Tandem Radical Cyclizations: a One-Step Synthesis of Stereoisomeric Tricyclo[6.3.0.02,6]undecanes From Acyclic Precursors

1995 ◽  
Vol 48 (2) ◽  
pp. 261 ◽  
Author(s):  
DP Curran ◽  
SN Sun
Keyword(s):  
Radical Cyclization ◽  
Radical Cyclizations ◽  
Low Concentration ◽  
One Step

Radical cyclization of (1E,5Z)-1-iodoundeca-1,5,10-triene with triphenyltin hydride provides one acyclic, one monocyclic, two bicyclic and four tricyclic products. At low concentration (0.002 M), the title tricycloundecane products resulting from triple cyclization predominate, but the stereoselectivity is low. Cyclization of (1E,5Z)-1-iodo-8,8-bis( phenylsulfonyl )undeca-1,5,10-triene followed by reductive desulfonylation provides a similar ratio of products to the parent. The results show that this class of triple cyclization occurs well, but the level of stereoselectivity must be raised for it to become synthetically useful.

scholarly journals Activation modes in biocatalytic radical cyclization reactions

2021 ◽  
Author(s):  
Yuxuan Ye ◽  
Haigen Fu ◽  
Todd K Hyster
Keyword(s):  
Heme Iron ◽  
Radical Cyclization ◽  
Cytochrome P450 Monooxygenases ◽  
Radical Cyclizations ◽  
Cyclization Reactions ◽  
Complex Molecules ◽  
P450 Monooxygenases ◽  
Non Heme Iron ◽  
Essential Reactions ◽  
Isopenicillin N

Abstract Radical cyclizations are essential reactions in the biosynthesis of secondary metabolites and the chemical synthesis of societally valuable molecules. In this review, we highlight the general mechanisms utilized in biocatalytic radical cyclizations. We specifically highlight cytochrome P450 monooxygenases (P450s) involved in the biosynthesis of mycocyclosin and vancomycin, non-heme iron- and α-ketoglutarate-dependent dioxygenases (Fe/αKGDs) used in the biosynthesis of kainic acid, scopolamine, and isopenicillin N, and radical S-adenosylmethionine (SAM) enzymes that facilitate the biosynthesis of oxetanocin A, menaquinone, and F420. Beyond natural mechanisms, we also examine repurposed flavin-dependent ‘ene’-reductases (ERED) for non-natural radical cyclization. Overall, these general mechanisms underscore the opportunity for enzymes to augment and enhance the synthesis of complex molecules using radical mechanisms.

Copper(i)-catalyzed 5-exo-trig radical cyclization/borylation of alkyl halides: access to functionalized pyrrolidine derivatives

2017 ◽  
Vol 15 (40) ◽  
pp. 8508-8512 ◽  
Author(s):  
Jie Cui ◽  
Hui Wang ◽  
Jian Song ◽  
Xiaochen Chi ◽  
Long Meng ◽  
...  
Keyword(s):  
Radical Cyclization ◽  
Alkyl Halides ◽  
One Step

This work reports the copper(i)-catalyzed 5-exo-trigradical cyclization/borylation of alkyl halides bearing an alkene moiety, during which a C–C bond and a C–B bond were formed in one step.

Oxidative radical cyclization to pyrroles under reducing conditions. Reductive desulfonylation of α-sulfonylpyrroles with tri-n-butyltin hydride

1994 ◽  
Vol 72 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Yulia Antonio ◽  
Ma. Elizabeth De La Cruz ◽  
Edvige Galeazzi ◽  
Angel Guzman ◽  
Brian L. Bray ◽  
...  
Keyword(s):  
Radical Addition ◽  
Radical Cyclization ◽  
Radical Cyclizations ◽  
Deuterium Labelling ◽  
Sulfonyl Group ◽  
Reducing Conditions ◽  
Oxidative Radical Cyclization

1-(2-Bromobenzyl)-2-alkanesulfonylpyrroles (1c, 1d) and 1-(4-bromobutyl)-2-methylsulfonfylpyrrols (8) undergo oxidative radical cyclization with partial or complete reductive desulfonylation to the pyrrolizidine derivatives 5 and 9 by an AIBN initiated reaction with tri-n-butyltin hydride. These cyclizations are suggested to proceed via a pseudo SRN1 process involving radical addition to the α position of the pyrrole nucleus not bearing the sulfonyl group. Reductive removal of the alkylsulfonyl moiety is proposed to occur in a second process after completion of the oxidative radical cyclization. The site of the radical addition is supported by deuterium labelling studies. Consistent with the timing of the loss of the sulonyl group is that 2-alkysulfonylpyrroles 11 are reductively desulfonylated under the same conditions that effect the oxidative radical cyclizations.

scholarly journals Asymmetric Redox-Neutral Radical Cyclization Catalyzed by Flavin-Dependent ‘Ene’-Reductases

2019 ◽  
Author(s):  
Michael Black ◽  
Kyle F. Biegasiewicz ◽  
Andrew J. Meichan ◽  
Daniel G. Oblinsky ◽  
bryan kudish ◽  
...  
Keyword(s):  
Ground State ◽  
Radical Cyclization ◽  
Radical Cyclizations ◽  
Single Electron Transfer ◽  
Mechanistic Studies ◽  
Neutral Radical ◽  
Bond Forming ◽  
Substrate Reduction ◽  
Reaction Proceeds ◽  
Transfer Mechanisms

<p>Flavin-dependent ‘ene’-reductases (EREDs) are exquisite catalysts for effecting stereoselective reductions. While these reactions typically proceed through a hydride transfer mechanism, we recently found that EREDs can also catalyze reductive dehalogenations and cyclizations via single electron transfer mechanisms. Here we demonstrate that these enzymes can catalyze redox-neutral radical cyclizations to produce enantioenriched oxindoles from a-haloamides. This transformation is a C–C bond forming reaction currently unknown in nature and one for which there are no catalytic asymmetric examples. Mechanistic studies indicate the reaction proceeds via the flavin semiquinone/quinone redox couple, where ground state flavin semiquinone provides the electron for substrate reduction and flavin quinone oxidizes the vinylogous a-amido radical formed after cyclization. This mechanistic manifold was previously unknown for this enzyme family, highlighting the versatility of EREDs in asymmetric synthesis.</p>

scholarly journals Evidence for a Radical Mechanism in Cu(II)-Promoted SnAP Reactions

Synlett ◽  
2019 ◽  
Vol 30 (04) ◽  
pp. 464-470 ◽  
Author(s):  
Michael Luescher ◽  
Jeffrey Bode
Keyword(s):  
Nitrogen Heterocycles ◽  
Radical Cyclization ◽  
Bioactive Molecules ◽  
Current Understanding ◽  
Radical Mechanism ◽  
Radical Trapping ◽  
Wide Range ◽  
Aldehydes And Ketones ◽  
One Step ◽  
Radical Clock

Saturated nitrogen heterocycles can be found with increasing abundance in bioactive molecules despite a limited number of methods to access these scaffolds. However, the coupling of recently introduced SnAP [tin (Sn) amine protocol] reagents with a wide range of aldehydes and ketones has proven to be a reliable, practical, and versatile one-step approach to saturated N-heterocycles. While effective, the lack of mechanistic understanding limits efforts to develop new catalytic and enantioselective variants. To distinguish between a polar or radical mechanism, we assessed Lewis and Brønsted acids, radical trapping experiments, and radical clock SnAP reagents reinforcing the current understanding of the SnAP protocol as a radical cyclization.

Total Synthesis of (+)-Mintlactone and (–)-Isomintlactone via SmI2-Induced Radical Cyclization

Synlett ◽  
2017 ◽  
Vol 28 (13) ◽  
pp. 1660-1662 ◽  
Author(s):  
Dian He ◽  
Zhen Wang ◽  
Xiaodong Wang ◽  
Huihong Wang ◽  
Xia Wu ◽  
...  
Keyword(s):  
Transition State ◽  
Total Synthesis ◽  
Natural Product ◽  
Radical Cyclization ◽  
One Step

A divergent strategy has been used to concisely and efficiently complete the synthesis of (+)-mintlactone and (–)-isomintlactone via SmI2-induced intramolecular radical cyclization, two rings and a stereocenter were constructed in one step. In the synthesis, the stereochemistry of the final natural product is set relative to the stereocenter of (–)-citronellol and favored coordination transition state of samarium atom with substrate.

scholarly journals Asymmetric Redox-Neutral Radical Cyclization Catalyzed by Flavin-Dependent ‘Ene’-Reductases

2019 ◽  
Author(s):  
Michael Black ◽  
Kyle F. Biegasiewicz ◽  
Andrew J. Meichan ◽  
Daniel G. Oblinsky ◽  
bryan kudish ◽  
...  
Keyword(s):  
Ground State ◽  
Radical Cyclization ◽  
Radical Cyclizations ◽  
Single Electron Transfer ◽  
Mechanistic Studies ◽  
Neutral Radical ◽  
Bond Forming ◽  
Substrate Reduction ◽  
Reaction Proceeds ◽  
Transfer Mechanisms

<p>Flavin-dependent ‘ene’-reductases (EREDs) are exquisite catalysts for effecting stereoselective reductions. While these reactions typically proceed through a hydride transfer mechanism, we recently found that EREDs can also catalyze reductive dehalogenations and cyclizations via single electron transfer mechanisms. Here we demonstrate that these enzymes can catalyze redox-neutral radical cyclizations to produce enantioenriched oxindoles from a-haloamides. This transformation is a C–C bond forming reaction currently unknown in nature and one for which there are no catalytic asymmetric examples. Mechanistic studies indicate the reaction proceeds via the flavin semiquinone/quinone redox couple, where ground state flavin semiquinone provides the electron for substrate reduction and flavin quinone oxidizes the vinylogous a-amido radical formed after cyclization. This mechanistic manifold was previously unknown for this enzyme family, highlighting the versatility of EREDs in asymmetric synthesis.</p>

NO3• Induced Self-Terminating Radical Oxygenations: Diastereoselective Synthesis of Anellated Pyrrolidines

2004 ◽  
Vol 57 (11) ◽  
pp. 1055 ◽  
Author(s):  
Arne Stademann ◽  
Uta Wille
Keyword(s):  
Nitrogen Atom ◽  
Radical Cyclization ◽  
Radical Cyclizations ◽  
Diastereoselective Synthesis ◽  
Reaction Sequence ◽  
Complex Interplay ◽  
Pyrrolidine Ring ◽  
Substitution Pattern ◽  
Nitrate Radicals ◽  
Oxidative Radical Cyclization

Anellated pyrrolidines 19–22 were obtained through a diastereoselective self-terminating, oxidative radical cyclization cascade by treating the cis-cyclopentyl substituted alkynyl amines 14–18 with photochemically generated nitrate radicals, NO3●. A fast and modular access to the starting materials 14–18 was developed, which readily enables variation of the substitution pattern at the pyrrolidine ring formed upon radical cyclization. The diastereoselectivity of this reaction sequence was found to be strongly influenced by the nature of the substituents at the nitrogen atom. This shows that a complex interplay of both steric and stereoelectronic effects orchestrates the stereoselectivity of 5-exo radical cyclizations of highly substituted radicals.

Sign in / Sign up

Export Citation Format

Share Document