Diels–Alder routes to angularly halogenated cis-fused bicyclic ketones: readily accessible cyclynone intermediates

Lee, Jun Hee; Kim, Woo Han

doi:10.1016/j.tetlet.2010.06.135

Cited by 13 publications

(19 citation statements)

References 12 publications

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“…11 This reactivity order was confirmed by performing a set of competition experiments. Under thermal conditions (Table 2, entries 1 and 2), the 2-halocycloalkenones, 12 and 17 , completely dominate the course of the DA reaction with 2,3-dimethyl-1,3-butadiene ( 13 ), providing adducts 15 and 19 in 55% and 69% yield, respectively.…”

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confidence: 66%

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Halocycloalkenones as Diels–Alder Dienophiles. Applications to Generating Useful Structural Patterns

Ross

Townsend

2012

J. Org. Chem.

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Halocycloalkenones are demonstrated to function as potent dienophiles in inter- and intramolecular Diels-Alder cycloadditions. We have found 2-brominated cycloalkenone dienophiles to be both highly endo selective and significantly more reactive than their non-halogenated parent compounds. A method for the facile conversion of brominated cyclobutanone DA adducts to synthetically useful cyclopropyl functional handles is described.

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confidence: 66%

“…Furthermore, the product observed from reaction with 2-bromocyclobutenone featured complete olefin migration. 9 Thus, following standard steroid numbering, the initial Δ 9 (11) cyclohexene double bond isomerized to Δ 8(9) , connecting the B and C rings through a tetrasubstituted olefin.…”

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confidence: 99%

Halocycloalkenones as Diels–Alder Dienophiles. Applications to Generating Useful Structural Patterns

Ross

Townsend

2012

J. Org. Chem.

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“…MeAlCl 2 ) allows for rather efficient Diels–Alder of 2-halo-cyclohex-2-enones and cyclopent-2-enones (Figure 2, 6+7→8 ) 10. The DA chemistry works with a range of dienes.…”

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A Straightforward Route to Functionalized trans-Diels−Alder Motifs

Lee

Zhang

2010

J. Am. Chem. Soc.

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A sequence consisting of Lewis acid-catalyzed Diels-Alder reaction on a 2-halocyclohexenone, followed by reductive alkylation provides a route to trans-fused octalinones bearing angular methyl groups with functionality corresponding to that which would have been possible from trans-directed Diels-Alder reaction.The concept of prioritized strategic bond disconnection (SBD), so well articulated by the Corey school, is clearly the most powerful resource yet devised in guiding retrosynthetic analysis (RSA)1 en route to complex targets. Recently, we have suggested an approach to RSA which is complementary to the paradigm of strategic bond disconnection. We refer to this mode of retrosynthesis as pattern recognition analysis (PRA).2 Here, the thought exercise focuses on identifying domains within the target. Particularly valuable is the identification of patterns which are accessible by doable chemistry. Indeed, the discernment of patterns around which a synthesis might be organized may well provoke the discovery of new reactions or reaction sequences to enable creation of the molecular architecture inherent in the patterns.One of the pillars of PRA is the notion of building cis-fused ring systems via the DielsAlder (DA) reaction.3 In PRA, the DA cycloaddition is more than a specific reaction type. More broadly, it really implies an overall logic, encompassing a variety of post-DA forays. The DA reaction has been a central implement in the field of chemical synthesis, both in the construction of relatively small molecules as well as for rather complex targets. The scope of PRA in synthetic planning would be much enhanced if the overall logic of the DA reaction could be marshalled to produce trans-fused structures. In principle, the ideal solution to this challenge would be to, somehow, change the stereochemical course of the DA reaction such that the cycloaddition event is antarafacial4 (Figure 1 , 2). While speculations about such a fascinating possibility continue, 5 we have been unable to generate any ideas of value along these lines. The next best approach would be to conduct suprafacial DA reactions, with the important caveat that one of the junction substituents may be replaced by another group with overall inversion of configuration (3→5). In that case, a trans junction would become available from the initial DA-derived cis junction. In intermolecular DA reactions, the junction substituents of the product arise from the dienophile. Hence, this type of exercise would require the use of appropriate dienophiles, carrying substituents amenable to inversion of configuration in the context of a hindered ring junction.6We recently reported instances wherein this line of conjecture could be reduced to practice, though in simplified form.7 The key discovery was that in a cis-decalinoid-like structure (3b), free radical-mediated reduction of a bridgehead C-nitro function can be achieved with inversion of configuration (cf. 3b→5b). While this feasibility demonstration was certainly encouraging, all of the function...

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“…The robustness of the methodology was further demonstrated by the inclusion of heteroatoms in the ϵ ‐position. These 4‐hydroxy‐2‐enals displayed higher reactivity and made full conversion at 4 °C possible to obtain the trans ‐ O ‐hetero‐Diels–Alder products 3 h and 3 i in high yields as well as excellent diastereo‐ and enantioselectivities (81–85 %, 20:1 to >20:1 d.r., 98–99 % ee ) [9] …”

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confidence: 99%

A Direct Organocatalytic Enantioselective Route to Functionalizedtrans‐Diels–Alder Products Having the Norcarane Scaffold

et al. 2021

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An enantioselective methodology to construct trans‐Diels–Alder scaffolds by organocatalysis with excellent selectivity, high yield and up to five contiguous stereocenters is presented. The reaction concept integrates the halogen effect and a novel discovered pseudo‐halogen effect to direct an endo‐selective, secondary‐amine catalyzed Diels–Alder reaction allowing for the subsequent formation of trans‐Diels–Alder cycloadducts featuring the norcarene scaffold. The methodology relies on the reaction between an in situ generated trienamine and an α‐brominated or α‐pseudo‐halogenated enone to form a fleeting cis‐Diels–Alder intermediate. The endo‐transition state‐enhanced by the (pseudo‐)halogen effect‐sets the stereochemistry that allows for a subsequent SN2‐like reaction at a tertiary center to obtain the trans‐Diels–Alder scaffold. The mechanism was investigated and supported by experimental results as well as computational studies.

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Diels–Alder routes to angularly halogenated cis-fused bicyclic ketones: readily accessible cyclynone intermediates

Cited by 13 publications

References 12 publications

Halocycloalkenones as Diels–Alder Dienophiles. Applications to Generating Useful Structural Patterns

Halocycloalkenones as Diels–Alder Dienophiles. Applications to Generating Useful Structural Patterns

A Straightforward Route to Functionalized trans-Diels−Alder Motifs

A Direct Organocatalytic Enantioselective Route to Functionalizedtrans‐Diels–Alder Products Having the Norcarane Scaffold

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