Pd-catalyzed ring opening of oxa- and azabicyclic alkenes with aryl and vinyl halides: efficient entry to 2-substituted 1,2-dihydro-1-naphthols and 2-substituted 1-naphthols

An efficient syntheses of 2-substituted 1,2-dihydro-1-naphthols and 2-substituted 1-naphthols has been developed that involves the sequential palladium-catalyzed ring opening of oxabicyclic alkenes with aryl and vinyl halides followed by oxidation of with IBX. In the first step of the sequence, a combination of Pd(OAc)2, PPh3, Zn, and PMP in dry DMF was employed to catalyze the ring opening of 7-oxabenzonorbornadienes with aryl and vinyl halides to afford the corresponding cis-2-substituted 1,2-dihydronaphthols in good to excellent yields. These reactions occurred under very mild conditions with a variety of aryl halides bearing electron-withdrawing or -donating groups. Similarly, a 7-azabenzonorbornadiene substituted with an electron-withdrawing group on the nitrogen atom underwent facile ring-opening reaction with aryl halides to provide cis-2-substituted (1,2-dihydro-1-naphthyl)carbamates in excellent yields. Oxidation of the intermediate 1,2-dihydro-1-naphthols using IBX yielded the corresponding 2-substituted 1-naphthols in good to excellent yields.     

Mannich反应合成3,6(8)-二取代-2,4-二氢-1,3-苯并噁嗪及其杀菌活性

以取代苯酚、多聚甲醛和取代苯胺为原料,在无催化剂的条件下,通过Mannich缩合反应合成了一系列新型3,6(8)-二取代-2,4-二氢-1,3-苯并噁嗪类化合物。 结果表明,取代苯酚和取代苯胺的取代基为供电子基时,合成产物的产率高于吸电子取代基的。 产物的结构用1H NMR、13C NMR、IR和MS等进行了表征。 初步测试了目标化合物的杀菌活性,部分化合物具有较好的杀菌活性。 当浓度为25 mg/L时,化合物4j和4d对菌核病菌的抑制率分别为86.1％和81.5％,化合物4i对灰霉病菌的抑制率为81.6％。     

Synthesis of sulfur-bridged piperazinediones by reaction of 3,6-dibromo-1,4-dimethyl-2,5-piperazinedione with geminal dithiols

The reaction of several geminal dithiols with 3,6-dibromo-1,4-dimethyl-2,5-piperazinedione gave in good yields piperazinedione derivatives substituted at the 3,6-position with a geminal dithiol-bridging group. These sulfur-bridged piperazinediones formally represent derivatives of the 2,4-dithia-6,8-diaza-7,9-dioxobicyclo[3.2.2]nonane ring system. Attempts to transform these sulfur-bridged piperazinediones to 3,6-epidithiopiperazinediones by removal of the bridging group common to the sulfur functionality were unsuccessful. Studies also are reported of addition of thioacetic acid to 3,6-dimethylene-2,5-piperazinedione to give 3,6-diacetylthio-3,6-dimethyl-2,5-piperazinedione. Conversion of the 3,6-diacetylthio derivative to the epithiopiperazinedione ring system yielded a mixture of epimono- and epidithiopiperazinediones.     

Tetracyclic phenothiazines. VII. Electron impact promoted mass spectral fragmentation of some pyrido[3,2,1-kl]phenothiazines

The mass spectral fragmentation pattern of a series of pyrido[3,2,1-kl]phenothiazines is reported. The major fragments are derived from the breakdown of the pyrido ring and substituents thereon. The 1,2-/2,3-unsaturated, unsubstituted and most of the 3-substituted compounds show the molecular ion as the base peak indicative of their relative stability toward electron impact. The genesis of the base peaks from the molecular ions of the 2,2-dithiophenyl substituted compounds probably involves a concerted expulsion of a neutral diphenyldisulfide molecule and hydrogen atom transfer from the 1-position to the 2-position in the pyrido ring. On the other hand, 2-thiophenyl substituted molecular ions lead to base peaks involving simultaneous ring opening of the pyrido ring, cleavage of phenylthiomethylene moiety as a radical and contractive ring closure to the pyrrole system. These two mechanisms appear to be diagnostic for distinguishing 2,3- versus 2,2-positional isomers. The McLafferty rearrangement takes place in the 2-thiophenyl and 2,2-dithiophenyl substituted compounds. The retro-Diels-Alder fragmentation of the pyrido ring occurs in varying degrees depending on the nature of the 2- and 3- substituents and also the presence or absence of unsaturation in the pyrido ring. In the 2-thiophenyl-3-keto compounds, thiophenyl group participation with 3-carbonyl carbon and oxygen atoms is observed in the genesis of some interesting ion fragments. The detection of metastable ions in the spectra of 1,2-dihydro-2-thiophenyl-, 1,2-dihydro-2,2-dithiophenyl-3-hydroxy-, and 1,2-dihydro-2,2-dithiophenyl-3-keto-3H-pyrido[3,2,1-kl]phenothiazines; and spectra of 1,2-dihydro-3-methyl-, 1,2-dihydro-2-carbethoxy-3-keto- and 1,2-dihydro-2-thiophenyl-3-keto-3H-pyrido[3,2,1-kl]pheno-thiazines at low voltage support major fragmentation pathways.     

Metallation of N-vinylpyrroles and -indoles with Hg(OAc)2: N-vinyl vs. pyrrole nucleophilic sites

N-Vinylpyrroles and -indoles bearing electron-withdrawing substituents at the pyrrole ring are mercurated, with 1 equivalent of Hg(OAc)(2) in dry MeCN (20-80 °C), regioselectively at the vinyl group (yields are almost quantitative), while their congeners without electron-withdrawing functions are mercurated both at the N-vinyl group and the pyrrole ring.     

Triphenylphosphine-induced ring contraction of 1,2-dioxines

Triphenylphosphine inserts into the peroxide bond of 1,2-dioxines, initiating ring contraction with loss of triphenylphosphine oxide. This process yields dihydrofuran oxides in 54-97% yield from oxirenyl[2,3-c][1,2]dioxines and dihydrofurans from 3,6-dihydro-1,2-dioxines with inversion of stereochemistry at either the 2 or 5 position in the furan product.     

One-pot regioselective annulation toward 3,4-dihydro-3-oxo-2H-1,4-benzoxazine scaffolds under controlled microwave heating

An efficient and general synthesis of 2-alkyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazines under controlled microwave heating has been established. It consists of a microwave-assisted reductive N-arylmethylation of substituted 2-aminophenols with aromatic aldehydes followed by a one-pot base-mediated regioselective O-alkylation of the N-arylmethyl-2-aminophenols with 2-bromoalkanoates to give the acyclic intermediates, which cyclize spontaneously to furnish the benzoxazine scaffolds in good to excellent yields. It was found that microwave heating over 180 °C was necessary for ring closure of the acyclic intermediates possessing an electron-withdrawing group.     

Enchainements heteroatomiques et leurs produits de cyclisation—III : Réactions de Diels-Alder entre vinylogues de thioamides et diénophiles acryliques fonctionnels linéaires et cycliques. Propriétés chimiques des 2H-thiopyrannes liées aux substituants en position 2 et 3

The thioamide vinylogues (2-aminovinyl thioketones) react as heterodienes with open-chain and cyclic dienophiles to give substituted 4-amino-3,4-dihydro-2H-thiopyrans, or substituted 2H-thiopyrans and substituted 7 - methyl - 7,7a - dihydro - 5H - thiopyranno[2,3 - c] - 5 - furanones respectively, in good agreement with calculated perturbation energy of second order.     

A rapid divergent synthesis of highly substituted delta-lactones

[reaction: see text] Nucleophilic 1,2-addition of (Z)-gamma-silyloxyvinylzinc reagents to ethyl glyoxylate followed by desilylation and cyclization affords 3,6-dihydro-3-hydroxypyran-2-ones in good chemical yields. In situ formation of allylic phosphates followed by reaction with RCu(CN)Li reagents affords substituted 5,6-dihydropyran-2-ones. The parent compound, 3,6-dihydro-3-hydroxypyran-2-one, undergoes allylic phosphate formation, cuprate-mediated allylic substitution, and 1,4-conjugate addition to afford trans-4,5-disubstituted tetrahydropyran-2-ones in a one-pot process.     

Facile synthesis of 1H-pyrazolo[1,2-a]pyridazine-5,8-dione derivatives by a one-pot, three-component reactions

Protonation of the highly reactive 1:1 intermediate produced in the reaction between alkyl or aryl isocyanides and electron-deficient acetylenic esters with 3,6-dihydroxypyridazine, leads to a vinylisonitrilium cation, which undergoes an addition reaction with the conjugate base of the 3,6-dihydroxypyridazine to produce dialkyl 3-(alkyl or arylamino)-5,8-dioxo-5,8-dihydro-1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylates in good yields at room temperature.     

Ring opening reaction of 3,6-Dihydro-2-(1H)pyrimidinones with hydroxylamine hydrochloride

1,4,6-Trisubstituted 3,6-dihydro-2-(1H)pyrimidinones (Ia-d) easily underwent the ring opening reaction with hydroxylamine hydrochloride to afford the oximes (IIa-d) in good yields. In the case of 3,6-dihydro-6-methyl-I-phenyl-2-(1H)pyrimidinone (Ie), 2-anilinobutyronitrile (III) was obtained in addition to the oxime (IIe). Dihydro-2-(1H)pyrimidinone (IV) and -thiones (V and VI) did not undergo the ring opening reaction.     

Stereodefined ring contraction-rearrangement of thiocoumarins to new fused benzo[b]thiophene derivatives

Mesoionic 1,3-oxazolium-5-olates (münchnones) react with thiocoumarins having an electron-withdrawing group at the 3-position to afford stereodefined fused polycyclic thienopyrroles. The reaction sequence seems to be triggered by a regiospecific dipolar cycloaddition followed by ring opening of the initial 1:1 cycloadduct and intramolecular rearrangement with an unusual ring contraction.     

Unexpected products via singlet oxygen oxygenation of functionalized 5,6-dihydro-1,4-oxathiins

[formula: see text] Single oxygen oxygenation of 5,6-dihydro-1,4-oxathiins substituted at C-3 with an electron-withdrawing group leads stereoselectively to ketosulfoxides 5 and 6, instead of the expected dicarbonyl compounds 3. A mechanism involving an unprecedented intramolecular rearrangement of the corresponding dioxetanes 2 is proposed.     

Divergent Reactivity of Thioalkynes in Lewis Acid Catalyzed Annulations with Donor–Acceptor Cyclopropanes

Efficient methods for the convergent synthesis of (poly)cyclic scaffolds are urgently needed in synthetic and medicinal chemistry. Herein, we describe new annulation reactions of thioalkynes with phthalimide‐substituted donor–acceptor cyclopropanes, which gave access to highly substituted cyclopentenes and polycyclic ring systems. With silyl‐thioalkynes, the Lewis acid catalyzed [3+2] annulation reaction with donor–acceptor cyclopropanes took place to afford 1‐thio‐cyclopenten‐3‐amines. On the other hand, an unprecedented polycyclic compound was formed with alkyl‐thioalkynes through a reaction pathway directly involving the phthalimide group. The two transformations proceeded in good yields and tolerated a large variety of functional groups.     

Unexpected formation of polysubstituted 1-azabutadienes and 1,3-dioxanes from the reaction of 3-fluoroalkyl-3-arylaminoacrylic acid esters with formaldehyde

[reaction: see text] The reaction of 3-fluoroalkyl-3-arylaminoacrylic acid esters with formaldehyde was described. In the presence of a catalytic amount of triethylamine, the reaction took place readily in acetonitrile at 70 degrees C to give the corresponding 2-fluoroalkyl-1-azabutadienes in good yields. cis-Fluoroalkylated 1,3-dioxanes were obtained predominantly when the aryl ring contained an electron-withdrawing group and the reaction was carried out at room temperature under catalysis of triethylamine and tetrabutylammonium bromide. A possible mechanism was proposed.     

Parallel synthesis of an indole-based library via an iterative Mannich reaction sequence

A library of 1,3-disubstituted indoles has been prepared via an iterative Mannich reaction sequence. The first Mannich reaction with secondary amines and formaldehyde preferentially yields 3-aminomethyl indoles, while the second Mannich reaction introduces an additional aminomethyl group at the N1-position of the indole ring. A library of 25 substituted indoles has thus been prepared in moderate to good yields with purity.     

Superacid-Catalyzed Reaction of Substituted Benzaldehydes with Benzene

Benzaldehydes bearing an electron-withdrawing group reacted with 2 equiv of benzene in the presence of a superacid, trifluoromethanesulfonic acid, to give substituted triphenylmethane in good yields. On the other hand, benzaldehydes bearing an electron-donating or a neutral group reacted under the similar conditions to give unsubstituted diphenylmethane and triphenylmethanol, together with substituted benzene. We propose a new mechanism of this reaction, which involves transalkylation as the key step.     

Electrochemical syntheses of heterocyclic compounds—I : Intramolecular electrochemical cyclization of formazans to tetrazolium salts

A novel way of tetrazolium salt preparation by anodic oxidation of formazan is described. Products were obtained in good yields and purity. The mechanism of oxidation was deduced from voltammetric data and by coulometry at controlled potential. Two main pathways were identified, one leading via radical-cation and dication to ring closure by nucleophilic addition, the other involves disproportionation of the radical-cation to dication plus original formazan. Oxidability of differently substituted 3-aroyl-1,5-diarylformazans depends on the electron-withdrawing powers of substituted rings.     

Efficient synthesis of aryl vinyl ethers exploiting 2,4,6-trivinylcyclotriboroxane as a vinylboronic acid equivalent

The synthesis of functionalized aryl vinyl ether derivatives can be readily achieved utilizing a room-temperature copper(II) acetate mediated coupling of substituted phenols with 2,4,6-trivinylcyclotriboroxane-pyridine complex in the presence of a suitable base. The scope of the procedure was demonstrated by the generation of an array of substituted aryl vinyl ethers. The reaction was seen to be tolerant of a diverse range of functional groups yielding products in high isolated yields. We have shown that one role of an amine base in the reaction sequence is the in situ generation of an amine coordinated boroxine ring. An X-ray crystal structure and low temperature (11)B NMR study of 2,4,6-trivinylcyclotriboroxane-pyridine complex demonstrated the nature of the tetracoordinate boron species, which may have a key role to play within the reaction sequence.     

Zn粉作为催化剂前体催化对甲苯磺酰胺/二溴海因与烯烃的区域选择性和立体选择性氨溴加成反应

Zn粉作为催化剂前体, 在反应中可被原位氧化成高效Zn(Ⅱ)-催化剂. 在该催化剂催化下, 以对甲苯磺酰胺和1,3-二溴-5,5-二甲基乙内酰脲(二溴海因)为氮源/卤素源, 二氯甲烷作溶剂, 建立了烯键上的高度区域选择和立体选择性氨溴加成反应新体系. 该方法在室温下可高产率地制得邻位氨基溴的加成产物, 最高收率可达99%. 实验结果表明, 当与双键直接相连的苯环对位有强给电子基团(CH₃O)时, 反应收率高, 并可得到唯一的氨溴加成产物(α-溴-β-氨基); 当与双键直接相连的苯环对位有强拉电子基团(NO₂)或弱拉电子基团(如Br和F)时, 该反应的产率相对较低, 但也能制得另一个唯一的氨溴加成产物异构体(α-氨基-β-溴型). 本文考察了20种不同结构底物的氨溴加成反应情况, 产物结构经过¹H NMR、¹³C NMR和元素分析确证, 并探讨了该反应的机理.