Organocatalytic Michael Cycloisomerization of Bis(enones): The Intramolecular Rauhut−Currier Reaction

Wang, Long Cheng; Luis, Ana Liza; Agapiou, Kyriacos; Jang, Hye Young; Krische, Michael J.

doi:10.1021/ja0121686

Cited by 246 publications

(74 citation statements)

References 9 publications

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“…A variety of Rauhut-Currier conditions, which modified both phosphine and solvent, were explored to determine the optimum method for conversion of 3 to 4 ( Table 1). [33][34][35][36] Consistent with previously reported tendencies in the Rauhut-Currier reaction, 32 the relatively more electrophilic alkenes in 3a and 3c, easily underwent tandem conjugate addition/Michael addition and subsequent phosphine elimination to afford the products, 4a and 4c respectively, in high yield. The regioselectivity of the tandem reaction in 3a and 3c is presumably founded on both electronic and steric principles.…”

Section: Methodssupporting

confidence: 82%

“…One pot tandem reactions, such as the RauhutCurrier reaction, are important for the efficient construction of complex chemical structures and therefore are an active research area in the synthetic community. [23][24][25][26][27][28][29][30][31] The intramolecular Rauhut-Currier reaction 32 has experienced a resurgence based on groundbreaking studies by Krische, 33 Murphy, 34,35 and Roush. 36 Under the influence of catalytic phosphine, conjugated systems can be merged to form a new ring while retaining one conjugated system for subsequent functionalization.…”

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confidence: 99%

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Enantioselective synthesis of bicarbocyclic structures with an all-carbon quaternary stereocenter through sequential cross metathesis and intramolecular Rauhut–Currier reaction

Qiao

Kumar

Malachowski

2010

Tetrahedron Letters

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Section: Methodssupporting

confidence: 82%

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confidence: 99%

Enantioselective synthesis of bicarbocyclic structures with an all-carbon quaternary stereocenter through sequential cross metathesis and intramolecular Rauhut–Currier reaction

Qiao

Kumar

Malachowski

2010

Tetrahedron Letters

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“…Although almost certainly reversible, such a site-selective, intermolecular conjugate addition reaction could trigger an intramolecular conjugate addition (see arrows in 4), resulting in the production of a key carbon-carbon bond and the carbocyclic ring of (ϩ)-harziphilone (for selected tandem conjugate addition͞Michael cyclization reactions see refs. [12][13][14][15][16][17]. A ␤-elimination of the heteroatom nucleophile might then generate 3 and set the stage for a final cycloisomerization to (ϩ)-harziphilone (2; P ϭ H).…”

mentioning

confidence: 99%

A nucleophile-catalyzed cycloisomerization permits a concise synthesis of (+)-harziphilone

Stark

Pekari

Sorensen

2004

Proc. Natl. Acad. Sci. U.S.A.

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Substantial structural transformations of much use in complex chemical synthesis can be achieved by channeling the reactivity of highly unsaturated molecules. This report describes the direct conversion of an acyclic polyunsaturated diketone to the HIV-1 Rev͞Rev-responsive element inhibitor harziphilone under mild reaction conditions. nucleophilic catalysis ͉ Baylis-Hillman reaction ͉ conjugate additions ͉ electrocyclizations ͉ domino reactions T he reactivity of activated polyenes is the basis for some of the most impressive structural transformations in nature and chemical synthesis. The biosyntheses of the complex structures of the polycyclic triterpenes from squalene and 2,3-oxidosqualene may be viewed as paragons for processes that build polycyclic molecular complexity directly from reactive polyenes (1-3). In connection with our efforts to channel the reactivity of activated polyunsaturated molecules, we sought mild reaction conditions under which compound 1 could be isomerized to the bicyclic structure of harziphilone (2), a naturally occurring inhibitor of the binding interaction between the HIV-1 Rev protein and the Rev-responsive element (RRE) of viral mRNA (4) (Scheme 1). This report describes an enantioselective synthesis of (ϩ)-harziphilone based on the general idea expressed in Scheme 1.The structure of (ϩ)-harziphilone (2) comprises fifteen carbon atoms, two six-membered ring systems, one carbocyclic and the other heterocyclic, a keto group, two contiguous hydroxylbearing stereocenters, and a pentadienyl side chain. All of the polar groupings of harziphilone are confined to the sixmembered carbocycle, whereas the hydrophobic pentadienyl moiety is displayed as a side chain on the ␣-pyran ring. Our approach to the problem of synthesizing this natural product was guided by the retrosynthetic analysis shown in Scheme 2.The independent early investigations of Büchi (5) and Marvell (6, 7) provided a sound basis for the proposal that the oxacyclic ring of harziphilone, with its particular arrangement of alkenes, could arise by a 6 -electrocyclization of a compound of type 3 (for selected examples of this type of valence isomerization in synthesis see refs. 8-11). With several electrophilic sites and a high degree of unsaturation, 3 was perceived to be a challenging objective for synthesis, and we elected to explore the possibility of producing this potentially transient intermediate in situ from a doubly activated, polyunsaturated acyclic compound of type 1. To implement this concept, we would seek a suitable heteroatom nucleophile that could attack the unsubstituted enone moiety in 1. Although almost certainly reversible, such a site-selective, intermolecular conjugate addition reaction could trigger an intramolecular conjugate addition (see arrows in 4), resulting in the production of a key carbon-carbon bond and the carbocyclic ring of (ϩ)-harziphilone (for selected tandem conjugate addition͞Michael cyclization reactions see refs. 12-17). A ␤-elimination of the heteroatom nucleophile might then genera...

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“…The Rauhut-Currier reaction is a hydrocarbation of an activated alkene with the α-C-H moiety of an activated alkene. Small trialkylphosphines are superior to amine nucleophiles such as DABCO, DBU, Et2NH and DMAP (4-Me2N-pyridine) [374][375][376]. The Rauhut-Currier reaction applied to allene esters and 2-phenylethylene-1,1-dicarbonitrile generates cyclohexene derivatives.…”

Section: The Rauhut-currier Reactionmentioning

confidence: 99%

Organocatalysis: Fundamentals and Comparisons to Metal and Enzyme Catalysis

et al. 2016

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Catalysis fulfills the promise that high-yielding chemical transformations will require little energy and produce no toxic waste. This message is carried by the study of the evolution of molecular catalysis of some of the most important reactions in organic chemistry. After reviewing the conceptual underpinnings of catalysis, we discuss the applications of different catalysts according to the mechanism of the reactions that they catalyze, including acyl group transfers, nucleophilic additions and substitutions, and C-C bond forming reactions that employ umpolung by nucleophilic additions to C=O and C=C double bonds. We highlight the utility of a broad range of organocatalysts other than compounds based on proline, the cinchona alkaloids and binaphthyls, which have been abundantly reviewed elsewhere. The focus is on organocatalysts, although a few examples employing metal complexes and enzymes are also included due to their significance. Classical Brønsted acids have evolved into electrophilic hands, the fingers of which are hydrogen donors (like enzymes) or other electrophilic moieties. Classical Lewis base catalysts have evolved into tridimensional, chiral nucleophiles that are N-(e.g., tertiary amines), P-(e.g., tertiary phosphines) and C-nucleophiles (e.g., N-heterocyclic carbenes). Many efficient organocatalysts bear electrophilic and nucleophilic moieties that interact simultaneously or not with both the electrophilic and nucleophilic reactants. A detailed understanding of the reaction mechanisms permits the design of better catalysts. Their construction represents a molecular science in itself, suggesting that sooner or later chemists will not only imitate Nature but be able to catalyze a much wider range of reactions with high chemo-, regio-, stereo-and enantioselectivity. Man-made organocatalysts are much smaller, cheaper and more stable than enzymes.

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Organocatalytic Michael Cycloisomerization of Bis(enones): The Intramolecular Rauhut−Currier Reaction

Cited by 246 publications

References 9 publications

Enantioselective synthesis of bicarbocyclic structures with an all-carbon quaternary stereocenter through sequential cross metathesis and intramolecular Rauhut–Currier reaction

Enantioselective synthesis of bicarbocyclic structures with an all-carbon quaternary stereocenter through sequential cross metathesis and intramolecular Rauhut–Currier reaction

A nucleophile-catalyzed cycloisomerization permits a concise synthesis of (+)-harziphilone

Organocatalysis: Fundamentals and Comparisons to Metal and Enzyme Catalysis

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