Oxidative Coupling Of 2-Alkyl-6,6-dimethylpentafulvenyl Anions

Cucl₂-Induced oxidative coupling of 2-(tert-butyl)-6,6-dimethylpentafulvenyl anion 9 predominantly takes place at C(7) and C(5) to give [7–7] and [7–5] coupling products 15 and 16 in 35 and 47% yields, respectively (Scheme 3) whose structures are elucidated from 1D- and 2D-NMR analysis. Compared with the product distribution observed for 6,6-dimethylpentafulvenyl anion 2 (Scheme 1), no coupling at C(2)/C(3) of 9 is observed. This means that, besides electronic effects, steric effect are also important in oxidative couplings of fulvenyl anions. The same couplings occur in the case of 2,3-bis(6,6-dimethylfulven-2-yl)-2,3-dimethylbutane dianion 10 as well but, due to electronic as well as conformational effects (Scheme 5), intermolecular coupling (to give polymers 17 , Scheme 4) is strongly favored over intermolecular coupling. Mechanisms explaining base-catalyzed isomerization 15a ? 15b ? 15c (Scheme 6) as well as isomerization 16a ? 16b (Scheme 7) are proposed.     

Synthese des Sesquiterpen-Ketones Shyobunon und seiner Diastereomeren

Synthesis of the Sesquiterpene Ketone Shyobunon and of its Diastereoisomers Shyobunon ( 12 ) and 6-epishyobunon ( 13 ) as well as their epimers 10 and 11 were synthetized in five steps from geranyl- ( 1 ) and nerylsenecionate ( 2 ), respectively. Ester enolate rearrangement [5] of 1 and 2 furnished the key intermediates 3 and 4 in high yield and in about 80% stereoselectivity [6] (Scheme 1). Conversion of the acid mixture 3 / 4 to the cyclohexanone derivatives 7 and 8 succeeded in 35–40% yield by means of cyclization of their acidchlorides with tin tetrachloride to the mixture of 5 and 6 , followed by HCl elimination with diazabicyclononene (DBN) (Scheme 2). Selective reduction of 7 to 10 and 11 , and 8 to 12 and 13 with triphenyltinhydride completed the synthesis. The relative configuration of 10 and 11 as well as of 12 and 13 were deduced from the ¹³C-NMR. spectra (Scheme 4, Table 2). The structure of ‘epishyobunone’ is revised: it has the structure 13 , and not 11 as described earlier [1]. This is discussed in connection with the rearrangement of acoragermacrone ( 16 ) [18] to shyobunone ( 12 ) and 6-epishyobunone ( 13 ) (Scheme 5).     

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.     

Oligonucleosides with a Nucleobase‐Including Backbone,Part 3, Synthesis of Acetyleno‐Linked Adenosine Dimers

The adenosine‐derived dimers 14a – d and 15b – d have been prepared by coupling the protected 8‐iodoadenosines 3 and 13 with the C(5′)‐ethynylated adenosine derivatives 5 , 6 , 11 , and 12 (Scheme 4). Similarly, the 5′‐epimeric dimer 16 was prepared by coupling 3 with the alkyne 8 (Scheme 5). The propargylic alcohol 4 was transformed into the N‐benzoylated alkyne 5 and into the amine 6 , while the epimeric alcohol 7 was converted to the epimeric amine 8 and the 5′‐deoxy analogues 11 and 12 (Scheme 3). Cross‐coupling of the iodoadenosine 13 with the alkyne 5 to 14a was optimised; it is influenced by the N‐benzoyl and the Et₃SiO group of the alkyne, but hardly by the N‐benzoyl group of the 8‐iodoadenosine. The alkyne is most reactive when it is O‐silylated, but not N‐benzoylated. Cross‐coupling of the 5′‐deoxyalkynes proceeded more slowly. The dimers 14a – d , 15b – d , and 16 were obtained in good yields (Table 2). Deprotection of 14d and 16 led to 18 and 20 , respectively (Scheme 5). The diols 17 and 19 and the hexols 18 and 20 prefer the syn‐conformation in (D₆)DMSO, completely for unit II and ≥80% for unit I; they exhibit partially persistent intramolecular O(5′)−H⋅⋅⋅N(3) H‐bonds. The persistence increases from 18% (unit I of 19 ), 32% (unit II of 17 and 19 ), 45% (unit I of 17 ), 52% (unit II of 18 and 20 ), and 55% (unit I of 20 ) to 82% (unit I of 18 ).     

Additionsreaktionen von 3-Dimethylamino-2,2-dimethyl-2H-azirin an Isothiocyanate

Addition Reactions of 3-Dimethylamino-2, 2-dimethyl- 2 H-azirine and Isothiocyanates. The title azirine readily reacts with two molecules of benzyl- or methylisothiocyanate to form the zwitterionic 1:2 addition compounds 4 and 13 , respectively (Scheme 2). The presumed 1:1 addition products, which are intermediates in the formation of 4 and 13 , cannot be detected. The structure of 4 and 13 follows from their spectroscopic and chemical properties. With water they give the thiourea derivates 5 and 14 , respectively; treatment with aqueous acid leads to the Δ²-1, 3-thiazolin-5-on-derivates 7 and 15 , respectively. With sodium borohydride compounds 8 and 16 , respectively, are obtained (Scheme 2). The zwitterionic compounds 4 and 13 are able to react further with one molecule of the isothiocyanates to give, in high-yield, triazines 9 and 18 , respectively (Scheme 3). The structure of these compounds was again derived from their spectroscopic data. The mechanism for the formation of 9 and 18 is given in Scheme 3. Acid catalysed hydrolysis of 9 and 18 lead to the trithiocyanuric acid derivates 12 and 20 , and to the spiro compounds 11 and 19 , respectively (Sceme 6). Reaction of 4 with one molecule of phenylisocyanate gives triazine 10 (Scheme 5). According to the X-ray analysis of the methyl compound 18 , there are strong steric interactions in this molecule which are due to the side chain. This is demonstrated by the small distances between C(2) … C(13), N(7) … C(11), and C(8) … C(11) (Table 4). These steric interactions, in addition, cause widening of the bond angles N(1)? C(2)? N(7) and C(9)? N(10)? C(11) (Fig.2). Furthermore, the triazine ring is no longer planar. This deformation of the ring diminishes repulsion between the methyl groups C(13) and C(15).     

Photochemische Reaktionen. 104. Mitteilung [1]. Zur Photospaltung der C,C-Oxiranbindung konjugierter γ, δ-Epoxy-enone: Photolyse von 4-Methyliden-5,6-epoxy-5,6-dihydro-β-jonon

The photoinduced cleavage of the C,C-oxirane bond of γ, δ-epoxy-enones: UV.-irradiation of 4-methylidene-5,6-epoxy-5,6-dihydro-β-ionone On ¹n, π*-excitation (λ ≥ 347 nm, pentane) 5 gives the isomeric bicyclic ether 10 in 75% yield (s. Scheme 2). In methanol the photoconversion of 5 to 10 is strongly reduced (12%) in favour of the formation of the methanol adduct 11 (43%). On photolysis in aqueous acetonitrile 5 is converted to the bicyclic ether 10 (9%), the dihydrofurane 12 (18%) as well as to the triketones 13A and 13B (7%), and 14 (23%). On ¹π, π*-excitation (λ = 254 nm) in pentane no 10 is formed, but 5 isomerizes to the tricyclic cyclopropyl compound 16 (59%), the allenic product 17 (10%), and the cyclopropene compound 18 (12%; s. Scheme 3). Photolysis in methanol furnishes 11 (63%), and 18 (4%), but no tricyclic cyclopropyl compound 16 . In a secondary photoreaction (λ = 254 nm) the dihydrofurane 12 is isomerized to the bicyclic cyclopropyl compound 20 . Evidence is given that the products 11 and 13 are formed by solvent addition to an intermediate ketonium ylide b (s. Scheme 12). The presence of b is further proven by the formation of 12 , a product of an electrocyclization of b . On photofragmentation of b carbenoids d and e are presumably formed (s. Scheme 14). 1,2-Hydrogen shift in d yields the allene derivative 17 , and cyclization of d gives the cyclopropene compound 18 . On the other hand, e cyclizes to the non isolated cyclopropene compound 69 which is transformed to 16 by an intramolecular [4 + 2]-cycloaddition. The present investigation shows that the photochemistry of 5 is determined by photoinduced C,C-bond cleavage of the oxirane ring. This is in sharp contrast to the photochemistry of conjugated γ, δ-epoxy-enones without the additional double bond in ε, ζ-position, where selective photocleavage of the C(λ), O-bond is observed.     

Unexpected Thermal Transformation of Aryl 3‐Arylprop‐2‐ynoates: Formation of 3‐(Diarylmethylidene)‐2,3‐dihydrofuran‐2‐ones

A number of aryl 3‐arylprop‐2‐ynoates 3 has been prepared (cf. Table 1 and Schemes 3 – 5). In contrast to aryl prop‐2‐ynoates and but‐2‐ynoates, 3‐arylprop‐2‐ynoates 3 (with the exception of 3b ) do not undergo, by flash vacuum pyrolysis (FVP), rearrangement to corresponding cyclohepta[b]furan‐2(2H)‐ones 2 (cf. Schemes 1 and 2). On melting, however, or in solution at temperatures >150°, the compounds 3 are converted stereospecifically to the dimers 3‐[(Z)‐diarylmethylidene]‐2,3‐dihydrofuran‐2‐ones (Z)‐ 11 and the cyclic anhydrides 12 of 1,4‐diarylnaphthalene‐2,3‐dicarboxylic acids, which also represent dimers of 3 , formed by loss of one molecule of the corresponding phenol from the aryloxy part (cf. Scheme 6). Small amounts of diaryl naphthalene‐2,3‐dicarboxylates 13 accompanied the product types (Z)‐ 11 and 12 , when the thermal transformation of 3 was performed in the molten state or at high concentration of 3 in solution (cf. Tables 2 and 4). The structure of the dihydrofuranone (Z)‐ 11c was established by an X‐ray crystal‐structure analysis (Fig. 1). The structures of the dihydrofuranones 11 and the cyclic anhydrides 12 indicate that the 3‐arylprop‐2‐ynoates 3 , on heating, must undergo an aryl O→C(3) migration leading to a reactive intermediate, which attacks a second molecule of 3 , finally under formation of (Z)‐ 11 or 12 . Formation of the diaryl dicarboxylates 13 , on the other hand, are the result of the well‐known thermal Diels‐Alder‐type dimerization of 3 without rearrangement (cf. Scheme 7). At low concentration of 3 in decalin, the decrease of 3 follows up to ca. 20% conversion first‐order kinetics (cf. Table 5), which is in agreement with a monomolecular rearrangement of 3 . Moreover, heating the highly reactive 2,4,6‐trimethylphenyl 3‐(4‐nitrophenyl)prop‐2‐ynonate ( 3f ) in the presence of a twofold molar amount of the much less reactive phenyl 3‐(4‐nitrophenyl)prop‐2‐ynonate ( 3g ) led, beside (Z)‐ 11f , to the cross products (Z)‐ 11fg , and, due to subsequent thermal isomerization, (E)‐ 11fg (cf. Scheme 10), the structures of which indicated that they were composed, as expected, of rearranged 3f and structurally unaltered 3g . Finally, thermal transposition of [¹⁷O]‐ 3i with the ¹⁷O‐label at the aryloxy group gave (Z)‐ and (E)‐[¹⁷O₂]‐ 11i with the ¹⁷O‐label of rearranged [¹⁷O]‐ 3i specifically at the oxo group of the two isomeric dihydrofuranones (cf. Scheme 8), indicating a highly ordered cyclic transition state of the aryl O→C(3) migration (cf. Scheme 9).     

Toward the Synthesis of Modified Carbohydrates by Conjugate Addition of Propane‐1,3‐dithiol to α,β‐Unsaturated Ketones

Selected 5‐substituted derivatives 4 of 1,1‐diethoxy‐5‐hydroxypent‐3‐yn‐2‐one were treated with propane‐1,3‐dithiol under various conditions. The unprotected hydroxy ketones underwent cyclization during the dithiol addition and gave the corresponding 3‐(diethoxymethyl)‐2‐oxa‐6,10‐dithiaspiro[4.5]decan‐3‐ols 5 in 80–90% yield as the only products (Scheme 3 and Table 1). These products can be regarded as partly modified carbohydrates in the furanose form. When the benzyl‐protected analogues 10‐Bn of the 1,1‐diethoxy‐5‐hydroxypent‐3‐yn‐2‐one derivatives were treated with the same dithiol, however, no cyclization occurred; instead the corresponding 3‐{2‐[(benzyloxy)methyl]‐1,3‐dithian‐2‐yl}‐1,1‐diethoxypropan‐2‐one derivatives 11‐Bn were formed in good yield (up to 99%; Table 4). These 1,3‐dithianes were and are in the process of being converted to a number of new carbohydrate analogues, and here are reported high‐yield syntheses of functionalized molecules 17 belonging to the 5,5‐diethoxy‐1,4‐dihydroxypentan‐2‐one family of compounds (Table 7), via 15‐Bn (Table 5) and 16‐Bn (Table 6 and Scheme 8).     

1,3-Dipole mit zentralem S-Atom aus der Umsetzung von Aziden mit Thiocarbonyl-Verbindungen: Eine unerwartete MeS-Wanderung im Abfangprodukt eines ‘Thiocarbonyl-aminids’ mit Dithiobenzoesäure-methylester

1,3-Dipoles with a Central S-Atom from the Reaction of Azides and Thiocarbonyl Compounds: An Unexpected MeS Migration in the Trapping Product of a ‘Thiocarbonyl-aminide’ with Methyl Dithiobenzoate Reaction of PhN₃ with O-methyl thiobenzoate ( 11a ) and thioacetate ( 11c ) as well as with the dithio esters 11b,d at 80° yields the corresponding imidates and thioimidates 12 (Scheme 3). The formation of 12 is rationalized by a 1,3-dipolar cycloaddition of the azide and the C?S group followed by successive elimination of N₂ and S. In the three-component reaction of 11b , PhN₃, and the sterically crowded thioketone 1a , 1,2,4-trithiolane 13a and 1,4,2-dithiazolidine 3a are formed in addition to 12b (Scheme 4). The heterocycles 13a and 3a are trapping products of 1a and ‘thiocarbonyl-thiolate’ 5a and ‘thiocarbonyl-aminide’ 2a (Ar?Ph), respectively (Scheme 6). These 1,3-dipoles are formed as reactive intermediates. Surprisingly, in the presence of catalytic amounts of acids, the major product is the (methyldithio)cyclobutyl thioimidate of type 14 (Scheme 5), formed by an acid-catalyzed MeS migration in dithiazolidine 17 . A reaction mechanism is proposed in Scheme 7.     

7‐Halogenated 7‐Deazapurine 2′‐Deoxyribonucleosides Related to 2′‐Deoxyadenosine, 2′‐Deoxyxanthosine,and 2′‐Deoxyisoguanosine: Syntheses and Properties

A series of 7‐fluorinated 7‐deazapurine 2′‐deoxyribonucleosides related to 2′‐deoxyadenosine, 2′‐deoxyxanthosine, and 2′‐deoxyisoguanosine as well as intermediates 4b – 7b, 8, 9b, 10b , and 17b were synthesized. The 7‐fluoro substituent was introduced in 2,6‐dichloro‐7‐deaza‐9H‐purine ( 11a ) with Selectfluor (Scheme 1). Apart from 2,6‐dichloro‐7‐fluoro‐7‐deaza‐9H‐purine ( 11b ), the 7‐chloro compound 11c was formed as by‐product. The mixture 11b / 11c was used for the glycosylation reaction; the separation of the 7‐fluoro from the 7‐chloro compound was performed on the level of the unprotected nucleosides. Other halogen substituents were introduced with N‐halogenosuccinimides ( 11a → 11c – 11e ). Nucleobase‐anion glycosylation afforded the nucleoside intermediates 13a – 13e (Scheme 2). The 7‐fluoro‐ and the 7‐chloro‐7‐deaza‐2′‐deoxyxanthosines, 5b and 5c , respectively, were obtained from the corresponding MeO compounds 17b and 17c , or 18 (Scheme 6). The 2′‐deoxyisoguanosine derivative 4b was prepared from 2‐chloro‐7‐fluoro‐7‐deaza‐2′‐deoxyadenosine 6b via a photochemically induced nucleophilic displacement reaction (Scheme 5). The pK_a values of the halogenated nucleosides were determined (Table 3). ¹³C‐NMR Chemical‐shift dependencies of C(7), C(5), and C(8) were related to the electronegativity of the 7‐halogen substituents (Fig. 3). In aqueous solution, 7‐halogenated 2′‐deoxyribonucleosides show an approximately 70% S population (Fig. 2 and Table 1).     

Nucleophilic Addition to C,C Double Bonds. Proximity and homoconjugative effects. Preliminary communication

Proximity effects alone as well as in combination with electronic effects are responsible for the observed phenomenon of base-catalyzed ether formation initiated by nucleophilic attack on a C, C double bond of the tricyclic olefin alcohols 1–10 (Scheme 1, Table 1). With compounds 1–4 , bearing a keto group, formation of the ethers 11–14 proceeds through a corresponding homoenolate b (Scheme 2) as an intermediate. In one case such a species could be trapped as the methyl ether 21 (Scheme 3). Special attention is given to the stereochemical course of the homoketonization. Ring opening in 21 under acidic conditions occurs regioselectively, however non-stereoselectively (Scheme 3). Full regio- and stereoselectivity (retention) is observed under basic conditions starting from the unsaturated keto alcohols 1 and 2 (Scheme 4) as well as from the keto ethers 11 and 12 (Scheme 5, Table 2).     

4-Amino-1,5-dihydro-2H-pyrrol-2-one aus Bortrifluorid-katalysierten Umsetzungen von 3-Amino-2H-azirinen mit Carbonsäure-Derivaten

4-Amino-1,5-dihydro-2H-pyrrol-2-ones from Boron Trifluoride Catalyzed Reactions of 3-Amino-2H-azirines with Carboxylic Acid Derivatives Reaction of 3-amino-2H-azirines 1 with ethyl 2-nitroacetate ( 6a ) in refluxing MeCN affords 4-amino-1,5-dihydro-2H-pyrrol-2-ones 7 and 3,6-diamino-2,5-dihydropyrazines 8 , the dimerization product of 1 (Scheme 2). Thus, 6a reacts with 1 as a CH-acidic compound by C? C bond formation via C-nucleophilic attack of deprotonated 6a onto the amidinium-C-atom of protonated 1 (Scheme 5). The scope of this reaction seems to be rather limited as 1 and 2-substituted 2-nitroacetates do not give any products besides the azirine dimer 8 (see Table 1). Sodium enolates of carboxylic esters and carboxamides 11 react with 1 under BF₃ catalysis to give 4-amino-1,5-dihydro-2H-pyrrol-2-ones 12 in 50–80% yield (Scheme 3, Table 2). In an analogous reaction, 3-amino-2H-pyrrole 13 is formed from 1c and the Li-enolate of acetophenone (Scheme 4). A reaction mechanism for the ring enlargement of 1 involving BF₃ catalysis is proposed in Scheme 6.     

Regioselectivity of the 1,3‐Oxathiolane Formation in the Lewis Acid‐Catalyzed Reaction of Thioketones with Asymmetrically Substituted Oxiranes

The reactions of the aromatic thioketone 4,4′‐dimethoxythiobenzophenone ( 1 ) with three monosubstituted oxiranes 3a – c in the presence of BF₃⋅Et₂O or SnCl₄ in dry CH₂Cl₂ led to the corresponding 1 : 1 adducts, i.e., 1,3‐oxathiolanes 4a – b with R at C(5) and 8c with Ph at C(4). In addition, 1,3‐dioxolanes 7a and 7c , and the unexpected 1 : 2 adducts 6a – b were obtained (Scheme 2 and Table 1). In the case of the aliphatic, nonenolizable thioketone 1,1,3,3‐tetramethylindane‐2‐thione ( 2 ) and 3a – c with BF₃⋅Et₂O as catalyst, only 1 : 1 adducts, i.e. 1,3‐oxathiolanes 10a – b with R at C(5) and 11a – c with R or Ph at C(4), were formed (Scheme 6 and Table 2). In control experiments, the 1 : 1 adducts 4a and 4b were treated with 2‐methyloxirane ( 3a ) in the presence of BF₃⋅Et₂O to yield the 1 : 2 adduct 6a and 1 : 1 : 1 adduct 9 , respectively (Scheme 5). The structures of 6a , 8c , 10a , 11a , and 11c were confirmed by X‐ray crystallography (Figs. 1 – 5). The results described in the present paper show that alkyl and aryl substituents have significant influence upon the regioselectivity in the process of the ring opening of the complexed oxirane by the nucleophilic attack of the thiocarbonyl S‐atom: the preferred nucleophilic attack occurs at C(3) of alkyl‐substituted oxiranes (O−C(3) cleavage) but at C(2) of phenyloxirane (O−C(2) cleavage).     

Untersuchungen über Allylgruppenwanderungen in aliphatischen Carbenium-Ionen

Investigations on the Migratory Aptitude of Allyl Groups in Aliphatic Carbenium-Ions The acetolysis (80°) of the 4-bromobenzenesulfonates given in Scheme 6 were investigated in regard to determine type allyl/methyl migratory aptitudes in the secondary carbenium ion a (Scheme 24). In all cases olefins (about 80%) and acetates (about 20%) were formed which can be derived from the rearranged tertiary carbenium ions b (being formed by allyl group migration) and c (being formed by methyl group migration). Olefin A and acetate H , originated in carbenium ion a, occurred in the acetolysis mixture only in minor amounts (<2%). By acetolysis of [l4C]-20, isolation of [¹⁴C]-4,5-dimethyl-l, 3-hexadiene ([¹⁴C]-45), and degradation of this diene (Scheme 16) it could be shown (4 Scheme 15) that the ions b and c (Scheme 24, R¹? R⁴?H) are not interconverted by a [1,2]-hydride shift (extent < 1%). Since olefin D arises by proton loss from ion b as well as from ion c , [¹⁴C]-4,5-dimethyl-l,4-hexadiene ([¹⁴C]? 44? D, R¹? R⁴? H) was also degraded (cf. Scheme 15 and Scheme 17). It was found that [¹⁴C]- 44 contained 48% of the label in the methyl group at C( 4 ) and 52% in the methyl groups at C( 5 ), i.e. 48% of 44 is formed via the allyl migration path and 52% via the methyl migration path. In addition, acetolysis of d3-20 and product analysis showed, that the d3-ally1 moiety migrates as expected only in a [1,2]-fashion. Product analysis of the acetolysis mixtures of erythro- and threo- 24 (cf. Scheme 19 and Tables 4 and 5) revealed that carbenium ion a must exist as an intimate ion pair (with the 4-bromobenzenesulfonyloxy-ion) which has lost its configuration at C( 1 ) only partially. This is indicated by reversed ratios (1: 11 and 10: 1, resp.) in the formation of erythro- and threo-2,3,4-trimethyl-l, 5-hexadiene (erythro- and threo- 77 ) arising from ion b (Scheme 24, R¹? R³ ? H, R⁴? CH,). The acetolysis of 1,2,2,4-tetramethyl-4-pentenyl4-bromobenzenesulfonate ( 23 ) was not studied in detail, but the appearance of a seventh product in the olefin part cannot be explained by the genesis paths in Scheme 24. Thus, it may be concluded that in this case a third tertiary carbenium ion d ₃ (Scheme 21) is produced by cyclization of a ₃. Cyclizations of this type are known to occur in carbenium ions bearing β-substituted allyl groups (see Scheme 22). The kinetic data of the acetolysis of all 4-bromobenzenesulfonates (Table 6) are in accord with a rate determining ionization step leading to a since all activation enthalpies resp. entropies are within 25.5 L± 0.6 kcal/mol resp. ?0.2 ± 1.7 e.u. The migratory aptitudes given in Table 7 show, that allyl groups migrate only slightly easier than methyl groups in ion a . This is in strong contrast to allyl substituted methylcyclohexadienyl cations (generated in the acid catalyzed dienone/phenol and dienol/benzene rearrange-ment) which undergo exclusively [1,2]-ally1 migrations (Schemes 3-5).     

Herstellung neuer polycyclischer Verbindungen durch intramolekulare Diels-Alder-Reaktionen von Cyclohexa-2,4-dien-1-on-Abkömmlingen

Synthesis of new polycyclic compounds by means of intramolecular Diels-Alder reactions of cyclohexa-2,4-dien-1-one derivatives Thermal rearrangement of mesityl penta-2,4-dienyl ether ( 1 ), consisting of the isomers E (93%) and Z (7%), furnished, besides mesitol, the two mesityl penta-1,3-dienyl ethers 2 (24%) and 3 (3%), and the two tricyclic ketones 4 (4,5%) and 5 (12,5%) (Scheme 1). A probable mechanism for this formation of 2 involves a [1,5]-hydrogen shift in (Z)- 1 . Isomerisation of (E)- 1 to (Z)- 1 at 145° occurs via reversible sigmatropic [3,3]- and [5,5]-rearrangements of (E)- 1 to the cyclohexadienones 38 and 39 respectively (see Chapter A p. 1710, and Scheme 15). Formation of 3 from either (Z)- 1 or 2 is rationalized by a series of pericyclic reactions as outlined in Chapter A and Scheme 16. The tricyclic ketones 4 and 5 are undoubtedly formed by internal Diels-Alder reactions of the 6-pentadienyl-cyclohexa-2,4-dien-1-one 6 (Scheme 2). In fact, at 80° 6 is converted into 4 (5%) and 5 (35%). At 80° the cyclohexadienone derivative 7 furnished the corresponding tricyclic ketones 8 (15%) and 9 (44%) (Scheme 2). 5 and 9 contain a homotwistane skeleton. 8 and 9 are easily prepared by reaction of sodium 2,6-dimethylphenolate with 3-methyl-penta-2,4-dienyl bromide at ambient temperature, followed by heating, and finally separation by cristallization and chromatography. The cyclohexadienones 6 and 7 have mainly (E)-configuration. Here too (E) → (Z) isomerization is a prerequisite for the internal Diels-Alder reaction, and this partly takes place intramolecularly through reversible Claisen and Cope rearrangements (Scheme 17). On the other hand, experiments in the presence of 3,5-d₂-mesitol have shown (Table 1) that intermolecular reactions, involving radicals and/or ions, are also operating (see Chapter B , p. 1712). Two different modi (I and II) exist for intramolecular Diels-Alder reactions (Scheme 18). Whereas only modus I is observed in the cyclization of 5-alkenyl-cyclohexa-l,3-dienes, in that of (2)-cyclohexadienones 6 and 7 (Scheme 2) both modi are operating. Only in modus 11-type transitions is the butadienyl conjugation of the side chain retained, so that modus 11-type addition is preferred (Chapter C p. 1716). Analogously to the synthesis of the tricyclic ketones 4 , 5 , 8 and 9 , the tricyclic ketone 15 (Scheme 4) and the tetracyclic ketone 11 (Scheme 3) are prepared from mesitol, pentenyl bromide and cycloheptadienyl bromide, respectively. From the polycyclic ketones derivatives such as the alcohols 16 , 17 , 18 , 19 , 23 , 24 and 25 (Schemes 9 and 11), policyclic ethers 20 , 21 , 22 and 26 (Scheme 10), epoxides 30 , 32 (Scheme 13), diketones 31 , 33 (Scheme 13) and ether-alcohols 35 and 36 (Scheme 14) have been prepared. Most of these conversions show high stereoselectivity.     

3-Triethylsilyloxypentadienyllithium,a Versatile 1,3-Diene- or Vinyl Ketone-Building Block

Deprotonation of the 3-trialkylsilyloxy-1,4-diene 3a and subsequent electrophilic substitution of the non-isolated 3-trialkylsilyoxypentadienyllithium 4 gives the α- and γ-products 8 and/or 6 in good yields. Whereas alkylation of 4 proceeds with variable regioselectivity (Table 1) aldehydes and ketones attack preferentially the γ-position of 4 (Table 2). The desired γ-products 6 may be directly subjected to inter- and intramolecular [4 + 2]-additions as demonstrated by the reactions 5a (? 6d ) → 7 and 6h → 19 (Schemes 4 and 12). Alternatively, smooth fluoride-promoted silylether-cleavage 6 → 11 (Scheme 8) provides a convenient approach to substituted vinyl ketones such as to the natural products 11f (Table 3). The stereoselective conversion 6k → 23 (Scheme 13) implies an endo-selective intramolecular Diels-Alder addition ( 26 → 23 ) and exemplifies the use of 4 as an equivalent of the hypothetical anion IV . Furthermore, some electrophilic substitutions of the hexadienyllithium 15 have been studied (Scheme 10).     

Preparation and Structures of 2‐Substituted 5‐Benzyl‐3‐methylimidazolidin‐4‐one‐Derived Iminium Salts,Reactive Intermediates in Organocatalytic Transformations Involving α,β‐Unsaturated Aldehydes

Preparations of the title compounds, 5 – 7 (Scheme 1 and Table 1), of their ammonium salts, 9 – 11 (Scheme 2 and Table 2), and of the corresponding cinnamaldehyde‐derived iminium salts 12 – 14 (Scheme 3 and Table 3) are reported. The X‐ray crystal structures of 15 cinnamyliminium PF₆ salts have been determined (Table 4). Selected ¹H‐NMR data (Table 5) of the ammonium and iminium salts are discussed, and structures in solution are compared with those in the solid state.     

Synthesis and Screening of New Chiral Ligands for the Copper‐Catalysed Enantioselective Allylic Substitution

The synthesis of the new chiral ligands 6ae, 8ae, 9ae , and 11ae starting from the chiral β‐[(Boc)amino]sulfonamide 3ae is reported. The β‐amino group of 3ae was deprotected and condensed with 3,5‐dichlorosalicylaldehyde ( 4 ) to yield the known Schiff base 5ae , which was then reduced to the amino compound 6ae (Scheme 3). Alternatively, condensation of the free amino compound with 2‐(diphenylphosphanyl)benzaldehyde ( 7 ) afforded the imino ligand 8ae which upon reduction yielded the amino ligand 9ae (Scheme 4). The free amino compound derived from 3ae was also coupled with 2‐(diphenylphosphanyl)benzoic acid ( 10 ) to give ligand 11ae (Scheme 5). These ligands were tested in the copper‐catalysed allylic substitution reaction of cinnamyl (=3‐phenylprop‐2‐enyl) phosphate 12 with diethylzinc as a nucleophile. Ligands 5ae, 6ae, 8ae , and 11ae gave excellent ratios (100 : 0) of the S_N2′/S_N2 products (Scheme 6 and Table 1). Ligand 11ce , identified from the screening of a small library of ligands of general formula 11 , promoted the allylic substitution reaction with moderate enantioselectivity (40% for the S_N2′ product 13 (Scheme 8 and Table 3)).     

[2 + 3]‐Cycloadditions of Phosphonodithioformate S‐Methanides with CS,NN,and CC Dipolarophiles

The reaction of the methyl (dialkoxyphosphinyl)‐dithioformates (= methyl dialkoxyphosphinecarbodithioate 1‐oxides) 10 with CH₂N₂ at − 65° in THF yielded cycloadducts which eliminated N₂ between − 40 and − 35° to give the corresponding phosphonodithioformate S‐methanides ( =methylenesulfonium (dialkoxyoxidophosphino)(methylthio)methylides) 11 (Scheme 3). These reactive 1,3‐dipoles were intercepted by aromatic thioketones to yield 1,3‐dithiolanes. Whereas the reaction with thiobenzophenone ( 12b ) led to the sterically more congested isomers 15 regioselectively, a mixture of both regioisomers was obtained with 9H‐fluorene‐9‐thione ( 12a ). Trapping of 11 with phosphono‐ and sulfonodithioformates led exclusively to the sterically less hindered 1,3‐dithiolanes 16 and 18 , respectively (Scheme 4). In addition, reactive CC dipolarophiles such as ethenetetracarbonitrile, maleic anhydride, and N‐phenylmaleimide as well as the NN dipolarophile dimethyl diazenedicarboxylate were shown to be efficient interceptors of 11 (Scheme 5).     

Glycosylidene Carbenes. Part 19. Regioselective glycosidation of allyl 2-deoxy-2-phthalimido-D-allopyranosides

The regio- and stereoselectivity of the glycosidation of the partially protected mono-alcohols 3 and 7 , the diols 2 and 8 , and the triol 4 by the diazirine 1 have been investigated. Glycosidation of the α-D -diol 2 (Scheme 2) gave regioselectively the 1,3-linked disaccharides 11 and 12 (80%, α-D /β-D 9:1), whereas the analogous reaction with the βD -anomer 8 led to a mixture of the anomeric 1,3- and 1,4-linked disaccharides 13 (12.5%), 14 (16%), 15 (13%), and 16 (20.5%; Table 2). Protonation of the carbene by OH–C(4) of 2 is evidenced by the observation that the α-D -mono-alcohol 3 did not react with 1 under otherwise identical conditions, and that the β-D -alcohol 7 yielded predominantly the β-D -glucoside 18 (52%) besides 14% of 17 . Similarly as for the glycosidation of the diol 2 , the influence of the H-bond of HO? C(4) on the direction of approach of the carbene, the role of HO? C(4) in protonating the carbene, and the stereoelectronic control in the interception of the ensuring oxycarbenium cation are evidenced by the reaction of the triol 4 with 1 (Scheme 3), leading mostly to the α-D -configurated 1,3-linked disaccharide 19 (41%), besides its anomer 20 (16%), and some 4-substituted β-D -glucoside 21 (9%). No 1,6-linked disaccharides could be detected. In agreement with the observed reactivity, the ¹H-NMR and IR spectra reveal a strong H-bond between HO? C(3) and the phthalimido group in the α-D -, but not in the β-D -allosides. The different H-bonds in the anomeric phthalimides are in keeping with the results of molecular-mechanics calculations.