4448-83-3

Upstream product

• 1903-29-3 cycloheptylideneacetic acid 
• 92984-49-1 cycloheptyliden-acetic acid methyl ester 
• 1903-23-7 ethyl cycloheptylideneacetate 
• 502-42-1 cycloheptanone 
• 4480-98-2 2-cycloheptylethanol 

Downstream Products

• 1393361-31-3 3-(cycloheptylidenemethyl)but-3-en-2-yl benzoate 
• 1443054-39-4 N-(2-cycloheptylideneethyl)-4-methyl-N-(4-oxobutyl)benzenesulfonamide 
• 1443054-38-3 N-(2-cycloheptylideneethyl)-N-(4-hydroxybutyl)-4-methylbenzenesulfonamide 
• 1443054-72-5 (3R,4R)-3-cycloheptenyl-1-tosylpiperidine-4-carbaldehyde 
• 84653-59-8 2',4',6'-trihydroxy-3'-(2-cycloheptylidene-ethyl)isovalerophenone 
• 93796-27-1 5,7-dihydroxy-6-isovalerylchroman-2-spirocycloheptane 
• 93796-25-9 3',5'-bis(cycloheptylidenemethyl)-2',4',6'-trihydroxyisovalerophenone 
• 93796-26-0 4,6-bis(2-cycloheptylidene-ethyl)-3,5,6-trihydroxy-2-isovalerylcyclohexa-1,4-dien-1-one 
• 93796-28-2 3-(2-cycloheptylidene-ethyl)-5,7-dihydroxy-6-isovalerylchroman-2-spirocycloheptane 

Relevant academic research and scientific papers

Chiral 1,2,3-Triazolium Salt Catalyzed Asymmetric Mono- and Dialkylation of 2,5-Diketopiperazines with the Construction of Tetrasubstituted Carbon Centers

Novel asymmetric mono- and dialkylation reactions of α-substituted 2,5-diketopiperazines catalyzed by new chiral spirocyclic-amide-derived triazolium organocatalysts have been developed, resulting in a range of enantioenriched 2,5-diketopiperazine derivatives containing one or two tetrasubstituted carbon stereocenters. The reactions feature high yields (up to 98%), and excellent cis-diastereo- and enantioselectivities (up to >20:1 dr, >99 % ee), and they provide a new asymmetric synthetic approach to important functionalized 2,5-diketopiperazine skeletons. Furthermore, a possible reaction mechanism was proposed based on both control experiments and extensive DFT calculations.

Visible-Light-Promoted Intramolecular α-Allylation of Aldehydes in the Absence of Sacrificial Hydrogen Acceptors

We report herein an unprecedented protocol for radical cyclization of aldehydes with pendant alkenes via synergistic photoredox, cobaloxime, and amine catalysis. The transformation was achieved in the absence of external oxidants, providing a variety of 5-, 6-, and 7-membered ring products with alkene transposition in satisfactory yields. The reaction exhibits wide functional group compatibility and occurs under mild conditions with extrusion of H2.

Copper-Catalyzed Enantio-, Diastereo-, and Regioselective [2,3]-Rearrangements of Iodonium Ylides

The first highly enantioselective, diastereoselective, and regioselective [2,3]-rearrangement of iodonium ylides has been developed as a general solution to catalytic onium ylide rearrangements. In the presence of a chiral copper catalyst, substituted allylic iodides couple with α-diazoesters to generate metal-coordinated iodonium ylides, which undergo [2,3]-rearrangements with high selectivities (up to >95:5 r.r., up to >95:5 d.r., and up to 97 % ee). The enantioenriched iodoester products can be converted stereospecifically into a variety of onium ylide rearrangement products, as well as compounds that are not accessible by classical onium ylide rearrangements.

General, Auxiliary-Enabled Photoinduced Pd-Catalyzed Remote Desaturation of Aliphatic Alcohols

A general, efficient, and site-selective visible light-induced Pd-catalyzed remote desaturation of aliphatic alcohols into valuable allylic, homoallylic, and bis-homoallylic alcohols has been developed. This transformation operates via a hybrid Pd-radical mechanism, which synergistically combines the favorable features of radical approaches, such as a facile remote C-H HAT step, with that of transition-metal-catalyzed chemistry (selective β-hydrogen elimination step). This allows achieving superior degrees of regioselectivity and yields in the desaturation of alcohols compared to those obtained by the state-of-the-art desaturation methods. The HAT at unactivated C(sp3)-H sites is enabled by the easily installable/removable Si-auxiliaries. Formation of the key hybrid alkyl Pd-radical intermediates is efficiently induced by visible light from alkyl iodides and Pd(0) complexes. Notably, this method requires no exogenous photosensitizers or external oxidants.

The synthesis of α,α-disubstituted α-amino acids via ichikawa rearrangement

An approach to α,α-disubstituted α-amino acids is reported. The key step is allyl cyanate-to-isocyanate rearrangement. As demonstrated, the resultant allyl isocyanates can be directly trapped with various nucleophiles, for instance, alcohols, amines, and organometallic reagents, to provide a broad range of N-functionalized allylamines. The developed method has been successfully applied in the synthesis of two bioactive peptides: 2-aminoadamantane-2-carboxylic acid derived P2X7-evoked glutamate release inhibitor and 4-amino-tetrahydropyranyl-4-carboxylic acid derived dipeptide GSK-2793660, which is currently in clinical trials as cathepsin C inhibitor for the treatment of cystic fibrosis, noncystic fibrosis bronchiectasis, ANCA-associated vasculitis and bronchiectasis.

Enantioselective intramolecular aldehyde α-alkylation with simple olefins: Direct access to homo-ene products

A highly selective method for the synthesis of asymmetrically substituted carbocycles and heterocycles from unactivated aldehyde-olefin precursors has been achieved via enantioselective SOMO-catalysis. Addition of a catalytically generated enamine radical cation across a pendent olefin serves to establish a general asymmetric strategy toward the production of a wide range of formyl-substituted rings with alkene transposition. Conceptually, this novel mechanism allows direct access to "homo-ene"-type products.

Geminal alkene-alkyne cross metathesis using a relay strategy

A relay strategy was employed to achieve an intermolecular ene-yne metathesis between 1,1-disubstituted alkenes and alkynes. The relay serves to activate an unreactive alkene which will not participate in ene-yne metathesis. The new relay cross ene-yne me

Discovery and preclinical profile of saxagliptin (BMS-477118): A highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

Efforts to further elucidate structure-activity relationships (SAR) within our previously disclosed series of β-quaternary amino acid linked L-cis-4,5-methanoprolinenitrile dipeptidyl peptidase IV (DPP-IV) inhibitors led to the investigation of vinyl substitution at the β-position of α-cycloalkyl-substituted glycines. Despite poor systemic exposure, vinyl-substituted compounds showed extended duration of action in acute rat ex vivo plasma DPP-IV inhibition models. Oxygenated putative metabolites were prepared and were shown to exhibit the potency and extended duration of action of their precursors in efficacy models measuring glucose clearance in Zuckerfa/fa rats. Extension of this approach to adamantylglycine- derived inhibitors led to the discovery of highly potent inhibitors, including hydroxyadamantyl compound BMS-477118 (saxagliptin), a highly efficacious, stable, and long-acting DPP-IV inhibitor, which is currently undergoing clinical trials for treatment of type 2 diabetes.

Cascade rearrangement of spiroepoxymethyl radicals into 2-oxocycloalkyl radicals: Evaluation of a two-carbon cycloalkanone ring expansion

Series of 2-bromomethyl- and 2-hydroxymethyl-1-oxaspiro[2.n]alkanes were prepared from cycloalkanones by initial Wadsworth-Horner-Emmons methodology to afford ester-substituted methylenecycloalkanes. The latter were selectively reduced to hydroxymethylmethylenecycloalkanes which were epoxidised with peroxyacetic acid. Homolytic reactions were studied by EPR spectroscopy which enabled transient 3-oxoalk-1-enyl radicals, and their cyclisation products, 2-oxocycloalkyl and 2-oxocycloalkylmethyl radicals, to be characterised. This evidence, together with end product analyses of organotin hydride reductions of the 2-bromomethyl-1-oxaspiro[2.n]alkanes, established that the initial spiroepoxymethyl radicals rearranged by a three-stage cascade of two consecutive β-scissions followed by a cyclisation. Cyclisations of the 3-oxoalk-1-enyl radicals took place mainly in the endo-mode to afford 2-oxocycloalkyl radicals, except for the 5-oxohept-6-enyl radical for which exo-cyclisation to generate the 2-oxocyclohexylmethyl radical was preferred. Kinetic data for the exo-and endo-cyclisations of the 4-oxohex-5-enyl radical were obtained from tributyltin hydride mediated reactions of 2-bromomethyl-1-oxaspiro[2.3]hexane.

98. A Regioselective Cyclohexannulation Procedure via Dienamine Cycloaddition. Synthesis of Functionalised Decalins

A regioselective cyclohexannulation procedure, whose key step involves the cycloaddition of dienamines 12-24 with methyl acrylate, allows the conversion of cycloalkanones 1-11 to bicyclic dienoates 25-37.The chemistry of 26 is briefly examined and, in the context of organoleptic studies concerning functionalised 5,5,9-trimethyldecalins, the transformation of 37 to ketones 44 and 46 as well as to acetates 53-56 is described.