of the methanol function at C(7), it could be shown that the furanone formation takes place at the stage of the corresponding lactol [3-²H₂]- 15b (cf. Scheme 6). Heptalene-1,2-dimethanols 4c and 4e , which are, at room temperature, in thermal equilibrium with their corresponding DBS forms 5c and 5e , respectively, are dehydrogenated by MnO₂ in CH₂Cl₂ to give the corresponding heptaleno[1,2-c]furans 6c and 6e as well as the heptaleno[1,2-c]furan-3-ones 7c and 7e and, again, in small amounts, the heptaleno[1,2-c]furan-1-ones 8c and 8e , respectively (cf. Scheme 8). Therefore, it seems that the heptalene-1,2-dimethanols are responsible for the formation of the furan-1-ones (cf. Scheme 7). The methylenation of the furan-3-ones 7a and 7e with Tebbe's reagent leads to the formation of the 3-methyl-substituted heptaleno[1,2-c]furans 23a and 23e , respectively (cf. Scheme 9). The heptaleno[1,2-c]furans 6a, 6d , and 23a can be resolved into their antipodes on a Chiralcel OD column. The (P)-configuration is assigned to the heptaleno[1,2-c]furans showing a negative Cotton effect at ca. 320 nm in the CD spectrum in hexane (cf. Figs. 3–5 as well as Table 7). The (P)-configuration of (–)- 6a is correlated with the established (P)-configuration of the dimethanol (–)- 5a via dehydrogenation with MnO₂. The degree of twisting of the heptalene skeleton of 6 and 23 is determined by the Me-substitution pattern (cf. Table 9). The larger the heptalene gauche torsion angles are, the more hypsochromically shifted is the heptalene absorption band above 300 nm (cf. Table 7 and 8, as well as Figs. 6–9).     

From 1-(Silyloxy)Butadiene to 4-Amino-4-Deoxy-DL-Erythrose and to 1-Amino-1-Deoxy-DL-Erythritol Derivatives via Hetero-Diels-Alder Reactions with Acylnitroso Dienophiles

Acylnitroso dienophiles 4 reacted instantly with 1-(silyloxy)butadiene 5α and led in good yield to the regioisomeric cycloadducts 6 (major) and 7 (minor; Scheme 2, Table 1). cis-Hydroxylation of these primary cycloadducts with OsO₄ (catalyst) occurred stereospecifically and in high yield (→ 8 and 9 , resp.; Scheme 2). It was followed by reductive ring cleavage to give either 1-amino-1-deoxy-DL -erythritol or 4-amino-4-deoxy-DL -erythrose derivatives 10 and 14 , respectively, depending on the nature of the reducing agent (Schemes 3 and 4).     

Asymmetric induction bny enantiotopically differentiating retro-claisen reaction of P{rochiral bicyclic β-diketones

The possibility of preparing cycloalkanones with an asymmetric β-C-atom by enantiotopically differentiating retro-Claisen reactions of bicyclic diketones a (Scheme l) is tested with the decalin-1,8-diones 1 and 7 , as well as with the bicyclo[3.3.0]octane-2,8-diones 10 and 11 . Treatment of the reactive dione 1 with chiral tetra-alkyl titanate catalysts results in a low optical induction (13%, Scheme 2). Cleavage with the Nasalts of a-amino-alcohols and hydrolysis of the resulting amides or esters gives much better optical yields, reaching 86% ee with dione 1 and (?)-ephedrine (Scheme 3). Almost as efficient is N-methylephedrine with 75% optical induction (Scheme 5). Lower enantiotopical differentiation is, however, observed with (?)-ephedrine and diones 7 (44% ee), 10 (8% ee), and 11 (48% ee) (Schemes 3 and 4, Table l), or with dione 1 and _L-prolinol (37% ee) or (?)-2-amino-1-butanol (11% ee) (Scheme 5, Table 2). The moderate chemical yields of these transformations (500–70%) can be ascribed to side-reactions of the ketones under the strongly basic conditions.     

Preparation and C-Alkylation of Enantiomerically Pure S-Phenyl Aziridinecarbothioates. On the Structure of Small-Ring Ester Lithium Enolates

Racemic and enantiomerically pure methyl N-(tert-butyl)-N-benzyl- and N-1-(phenylethyl)aziridinecarboxylates are prepared by known methods and converted to phenyl thioesters ( 1 , 2 , 15 , 16 ; Schemes 2 and 3). These are deprotonated with lithium diisopropylamide (LDA) and BuLi (for removal of diisopropylamine) in THF at dry-ice temperature. The resulting lithiated species are surprisingly stable and are deuterated, alkylated (CH₃, C₂H₅, allyl, benzyl), and added to aldehydes and nitroolefins in good yields (50–80 %, 18 examples; Schemes 1 and 4–6). The configurational stability of the lithiated species is studied, and conclusions about their structures are drawn. Thus, a C(α)-lithiated ester (see L , Scheme 9) or an O-lithiated ‘enolate’ (see M ) with pyramidalized C(β)-atom is proposed for the species from levorotatory S-phenyl N-benzylaziridinecarbothioate which does not undergo racemization after 1 h at ?60° (THF solution).     

Synthesis of an Isotopically Isomeric Mixture of 1,4,6,8-Tetramethyl[13C2]azulene and Its Thermal Reaction with Dimethyl Acetylenedicarboxylate

Sodium [1,3-¹³C₂]cyclopentadienide in tetrahydrofuran (THF) has been prepared from the corresponding labelled [¹³C₂]cyclopentadiene which was synthesized from ¹³CO₂ and (chloromethyl)trimethylsilane (cf. Scheme 10) according to an established procedure. It could be shown that the acetate pyrolysis of cis-cyclopentane-1,2-diyl diacetate (cis- 22 ) at 550 ± 5° under reduced pressure (60 Torr) gives five times as much cyclopentadiene as trans- 22 . The reaction of sodium [1,3-¹³C₂]cyclopentadienide with 2,4,6-trimethylpyrylium tetrafluoroborate in THF leads to the formation of the statistically expected 2:2:1 mixture of 4,6,8-trimethyl[1,3a-¹³C₂], -[2,3a-¹³C₂]-, and -[1,3-¹³C₂]azulene ( 20 ; cf. Scheme 7 and Fig. 1). Formylation and reduction of the 2:2:1 mixture [¹³C₂]- 20 results in the formation of a 1:1:1:1:1 mixture of 1,4,6,8-tetramethyl[1,3-¹³C₂]-, -[1,3a-¹³C₂]-, -[2,3a-¹³C₂]-, -[2,8a-¹³C₂]-, and -[3,8a-¹³C₂]azulene ( 5 ; cf. Scheme 8 and Fig. 2). The measured ²J(¹³C, ¹³C) values of [¹³C₂]- 20 and [¹³C₂]- 5 are listed in Tables 1 and 2. Thermal reaction of the 1:1:1:1:1 mixture [¹³C₂]- 5 with the four-fold amount of dimethyl acetylenedicarboxylate (ADM) at 200° in tetralin (cf. Scheme 2) gave 5,6,8,10-tetramethyl-[¹³C₂]heptalene-1,2-dicarboxylate ([¹³C₂]- 6a ; 22%), its double-bond-shifted (DBS) isomer [¹³C₂]- 6b (19%), and the corresponding azulene-1,2-dicarboxylate 7 (18%). The isotopically isomeric mixture of [¹³C₂]- 6a showed no ¹J(¹³C,¹³C) at C(5) (cf. Fig. 3). This finding is in agreement with the fact that the expected primary tricyclic intermediate [7,11-¹³C₂]- 8 exhibits at 200° in tetralin only cleavage of the C(1)? C(10) bond and formation of a C(7)? C(10) bond (cf. Schemes 6 and 9), but no cleavage of the C(1)? C(11) bond and formation of a C(7)? C(11) bond. The limits of detection of the applied method is ≥96% for the observed process, i.e., [1,3a-¹³C₂]- 5 + ADM→ [7,11-¹³C₂]- 8 →[1,6-¹³C₂]- 9 →[5,10a-¹³C₂]- 6a (cf. Scheme 6).     

Synthesis of Polyalkylphenyl Prop‐2‐ynoates and Their Flash Vacuum Pyrolysis to Polyalkylcyclohepta[b]furan‐2(2H)‐ones

A new method for the smooth and highly efficient preparation of polyalkylated aryl propiolates has been developed. It is based on the formation of the corresponding aryl carbonochloridates (cf. Scheme 1 and Table 1) that react with sodium (or lithium) propiolate in THF at 25 – 65°, with intermediate generation of the mixed anhydrides of the arylcarbonic acids and prop‐2‐ynoic acid, which then decompose almost quantitatively into CO₂ and the aryl propiolates (cf. Scheme 11). This procedure is superior to the transformation of propynoic acid into its difficult‐to‐handle acid chloride, which is then reacted with sodium (or lithium) arenolates. A number of the polyalkylated aryl propiolates were subjected to flash vacuum pyrolysis (FVP) at 600 – 650° and 10⁻² Torr which led to the formation of the corresponding cyclohepta[b]furan‐2(2H)‐ones in average yields of 25 – 45% (cf. Scheme 14). It has further been found in pilot experiments that the polyalkylated cyclohepta[b]furan‐2(2H)‐ones react with 1‐(pyrrolidin‐1‐yl)cyclohexene in toluene at 120 – 130° to yield the corresponding 1,2,3,4‐tetrahydrobenz[a]azulenes, which become, with the growing number of Me groups at the seven‐membered ring, more and more sensitive to oxidative destruction by air (cf. Scheme 15).     

Aromatische [1,5s]-sigmatropische H-Verschiebungen in Arylallenen

1-Mesityl allene ( 1 ), 1-mesityl-3-methyl allene ( 2 ) and 1-mesityl-3,3-dimethyl allene ( 3 ) rearrange thermally at 150–190° in decane via [1,5s]sigmatropic H-shifts to yield the o-quinodimethanes 4 , which cyclise to give the 1,2-dihydronaphthalenes 5 and 6 and/or undergo [1,7 a]sigmatropic H-shifts to give 1-mesityl-(Z)-buta-1, 3-dienes (Z)- 7 and (Z)- 8 , respectively (Schemes 1,3,4 and 5) in almost quantitative yields. The activation parameters of these isomerisations are given in Table 1. 1-Mesityl-1-methyl allene ( 9 ) isomerises at 190° to give 4,5,7-trimethyl-1,2-dihydronaphthalene ( 17 ) in 50% yield (Scheme 6). 2′-Isopropylphenyl allene ( 10 ) in decane rearranges at 170° to 1-(Z)-propenyl-2-isopropenyl-benzene ((Z)- 19 , Scheme 7). Deuterium labelling experiments show that the rate determining step is an aromatic [1,5s]sigmatropic hydrogen shift from an sp³- to an sp-hybridised carbon atom. The primary kinetic isotopic effect (k_H/k_D) is 3.45, while the secondary βisotopic effect is 1.20 (Scheme 7 and Table 2).     

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).     

Molecular Recognition of Pyranosides by a Family of Trimeric, 1,1′-Binaphthalene-Derived Cyclophane Receptors

The synthesis and carbohydrate-recognition properties of a new family of optically active cyclophane receptors, 1 – 3 , in which three 1,1′-binaphthalene-2,2′-diol spacers are interconnected by three buta-1,3-diynediyl linkers, are described. The macrocycles all contain highly preorganized cavities lined with six convergent OH groups for H-bonding and complementary in size and shape to monosaccharides. Compounds 1 – 3 differ by the functionality attached to the major groove of the 1,1′-binaphthalene-2,2′-diol spacers. The major grooves of the spacers in 2 are unsubstituted, whereas those in 1 bear benzyloxy (BnO) groups in the 7,7′-positions and those in 3 2-phenylethyl groups in the 6,6′-positions. The preparation of the more planar, D₃-symmetrical receptors (R,R,R)- 1 (Schemes 1 and 2), (S,S,S)- 1 (Scheme 4), (S,S,S)- 2 (Scheme 5), and (S,S,S)- 3 (Scheme 8) involved as key step the Glaser-Hay cyclotrimerization of the corresponding OH-protected 3,3′-diethynyl-1,1′-binaphthalene-2,2′-diol precursors, which yielded tetrameric and pentameric macrocycles in addition to the desired trimeric compounds. The synthesis of the less planar, C₂-symmetrical receptors (R,R,S)- 2 (Scheme 6) and (S,S,R)- 3 (Scheme 9) proceeded via two Glaser-Hay coupling steps. First, two monomeric precursors of identical configuration were oxidatively coupled to give a dimeric intermediate which was then subjected to macrocyclization with a third monomeric 1,1′-binaphthalene precursor of opposite configuration. The 3,3′-dialkynylation of the OH-protected 1,1′-binaphthalene-2,2′-diol precursors for the macrocyclizations was either performed by Stille (Scheme 1) or by Sonogashira (Schemes 4, 5, and 8) cross-coupling reactions. The flat D₃-symmetrical receptors (R,R,R)- 1 and (S,S,S)- 1 formed 1 : 1 cavity inclusion complexes with octyl 1-O-pyranosides in CDCl₃ (300 K) with moderate stability (ΔG⁰ ca. −3 kcal mol⁻¹) as well as moderate diastereo- (Δ(ΔG⁰) up to 0.7 kcal mol⁻¹) and enantioselectivity (Δ(ΔG⁰)=0.4 kcal mol⁻¹) (Table 1). Stoichiometric 1 : 1 complexation by (S,S,S)- 2 and (S,S,S)- 3 could not be investigated by ¹H-NMR binding titrations, due to very strong signal broadening. This broadening of the ¹H-NMR resonances is presumably indicative of higher-order associations, in which the planar macrocycles sandwich the carbohydrate guests. The less planar C₂-symmetrical receptor (S,S,R)- 3 formed stable 1 : 1 complexes with binding free enthalpies of up to ΔG⁰=−5.0 kcal mol⁻¹ (Table 2). With diastereoselectivities up to Δ(ΔG⁰)=1.3 kcal mol⁻¹ and enantioselectivities of Δ(ΔG⁰)=0.9 kcal mol⁻¹, (S,S,R)- 3 is among the most selective artificial carbohydrate receptors known.