Stereoselective carbonyl reductions of chloro-substituted 8-oxabicyclo[3.2.1]oct-6-en-3-ones

The lithium aluminium hydride reduction of 2,2,4,4-tetrachloro-8-oxabicyclo[3.2.1]oct-6-en-3-one (8) was reinvestigated. In contrast to most halogeno-substituted oxabicyclic ketones, which give predominantly the corresponding endo alcohols, the expected (3endo)-2,2,4,4-tetrachloro-8-oxabicyclo[3.2.1]oct-6-en-3-ol (9n) is formed in a minute proportion. An X-ray structure analysis of the dominating product gave proof of the exo-alcohol, i.e., (3exo)-2,2,4,4-tetrachloro-8-oxabicyclo[3.2.1]oct-6-en-3-ol (9x). On the other hand, reduction of trichloroketone 11, 2,2,endo-4-trichloro-8-oxabicyclo[3.2.1]oct-6-en-3-one, and the methoxy-substituted chloroketones 13 and 14 provided the corresponding endo alcohols (12 and 15).     

Substituierte 9-Oxabicyclo[4.2.1]- und 9-Oxabicyclo[3.3.1]nonane IV. endo,endo-2,5-Dihydroxy-9-oxabicyclo[4.2.1]nonan,endo, endo-, endo,exo- und exo,exo-2,6-Dihydroxy sowie endo,exo-2,7-Dihydroxy-9-oxabicyclo[3.3.1]nonan; Darstellung und Umwandlungsprodukte

The synthesis of the following compounds and reaction products thereof are described: endo, endo-2,5-dihydroxy-9-oxabicyclo[4.2.1]nonane ( 3–5 ), epimeric 2,6-dihydroxy-9-oxabicyclo[3.3.1]nonanes (endo, endo: 6–8 , exo, exo: 29–32 , and endo, exo: 43–45 ), and endo, exo 2,7-dihydroxy-9-oxabicyclo[3.3.1]nonane ( 46–50 ).     

1,2-Dialkoxycarbonylhydrazine derivatives of pyrroles and indolizines. A new synthesis of cycl[3.2.2]azines

The reaction of pyrroles $\text{1}$ with diisopropyl azodicarboxylate $\text{2}$ yields 2- and 2,5-substituted derivatives. 3- and 1,3-substituted indolizines $\text{5}$ and $\text{6}$ are formed by the same route. Cycl[3.2.2]azines $\text{7}$ have been obtained from $\text{5}$ and $\text{6}$ with dimethyl acetylenedicarboxylate.     

Oxymercuration. Substituted 9-oxabicyclo[4.2.1]- and 9- oxabicyclo[3.3.1]nonanes

Oxymercuration of cis, cis-1, 5-cyclooctadiene ( 1 ), followed by treatment with potassium iodide and subsequent reaction with iodine, leads to six isomeric diiodides which represent the three possible stereoisomers 2 , 3 , and 4 of 2, 5-diiodo-9-oxabicyclo[4.2.1]nonane as well as 5 , 6 , and 7 of 2, 6-diiodo-9-oxabicyclo[3.3.1]nonane. The isolation, structure determination and some reactions of these diiodo compounds 2 – 7 are described.     

Stereoselective synthesis of highly substituted 8-oxabicyclo[3.2.1]octanes and 2,7-dioxatricyclo[4.2.1.03,8]nonanes

The synthesis of new polyhydroxylated 8-oxabicyclo[3.2.1]octanes and 2,7-dioxatricyclo[4.2.1.0^3,8]nonanes is described. These structures is an interesting synthetic blocks for potential bioactive molecules. The precursor, 3-chloro-8-oxabicyclo[3.2.1]oct-6-ene-2,4-dione was obtained from reaction of tetrachlorocyclopropene with furan, then it was involved in carbonyl groups reduction and double bond oxidation, resulted in the formation of a polyhydroxylated derivatives, differently substituted at C-3 position, with five new stereocenters.Using intramolecular transannular hydroxycyclization, bicyclic epoxy diacetate was transformed into 2,7-dioxatricyclo[4.2.1.0^3,8]nonane in high yield through an alkoxide intermediate. Compounds thus obtained have a structure close to certain molecules with antitumor and glycosidase inhibitors activity.     

9-Hydroxy [7]metacyclophane

A new pyrolytic access to a metacyclophane has been found by the flash vacuum thermolysis of spiro[5,7]trideca-l,4-dien-3-one ($\text{4}$) which gave 9-hydroxy[7]metacyclophane (7) , and 4-(6-heptenyl)phenol (8) . The mechanism of formation of 7 and 8 from the intermediate diradical ($\text{6}$) is discussed.     

Photochemical rearrangement of 8-oxabicyclo[3.2.1]oct-6-en-2-ones

Irradiation of 8-oxabicyclo[3.2.1]oct-6-en-2-ones results in a 1,3-acyl rearrangement. The initial photoproduct undergoes a subsequent reaction involving hydrogen transfer followed by intramolecular cycloaddition of a ketene intermediate.     

1,4-cycloheptylene and the related allylic diradicals. Thermal nitrogen extrusion from 6,7-diazabicyclo[3.2.2]Non-6-enes

Thermal nitrogen extrusion of 2-methylene-6,7-diazabicyclo[3.2.2]non-6-enes and 6,7- diazabicyclo[3.2.2]nona-2,6-diene,6 proceeded easily to give closure and cleavage products $\text{via}$ the corresponding 5-methylene-1,4-cycloheptylenes and 4-cyclohepten-1,3-ylenes, respectively.     

Über Heterocyclen, 16. Mitt.: Über das 1,4-Dimethyl-3-acetoxy-7-acetamido-2-oxabicyclo [2,2,1]heptan

Zusammenfassung 3,4-Dihydro-2H-pyran-2-aldehyd bzw. 2,5-Dimethyl-3,4-dihydro-2H-pyran-2-aldehyd reagieren mit Acetamid bzw. Harnstoffen zu Pyranylmethylenbisamiden bzw.-bisureiden. Die Dimethylpyranaldehydaminale werden durch Essigsäureanhydrid zum 1,4-Dimethyl-3-acetoxy-7-acetamido-2-oxabicyclo[2,2,1]-heptan umgewandelt. Die Struktur dieser Verbindung wird bewiesen.

---

3,4-Dihydro-2H-pyran-2-aldehyde and 2,5-dimethyl-3,4-dihydro-2H-pyran-2-aldehyde, resp. react with acetamide or ureas to give pyranylmethylenebisamides and-bisureides. The dimethylpyranaldehydeaminals are converted by acetic anhydride to 1,4-dimethyl-3-acetoxy-7-acetamido-2-oxabicyclo[2.2.1]-heptane. The structure of this compound has been proved by chemical and physical methods.

     

Theoretical Study of Mechanism and Regioselectivity of 1,3-dipolar Cycloaddition of N-[methyl]-C-[5-nitro-2-furyl] Nitrilimine with Dimethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylate

The mechanism and regioselectivity of 1,3-dipolar cycloaddition of N-[methyl]-C-[5-nitro-2-furyl] nitrilimine with dimethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylate were investigated using activation energy calculations and density functional theory-based re-activity indexes. The reaction proceeds by an asynchronous concerted mechanism. The calculations are performed at the B3LYP/6-31G(d) level of theory and the obtained results are in agreement with experimental outcome.     

Photochemistry of azole N-oxides. Facile photoisomerisation of 2H-imidazole N-oxides to 1,3-diaza-6-oxabicyclo[3.1.0]hex-3-enes and synthesis of a 1,3-diaza-4,7-dioxatricyclo[4.1.0.1,603,5]heptane

Ultraviolet irradiation of a series of 2H-imidazole N-oxides 2 has been shown to effect a clean isomerisation to derivatives of the new ring system, 1,3-diaza-6-oxabicyclo[3.1.0]hex-3-ene, 7 . Epoxidation of a representative 7 has given access to the hitherto inaccessible trans-fused 1,3-diaza-4,7-dioxatricyclo[4.1.0. ^1,60^3,5]-heptane ring system 9 .     

Acetolyses of 1-Substituted trans-7,8-Dichlorodibenzobicyclo [2.2.2] octadienes

The preparations and silver-assisted acetolyses of the 1-methoxy ($\text{5}$), 1-methyl ($\text{6}$), 1-carbomethoxy ($\text{7}$), and 1-nitro ($\text{8}$) derivatives of $\text{trans}$-7,8-dichlorodibenzobicyclo [2.2.2] octa-2,5-dienes are described. Rearranged products possessing the dibenzobicyclo [3.2.1] octadiene skeleton were identified. With compound $\text{5}$, the P₈:P₇ ratio (ratio of products derived from ionizations of C₈-Cl and C₇-C1 bonds) was 1.3. For $\text{6}$ and $\text{7}$, the corresponding P8 P7 ratios were 0.4 and 33 respectively. Acetolysis of $\text{8}$ led to products in detectable quantities from ionization of the C₈-C1 bond only. The data support the proposal by Cristol that the transition states for these solvolytic rearrangements more closely resemble phenonium ion-like intermediates than benzyl cations.     

Simple synthesis of substituted 3-oxabicyclo[3.1.0]hexan-2-ones and their rearrangement in the presence of lithium iodide

2-Alkenylidenemalonic ester monoepoxides react with organolithium and organomagnesium compounds to give 1-ethoxycarbonyl-4-alkyl-6-alkenyl(alkyl, aryl, alkynyl)-3-oxabicyclo[3.1.0]hexan-2-ones in high yields. The latter, when an alkenyl fragment is present, undergo rearrangement in the presence of LiI to substituted 1-ethoxycarbonyl-3-oxabicyclo[3.3.0]-6-octen-2-ones or 3-(1,3-butadienyl)-4-butanolides.Institute of Chemistry, Bashkir Science Center, Ural Branch, Russian Academy of Sciences, Ufa 450054. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 4, pp. 946–954, April, 1992.     

Acid-Catalyzed Rearrangements of 5,6-exo-Epoxy-7-oxabicyclo[2.2.1]hept-2-yl Derivatives. Migratory Aptitudes of Acyl vs. Alkyl Groups in Wagner-Meerwein Transpositions

In the presence of HSO₃F/Ac₂O in CH₂CL₂, 2-exo- and 2-endo-cyano-5,6-exo-epoxy-7-oxabicyclo[2.2.1]hept-2-yl acetates ( 6a , b ) gave products derived from the epoxide-ring opening and a 1,2-shift of the unsubstituted alkyl group (σ bond C(3)–C(4)). In contrast, under similar conditions, the 5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptan-2-one ( 6c ) gave 5-oxo-2-oxabicyclo[2.2.1]heptane-3,7-diyl diacetates 20 and 21 arising from the 1,2-shift of the acyl group. Acid treatment of 5,6-exo-epoxy-2,2-dimethoxy-7-oxabicyclo[2.2.1]heptane ( 6d ) and of 5,6-exo-epoxy-2,2-bis(benzyloxy)-7-oxabicyclo[2.2.1]heptane ( 6e ) gave minor products arising from epoxide-ring opening and the 1,2-shift of σ bond C(3)–C(4) and major products ( 25 , 29 ) arising from the 1,3-shift of a methoxy and benzyloxy group, respectively. Under similar conditions, 5,6-exo-epoxy-2,2-ethylenedioxy-7-oxabicyclo[2.2.1]heptane ( 6f ) gave 1,1-(ethylenedioxy)-2-(2-furyl)ethyl acetate ( 32 , major) and a minor product 33 , arising from the 1,2-shift of σ bond C(3)–C(4). The following order of migratory aptitudes for 1,2-shifts toward electron-deficient centers has been established: acyl > alkyl > alkyl α-substituted with inductive electron-withdrawing groups. This order is valid for competitive Wagner-Meerwein rearrangements involving equilibria between carbocation intermediates with similar exothermicities.     

Eine einfache photochemische synthese von cyclopent[d][1,3]oxazinen aus 2,4-cyclohexadienimin-derivaten

A synthesis of cyclopent[d][1,3]oxazines $\text{8}$ is reported involving the photochemically induced transformation of 2,4-cyclohexadienimines $\text{4}$ via dienylketenimine intermediates $\text{6}$ and the dihydroderivatives $\text{7}$.     

The photochemical synthesis of novel heterocyclic compounds from s-triazolo[4,3-b]pyridazine (II)

s-Triazolo[4,3-b Jpyridazine (I) photochemically reacted with dihydropyran; 2,3-dihydro-p-dioxin; 2,5-dihydrofuran; 2,5-dimethoxy-2,5-dihydrofuran; and 1,3-dioxep-5-ene to give a new series of substituted pyrrolo[1,2-b]-.s-triazoles (II-IX). In most reactions, two or more products were formed. The following compounds have been prepared from I: 9-methylene-4a,5,6,7,8a,9-hexahydropyrano[2,3 :4,5]pyrrolo[1,2-b]-s-triazole (Ha), the corresponding 9-cyanomethyl product (III), and 9-methylene-4a,7,8,8a-tetrahydro-6H,9H-pyrano[3′,2′:4,5]pyrrolo[1,2-b]-s-triazole (IIb) from dihydropyran; 9-methylene-4a,6,7,8a-tetrahydro-9H-p-dioxino[2′,3′:4,5]-pyrrolo[1,2-6]-s-triazole (IV) from 2,3-dihydro-p-dioxin; 8-methylene-4a,5,7a,8-tetrahydro-7H-furo[3′,4′:4,5]pyrrolo[1,2-b]-s-triazole (V) and the corresponding 8-cyanomethyl product (VI) from 2,5-dihydrofuran; 8-cyanomethyl-5,7-dimethoxy-4a,5,7a,8-tetrahydro-7H-furo[3′,4′:4,5]-pyrrolo[1,2-6]-s-lriazole (VII) from 2,5-dimethoxy-2,5-dihydrofuran; and 10-methylene-4a,5,9a,10-tetrahydro-9H-[1,3]dioxepino[5′,6′:4,5]pyrrolo[1,2-b]-s-triazole (VIII) and the corresponding 10-cyanomethyl product (IX) from 1,3-dioxep-5-ene. The addition of several other compounds (1,2,3,6-tetrahydropyridine, 1-acetylimidazole, 3-sulfolene, 2,3-dihydro-p-dithiin, and vinylene carbonate) was attempted, but no reactions were observed.     

Preparation of 5-amino-7(6H)-furazano[3,4-d]pyrimidinone an analog of pterin

5-Aminofurazano[3,4-d]pyrimidines carrying a variety of substituents at position 7 suffer ring cleavage by either acid or base to give 4-guanidino-3-furazancarboxylic acid ($\text{6}$), the esters of which can be recyclised to give the pterin analog 5-amino-7(6H)-furazano[3,4-d]pyrimidinone (9). The pyrimidine ring of (9) is cleaved by hydrolysis, and the furazan ring by hydrogenolysis.     

Phosphorus heterocycle synthesis by RPX2,· AlX3 addition to [1,n]dienes VII.

The RPX₂·AlX₃ complex ($\text{1}$) reacts with unsaturated ketones and imines to give novel 7-oxa and 7-aza-2-phosphabicyclo[2.2.1]heptanes (compounds $\text{3}$ and $\text{6}$ respectively).A new 1,3-dipolar addition of (CH₃)₂ CCH₂P?XR to nArN=C=S was disclosed resulting in the formation of the 2-imino-1,3-thiaphospholanes ($\text{7}$).