40203-74-5Relevant academic research and scientific papers
Complementary regioselective cyclopropyl ring openings of 6- formyl-spirobicyclo[5.2]octane mediated by TMSC1 and TBAI
Huang, He,Forsyth, Craig J.
, p. 16341 - 16348 (1997)
Absolute control over the regioselectivity of trimethylsilyl halide-induced cyclopropane fragmentation of a spirofused cyclopropyl carboxaldehyde has been achieved by simply varying the reaction stoichiometry and the nature of the halide. Treatment of 6-formyl- spirobicyclo[5.2]octane with a large excess of TMSC1 gave 3-(1- chlorocyclohexyl)propanal (84% yield), whereas 2-(1- iodomethylcyclohexyl)ethanal (86% yield) was obtained using 10 equivalents each TMSC1 and n-Bu4NI (TBAI). Use of only a moderate excess of TMSC1 or TMSC1 and TBAI gave the rearranged product 3-(1- cyclohexenyl)-propanal.
Controlling Enantioselectivity and Diastereoselectivity in Radical Cascade Cyclization for Construction of Bicyclic Structures
Lee, Wan-Chen Cindy,Mckillop, Alexander M.,Wang, Duo-Sheng,Zhang, Congzhe,Zhang, X. Peter
supporting information, p. 11130 - 11140 (2021/07/31)
Radical cascade cyclization reactions are highly attractive synthetic tools for the construction of polycyclic molecules in organic synthesis. While it has been successfully implemented in diastereoselective synthesis of natural products and other complex compounds, radical cascade cyclization faces a major challenge of controlling enantioselectivity. As the first application of metalloradical catalysis (MRC) for controlling enantioselectivity as well as diastereoselectivity in radical cascade cyclization, we herein report the development of a Co(II)-based catalytic system for asymmetric radical bicyclization of 1,6-enynes with diazo compounds. Through the fine-tuning of D2-symmetric chiral amidoporphyrins as the supporting ligands, the Co(II)-catalyzed radical cascade process, which proceeds in a single operation under mild conditions, enables asymmetric construction of multisubstituted cyclopropane-fused tetrahydrofurans bearing three contiguous stereogenic centers, including two all-carbon quaternary centers, in high yields with excellent stereoselectivities. Combined computational and experimental studies have shed light on the underlying stepwise radical mechanism for this new Co(II)-based cascade bicyclization that involves the relay of several Co-supported C-centered radical intermediates, including α-, β-, γ-, and ?-metalloalkyl radicals. The resulting enantioenriched cyclopropane-fused tetrahydrofurans that contain a trisubstituted vinyl group at the bridgehead, as showcased in several stereospecific transformations, may serve as useful intermediates for stereoselective organic synthesis. The successful demonstration of this new asymmetric radical process via Co(II)-MRC points out a potentially general approach for controlling enantioselectivity as well as diastereoselectivity in synthetically attractive radical cascade reactions.
Pd-catalyzed regioselective C?H alkenylation and alkynylation of allylic alcohols with the assistance of a bidentate phenanthroline auxiliary
Hirano, Koji,Miura, Masahiro,Xu, Shibo
supporting information, p. 9059 - 9064 (2020/12/02)
A Pd-catalyzed regioselective C?H alkenylation of allylic alcohols with electron-deficient alkenes has been developed. The key to success is the introduction of bidentately coordinating phenanthroline directing group, which enables the otherwise challenging and regioselective C?H activation at the proximal alkenyl C?H bonds over the conceivably competitive allylic C?O bond activation. The same Pd/phenanthroline system is efficient for the C?H alkynylation of allylic alcohols with alkynyl bromides.
Microwave-Assisted Synthesis of Phenylpropanoids and Coumarins: Total Synthesis of Osthol
Konrádová, Daniela,Kozubíková, Hana,Dole?al, Karel,Pospí?il, Ji?í
supporting information, p. 5204 - 5213 (2017/09/29)
Herein we describe a one-pot microwave-assisted method for the synthesis of cinnamic acid and coumarin derivatives. The synthesis begins with an aldehyde synthon, and the chosen reaction conditions determine whether a cinnamic acid or coumarin derivative is formed. A regioselective Claisen rearrangement was also efficiently incorporated into the synthetic sequence to further increase the complexity of the product. Notably, this approach provides high product yields and selectivities without the need of a phenol protecting group.
Chemical assembly systems: Layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients
Ghislieri, Diego,Gilmore, Kerry,Seeberger, Peter H.
supporting information, p. 678 - 682 (2015/03/04)
While continuous chemical processes have attracted both academic and industrial interest, virtually all active pharmaceutical ingredients (APIs) are still produced by using multiple distinct batch processes. To date, methods for the divergent multistep continuous production of customizable small molecules are not available. A chemical assembly system was developed, in which flow-reaction modules are linked together in an interchangeable fashion to give access to a wide breadth of chemical space. Control at three different levels - choice of starting material, reagent, or order of reaction modules - enables the synthesis of five APIs that represent three different structural classes (γ-amino acids, γ-lactams, β-amino acids), including the blockbuster drugs Lyrica and Gabapentin, in good overall yields (49-75%).
Use of silver carbonate in the Wittig reaction
Jedinak, Lukas,Rush, Latoya,Lee, Mijoon,Hesek, Dusan,Fisher, Jed F.,Boggess, Bill,Noll, Bruce C.,Mobashery, Shahriar
, p. 12224 - 12228 (2014/01/06)
An efficient synthesis of olefins by the coupling of stabilized, semistabilized, and nonstabilized phosphorus ylides with various carbonyl compounds in the presence of silver carbonate is reported. Wittig olefination of aromatic, heteroaromatic, and aliphatic aldehydes (yields >63%) and a ketone (yield 42%) are demonstrated. These reactions proceed overnight at room temperature, under weakly basic conditions, and as such extend the applicability of the Wittig reaction to base-sensitive reactants.
P[N(i-Bu)CH2CH2]3N: Nonionic Lewis base for promoting the room-temperature synthesis of α,β-unsaturated esters, fluorides, ketones, and nitriles using Wadsworth - Emmons phosphonates
Chintareddy, Venkat Reddy,Ellern, Arkady,Verkade, John G.
supporting information; experimental part, p. 7166 - 7174 (2010/12/25)
The bicyclic triaminophosphine P(RNCH2CH2) 3N (R = i-Bu, 1c) serves as an effective promoter for the room-temperature stereoselective synthesis of α,β-unsaturated esters, fluorides, and nitriles from a wide array of aromatic, aliphatic, heterocyclic, and cyclic aldehydes and ketones, using a range of Wadsworth-Emmons (WE) phosphonates. Among the analogues of 1c [R = Me (1a), i-Pr (1b), Bn (1d)], 1a and 1b performed well, although longer reaction times were involved, and 1d led to poorer yields than 1c. Functionalities such as cyano, chloro, bromo, methoxy, amino, ester, and nitro were well tolerated. We were able to isolate and characterize (by X-ray means; see above) the reactive WE intermediate species formed from 2b and 1c.
DERIVATIVES OF 5,9-METHANOCYCLOOCTA[B]PYRIDIN-2-(1H)-ONE, THEIR PREPARATION AND USE AS ANALGESICS
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Page/Page column 17, (2009/05/28)
A compound of Formula I, a pharmaceutically-acceptable salt or a hydrate thereof, wherein R1 is H, or C1-4 alkyl; R2 is H, halogen, or C1, alkyl; R3 is H, halogen, or C1-4 alkyl, and R4 is C1-6 alkyl, aryl; or ═CR3R4 is cyclopentylidene, cyclohexylidene, 1-methylpiperidin-4-ylidene, or inden-1-ylidene; R5 is independently at each occurrence F, Cl, Br, CF3, R9, OR9, NR9R10, NO2, CN, COOR9, O2CR9, CONR9R10, NR9C(O)R10, heterocyclic group, aryl, or a group of Formula II; R6 is H, halogen, or C1-4 alkyl; R7 is H, halogen, or C1-4 alkyl; R8 is H, C1, alkyl group; R9 is H, or C1-6 alkyl; R10 is H, or C1-6 alkyl; R11 is H, or C1-4 alkyl; R12 is H, or C1-4 alkyl; m is 0, 1, or 2; when R5 is F, Cl, Br, CF3, R9, OR9, NR9R10, NO2, CN, COOR9, O2CR9, CONR9R10, NR9C(O)R10, heterocyclic group, or aryl, n is 1, 2, 3, or 4; when R5 is the group of Formula II, n is 0, 1, 2, 3, or 4; x is 0, 1, 2, 3, or 4.
ANALGESIC 5, 9 - METHANOCYCLOOCTA (b) PYRIDIN - 2 (1H) - ONE DERIVATIVES, THEIR PREPARATION METHOD AND USE
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Page/Page column 16, (2009/04/23)
Compounds represented by the Formula I or salts, hydrates thereof, wherein R1, R8, R11 and R12 are H or C1-4 hydrocarbonyl respectively; R2, R3, R6 and R7 are H, halogen or C1-4 hydrocarbonyl respectively; R4 is C1-6 hydrocarbonyl or Ar; or =CR4R3 is cyclopentylidene, cyclohexylidene, 1-methylpiperidyl-4-idene or indenyl-1-idene; R5 is H, 1-4 same or different F, Cl, Br, CF3, R9, OR9, NR9R10, NO2, CN, COOR9, O2CR9, CONR9R10, NR9C(O)R10, heterocyclic, aryl or groups represented by the Formula II respectively; R9 and R10 are H or C1-6 hydrocarbonyl; Ar is aromatic ring; m is 0, 1 or 2; n is 0, 1, 2, 3 or 4, for treating mammal pain, functional painful syndrome, organic painful syndrome or tissue painful syndrome, and their preparation method.
SOLUBLE EPOXIDE HYDROLASE INHIBITORS
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Page/Page column 93, (2008/12/06)
Disclosed are alpha keto amide and alpha hydroxy amide compounds and compositions that inhibit soluble epoxide hydrolase (sEH), methods for preparing the compounds and compositions, and methods for treating patients with such compounds and compositions. The compounds, compositions, and methods are useful for treating a variety of sEH mediated diseases, including hypertensive, cardiovascular, inflammatory, pulmonary, and diabetic-related diseases.
