The indenobenzazepine-spirobenzylisoquinoline rearrangement; stereocontrolled syntheses of (±)-raddeanine and (±)-yenhusomine

Stereoselective rearrangement of indenobenzazepine cis ketols $\text{2}$ and $\text{5}$ with TPAA in pyridine produces spirobenzylisoquinolines $\text{3}$ and $\text{6}$, respectively. The latter product is also obtained by rearrangement of trans ketol $\text{7}$. The transformation of ketols $\text{5}$ and $\text{7}$ must, therefore, proceed through the intermediacy of aziridinium cation $\text{9}$. A similar process obtains in the transformation of $\text{2}$ to $\text{3}$. NaBH₄ reduction of $\text{3}$ gives (±)-raddeanine ($\text{4}$). Rearrangement of diol $\text{10}$ supplies $\text{4}$ directly. (±)-Yenhusomine ($\text{13}$) is obtained from the reamangement of either diol, $\text{11}$ or $\text{12}$. In like fashion, diols $\text{14}$ and $\text{15}$ supply spirobenzylisoquinoline $\text{17}$.     

Base catalyzed rearrangement of some bicyclic ketol acetates.

The ketol $\text{3a}$ and its acetate $\text{3b}$ when refluxed in methanolic potassium hydroxide (5%) were found to rearrange to 4-methyl-8-acetyl-5,6,7,8-tetrahydro-1-naphthol $\text{4}$. The epimeric acetate $\text{3c}$ also behaved likewise. A mechanism is suggested for the rearrangement.     

An unusual rearrangement of eudesmane skeleton

The lactone $\text{5}$ was found to be a co-product of the BF₃ etherate induced cyclization of epoxyisogermacrone $\text{2}$. The keton $\text{3}$ when treated with 100% HCOOH afforded the lactone $\text{5}$ while under the same conditions the ketol $\text{4}$ gave the corresponding ester $\text{6}$. A mechanism is suggested for the rearrangements.     

1-methyl-(D3)-trishomocubane

The acid catalysed rearrangement of 8-methyl-pentacyclo(5.4.0.0^2,6.0^3,10.0^5,9)undecan-8-endo-o1 ($\text{8}$) to 3-methyl-(D₃)-trishomocuban-4-o1 ($\text{9}$) provided the key step to the synthesis of the title compound ($\text{11}$).     

The synthesis and x-ray crystal structure of a tetracyclo[4.2.1.1.2,503,7]decane derivative. A rigid,twist boat-containing ring system.

Attempted intramolecular pinacolization of cage diketone $\text{4}$ unexpectedly gave ketol $\text{5}$ instead. Compound $\text{5}$ was shown to possess the rare tetracyclo[4.2.1.1.^2,50^3,7]decane ring system by means of an X-ray crystal structure of hydroxy-mesylate $\text{10}$ derived from $\text{5}$ by sodium borohydride reduction followed by mesylation. A possible mechanism for the transformation of $\text{4}$ into $\text{5}$ is presented, and certain noteworthy features of the crystal structure of $\text{10}$ are discussed. The base-catalysed fragmentation of $\text{10}$ to give enone $\text{11}$ is also described.     

BH3 THF reduction of 3-methylisoxazolo [4,5-c]pyridines

3-Methylisoxazolo[4,5-c]pyridine $\text{1}$ on reduction with BH₃:THF gave, via the isolable complex $\text{4}$, the tetrahydroisoxazolopyridine $\text{5}$. The presence of two chlorine atoms at the 4 and 6 positions directed borane attact to the isoxazole ring, yielding the aminoethylpyridine $\text{8}$. Both types of reduction were obtained with 6-chloroisoxazolo[4,5-c]pyridine $\text{7}$.     

Crystal engineering in the solid state photochemistry of cyclohexenones

Previous results from our laboratory plus a simple conformational analysis argument lead to the prediction that irradiation of cyclohexenone $\text{1}$ in the solid state will give ketol $\text{2}$. An independent synthesis of $\text{2}$ plus a determination of the solid state conformation of $\text{1}$ by X-ray crystallography show this prediction to be correct.     

The invention of new radical chain reactions. part X: High yield radical addition reactions of αβ-unsaturated nitroolefins. An expedient construction of the 25-hydroxy-vitamin D3 side chain from bi

Radicals derived from thiohydroxamic esters $\text{3}$ readily add to nitroolefins $\text{5}$ (Z = NO₂) to give good yields of α-nitrosulphides. These adducts, where the structure permits, are easily oxidised to carboxylic acids $\text{8}$ by treatment with alkaline hydrogen peroxide. Reductive cleavage to the corresponding aldehydes or ketones $\text{9}$ is efficiently carried out by the action of TiCl₃. Addition of methyl magnesium iodide to the methyl ketone derived from 3α-acetoxy 11-oxo cholanic acid gives steroid $\text{10}$ possessing the 25-hydroxycholesterol side chain of the vitamin D₃ metabotites. Radical additions to 1-phenylthio-2-nitropropene $\text{11}$ have been briefly studied.     

Oxidative addition of dimethylphosphite to iridium(I) and rhodium(I) complexes: Stereoselective reduction of 4-t-butylcyclohexanone

Dimethylphosphite, (CH₃O)₂P(O)H, adds oxidatively to iridium(I) and rhodium(I) complexes to give hydrido-iridium(III) or -rhodium(III) dimethylphosphonate complexes. A complex Ir(H)Cl[P(O)(OCH₃)₂][P(OH)(OCH₃)₂]₃ obtained from [IrCl(C₈H₁₄)₂]₂ and dimethylphosphite catalyses the stereo-selective reduction of 4-t-butylcyclohexanone to $\text{97}\text{3}$cis/trans-4-t-butylcyclohexanol, the ratio being identical with that obtained using the Henbest catalyst iridium(IV) chloride, phosphorous acid or one of its esters, and aqueous isopropanol.     

Revised structure for fumarofine,an indenobenzazepine type alkaloid

Fumarofine is not a spirobenzylisoquinoline. Rather, it is the first know reduced indenobensazepine alkaloid, and possesses the cis B/C fused structure $\text{7}$. Rearrangement of synthetic spirobensylisoquinoline $\text{12}$ using methanesulfonyl chloride furnished indenobensazepine $\text{14}$. Osmium tetroxide oxidation of $\text{14}$ gave cis-glysol $\text{15}$. O-Methylfumarofine ($\text{8}$) was then obtained through pyridinium chlorochromate oxidation of $\text{15}$.     

H3N·PF5 and H2NPF5−, new compounds in the system H3N/PF5

Phosphorus pentafluoride was reported long ago to give adducts 2 PF₅ ·5 NH₃ (1) and nNH₃·PF₅ (n= 1 ? 4) (2). None of the compounds was characterised in detail. Repeating the reaction of PF₅ and NH₃ we found the adduct H₃N·PF₅, $\text{1}$, in 8% yield besides (H₂N) ₂PF₃ (3) and NH₄PF₆. However, HF and (F₂P=N)₃ gave $\text{1}$ in 41% yield. The ¹H, ¹⁹F, and ³¹P n.m.r. spectra of $\text{1}$ exhibit ¹⁴NH, ¹⁴NPF(cis), and ¹⁴NP coupling. The x-ray structure determination shows almost perfect octahedral geometry at phosphorus with a PN bond length of 1.842 ā. Compound $\text{1}$ is soluble in water without decomposition. Treatment with NH₃ leads to the anion H₂NPF₅^?. Upon heating $\text{1}$ forms in good yield H₂NPF₄ and NH₄PF₆. Without a solvent $\text{1}$ and NH₃ react to give (H₂N) ₂PF₃. A mechanism for the ammonolysis of PF₅ is proposed.     

Reaction of acylaminocyanoesters with 2,4-bis (4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide leading to substituted aminothiazoles. Crysta

2-Acylamino-2-cyanoacetic acid ethyl esters $\text{2a-c}$ react with 2,4-bis (4-methoxyphenyl)-1, 3, 2, 4-dithiadiphosphetane 2,4-disulfide $\text{1}$ in refluxing benzene with formation of 2-alkyl(aryl)-5-aminothiazole-4-carboxylic acid ethyl esters $\text{3a-c}$. Structure $\text{3}$ was established by spectroscopic means and an X ray crystallographic investigation of $\text{3a}$. X-Ray analysis revealed that the thiazole ring, exocyclic nitrogen and carbonyl group forming a hydrogen-bonded cycle are nearly coplanar. A resonance interaction is manifested by distinctly shortened /1.447 (3)/ C_(carbonyl)-C_(thiazole) distance.     

Synthesis of 4a-, 4e-phenyladamantanones and 2,4-o-benzenoadamantane by π-route

The acid catalysed reaction of 4-oxa-homoadamantan-5-one ($\text{1}$) with benzene yielded a mixture of 4^a-phenyladamantan-2-one ($\text{7}$), the equatorial isomer' ($\text{8}$) and 2-phenyl-2,4-o- benzenoadamantane ($\text{9}$) A plausible reaction pathway for the occurrence of $\text{9}$. is put forward. The structure of $\text{9}$, was deduced from spectroscopic data and reaction of the proposed intermediate 2,4^a-diphenyladamantan-2-ol ($\text{11}$) with acid. 2,4-o-Ben-zenoadamantane ($\text{16}$) is prepared likewise.     

Reaction of ortho-palladated dimethylbenzylamine with styrene: Unexpected salt effect

Treatment of ortho-palladated complex $\text{I}$ with styrene in benzene - acetic acid mixture gives complex $\text{IV}$. The reaction is strongly accelerated in the presence of NaClO₄ or LiClO₄.     

Synthesis of phosphatidyl-β-glucosyl glycerol containing a dioleoyl diglyceride moiety : Application of the tetraisopropyldisiloxane-1,3-diyl (tips) protecting group in sugar chemistry. part IV

The preparation of phosphatidyl-β-glucosyl diglyceride $\text{12c}$ is described. The synthesis of glycophospholipid $\text{12c}$ was accomplished by using: (a) the levulinoyl group for the temporary protection of the glucose hydroxyl functions of $\text{6b}$, which could then be converted into the dioleoyl substituted derivative $\text{7c}$; (b) the tetraisopropyldisiloxane-1,3-diyl (TIPS) group to protect the 3'- and 4'-hydroxyl groups of $\text{7c}$, in a two step procedure, to afford compound $\text{8}$; (c) a 2,4-dichlorophenyl protected phosphatidic acid derivative $\text{11}$. Compound $\text{11}$ could be selectively coupled to the primary hydroxyl function of $\text{8}$ to afford the fully protected glycophospholipid $\text{12a}$. Finally, removal of the 2,4-dichlorophenyl and TIPS protecting groups from $\text{12a}$ was performed with syn-4-nitrobenzaldoximate and fluoride ions, respectively, to afford glycophospholipid $\text{12c}$.     

Condensation of a p-diazooxide with dimethyl acetylenedicarboxylate: formation of a spiro [4.5] Decatetraenone and a nonenolizable naphthalenone in a single reaction

The condensation of p-diazooxide $\text{1}$ with dimethyl acetylenedicarboxylate at 90°–100°C yields two C₂₆H₃₂O₉ products, corresponding to addition of two molecules of ester to one of the carbene $\text{2}$. The major product is the novel spirodecatetraenone $\text{4}$, and the minor product is the remarkable, nonenolizable naphthalenone $\text{5}$. Spirodecatetraenone $\text{4}$ is not a precursor of $\text{5}$, since the former is stable to acids and rearranges only above 200° to give the blocked azulenone $\text{8}$. A mechanism for the concomitant formation of product $\text{4}$ and $\text{5}$ is proposed.     

A new method for the 1, 4-oxygenation of 1-alkylated cyclopentadienes

The diene $\text{1}$ was efficiently transformed into the ketol $\text{2}$ by a three-step process which includes a novel oxygenation by a chlorochromate reagent.     

Acid - catalyzed rearrangement of butyl 2-0-acetyl-4,5-anhydro-3,6-dideoxy-hexaldonate. Synthesis of racemic epiallomuscarine and epimuscarine

Butyl 2-0-acetyl-4,5-anhydro-3,6-dideoxy-DL-xylo-hexaldonate ($\text{4}$) in the presence of SnCl₄ underwent an intramolecular rearrangement to give 2,5-anhydro ester $\text{7}$. On the other hand the lyxo epimeric epoxide $\text{5}$ under the same conditions afforded esters $\text{7}$ and $\text{8}$. Ester $\text{7}$ was transformed into racemic epiallomuscarine ($\text{12}$), whereas the isomer $\text{8}$ into racemic epimuscarine ($\text{13}$).     

Biomimetic synthesis of bacterial c50 carotenoids decaprenoxanthin and c.p. 450

Alkylation of the distal double bond of pseudoionone $\text{4}$ has been carried out with isoprene epoxide (ZnCl₂ /MeNO₂ ) leading directly to α-$\text{cis 10 a}$, α-$\text{trans}$$\text{10b}$ and γ $\text{10c}$ hydroxyprenylionones. The α-$\text{cis}$ and γ-isomers have been converted in few steps into the C₅₀ carotenoids decaprenoxanthin $\text{1}$ and C.p. 450 $\text{3}$ respectively.     

New synthesis of benzo [a]quinolizidin-2-ones via protected 2-aryl-4-piperidones

A new synthesis of 9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-benzo aquinolizin-2-one ($\text{1a}$ and its 3-ethyl derivative $\text{1b}$ via the corresponding 2-(3,4-dimethoxyphenyl)-4-piperidone ethylene acetals $\text{7}$ is reported. Alkylation of 2-arylpipendires $\text{7}$ with 2-bromoethanol followed by oxidation of the resulting amino alcohols $\text{9}$ with oxalyl chloride and dimethyl sulfoxide afforded the aldehydes $\text{10}$, which were cyclized with hydrochloric acid to give 7-hydroxybenzo[α]quinolizidines $\text{11}$. The reduction of $\text{1}$ with trinethylsilane and subsequent acid hydrolysis led to benzo aquinolizidin-2-ones $\text{1}$.