Selective reductive dimerization of homocubane series oximes

The mixture of di- and monoethylene ketals obtained by the reaction of 1,9-dibromopentacyc lo[5.4.0.0^2,6.0^3,10.0^5,9]-undeca-8,11-dione followed by hydrolysis and ring contraction by Faworsky method was converted into a mixture of ethylene ketals of 7-bromopentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decan-6-one-4- and 5-bromopentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decan-6-one-8-carboxylic acid where the carboxy group was replaced by bromine along the procedure of Hunsdiecker-Borodine-Cristol. 6-Ethylene ketal of the pentacyclo[5.3.0.0^2,5.0^3,9.0^4,8] decan-6-one obtained by the debromination of ethylene ketals of 4,7- and 5,8-dibromopentacyclo[5.3.0.0^2,5.0^3,9.0^4,8] decan-6-one was hydrolyzed to ketone whose oxime was selectively reduced on a platinum catalyst into the di-6-pentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decylamine. The reaction of reductive dimerization was also characteristic of pentacyclo[4.3.0.0^2,5.0^3,8.0^4,7]-nonan-9-one and pentacyclo[6.3.0.0^2,6.0^3,10.0^5,9]undecan-4-one oximes, whereas the composition of the reduction products of pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecan-8-one oxime depended on the amount of the catalyst.     

Nucleophilic eliminative ring fission of bridgehead substituted 1,3-bishomocubyl acetates

The base induced cage fission of three different types of functionalized bridgehead substituted 1,3-bishomocubyl acetates, vizA,B and C is described. The synthesis of two 6-functionalized 1,3-bishomocubyl 4-acetates (type A), viz4-acetoxypentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decan-6-one 5 and its ethylene acetal 6 has been accomplished starting from the readily available Diels-Alder adduct 4. The synthesis of three 1,3-bishomocubyl 8-acetates (type B), viz 8-acetoxypentacyclo[5.3.0^2,5.0^3,9.0^4,8]decan-6-one 15, its ethylene acetal 16 and the parent acetate 20 has been carried out starting from the cyclopentadiene-benzoquinone adduct 7. Base induced homoketonization of 6, 16 and 20 leads regio- and stereospecifically to the thermodynamically favored half cage ketones 22,28 and 31, respectively. In contrast, the cage opening of the β-ketoacetates 5 and 15 is essentially directed by the β-ketone function. In the case of 5, regiospecific cleavage of the central C₄-C₅ bond is observed producing in a stereospecific manner diketone 25 in quantitative yield. Under similar conditions, acetate 15 gives a complex mixture of cage opened products arising from further fragmentation of the initially formed diketone 34. Deuterium labeling experiments reveal an anti-Bredt behavior of half cage ketones 28 and 31. The synthesis of a bridgehead acetate of type C has been accomplished by stereoselective reduction of ketone acetate 5 with LiAlH(t-OBu)₃ followed by mesylation. A mixture of epimers 36a and 36b (ratio 1:4) is obtained from which the predominant anti-epimer 36b could be isolated. An X-ray analysis established its structure. Base induced cage fission of 36b leads regiospecifically to tetracyclo[5.3.0.0^2,5.04,8]decenone 37. In contrast the syn-epimer 36a, under similar conditions, only affords the bridgehead alcohol 38.     

Convenient preparative synthesis of pentacyclo[5.3.0.02,5.03,9.04,8]decane (<Emphasis Type="Italic">C</Emphasis><Subscript>2</Subscript>-Bishomocubane)

By reaction of pentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decane-6,10-dione 6-ethyleneketal with lithium aluminum hydride the corresponding hydroxyketal was obtained whose hydroxy group was replaced by chlorine at boiling in CCl₄ in the presence of a 15% molar excess of triphenylphosphine. 6-Ethyleneketal of pentacyclo-[5.3.0.0^2,5.0^3,9.0^4,8]decan-6-one obtained by dechlorination of the chloroketal in a system lithium-t-BuOH in THF was hydrolyzed to ketone by heating in 10% sulfuric acid in the presence of THF. The obtained ketone was reduced along Wolf-Kishner reaction to pentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decane.     

A decisive electronic effect of a bridgehead methoxy substituent on the electrophilic cage opening of 1,3-bishomocubanones

4-Methoxypentacyclo[5.3.0.0^2,5.0^3,9.0^,4,8] decan-6-ones 4 and 9 undergo an acid catalysed cage fragmentation to give tricyclodecenediones 6 and 10, respectively. With silver cations under basic conditions, an unusual oxidative cage fission reaction is observed leading to tetracyclo[4.3.0.0^2,40^3,8]nonan-5-one 7-carboxylic acids.     

Control of cage opening reactions in the 1,3-bishomocubane and homocubane systems

The synthesis and base-induced cage opening of 5-fucctionalized homocubyl alcohols 22 (R is some protective group) is described. In a first approach, the synthesis of 22 has been attempted starting from tricyclic enol 14 and involving the Favorskii cage contraction of l,3-bishomocubanones 24. Unexpectedly, 4-methoxypentacyclo [5.3.0.0^2,5.0^3,9.0^4,8]decan-6-ones 24b and 29 undergo a facile add-catalyzed cage fragmentation to give tricyclo[5.3.0.0^2,5]decene diones 28a and b, respectively. The Favorskii cage contraction of 24 to homocubane carboxylic add 25c has been accomplished for the MEM-protected 24c, albeit in low yield. With silver cations under basic conditions, 24b and c undergo an unusual oxidative cage fission reaction leading to tetracyclo[4.3.0.0^2,4.0^3,8]nonan-5-one 7-carboxylic acids 40 and 41. An efficient route to 4-bromohomocubyl acetate 48 has finally been accomplished starting from 4,5-dibromo-l,3-bishomocubanone 43. Base-induced homoketonization of 48 is essentially directed by the 5-bromine atom and a regioapedfic cleavage of the central C₄–C₅ bond is observed, producing, in a stereospecific manner, 10-oxapeatacyclo [5.3.0.0^2,6.0^3,9.0^4,8]decane 51.     

Formation of novel polycyclic cage compounds through ‘uncaging’ of readily accessible higher cage compounds

The synthesis of the novel cage compounds 7-halomethyl-8-(carbomethoxy)tetracyclo[4.2.1.1^4,7.0^2,5]deca-3-(11)-ene-10-ones, methyl-4-methylene-6-oxopentacyclo[5.4.0.0.^2,5.0^3,10.0^7,9]undecane-9-carboxylate, 3-chloromethyl-4-(carbomethoxy)tetracyclo[4.2.1.1.^3,8.0^2,5]deca-7(11)ene-10-one, 2-bromo-5-methyl-8-methylene-6-oxotricyclo[5.3.0.0^3,9]decane-4-carboxylic acid and 2-bromo-5-methyl-8-methylene-6-oxotricyclo[5.3.0.0^3,9]decane-4-methyl carboxylate, achieved through base catalyzed rearrangement, is described.     

The preparation and properties of cage polycyclic systems—III: The cleavage in alkaline conditions of acetals derived from pentacyclo[5.3.0.02,5.03,9.04,8]decane and pentacyclo[4.3.0.02,5.03,8.04,7]nonane systems

The synthesis of some acetals derived from pentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decane is described. The reductive cleavage of an ethylenedioxy group

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and a dimethoxy group

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in pentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decane and pentacyclo[4.3.0.0^2,5.0^3,8.0^4,7]nonane systems to give the methylene group is shown to occur in alkaline conditions in the presence of hydrazine. Evidence is presented for a mechanism which involves initial cleavage of the acetal by alkali to form the ketone. The substitution of a Br atom in the position neighbouring the CO group of 5-bromo-6,6-ethylenedioxypentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decan-10-one facilitates the Wolff-Kishner reaction to such an extent that hydrazine hydrate is a sufficiently strong base to induce the decomposition of the hydrazone directly.     

Chemistry of strained polycyclic compounds—V : The stereospecific cationic cage expansion reaction of 4-homocubane carbinols to 1,3-bishomocubane bridgehead alcohols

The cationic rearrangement of four homocubane bridgehead carbinols viz dimethyl 4-(1-bromopentacyclo[4.3.0.0^2,5.0^3,8.0^4,7]nonyl-9-one ethylene ketal) carbinol 2, diphenyl 4-(1-bromopentacyclo[4.3.0.0^2,5.0^3,8.0^4,7]nonyl-9-one ethylene ketal) carbinol 3, 4-(1-bromopentacyclo[4.3.0.0^2,5.0^3,8.0^4,7] nonyl-9-one ethylene ketal) carbinol 4 and 4-(1-bromopentacyclo[4.3.0.0^2,5.0^3,8.0^4,7]nonyl) carbinol 16, has been studied undervarious conditions.Exclusive migration of the C₄C₇ (or the equivalent C₃C₄ bond) in the homocubane skeleton was observed leading to 1,3-bishomocubane bridgehead alcohols. Relief of cage constraint governs the selective course of these cage expansions.     

Zur Photochemie von (Z,Z)-2,7-Cyclodecadien-1-on und 4,8-Cyclododecadien-1-on. Synthese und Eigenschaften von Tricyclo[5.3.0.02,8]decan-Systemen

On the Photochemistry of (Z,Z)-2,7-Cyclodecadien-1-one and 4,8-Cyclododecadien-1-one. Synthesis and Properties of Tricyclo[5.3.0.0^2,8]decane Systems Irradiation of (Z,Z)-2,7-cyclodecadien-1-one ( 3 ) yields (Z,Z)-3,7-cyclodecadien-1-one ( 12 ) or tricyclo-[5.3.0.0^2,8]decan-4-one ( 16 ), depending on the reaction conditions. Irradiation of 4,8-cyclododecadien-1-one ( 28 ) results also in a light-induced transannular [2 + 2] cycloaddition, yielding tetracyclo[7.3.0.0^2,100^3,6]dodecan-1-one ( 30 ). Starting from 16 , the preparation of tricyclo[5.3.0.0^2,8]dec-4-ene ( 19 ), tricyclo[5.3.0.0^2,8]dec-4-ene ( 21 ) and tricyclo[5.3.0.0^2,8]deca-3,5-diene ( 24 ) is described. The ¹H-NMR and ¹³C? NMR spectra of the newly prepared compounds are discussed. In the case of 19, 21 , and 24 , the electronic structure is discussed on hand of their PE spectra.     

Chemistry of strained polycyclic compounds—IX: The synthesis and homoketonization of 4-substituted homocuneane acetates

The synthesis of three bridgehead homocuneanes acetates viz 1-bromopentacyclo [4.3.0.0^2.4.0^3.8.0^5.7]nonan-9-one ethylene ketal 4-acetate (10), 1-bromopentacyclo[4.3.0.0^2.4.0^3.8.0^5.7]nonane 4-acctate (22) and pentacyclo[4.3.0.0^2.4.0^3.8.0^5.7]nonane-9-one ethylene ketal 4-acetate (31) is described, starting from the readely available homocubane carboxylic acid (4). The base and acid catalyzed homoketonization reaction of these acetates has been studied. Under basic conditions the acetates (10, 22 and 31) are converted into tettacyclo[4.3.0.0^2.4.0^3.8]nonane derivatives by a cyclopropanol ring cleavage. This homoketonization reaction is a stereospecific process proceeding with retention of configuration. The effect of cage strain on the stereochemistry of base induced homoketonization of bridgehead cage alcohols is discussed.The acid catalyzed homoketonization of acetate (10) was also found to occur exclusively with retention of configuration.     

Tetracyclo[5.3.0.02,803,6]deca-4,9-diene. A new (CH)10 hydrocarbon

Irradiation of tricyclo[5.3.0.0^2,8]deca-3,5-dien-9-one ethylene acetal yields tetracyclo[5.3.0.0^2,80^3,6]dec-4-en-9-one ethylene acetal as main product which can be converted to the title compound, a new (CH)¹⁰ hydrocarbon.     

Short intramolecular oh...π - electron distances in rigid polycyclic structures : Synthesis and IR-spectroscopic study of tetracyclo[5.3.0.0.2,5.0.4,8]dec-9-en-3-ol and the 3-methyl derivative

Two strained bridgehead cage alcohols with a very short intramolecular OH...π distance, tetracyclo[5.3.0.0.^2,5.0.^4,8 dec-9-en-3-ol and its 3-methyl derivative, have been synthesized. The IR spectra have been studied and discussed in relation to the starting ketone tetracyclo[5.3.0.^2,5.0.0.^4,8] dec-9-en- 3-one.Considerable attractive OH-proton...π-electron interaction on the one hand and repulsive steric and oxygen-lone-pair... π forces on the other hand lead to a position of the hydroxyl bond, practically parallel to the double bond. Non-bonding proton..proton interaction in the 3-methyl compound causes increased C-H stretching frequencies of the alkyl groups involved. The IR-data of the ketone confirms the presence of non-bonding π-orbital interaction and shows the C=O vibration is subject to Fermi resonance.     

The Adamantane Rearrangement of Tricyclo[4.2.2.01,5]decane to Tricyclo[5.3.0.04,8]decane

Regioselective generation of the C(2)-carbocation a of tricyclo[4.2.2.0^1,5]decane ( 1 ) by treatment of both corresponding epimeric alcohols 5 and 6 with BF₃ and trapping the rearranged tricyclo[5.3.0.0^4,8]decan-7-yl carbocation b with Et₃SiH as hydride-ion donor (ionic hydrogenation) gives the corresponding hydrocarbon 3 as sole product in almost quantitative yield. The latter is a known intermediate in the Lewis-acid-catalyzed rearrangement of 1 to adamantane ( 4 ).     

The Novel Adamantane Isomer 2,5-Trimethylenenorbornane (Tricycio-[5.3.0.3,9]decane, 4-Homotwistbrendane)

A synthesis of the novel C₁₀H₁₆ hydrocarbon 2,5-trimethylenenorbornane (tricyclo[5.3.0.0^3,9]decane, 1 ), one of the 19 members of the ‘adamantaneland’, and its Lewis-acid-catalyzed rearrangement is described.     

Base-promoted rearrangement of cage α-haloketones—II : 12-oxa-3,5,9,10-tetrachlorohexacyclo[5.4.1.02,6.03,10.05,9.08,11]-dodecane-4-one

A synthesis of 12-oxa-3,5,9,10-tetrachlorohexacyclo[5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecane-4-one (6) from 4,4-dimethoxy-2,3,5,6-tetrachloropentacyclo [[5.4.0.0^2,6.0^3,10.0^5,9]undecane-8,11-dione (1) is described. Reaction of 6 with sodium hydroxide in refluxing benzene, toluene, or tetrahydrofuran affords 11-oxa-3,4,5-exo-6-tetrachloropentacyclo [[6.2.1.0^2,7.0^4,10.0^5,9]undecane-endo-3-carboxylic acid (7a, 80·2% yield). The corresponding reaction of 6 with refluxing aqueous sodium hydroxide solution affords 4,12-dioxa-8,11-dichlorohexacyclo-[5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecane-1-carboxylic acid (8a, 66·5% yield). A mechanism which accounts for the formation of 7a and 8a from 6 is presented.     

Reactions of the 1-halo-7-(2-hydroxyethoxy)cycloheptenes and the 3-halo-4-(2-hydroxyethoxy)bicyclo[3.2.1]oct-2-enes with potassium t-butoxide

Reactions of 1 - bromo - 7 - (2 - hydroxyethoxy)cycloheptene 2 and its chloro analogue 3 with potassium t-butoxide in dimethyl sulphoxide or tetrahydrofuran gave cycloheptatriene and cis - 8,11 - dioxabicyclo[5.4.0]undec - 2 - ene 18 as the major products together with small amounts of the trans-isomer 17,8,11-dioxabicyclo[5.4.0]undec - 1(7) - ene 14, 8,11 - dioxabicyclo[5.4.0] - undec - 1 - ene 19, cyclohept - 2 - enone ethylene ketal 15, cyclohept - 3 - enone ethylene ketal 16, and 1- and 2 - t - butoxycyclohepta - 1,3 - diene 20. Similar reactions of 3 - bromo - and 3 - chloro - 4 - (2 - hydroxyethoxy)bicyclo[3.2.1]oct - 2 - ene 4 and 5 gave 4,7 - dioxatricyclo[7.2.1.0^3,8]dodeca - 2 - ene 26 as the major product together with small amounts of 3,6 - dioxatricyclo[7.2.1.0^2,7]dodeca - 2(7) - ene 27 and bicyclo[3.2.1]oct - 3 - ene - 2 - one ethylene ketal 28. Mechanisms for these transformations are discussed.     

Alkylations of tricyclo[5.2.1.0]deca-4,8-dien-3-one by a cuprate reaction

Alkylation at C₆ of tricyclo[5.2.1.0^2,6]deca-4,8-dien-3-one (R=H) was achieved by treatment of 6-bromotricyclo[5.2.1.0^2,6]deca-4,8-dien-3-one with lithium dimethylcuprate and subsequently with an appropriate electrophile. The best results were obtained in THF as the solvent. A wide range of alkyl halides, bromo ketones and esters, and acetyl chloride resulted in C₆-tricyclo[5.2.1.0^2,6]deca-4,8-dien-3-ones in moderate to good yields. This alkylation reaction proceeds via a C₆-carbanionic Cu intermediate, which is likely stabilized by the enone olefinic bond. 6-Bromo-endo-tricyclo[5.2.1.0^2,6]dec-8-en-3-one, which lacks this double bond, behaves differently. Treatment with lithium dimethylcuprate leads to dehydrobromination to give tricyclo[5.2.1.0^2,6]deca-2(6),8-dien-3-one in high yield.     

Studies on acid-catalysed σ-bond cleavage of aromatic conjugated cyclopropyl ketones: A new synthetic route to some hydroaromatic spiro compounds

Acid-catalysed cleavage of the aromatic conjugated cyclopropane σ-bond of the 3,4-benztricyclo[5.3.0^1,7.0^2,7]decan-10-one system has been studied and regioselective ring cleavage via the corresponding benzyl carbonium ion demonstrated giving rise to the respective spiro compounds.     

Synthesis of a tetracyclodecenone with two orthogonal π-electron systems via a 1,3-through cage elimination in a bridgehead substituted 1,3-bishomocubyl acetate

Stereoselective reduction of 1,3-bishomocubanone acetate $\text{1}$ followed by mesylation leads to an epimeric mixture of mesylates $\text{3}$. Base induced homoketonization of the anti-epimer $\text{3b}$ affords tetracyclo[5.3.0.0^2,5 O^4,8]decenone $\text{4}$.