Lewis acid-catalyzed intermolecular [4 + 2] cycloaddition of 3-alkoxycyclobutanones to aldehydes and ketones

Intermolecular [4 + 2] cycloaddition between 3-alkoxycyclobutanones and aldehydes or ketones by the activation with boron trifluoride etherate is reported. The carbonyl compounds are inserted into the less substituted C2-C3 bond of the cyclobutanone ring of 6-alkyl-2-oxabicyclo[4.2.0]octan-7-ones to afford 1-alkyl-5,7-dioxabicyclo[4.4.0]decan-2-one derivatives regioselectively (>99:1) and diastereoselectively. On the other hand, [4 + 2] cycloaddition of 3-ethoxy-2,2-dialkylcyclobutanones at low temperature proceeds at the more substituted C2-C3 bond to yield 3,3-dialkyl-6-ethoxy-2,3,5,6-tetrahydro-4H-pyran-4-one derivatives with high regioselectivities. This [4 + 2] cycloaddition is developed into a one-pot synthesis of tri- or tetrasubstituted dihydro-gamma-pyrones from 3-ethoxycyclobutanones which are readily prepared from acid chloride and ethyl vinyl ether. The two regioselectivities observed in ring-opening of cyclobutanones can ascribe to thermodynamic stabilities of zwitterionic intermediates generated from tetrahydropyran-fused cyclobutanones and 3-ethoxycyclobutanones.     

Aktivierte Chinone: regiospezifische Synthesen von substituierten Dibenzo [b,d]pyran-6-onen und Benzo [b]naphtho [d]pyran-6-onen

Activated Quinones: Regiospecific Syntheses of Substituted Dibenzo [b, d]pyran-6-ones and Benzo[b]naphtho [d]pyran-6-ones The reaction of 2-methoxycarbonyl-1, 4-benzoquinone (1) with substituted phenols leads in an acid-catalyzed, regiospecific way to substituted dibenzo [b, d]-pyran-6-ones (compounds 3 and 6 ). The cycloaddition of 1,3-butadiene to the latter yields compounds 7. Tautomerisation of 7 and oxidation gives the benzo[b]-naphtho[d]pyran-6-ones 8 and 10 , respectively.     

Synthesis of Methyl-6-methyl Tricyclo[5.2.1.02,6]decan-9-one-2-carboxylate: Potential Intermediate to Isocomene and Cuprenolide

A facile synthesis of methyl-6-methyl tricyclo [5.2.1.0^2,6]decan-9-one-2-carboxylate 7, a potential intermediate to isocomene 6 and cuprenolide 8 is described.     

Intramolecular hydrogen abstraction promoted by amidyl radicals. Evidence for electronic factors in the nucleophilic cyclization of ambident amides to oxocarbenium ions

A tandem 1,5-hydrogen atom transfer/radical oxidation/nucleophilic cyclization mechanism is proposed for the intramolecular hydrogen abstraction reaction promoted for primary carboxamidyl radicals. The electron-withdrawing capacity of the C-5 substituent can switch the reaction to give exclusively bicyclic spirolactams (6-oxa-1-azaspiro[4.5]decan-2-one) when R(1) = H or spirolactones (1,6-dioxaspiro[4.5]decan-2-one) when R(1) = OAc. With a substituent of medium polarity (R(1) = OMe), a mixture of lactones and lactams is formed.     

Synthesis of a new series of 8-substituted-2,8-diazaspiro[4.5]decan-3-ones

A new series of 8-substituted-2,8-diazaspiro[4.5]decan-3-ones has been synthesized and tested in in vitro and in vivo assays predictive for cholinergic activity, in comparison with the muscarinic agent RS-86. Preliminary pharmacological data indicate that the compounds are devoid of significant cholinergic properties.     

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.     

Über die Reaktionen von Guanidin bzw. Harnstoff mit Aminonitrilen

The aminonitriles3a–f react with guanidine inDMF to yield the 5,5-resp. 5-subtituted imidazolidine-2,4-diimines2a–d resp.2f, whereas2e could not be isolated. 7,14-diazadispiro[5.1.5.2]-pentadecan-15-on (7)¹, 4-imino-1,3-diazaspiro[4.5]decan-2-one (8a)¹ and the 2,4-diaminotriazine (9)¹ were isolated as byproducts.1-Aminocyclohexancarbonitrile (3a) reacts with urea to the 4-imino-1,3-diazaspiro[4.5]decan-2-one (8a)¹;8a can be prepared from (1-cyancyclohexyl)urea (11a) as well. The structures of the new compounds are proved by NMR-, IR- and mass spectra and the mechanism of the reaction is discussed.

Herrn Prof. Dr.G. Zigeuner zum 60. Geburtstag gewidmet.     

Mannich Condensation of exo-2,exo-6-Tricyclo[5.2.1.02,6]decan-8-one

Mannich condensation of exo-2,exo-6-tricyclo[5.2.1.02,6]decan-8-one with paraformaldehyde and dimethylamine hydrochloride results in the addition of dimethylaminomethyl fragment at the C⁹ atom to give the exo-9-isomer. The reaction of exo-9-dimethylaminomethyl-exo-2,exo-6-tricyclo[5.2.1.02,6]decan-8-one with hydroxylamine hydrochloride in alcoholic alkali yields the corresponding Z-oxime which undergoes selective rearrangement into exo-10-dimethylaminomethyl-9-aza-exo-2,exo-6-tricyclo[5.3.1.02,6]undecan-8-one by the action of sulfuric acid in acetonitrile.     

Spiroimidazolidinone library derivatives on SynPhase lanterns

Optimization and solid-phase synthesis of new spiroimidazolidinone derivatives as highly functionalized templates is reported. The synthesis of 1,4,8-triazaspiro[4.5]decan-2-one derivatives was performed on SynPhase lanterns from dipeptides anchored on the solid support and N-protected piperidone. A library of 180 discrete compounds was prepared.     

Synthesis of 6-Substituted/Unsubstituted- 7,9-diaryl-1,2,4,8-tetraazaspiro[4.5]- decan-3-thiones

Abstract

Some 2,6-diarylpiperidin-4-one thiosemicarbazones (1a–8a), obtained from the corresponding 2,6-diarylpiperidin-4-ones (1–8) on oxidative cyclization with H₂O₂ at 0°C provide 7,9-diaryl-1,2,4,8-tetraaza spiro[4.5]decan-3-thiones (1b–8b) in excellent yields. The structures of these compounds have been established on the basis of their elemental, analytical and spectral data.     

A novel and expeditious approach to unusual spirolactam building blocks

A rapid access to 7-azaspiro[4.5]decan-6-ones 1 involving three regio- and chemoselective reactions starting from tetrabromonorbornyl derivatives is described. The alkaline H(2)O(2) cleavage reaction of monosubstituted alpha-diketones 9 furnished the potential bridged bicyclic lactones 10in a highly regio- and stereoselective manner. The radical-mediated, intermolecular bridgehead C-C bond formation of the versatile bridged lactones 10 with acrylonitrile followed by LAH reduction of the adduct 13 intriguingly leads to the formation of novel spirolactam building blocks 1.     

Cyclic hydroxamic acids derived from α-amino acids 1. Regioselective synthesis,structure, NO-donor and antimetastatic activities of spirobicyclic hydroxamic acids derived from glycine and DL-alanine

The reactions of glycine hydroxamic and DL-alanine hydroxamic acids with triacetonamine are chemoselective and afford 1-hydroxy-7,7,9,9-tetramethyl-1,4,8-triazaspiro[4.5]decan-2-one (3) and (±)-1-hydroxy-3,7,7,9,9-pentamethyl-1,4,8-triazaspiro[4.5]decan-2-one (4), respectively. The X-ray diffraction study showed that compound 3 crystallizes as a solvate with MeCN (1: 1). As shown by ESR measurements, spiro hydroxamic acids 3 and 4 are NO donors in in vitro biological systems. The NO-donor activity of compounds 3 and 4 was found to be substantially higher in the presence of DMSO. Homologue 4 is a stronger NO donor than 3. Compound 4 also exhibits high antimetastatic activity (81%) on the B16-melanoma model.     

Spirovetivanes from silylated 1-hydroxycyclopropanecarboxaldehyde.

The spiro[4.5]decan-2-one and a spirovetivane, key intermediates of the [4.5] spirobicyclic sesquiterpenes, have been prepared from silylated 1-vinylcyclopropanols. A selective desilylation of enol ethers is featured.     

Green,Microwave-Assisted Approach to the Synthesis of Arylidene-Substituted Spiro[4,5]decan-8-one Derivatives in Water

A green approach to the synthesis of arylidene-substituted spiro[4,5]decan-8-one derivatives was successfully realized via the mild, base-catalyzed reaction of aromatic aldehydes with 1,4-dioxa-spiro[4.5]decan-8-one in water under microwave irradiation. This protocol has the prominent advantages of environmental friendliness, short reaction time, excellent yields, low cost, easy operation, and broad scope of applicability.     

Cyclic hydroxamic acids derived from α-amino acids 2. Regioselective synthesis,crystal structure,and antitumor activity of spiropiperidine-imidazolidine hydroxamic acids based on glycine and dl-alanine

Regioselective cyclocondensation of glycine hydroxamic and dl-alanine hydroxamic acids with 1-methylpiperidin-4-one gave 1-hydroxy-8-methyl-1,4,8-triazaspiro[4.5]decan-2-one (5) and (±)-1-hydroxy-3,8-dimethyl-1,4,8-triazaspiro[4.5]decan-2-one (6), respectively. The X-ray diffraction data showed that acid 6 formed racemic crystals with two independent molecules, whose structure was studied and compared with the analog obtained earlier. The in vivo tests on the leukemia P388 and L1210 models showed that the low-toxic spirocyclic hydroxamic acids 5 and 6 were the adjuvants of clinic cytostatics cisplatin and cyclophosphamide. Chemotherapy of the leukemias P388 and L1210 was more efficient with the combination of acid 6 with cisplatin and cyclophosphamide, respectively.     

Syntheses of Stable α-Silyloxyepoxides and α-Chloroalkyl Silyl Ethers Derivatives of 3,10-Dioxa-5-azatricyclo[5.2.1.02,6]dec-4-enes

The Diels-Alder adduct (±)-5 of furan to 1-cyanovinyl acetate was converted to (1RS,2RS,6RS,7SR,8SR,10RS)-10-{[(tert-butyl)dimethylsilyl]-oxy}-4-ethoxy (1) and -4-phenyl-3,9,11-trioxa-5-azatetracyclo[5.3.1.0^2,6.0^8,10]-undec-4-ene (2). These compounds reacted with TiCl₄ to afford stable (1RS,2RS,6RS,7SR,8SR,9SR)-9-{[(tert-butyl)dimethylsilyl]oxy}-9-chloro-4-ethoxy-3,10-dioxa-5-azatricyclo[5.2.1.0^2,6]decan-8-ol (3) and (1RS,2RS,6RS,7SR,8SR,9SR)-9-{[(tert-butyl)dimethylsilyl]oxy}-9-chloro-4-phenyl-3,10-dioxa-5-azatricyclo[5.2.1.0^2,6]decan-8-ol (4), respectively.     

Computational analysis of the nucleophilic eliminative ring fission of bridgehead substituted 1,3-bishomocubyl acetates

Molecular mechanics (MM2) calculations on the conceivable seco-cage structures by homoketonization of two types of bridgehead substituted 1,3-bishomocubyl acetates, viz. type A : 4-acetoxy-pentacyclo[5.3.0.0^2,5.0^3,9.0^4,8] decan-6-one and its ethylene ketal, and type B: 8-acetoxypentacyclo [5.3.0.0^2,5.0^3,9.0^4,8]decan-6-one, its ethylene ketal and 8-acetoxypentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decane were performed.     

Reaction of substituted chalcones with methyl 1-bromocycloalkanecarboxylates and zinc

Methyl 1-bromocyclopentane-and 1-bromocyclobutanecarboxylates react with zinc and substituted chalcones to form spiro-3,4-dihydropyran-2-one derivatives: 8, 10-diaryl-7-oxaspiro[4.5]dec-8-en-6-ones and 7,9-diaryl-6-oxaspiro[3.5]non-7-en-5-ones, respectively.     

Synthesis and Biological Applications of Some Novel Spiro Heterocycles Containing 1,3,4‐Thiadiazine,Thiazole, and Oxazole Derivatives

2‐Ethoxy carbonylcyclopentanone (1) has been brominated to yield 2‐bromo‐2‐ethoxy carbonylcyclopentanone (2) which on further reaction with substituted thiosemicarbazones, thiocarbohydrazones, thiocarbamides and carbamides has furnished 1 ‐ thia‐3,4‐diaza‐5,7‐dioxo‐2‐[(substituted benzylidine)‐amino]spiro[4.5]dec‐2‐ene (3a–e) , 1‐thia‐3,4‐diaza‐5,7‐dioxo‐2‐[(substituted benzylidine)‐hydrazino] spiro[4.5]dec‐2‐ene (4a–e) , 1‐thia‐3‐aza‐2‐(substituted imino)‐4,6‐dioxo‐spiro[4.4]nonane (5a–f) and 1‐oxa‐3‐aza‐2‐(substituted imino)‐4,6‐dioxo‐spiro[4.4]nonane (6a–g) respectively. The structures of the compounds have been elucidated on the basis of spectral analysis.     

对甲苯磺酸催化下二乙酰苯与含有羟基的苯甲醛的Aldol缩合反应

以对甲苯磺酸(p-TsOH)作催化剂, 二乙酰苯与含有羟基的苯甲醛发生aldol缩合反应, 合成了3个1,3-双[3-(取代苯基)丙烯酰基]苯衍生物1～3, 3个1,4-双[3-(取代苯基)丙烯酰基]苯衍生物4～6和2个中间体7, 8, 中间体7, 8再与含有羟基的苯甲醛发生aldol反应合成了3个1-[3-(4-羟基苯基)丙烯酰基]-4-[3-(取代苯基)丙烯酰基]苯衍生物9～11, 反应均能在2～6 d内完成, 操作和后处理简便. 以上11个新化合物均未见报道, 其结构经1H NMR, IR, MS和HRMS加以确证.