505-03-3Relevant academic research and scientific papers
Borane-mediated aldol cycloreduction of monoenone monoketones: Diastereoselective formation of quaternary centers
Huddleston, Ryan R.,Cauble, David F.,Krische, Michael J.
, p. 11 - 14 (2003)
Exposure of monoenone monoketones to catecholborane in THF at ambient temperature results in tandem 1,4-reduction-aldol cyclization. For aromatic and heteroaromatic enones, six-membered cyclic aldol products are formed in excellent yield with high levels of syn diastereoselectivity. Five-membered ring formation proceeds less readily, but the yield of cyclized product is improved through introduction of Rh(I) salts.
Asymmetric sequential allylic transfer strategy for the synthesis of (-)-adaline and (-)-euphococcinine
Lee, Bobin,Kwon, Jisook,Yu, Chan-Mo
, p. 1498 - 1500 (2009)
Enantioselective synthesis of the piperidine alkaloids, (-)-adaline (1) and (-)-euphococcinine (2), were achieved from 7 in a six-step sequence through stepwise allylic transfer reactions. Dramatic additive effect of Bu3SnF for the conversion of 3 into 9 was observed to expedite the process to afford the cyclized products in good yields. Georg Thieme Verlag Stuttgart.
Can a Ketone Be More Reactive than an Aldehyde? Catalytic Asymmetric Synthesis of Substituted Tetrahydrofurans
Lee, Sunggi,Bae, Han Yong,List, Benjamin
supporting information, p. 12162 - 12166 (2018/09/11)
O-heterocycles bearing tetrasubstituted stereogenic centers are prepared via catalytic chemo- and enantioselective nucleophilic additions to ketoaldehydes, in which the ketone reacts preferentially over the aldehyde. Five- and six-membered rings with both aromatic and aliphatic substituents, as well as an alkynyl substituent, are obtained. Moreover, 2,2,5-trisubstituted and 2,2,5,5-tetrasubstituted tetrahydrofurans are synthesized with excellent stereoselectivities. Additionally, the synthetic utility of the described method is demonstrated with a three-step synthesis of the side chain of anhydroharringtonine.
Rhodium-Catalyzed Asymmetric Conjugate Alkynylation/Aldol Cyclization Cascade for the Formation of α-Propargyl-β-hydroxyketones
Choo, Ken-Loon,Lautens, Mark
supporting information, p. 1380 - 1383 (2018/03/09)
A rhodium-catalyzed conjugate alkynylation/aldol cyclization cascade was developed. Densely functionalized cyclic α-propargyl-β-hydroxyketones were synthesized with simultaneous formation of a C(sp)-C(sp3) bond, a C(sp3)-C(sp3) bond, as well as three new contiguous stereocenters. The transformation was achieved with excellent enantio- and diastereoselectivities using BINAP as the ligand. The synthetic utility of the newly installed alkynyl moiety was exhibited by subjecting the products to an array of derivatizations.
Transaminase Triggered Aza-Michael Approach for the Enantioselective Synthesis of Piperidine Scaffolds
Ryan, James,?iau?iulis, Mindaugas,Gomm, Andrew,Maciá, Beatriz,O’Reilly, Elaine,Caprio, Vittorio
supporting information, p. 15798 - 15800 (2016/12/22)
The expanding “toolbox” of biocatalysts opens new opportunities to redesign synthetic strategies to target molecules by incorporating a key enzymatic step into the synthesis. Herein, we describe a general biocatalytic approach for the enantioselective preparation of 2,6-disubstituted piperidines starting from easily accessible pro-chiral ketoenones. The strategy represents a new biocatalytic disconnection, which relies on an ω-TA-mediated aza-Michael reaction. Significantly, we show that the reversible enzymatic process can power the shuttling of amine functionality across a molecular framework, providing access to the desired aza-Michael products.
Palladium-Catalyzed Long-Range Deconjugative Isomerization of Highly Substituted α,β-Unsaturated Carbonyl Compounds
Lin, Luqing,Romano, Ciro,Mazet, Clément
supporting information, p. 10344 - 10350 (2016/08/31)
The long-range deconjugative isomerization of a broad range of α,β-unsaturated amides, esters, and ketones by an in situ generated palladium hydride catalyst is described. This redox-economical process is triggered by a hydrometalation event and is thermodynamically driven by the refunctionalization of a primary or a secondary alcohol into an aldehyde or a ketone. Di-, tri-, and tetrasubstituted carbon-carbon double bonds react with similar efficiency; the system is tolerant toward a variety of functional groups, and olefin migration can be sustained over 30 carbon atoms. The refunctionalized products are usually isolated in good to excellent yield. Mechanistic investigations are in support of a chain-walking process consisting of repeated migratory insertions and β-H eliminations. The bidirectionality of the isomerization reaction was established by isotopic labeling experiments using a substrate with a double bond isolated from both terminal functions. The palladium hydride was also found to be directly involved in the product-forming tautomerization step. The ambiphilic character of the in situ generated [Pd-H] was demonstrated using isomeric trisubstituted α,β-unsaturated esters. Finally, the high levels of enantioselectivity obtained in the isomerization of a small set of α-substituted α,β-unsaturated ketones augur well for the successful development of an enantioselective version of this unconventional isomerization.
Efficient and Selective Cu/Nitroxyl-Catalyzed Methods for Aerobic Oxidative Lactonization of Diols
Xie, Xiaomin,Stahl, Shannon S.
supporting information, p. 3767 - 3770 (2015/04/14)
Cu/nitroxyl catalysts have been identified that promote highly efficient and selective aerobic oxidative lactonization of diols under mild reaction conditions using ambient air as the oxidant. The chemo- and regioselectivity of the reaction may be tuned by changing the identity of the nitroxyl cocatalyst. A Cu/ABNO catalyst system (ABNO = 9-azabicyclo[3.3.1]nonan-N-oxyl) shows excellent reactivity with symmetrical diols and hindered unsymmetrical diols, whereas a Cu/TEMPO catalyst system (TEMPO = 2,2,6,6-tetramethyl-1-piperidinyl-N-oxyl) displays excellent chemo- and regioselectivity for the oxidation of less hindered unsymmetrical diols. These catalyst systems are compatible with all classes of alcohols (benzylic, allylic, aliphatic), mediate efficient lactonization of 1,4-, 1,5-, and some 1,6-diols, and tolerate diverse functional groups, including alkenes, heterocycles, and other heteroatom-containing groups.
Proline-Catalyzed Knoevenagel Condensation/[4+2] Cycloaddition Cascade Reaction: Application to Formal Synthesis of Averufin
Tan, Haibo,Chen, Xinzheng,Chen, Huiyu,Liu, Hongxin,Qiu, Shengxiang
supporting information, p. 4956 - 4963 (2015/08/03)
A remarkable proline-catalyzed method for the construction of biologically interesting oxygen-bridged tricyclic ketal skeletons was uncovered by starting from a variety of readily available cyclic 1,3-diketones and either 1,4- or 1,5-dicarbonyl substrates. The approach, which mimics a biosynthetic Knoevenagel condensation/[4+2] cycloaddition sequence, establishes a viable synthetic strategy for the efficient formal synthesis of averufin. A remarkable proline-catalyzed Knoevenagel condensation/[4+2] cycloaddition cascade reaction was uncovered for the construction of biologically interesting tricyclic ketal skeletons. This approach mimics a biosynthetic sequence and establishes a viable synthetic strategy for the efficient formal synthesis of averufin.
Ready access to functionally embellished cis -hydrindanes and cis -decalins: Protecting group-free total syntheses of (±)-nootkatone and (±)-Noreremophilane
Handore, Kishor L.,Seetharamsingh,Reddy, D. Srinivasa
, p. 8149 - 8154 (2013/09/12)
A simple and efficient synthesis of functionalized cis-hydrindanes and cis-decalins was achieved using a sequential Diels-Alder/aldol approach in a highly diastereoselective manner. The scope of this method was tested with a variety of substrates and was successfully applied to the synthesis of two natural products in racemic form. The highlights of the present work provide ready access to 13 new cis-hydrindanes/cis-decalins, a protecting group-free total synthesis of an insect repellent Nootkatone, and the first synthesis of a Noreremophilane using the shortest sequence.
Pyridine is an organocatalyst for the reductive ozonolysis of alkenes
Willand-Charnley, Rachel,Fisher, Thomas J.,Johnson, Bradley M.,Dussault, Patrick H.
supporting information; experimental part, p. 2242 - 2245 (2012/06/30)
Whereas the cleavage of alkenes by ozone typically generates peroxide intermediates that must be decomposed in an accompanying step, ozonolysis in the presence of pyridine directly generates ketones or aldehydes through a process that neither consumes pyridine nor generates any detectable peroxides. The reaction is hypothesized to involve nucleophile-promoted fragmentation of carbonyl oxides via formation of zwitterionic peroxyacetals.
