Organocatalytic Enantioselective Cycloaddition Reactions of Dienamines with Quinones

Johansen, Tore Kiilerich; Gómez, Clarisa Villegas; Bak, Jesper R.; Davis, Rebecca L.; Jørgensen, Karl Anker

doi:10.1002/chem.201303526

Cited by 45 publications

(16 citation statements)

References 43 publications

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“…In a related study, Jørgensen et al described the intermolecular [4+2]-cycloaddition reaction between quinone derivatives 116 and β-disubstituted enals 115 ( Scheme 31 ). 46 The reaction tolerated different substituents at the β-position of the enals. Based on DFT calculations, the authors found that the Diels–Alder reaction proceeded in a two-step manner with endo -selectivity due to a favourable electrostatic interaction in the formed zwitterionic intermediate.…”

Section: 5-reactivity: [4+2]-diels–alder Cycloadditions Of Electronmentioning

confidence: 99%

Old tricks, new dogs: organocatalytic dienamine activation of α,β-unsaturated aldehydes

2016

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Section: 5-reactivity: [4+2]-diels–alder Cycloadditions Of Electronmentioning

confidence: 99%

Old tricks, new dogs: organocatalytic dienamine activation of α,β-unsaturated aldehydes

2016

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“…Indeed, computational studies revealed a kinetically controlled [4+2] Diels−Alder reaction pathway with interactions in the product iminium ion transition state controlling the stereochemical outcome of the reaction. 2,6 In the case of diethyl azodicarboxylate (DEAD) as electrophile, a downstream isomerization of the double bond in the product was proposed to be responsible for the synthetically observed γfunctionalized unsaturated aldehydes. 2,32 For other [4+2] cycloadditions of dienamines, the higher stabilization of the zwitterionic endo-iminium intermediate and the corresponding reaction pathway was identified to be responsible for the high stereoselectivity.…”

Section: ■ Introductionmentioning

confidence: 99%

Remote-Stereocontrol in Dienamine Catalysis: Z-Dienamine Preferences and Electrophile–Catalyst Interaction Revealed by NMR and Computational Studies

et al. 2016

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Catalysis with remote-stereocontrol provides special challenges in design and comprehension. One famous example is the dienamine catalysis, for which high ee values are reported despite insufficient shielding of the second double bond. Especially for dienamines with variable Z/E-ratios of the second double bond, no correlations to the ee values are found. Therefore, the structures, thermodynamics, and kinetics of dienamine intermediates in SN-type reactions are investigated. The NMR studies show that the preferred dienamine conformation provides an effective shielding if large electrophiles are used. Calculations at SCS-MP2/CBS-level of theory and experimental data of the dienamine formation show kinetic preference for the Z-isomer of the second double bond and a slow isomerization toward the thermodynamically preferred E-isomer. Modulations of the rate-determining step, by variation of the concentration of the electrophile, allow the conversion of dienamines to be observed. With electrophiles, a faster reaction of Z- than of E-isomers is observed experimentally. Calculations corroborate these results by correlating ee values of three catalysts with the kinetics of the electrophilic attack and reveal the significance of CH-π and stacking interactions in the transition states. Thus, for the first time a comprehensive understanding of the remote stereocontrol in γ-functionalization reactions of dienamines and an explanation to the "Z/E-dilemma" are presented. The combination of bulky catalyst subsystems and large electrophiles provides a shielding of one face and causes different reactivities of E/Z-dienamines in nucleophilic attacks from the other face. Kinetic preferences for the formation of Z-dienamines and their unfavorable thermodynamics support high ee values.

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“…This core structure is found in compounds of the Withanolide family such as Salpichrolides and Nicandrenon 29. 2,6‐Dimethylbenzoquinone ( 10 a ) was found to react with the enals 1 d , e to form their respective products 11 a , b in high yields and excellent stereoselectivities in the presence of 5 mol % of the catalyst 3 18e. 30 By the employment of 2,5‐dimethylbenzoquinone ( 10 b ) and menadione ( 10 c ) excellent results were also achieved ( 11 c , d ).…”

Section: Methodsmentioning

confidence: 96%

Organocatalytic Asymmetric Formation of Steroids

et al. 2014

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A novel and simple one-step approach for the construction of optically active steroids in a highly stereoselective manner by using organocatalysis is presented. The reaction of (di)enals with cyclic dienophiles in the presence of a TMS-protected prolinol catalyst leads to the construction of important 14 β-steroids. This new reaction allows an easy access to optically active steroids with a variety of substituents in the A ring in high yields and up to greater than 99 % ee. The reaction has been extended to include the construction of B- and D-homosteroids as well as steroids containing heteroatoms in the B ring. The angular substituent at C13 can be varied and alkyl, ester, and sulfone functionalities are introduced with excellent stereoselectivities. Simple synthetic procedures provide access to a range of naturally occurring steroids such as estrone and related analogues.

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Organocatalytic Enantioselective Cycloaddition Reactions of Dienamines with Quinones

Cited by 45 publications

References 43 publications

Old tricks, new dogs: organocatalytic dienamine activation of α,β-unsaturated aldehydes

Old tricks, new dogs: organocatalytic dienamine activation of α,β-unsaturated aldehydes

Remote-Stereocontrol in Dienamine Catalysis: Z-Dienamine Preferences and Electrophile–Catalyst Interaction Revealed by NMR and Computational Studies

Organocatalytic Asymmetric Formation of Steroids

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