230287-23-7

Upstream product

• 4746-97-8 cyclohexanedione monoethylene ketal 
• 100-46-9 benzylamine 
• 62-53-3 aniline 

Downstream Products

• 131511-13-2 4-(N-benzylamino)cyclohexanone ethylene acetal 
• 419569-90-7 1'-benzyl-2'-oxo-1',2',4',6',7',7a'-hexahydrospiro[1,3-dioxolane-2,5'-[5H]indole]-3'-acetic acid 
• 945386-60-7 C₁₈H₂₃NO₂ 
• 880151-60-0 N-(1-allyl-4-oxocyclohexyl)-N-benzyl-2-chloroacetamide 
• 880151-61-1 N-(1-allyl-4-oxocyclohexyl)-N-benzyl-2-iodoacetamide 
• 880151-59-7 2-chloro-N-(8-allyl-1,4-dioxaspiro[4,5]dec-8-yl)-N-benzylacetamide 

Relevant academic research and scientific papers

Radical Cyclizations in the Synthesis of 3-Methyl-cis-octahydroindol-5-ones

Three approaches to the stereoselective synthesis of 3-methyl-cis-octahydroindoles through a 5-endo-trig radical cyclization are described. First, starting from an N-vinyl-α-chloroacetamide, the cyclization was followed by lactam methylenation and hydrogenation. Second, starting from an alkyne-tethered enamide, the cyclization was promoted by Bu3SnH, and this was followed by protonolysis of the vinylstannane and hydrogenation of the exocyclic alkene. Third, through a 2,2-dichloropropanamide cyclization onto an alkenyl bond, and hydrogenation of the resulting endocyclic double bond; this represents the most efficient sequence to form the target compounds. 1,5-Enyne cyclizations through a 5-endo-trig process are reported. Here, a remote functional group (ketal or ketone), allowed the diastereoselectivity of the octahydroindole ring formation to be reversed through steric control of the facial selectivity in the hydrogen radical delivery step.

Enantioselective Silver and Amine Co-catalyzed Desymmetrizing Cycloisomerization of Alkyne-Linked Cyclohexanones

A silver(I) and amine co-catalyzed desymmetrization of 4-propargylamino cyclohexanones for the direct enantioselective synthesis of 2-azabicyclo[3.3.1]nonanes is described. Exploiting reactivity arising from dual activation of the pendant terminal alkyne by silver(I) and the ketone moiety through transient enamine formation, this synthetically relevant transformation is easy to perform, efficient and broad in scope. High enantioselectivity (up to 96 % ee) was achieved by exploiting a significant matching effect between the chirality of a cinchona alkaloid-derived aminophosphine ligand for the silver(I) salt and the 2-bis(aryl)methylpyrrolidine catalyst which was rationalized by DFT calculations. This allowed for the preparation of both enantiomers of the bicyclic product with near-identical stereocontrol.

Synthesis of the tetracyclic ABCD ring systems of madangamines D-F

Synthesis of the tetracyclic cores of madangamines D-F was achieved, featuring a reductive radical process from an ethoxycarbonyldichloroacetamide to build the morphan nucleus, a Mitsunobu-type aminocyclization toward the common diazatricyclic intermediate, and ring-closing metathesis reactions for the macrocyclization step leading to the 13- to 15-membered rings.

Spirocyclic Cyclohexane Compounds

Spirocyclic cyclohexane compounds corresponding to formula I In which R1, R2, R3 and R5 through R10 and X have defined meanings, a process for their preparation, pharmaceutical compositions containing such compounds, and the use of such spirocyclic cyclohexane compounds in the treatment and/or inhibition of pain and other conditions mediated by the ORL-1 or the ?-opioid receptor.

New insights into NIS-promoted aminocyclization. Synthesis of decahydroquinolines from 2-allylcyclohexylamines

Equation Presented Bishomoallylic secondary amines embodying the 2-allyl-N-benzylcyclohexylamine unit react with NIS to undergo cyclization through 6-endo processes in either the cis or trans series. Nevertheless, when the resulting cis-3-iododecahydroqui

Synthesis of enantiopure 1-azaspiro[4.5]decanes by iodoaminocyclization of allylaminocyclohexanes

The 5-endo iodine-promoted ring closure of 4-allyl-4-(alkylamino) cyclohexanone derivatives gives the corresponding 1-azaspiro[4.5]decanes in good yields. The reaction was tested with enantiopure homoallylamines to evaluate the diastereoselectivity of the process and to provide a route for possible intermediates to the natural products embodying this azabicyclic ring. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Studies on a total synthesis of the microbial immunosuppresive agent FR901483

A strategy is outlined for construction of the fungal immunosuppressant FR901483 (1). It was possible to convert 1,4-cyclohexanedione monoethylene ketal in five simple steps to iodoacetamide ketone 10, which was cyclized in good yield to the key bridged keto lactam 11 containing the A/B 2-azabicyclo-[3.3.1] nonane ring system of the natural product. This intermediate could be transformed to N-Boc lactam 16, whose derived enolate underwent stereoselective hydroxylation with the Davis oxaziridine to produce alcohol 17 having the desired C-2 configuration. Compound 17 was then converted in three steps to alkoxy carbamate 20. The N-acyliminium ion derived from intermediate 20 could be alkylated in good overall yield with p-methoxybenzylmagnesium chloride to afford a 5:4 mixure of the desired PMB product 21 and the epimer 23. In an attempt to improve the stereoselectivity in this alkylation, the inverted C-4 protected alcohol N-Boc lactam 33 was prepared and its enolate was hydroxylated. Inexplicably, the product of this reaction was the undesired equatorial alcohol 34. Some model systems were investigated toward annulation of the C-ring of the natural product. It was found that homoallylic amine 40 could be cyclized with PhSCl in the presence of silica gel to generate the desired 5-endo tetracyclic product 42 in moderate yield. This cyclization protocol was also successfully applied to the actual FR901483 system 22, leading to the requisite tricycle 43.

A new synthetic entry to the tricyclic skeleton of FR901483 by palladium-catalyzed cyclization of vinyl bromides with ketone enolates

A new synthetic entry to the FR901483 core is described. The Pd-mediated cyclization of amino-tethered vinyl halides and ketone enolates from the azaspiro[4.5]decan-8-ones 5 and 10 gives the functionalized 7,10a-methanoperhydropyrrolo[1,2-a]azocines 1 and 11, respectively.

Aromatization of 1,6,7,7a-tetrahydro-2H-indol-2-ones by a novel process. Preparation of key-intermediate methyl 1-benzyl-5-methoxy-1H-indole-3-acetate and the syntheses of serotonin, melatonin, and bufotenin

Imine 7 of 1,4-cyclohexanedione mono-ethylene ketal 6 was reacted with maleic anhydride, affording the cyclized adduct 8. Methyl esterification of 8, accompanied by transacetalization, led to the dihydrooxindole derivative 10. Aromatization of 10 was then accomplished with POCl3, leading directly to the key-intermediate title compound 11 in 74% yield from ketone 6. Serotonin, melatonin, and bufotenin were then obtained by standard reactions.

Reaction of Cyclohexanones Imines with Substituted Nitroolefins. New Synthesis of Tetrahydroindole Derivatives

The Michael-type addition of cyclohexanones imines, reacting as their secondary enamine tautomers, to β-substituted nitroolefins is followed by a cyclization reaction with elimination of the nitro group to afford substituted tetrahydroindoles. When a 2-methylcyclohexanone imine is reacted, an unexpected inversion of the regioselectivity is observed when compared with β-substituted ethylenic esters, thus allowing to obtain also substituted tetrahydroindoles. - Keywords: Imines; Michael reactions; Regioselection; Indoles