Direct Transformation of Simple Enals to 3,4‐Disubstituted Benzaldehydes under Mild Reaction Conditions via an Organocatalytic Regio‐ and Chemoselective Dimerization Cascade

Song, Xixi; Zhang, Xinshuai; Zhang, Shilei; Li, Hao; Wang, Wei

doi:10.1002/chem.201201709

Cited by 13 publications

(7 citation statements)

References 30 publications

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“…The dimerized product was obtained in 58 % yield, and its structure was identified by NMR spectroscopy. The formation of this aromatized product for 2C occurs because of the transformation of the iminium ion to an enamine at room temperature …”

Section: Resultsmentioning

confidence: 99%

Enantioselective 1,3‐Dipolar Cycloaddition Reactions of C‐Carboxy Ketonitrones and Enals with MacMillan Catalysts: Evidence of a Nonconcerted Mechanism

et al. 2017

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Highly diastereo‐ and enantioselective 1,3‐dipolar cycloadditions between functional ketonitrones and β‐substituted enals are promoted by MacMillan imidazolidinium organocatalysts. A study of the reaction scope shows that high selectivities are conserved if the N‐protecting group or the ester function is varied. However, the reaction is sensitive to steric interactions with the C substituent of the nitrone. In all cases, the reaction proceeds with high exo selectivity. In most cases, a third diastereomer, incompatible with a concerted mechanism, was also observed, albeit in minute amounts. DFT calculations suggest that the cycloaddition proceeds in a nonconcerted fashion by an initial oxa‐Michael‐type addition of the nitrone to the double bond followed by a cyclization. This mechanism explains the formation of the observed minor diastereomers. In addition, the diastereo‐ and enantioselectivities of the reaction were shown to be intermediately thermodynamically controlled, and the diastereomeric ratio is modulated by the kinetics of iminium hydrolysis.

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Section: Resultsmentioning

confidence: 99%

Enantioselective 1,3‐Dipolar Cycloaddition Reactions of C‐Carboxy Ketonitrones and Enals with MacMillan Catalysts: Evidence of a Nonconcerted Mechanism

et al. 2017

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“…Surprisingly, a 90% selectivity of p-MBA was obtained with a yield of 90% and a formation rate of 0.33 mmol p-MBA mmol cat. À1 h À1 , which is about six times of the report (using 2-butenal as reactants, Hong et al, 2006;Song et al, 2012). Notably, the ratio of p-MBA to o-MBA is up to 30 (see Table S1), which is more than two orders of magnitude higher than the literature (Moteki et al, 2016;Wang et al, 2019).…”

Section: Ll Open Accessmentioning

confidence: 62%

“…Organic amines, such as tetrahydropyrrole (THP) and its derivatives, could catalyze enals to yield p- methyl benzaldehyde derivatives ( Hong et al., 2006 , 2007 ; Song et al., 2012 ), although the reaction intermediates and mechanism have not been investigated. Furthermore, the system that can directly catalyze the self-condensation of acetaldehyde and then, aromatize enal intermediates to para -aromatic aldehydes has not been reported yet.…”

Section: Introductionmentioning

confidence: 99%

Direct synthesis of p-methyl benzaldehyde from acetaldehyde via an organic amine-catalyzed dehydrogenation mechanism

et al. 2021

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Summary p -Methyl benzaldehyde ( p -MBA) is a class of key chemical intermediates of pharmaceuticals. Conventional industrial processes for p -MBA production involve the consecutive photochlorination, amination, and acid hydrolysis of petroleum-derived p -xylene, while producing vast pollutants and waste water. Herein, we report a direct, green route for selective synthesis of p -MBA from acetaldehyde using a diphenyl prolinol trimethylsilyl ether catalyst. The optimized p -MBA selectivity is up to 90% at an acetaldehyde conversion as high as 99.8%. Intermediate structure and 18 O-isotope data revealed that the conversion of acetaldehyde to p -methylcyclohexadienal intermediates proceeds in an enamine-iminium intermediate mechanism. Then, controlled experiments and D-isotope results indicated that the dehydrogenation of p -methylcyclohexadienal to p -MBA and H 2 is catalyzed by the same amines through an iminium intermediate. This is an example that metal-free amines catalyze the dehydrogenation (releasing H 2 ), rather than using metals or stoichiometric oxidants.

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“…Further study showed that an unprecedented organocatalytic Michael-aldol aromatization cascade occurred involving a dienamineiminium occurred in the reaction, without requiring an additional oxidant (Scheme 22). [49] In 2014, Sparr and co-workers reported a novel synthetic strategy for the atroposelective preparation of unsymmetrically substituted 1,1'-binaphthalene-2-carbaldehydes 108 by secondary amine-catalyzed (3 + 3) benzannulation (Scheme 23). [50] The experiments showed when the tertiary amine catalyst (such as MacMillan imidazolidinones) was used, the desired products were obtained in the absence of atroposelectivity, which suggested that competing general-base catalysis is operational.…”

Section: Secondary Amine-catalyzed Benzannulation Reactionsmentioning

confidence: 99%

Recent Advances in Organocatalyst‐Mediated Benzannulation Reactions

2020

Adv Synth Catal

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Aromatic compounds are omnipresent in organic chemistry, which are the broadest skeletons of bioactive molecules, medicines, and materials. Due to their importance, conventional methods to assemble aromatic rings have attracted considerable attention. The direct formation of benzene cores from readily available acyclic precursors offers a highly versatile and superior approach to prepare both small organic molecules and sophisticated natural products. Recently, organocatalyst-mediated annulation reaction, including phosphine-, tertiary amine-, secondary amine-, primary amine-, and NHC-mediated benzannulation reactions, is considered as an efficient method to access multi-substituted arenes. In this review, we will emphasize the selected examples of organocatalyst-mediated benzannulation reactions of available acyclic precursors for the construction of diverse aromatics.

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Direct Transformation of Simple Enals to 3,4‐Disubstituted Benzaldehydes under Mild Reaction Conditions via an Organocatalytic Regio‐ and Chemoselective Dimerization Cascade

Abstract: COMMUNICATIONScheme 4. A proposed reaction mechanism for the formation of benzaldehydes 2.Scheme 5. Transformation of two key intermediates 16 and 17 to benzaldehydes. In the proposed reaction mechanism, this involves Michaelaldol aromatization (see Scheme 4).

Cited by 13 publications

References 30 publications

Enantioselective 1,3‐Dipolar Cycloaddition Reactions of C‐Carboxy Ketonitrones and Enals with MacMillan Catalysts: Evidence of a Nonconcerted Mechanism

Enantioselective 1,3‐Dipolar Cycloaddition Reactions of C‐Carboxy Ketonitrones and Enals with MacMillan Catalysts: Evidence of a Nonconcerted Mechanism

Direct synthesis of p-methyl benzaldehyde from acetaldehyde via an organic amine-catalyzed dehydrogenation mechanism

Recent Advances in Organocatalyst‐Mediated Benzannulation Reactions

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