4‐Substituted 2,3‐Dihydroisoxazoles as Masked Azomethine Ylides: Access to Pyrrole Derivatives by 1,5‐ and 1,7‐Dipolar Electrocyclizations of Enynyl Derivatives

The enynyl‐substituted 2,3‐dihydroisoxazoles (‘isoxazolines') 9 – 14 were prepared by highly (Z)‐selective Peterson olefination reaction from the corresponding carbaldehydes 6 – 8 . On short‐time thermolysis (280 – 406°/10 s) the TMS derivatives 9 – 11 give rise to the annulated pyrrolines 18 – 20 , which, in some cases, suffer CH₄ elimination affording the pyrroles 15 – 17 . In contrast, thermolysis of the terminal alkyne derivatives 12 – 14 leads to the bicyclic compounds 21 – 23 . The reaction pathways are discussed on the basis of the formation of conjugated azomethine ylides as key intermediates, which either undergo a 1,5‐cyclization to 18 – 20 or a 1,7‐ring‐closure affording cycloallene intermediates of type V , which are further transformed into the azepino pyrroles 21 – 23 .     

Asymmetric α-Acetoxylation of Carboxylic Esters. Preliminary Communication

Using the readily accessible chiral auxiliaries 1 – 3 the sulfonamide-shielded O-silylated esters 5 underwent π-face-selective α-acetoxylation on successive treatment with Pb(OAc)₄ and NEt₃ HF to give after recrystallization α-acetoxy ester 6 in 55–67% yields and in 95–100% d.e. Starting from conjugated enoates addition of RCu and subsequent acetoxylation 10 → 11 → 12 yielded α,β-bifunctionalized esters 12 with >95% configurational control at both C_α and C_β. Nondestructive removal of the auxiliary ( 6 → 7 , 6 → 8 and 12 → 13 ) gave either α-hydroxycarboxylic acids or terminal α-glycols in high enantiomeric purity. The prepared glycols 8c and 13a are key intermediates for previously reported syntheses of the natural products 16 and 17 , respectively.     

Heterotricyclodecane XXII 2-Aza-7-thia-isotwistane

2-Aza-7-thia-isotwistanes . 2-Aza-7-thia-isotwistanes were synthesized either starting from suitable 9-thiabicyclo[3.3.1]nonenes by olefin-amination ( 1 → 4 , 2 → 5 , 3 → 6 , 8 → 10 and 9 → 11 ) as well as by intramolecular substitution ( 25 → 26 ) or by molecular rearrangement starting from twistanes ( 21 → 19 and 22 → 10 ). From the isotwistanes thus obtained several other compounds ( 7 , 12 – 18 , 20 , 23 and 24 ) were prepared, too.     

The Total Synthesis of (±)-Isocomene by an Intramolecular Ene Reaction. Preliminary communication

The racemic sesquiterpene isocomene ( 1 ) has been synthesized starting from 1,7-octadien-3-one ( 2 ) in a stereoselective manner (Scheme 2). In the key step 4 → 5 the C(7), C(8)-bond was formed by an intramolecular thermal ene reaction. Further elaboration of 5 involved the ring contraction 6 → 7 , the elimination 8 → 9 and the final olefin isomerization 9 → 1 .     

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).     

Cyclic allenes or diradicals in the cyclization reactions of dienynes generated by photolysis of alkynylcyclohexadienones

Reported here are some rearrangements involving the electrocyclic ring closure of dieneynes 7. Such ring closures are envisaged to possibly give strained substituted cyclic allenes 8 which could also behave as diradicals 8a. The results show that compounds such as 5 rearrange to cyclohexadienones 9a, 9b, or 11 through these kind of intermediates. Theoretical calculations performed on simple models similar to the intermediates suggest that the nature of these intermediates correspond to that of cyclic allenes.     

Photochemical reactions. 146th communication. Photochemistry of conjugated methano-epoxydienes: Participation of the neighboring cyclopropane ring in product formation via carbonyl ylide and carbene intermediates

On singlet excitation (λ = 254 nm, THF, pentane or hexane), the diastereoisomeric methano-epoxydienes (E)- 6 and (E)- 7 undergo interconversion and yield the products 8 – 11 . The main process is the cleavage of the oxirane ring to the vinyl carbene intermediate e which undergoes addition to the adjacent double bond furnishing the cyclopropene 8 . The alternative carbene intermediate f is evidenced by the formation of the cyclobutene 10 . For the fragmentation leading to 11 , the carbene f as well as the dipolar species h are considered as possible intermediates. On triplet sensitization (acetone, λ > 280 nm), (E)- 7 shows behavior typical of epoxydienes, undergoing fission of the C? O bond of the oxirane ring and isomerization to the compounds 13 , 14 and (E/Z)- 15 .     

Photochemische Reaktionen. 117. Mitteilung [1] Zur Photochemie von 5,6-Epoxydienen und konjugierten 5,6-Epoxytrienen

Photochemistry of 5,6-Epoxydienes and of Conjugated 5,6-Epoxytrienes On singulet excitation (δ = 254 nm) the 5,6-epoxydiene 6 and the conjugated 5,6-epoxytrienes 7 and 8 exclusively give products arising from cleavage of the C, C-bond of the oxirane (cf. 6 → 9 , 10 , 11 ; 7 → (E)- 15 , 16 , 17 ; 8 → 18 (A+B) , 19 (A+B) , 20 , 21 ). The dihydrofuran compounds 11 and (E/Z)- 15 are formed by cyclization of a ketonium-ylide a and d , respectively. Photolysis of a gives the carbene b which yields the cyclopropene 9 , whereas d forms photochemically the carbenes f and g which yield the methano compounds 16 and 17 . The isomeric cyclopropene derivatives 20 and 21 are products of the intermediates h and i , respectively, which are formed by photolysis of the ylide e . The cyclopropene 21 isomerizes by intramolecular cycloadditions to 18 (A+B) and 19 (A+B) . - On triplet excitation (λ?LD nm; 280 nm; acetone) 6 undergoes cleavage of the C(5), O-bond and isomerizes to 12 and 14 . However, 7 is converted by cleavage of the C, C-bond of the oxirane to yield 15 . On treatment with BF₃O(C₂H₅)₂ 6 gives 14 , whereas 7 yields 22 , and 8 forms 23 and 24 .     

Route Scouting towards a Methyl Jasmonate Precursor

For the synthesis of methyl jasmonate ( 1 ), via the strategic intermediates 3, 4 , and 6a , we constructed a synthetic network via the diverse intermediates 7 – 10, 13, 14, 17 , and 18 . This allowed us to compare the efficiency of more than 20 novel routes. The most productive pathway with a total yield of 38% is represented by the sequence→ 5a → 5m → 13b → 13a → 6a → 4 and proceeds via sequential bromination, basic elimination, decarbomethoxylation, isomerization, and finally Lindlar hydrogenation. The shortest selective way, 2a →[(E,E)‐ 12b ]→ 3 → 4 , is a two‐pot sequence using a modification of Naef's method, based on an aldol condensation between inexpensive cyclopentanone ( 2a ) and crotonaldehyde, with in situ Corey? Chaykovsky cyclopropanation under phase transfer conditions. The key intermediate 3 was then simply pyrolyzed to afford 4 in 27% total yield. The alternative isomerization method via the six‐step deviation→ 5a → 5c → 8c → 13a → 6a → 4 was longer, although more efficient, with a total yield of 32%. Alternatively, a yield of 34% was obtained via the five‐step sequence→ 5a → 5c → 2h → 2i → 4 . Another favored six‐step pathway,→ 5a → 5c → 2h → 17a → 14a → 4 afforded the target compound in 35% total yield.     

Stereochemistry of the Robinson Anellation: Studies on the Mode of Formation of the Intermediate Hydroxy Ketones

The stereochemical outcome of the base-catalyzed cyclization of diketones 5 – 8 has been investigated under protic conditions (Scheme 3). The more stable trans-fused ketols are preferentially formed in kinetically controlled aldol reactions, when the incipient angular substituent R = H (6 → 10a ) or CN ( 7 → 11a , 8a → 12a ). For R = Me (as in 5 ), axial attack of the side-chain enolate double bond on the ring C?O group results in the rather selective formation of cis- 9b. It is assumed that these cyclizations are controlled by relative product stabilities (product-like transition state) and steric effects. The competition between fused (e.g. 9 ) and bridged ketol (e.g. 13 ) formation in these cyclizations is discussed. The cis-fused (‘steroid’) ketols were readily equilibrated with their trans-counterparts (9b ? 9a, 10b ? 10a, 11b ? 11a) under aprotic conditions (5 mol-% of LDA, THF, 0°), thus, allowing assessments of relative stabilities.     

四氟乙烯齐聚体的反应 四氟乙烯四、五聚体和芳香胺的反应

前已报道四氟乙烯四聚体(全氟-3,4-甲基己烯-3)(1)、五聚体(全氟-3,4-二甲基-4-乙基己烯-2)(2)和脂肪烷氧以及脂肪胺的亲核反应.本文报道化合物1,2和芳香胺如苯胺、β-萘胺的反应.由于烯烃1、2双键处于分子中间,因而当亲核试剂进攻时,双键容易发生重排,生成的末端基烯烃更具反应性,故导致一取代、二取代、三取代以及环化降解等复杂产物.     

Furopyridines. XIII. Reaction of 2-methylfuro[2,3-b]-, -[3,2-b]-, -[2,3-c]- and -[3,2-c]pyridines with lithium diisopropylamide

Lithiation of 2-methylfuro[2,3-b]- 1a , -[2,3-c]- 1c and -[3,2-c]pyridine 1d with lithium diisopropylamide at ?75° and subsequent treatment with deuterium chloride in deuterium oxide afforded 2-monodeuteriomethyl compounds 2a, 2c and 2d , while 2-methylfuro[3,2-b]pyridine 1b gave a mixture of 1b, 2b , 2-methyl-3-deuteriofuro[3,2-b]pyridine 2′b and 2-(1-proynyl)pyridin-3-ol 5 . The same reaction of 1a at ?40° gave 3-(1,2-propadienyl)pyridin-2-ol 3 and 3-(2-propynyl)pyridin-2-ol 4 . Reaction of the lithio intermediates from 1a, 1c and 1d with benzaldehyde, propionaldehyde and acetone afforded the corresponding alcohol derivatives 6a, 6c, 6d, 7a, 7c, 7d, 8a, 8c and 8d in excellent yield; while the reaction of lithio intermediate from 1b gave the expected alcohols 6b and 8b in lower yields accompanied by formation of 3-alkylated compounds 9, 11, 12 and compound 5 . While reaction of the intermediates from 1a, 1b and 1d with N,N-dimethylacetamide yielded the 2-acetonyl compounds 13a, 13b and 13d in good yield, the same reaction of 1c did not give any acetylated product but recovery of the starting compound almost quantitatively.     

Säure-Additionen an ‘Push-Pull’-Enine. Erste Beobachtung einer Umlagerung von 5-Chloro-5-(dialkylamino)pentadienalen

Reaction of ‘Push-Pull’ Enynes with Acids. First Observation of a Rearrangement of 5-Chloro-5-(dialkylamino)pentadienals ‘Push-pull’-enynes 7 react easily with HCl as well as with AcOH to give 5-amino-5-chloropentadienals 8 and 5-(acetoxy)-5-aminopentadienals 13 as well as the corresponding ketones. In view of a postulated rearrangement of compounds 8 and 13 (Scheme 2), both types of compounds have been treated with traces of acid. While no definite reaction is observed in case of 13 , HCl-addition products 8 easily and quantitatively rearrange to give 2H-pyran-2-iminium chlorides 10 which are the postulated intermediates of the rearrangement 8 → 12 (Scheme 2).     

Thermal Reactions of Epoxyenones and Epoxydienes in the Ionone Series

On flash vaccum thermolysis at temperatures between 390 and 585°, the epoxyenones 1 – 9 and the epoxydienes 10 – 12 undergo various types of reactions involving C? C and/or C? O bond cleavage in the oxirane ring. Thus, the compounds 1 , 4 – 9 , 11 , and 12 were transformed to the divinyl ethers 13 , 20 , 21 , 24 , 25 , 29 , and 38 by a reversible [1,5] homosigmatropic H-shift. On thermolysis of the epoxides 1 – 12 , several products formed via carbonyl-ylide intermediates were also isolated. The extent of the formation of ylide products is clearly related to the conjugating ability of the functional groups neighboring the oxirane. Thus, the epoxides 3 , 5 , and 7 – 10 , bearing a C(3)?C(4) bond, a 5-oxo function, a 3,4-epoxy or a 3,4-methano group, preferentially underwent reactions via a carbonyl-ylide intermediate. As a further reaction pathway, the epoxides 1 – 12 undergo cleavage of the C–O bonds of the oxirane, which, however, is presumably an acid-catalyzed rather than a thermal reaction.     

Novel C9 and C11 Hydrocarbons from the Brown Alga Cutleria multifida; Sigmatropic and Electrocyclic Reactions in Nature. Part VI

In addition to the known C₁₁H₁₆ hydrocarbons multifidene ( 4 ), aucantene ( 2 ), and ectocarpene ( 5 ), the marine brown alga Cutleria multifida produces trace amounts of the C₉H₁₂ hydrocarbon 7-melhylcycloocta-1,3,5-triene ( 8 ) and its valence tautomer 7-methylbicyclo[4.2.0]octa-2,4-diene, A second novel C₉H₁₂ hydrocarbon is 6-vinyicyclo-hepta-1,4-diene ( 9 ), a lower homologue of ectocarpene ( 5 ). Among the C₁₁H₁₆ hydrocarbons, 7-((1E/Z)-prop-l-enyl)cycloocta-1,4-diene ( 10 / 11 ) is found for the first time. The structure of all new products is confirmed by synthesis and spectroscopic data. The biosynthesis of the new hydrocarbons 8 – 11 is obviously linked to the pathways which lead to the major products giffordene ( 7 ), (6S)-ectocarpene ((6S)- 5 ), and (4R,5R)-aucantene ((4R,5R)- 2 ). Consecutive reactions of certain thermolabile primary products proceed via electrocyclic ring closure, 3,3-sigmatropic rearrangement, or a 1,7-sigmatropic H-shift.     

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).     

Experimental and theoretical analyses of azulene synthesis from tropones and active methylene compounds: reaction of 2-methoxytropone and malononitrile

A representative azulene formation from an active troponoid precursor (2-methoxytropone) and an active methylene compound (malononitrile) has been analyzed both experimentally and theoretically. (2)H-Tracer experiments using 2-methoxy[3,5,7-(2)H(3)]tropone (2-d(3)) and malononitrile anion give 2-amino-1,3-dicyano[4,6,8-(2)H(3)]azulene (1-d(3)) in quantitative yield. New and stable (2)H-incorporated reaction intermediates have been isolated, and main intermediates have been detected by careful low-temperature NMR measurements. The detection has been guided by mechanistic considerations and B3LYP/6-31(+)G(d) calculations. The facile and quantitative one-pot formation of azulene 1 has been found to consist of a number of consecutive elementary processes: (a) The troponoid substrate, 2-methoxytropone (2), is subject to a nucleophilic substitution by the attack of malononitrile anion (HC(CN)(2)(-)) to form a Meisenheimer-type complex 3, which is rapidly converted to 2-troponylmalononitrile anion (5). (b) The anion 5 is converted to an isolable intermediate, 2-imino-2H-cyclohepta[b]furan-3-carbonitrile (6), by the first ring closure in the reaction. (c) A nucleophilic addition of the second HC(CN)(2)(-) toward the imine 6 at the C-8a position produces the second Meisenheimer-type adduct 7. (d) The second ring closure leads to 1-carbamoyl-1,3-dicyano-2-imino-2,3-dihydroazulene (11). A base attacks the imine 11, which results in generation of a conjugate base 12 of the final product, azulene 1.     

Synthesis and Chemical Transformations of 4, 5-Homosnoutene Derivatives: An Attempted New Access onto the (CH)12 Energy Hypersurface

Pentacyclo[6. 4. 0^{2, 4}. 0^{3, 10}. 0^{7, 9}]dodeca-5, 11-diene( 4 ) is proposed as new potential precursor of the truncated tetrahedrane 1 . The synthesis of several new pentacyclo[5. 4. 0. 0^{2, 4}. 0^{3, 9}. 0^{6, 8}] undec-10-ene (4, 5-homosnoutene) derivatives including homosnouten-5-one( 10 ), 5-methylidenehomosnoutene( 19a ) as well as homosnoutene-5-carb-aldehyde( 17b ) and their reactions directed toward ring enlargement to the skeleton of 4 are reported. Although all the homosnoutenes resisted ring expansions, several unexpected new polycyclic systems were obtained. Any intermediate developing a cationic center at C(5) of the skeleton of 10 rearranged with release of strain and opening of one or both three-membered rings to give compounds such as 22 and 23 . The aminomethyl derivatives 13a and 13b, upon diazotation, underwent a remarkable fragmentation to give 10 and homosnouten-5-o1(20), respectively. The 5-(dibromomethyl) homosnouten-5-o1( 14 ), upon treatement with t-BuLi, rearranged to the pentacyclic ether 15 , while the carbine 11b , generated by the thermal or photochemical decomposition of the tosylhydrazone salt of 17c , solely gave 19a by C, H insertion. The 1, 1-dicyclopropylethene unit in 19c was excited selectively upon irradiation, but the products 26 and 27 of this photochemical rearrangement were derived only from n-participation in diradical intermediates 25a-25c .     

Structures of Ring-Enlargement Products

Crystal structures have been determined of methyl trans-1-hydroxy-6-nitro-3-oxobicyclo[4.4.0]decane-2-carboxylate ( 19 ), cis-3-methyl-6-nitro-2-oxabicyclo[4.4.0]decan-1-ol ( 2 ), cis-7-hydroxy-1-nitrobicyclo[5.4.0]undecan-9-one ( 13 ), and the medium-ring compounds 2-acetyl-4-nitrocyclooctanone ( 9 ), methyl 5-nitro-2-oxocyclooctane-carboxylate ( 4 ), 2-acetyl-4-nitrocyclononanone ( 11 ), 2-acetyl-4-nitrocyclodecanone ( 15 ), benzyl 5-nitro-2,11-dioxocycloundecanecarboxylate ( 24 ), methyl 5-nitro-2,12-dioxocyclododecanecarboxylate ( 21 ), and 8-nitro-11-oxo-13-tridecanolide ( 7 ), which are intermediates, side products, or end products of the ‘Zip’ ring-enlargement reaction. The conformations of most of the medium-ring compounds are very similar to equal-sized ring compounds previously determine by other authors.     

7-Halogenated 7-Deaza-2′-deoxyinosines

The synthesis of the 7-deaza-2′-deoxyinosine derivatives 3a – c with chloro, bromo, and iodo substituents at position 7 is described. Glycosylation of the 7-halogenated 6-chloro-7-deazapurines 4a – c or of the 7-halogenated 6-chloro-7-deaza-2-(methylthio)purines 9a – c with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D -erythro-pentofuranosyl chloride ( 5 ) furnished the intermediates 7a – c and 11a – c , respectively, which gave, upon deprotection, the desired nucleosides 3a – c .