1518-20-3Relevant academic research and scientific papers
Chiral cyclopentadienyl RhIII-catalyzed enantioselective cyclopropanation of electron-deficient olefins enable rapid access to UPF-648 and oxylipin natural products
Duchemin, Coralie,Cramer, Nicolai
, p. 2773 - 2777 (2019/03/05)
Chiral cyclopentadienyl RhIII complexes efficiently catalyze enantioselective cyclopropanations of electron-deficient olefins with N-enoxysuccinimides as the C1 unit. Excellent asymmetric inductions and high diastereoselectivities can be obtained for a wide range of substrate combinations. The reaction proceeds under mild conditions without precautions to exclude air and water. Moreover, the synthetic utility of the developed method is demonstrated by concise syntheses of members of the oxylipin natural products family and the KMO inhibitor UPF-648.
Facile construction of three-membered rings via benzyne-promoted Darzens-type reaction of tertiary amines
Xu, Ya-Nan,Tian, Shi-Kai
, p. 1632 - 1638 (2018/12/13)
A range of tertiary amines having electron-withdrawing groups were activated in situ by benzyne, generated from 2-(trimethylsilyl)phenyl triflate and a fluoride source, and participated in the Darzens-type reaction with carbonyl compounds, imines, and vinyl ketones to afford structurally diverse epoxides, aziridines, and cyclopropanes, respectively, in moderate to excellent yields with high trans-selectivity. The reaction involves in situ formation of unstrained ammonium ylides from tertiary amines and benzyne, proceeds in the absence of transition metals and strong bases, and tolerates a wide variety of functional groups.
Stereodivergent Rhodium(III)-Catalyzed cis-Cyclopropanation Enabled by Multivariate Optimization
Piou, Tiffany,Romanov-Michailidis, Fedor,Ashley, Melissa A.,Romanova-Michaelides, Maria,Rovis, Tomislav
supporting information, p. 9587 - 9593 (2018/08/07)
The design of stereodivergent transformations is of great interest to the synthetic community as it allows funneling of a given reaction pathway toward one stereochemical outcome or another by only minor adjustments of the reaction setup. Herein, we present a physical organic approach to invert the sense of induction in diastereoselective cyclopropanation of alkenes with N-enoxyphthalimides through rhodium(III) catalysis. Careful parametrization of catalyst-substrate molecular determinants allowed us to interrogate linear-free energy relationships and establish an intuitive and robust statistical model that correlates an extensive number of data points in high accuracy. Our multivariate correlations-steered mechanistic investigation culminated with a robust and general diastereodivergent cyclopropanation tool where the switch from trans- to cis-diastereoinduction is attributed to a mechanistic dichotomy. Selectivity might be determined by the flexibility of rhodacyclic intermediates derived from ring-opened versus -unopened phthalimides, induced by both their respective ring size and the Sterimol B1 parameter of the CpX ligand on rhodium.
Divergent Synthesis of Cyclopropane-Containing Lead-Like Compounds, Fragments and Building Blocks through a Cobalt Catalyzed Cyclopropanation of Phenyl Vinyl Sulfide
Chawner, Stephen J.,Cases-Thomas, Manuel J.,Bull, James A.
, p. 5015 - 5024 (2017/09/22)
Cyclopropanes provide important design elements in medicinal chemistry and are widely present in drug compounds. Here we describe a strategy and extensive synthetic studies for the preparation of a diverse collection of cyclopropane-containing lead-like compounds, fragments and building blocks exploiting a single precursor. The bifunctional cyclopropane (E/Z)-ethyl 2-(phenylsulfanyl)-cyclopropane-1-carboxylate was designed to allow derivatization through the ester and sulfide functionalities to topologically varied compounds designed to fit in desirable chemical space for drug discovery. A cobalt-catalyzed cyclopropanation of phenyl vinyl sulfide affords these scaffolds on multigram scale. Divergent, orthogonal derivatization is achieved through hydrolysis, reduction, amidation and oxidation reactions as well as sulfoxide–magnesium exchange/functionalization. The cyclopropyl Grignard reagent formed from sulfoxide exchange is stable at 0 °C for > 2 h, which enables trapping with various electrophiles and Pd-catalyzed Negishi cross-coupling reactions. The library prepared, as well as a further virtual elaboration, is analyzed against parameters of lipophilicity (ALog P), MW and molecular shape by using the LLAMA (Lead-Likeness and Molecular Analysis) software, to illustrate the success in generating lead-like compounds and fragments.
Rh(III)-catalyzed cyclopropanation initiated by C-H activation: Ligand development enables a diastereoselective [2 + 1] annulation of N-enoxyphthalimides and alkenes
Piou, Tiffany,Rovis, Tomislav
, p. 11292 - 11295 (2014/09/17)
N-Enoxyphthalimides undergo a Rh(III)-catalyzed C-H activation initiated cyclopropanation of electron deficient alkenes. The reaction is proposed to proceed via a directed activation of the olefinic C-H bond followed by two migratory insertions, first across the electron-deficient alkene and then by cyclization back onto the enol moiety. A newly designed isopropylcyclopentadienyl ligand drastically improves yield and diastereoselectivity.
Cyclopropanation of α,β-Unsaturated Carbonyl Compounds and Nitriles with Diazo Compounds. The nature of the Involvement of Transition-Metal Promoters
Doyle, Michael P.,Dorow, Roberta L.,Tamblyn, William H.
, p. 4059 - 4068 (2007/10/02)
In the presence of molybdenum hexacarbonyl or molybdenum(II) acetate, ethyl diazoacetate and α-diazoacetophenone react with α,β-unsaturated carbonyl compounds and nitriles to form derivative cyclopropane and vinyl CH insertion products.In the absence of these promoters or in the presence of catalytic amounts of pyridine, 2-pyrazolines are the major or sole reaction products.Kinetic investigations for reactions between ethyl diazoacetate and α,β-unsaturated esters and nitriles in the presence of Mo(CO)6, Mo2(OAc)4, or pyridine demonstrate the absence of any significant influence by these molybdenum promoters or pyridine on the rates and activation parameters for ethyl diazoacetate decomposition.Representative 1-pyrazolines have been synthesized and observed to undergo dinitrogen extrusion without apparent influence by molybdenum promoters.The composite results suggest that these molybdenum promoted reactions occur by dipolar cycloaddition of diazocarbonyl compounds to α,β-unsaturated systems and that the derivative 1-pyrazoline intermediates undergo dinitrogen extrusion to form the observed cyclopropane and vinyl CH insertion products.Molybdenum promoters function to inhibit competitive tautomerization of the initially formed cycloaddition products.The relative effectiveness of a broad selection of transition-metal compounds in directing reactions between ethyl diazoacetate and α,β-unsaturated esters and nitriles to cyclopropane products is described.The cycloaddition / dinitrogen extrusion pathway is presented as a viable mechanism for cyclopropanation of α,β-unsaturated systems by diazo compounds, even for reactions performed in the presence of traditional cyclopropanation catalysts.
