Asymmetric Access to the Smallest Enolate Intermediate via Organocatalytic Activation of Acetic Ester

Chen, Shaojin; Hao, Lin; Zhang, Yuexia; Tiwari, Bhoopendra; Robin, Yonggui

doi:10.1021/ol402877n

Cited by 85 publications

(25 citation statements)

References 71 publications

(17 reference statements)

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“…[139][140][141] Through the formation of acyl azolium intermediates with the esters, chiral NHCs 352, 353, 354,a nd 355 could activate the a-C of 346,w hich then underwent domino Michael/cyclization reactions with a,b-unsaturated substrates to yield the desired productsi ng ood to high stereoselectivities.As imilarN HC-catalyzed domino reactiono f 346 with the isatin-derived a,b-unsaturated imine 351 providedaspirooxindole 350 in am oderate yield and stereoselectivity. [142] They furtheru tilized the chiral NHC catalyst 358 to functionalize the inert b-sp 3 carbon of saturated esters 356.…”

Section: Esters As Substratesmentioning

confidence: 99%

Recent Progress in Organocatalytic Asymmetric Domino Transformations

2017

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Sustainability in chemical synthesis is a major aspect of the current synthetic endeavors and, therefore,m imicking the biological process in the laboratory nowadays has the highest priority.T owards achieving this goal, designingorganic reactions in domino mode rathert han the multistep synthetic pathways andu sing organocatalysisi nstead of metal catalysis have received al ot of attention due to the inherenta dvantageso ft hese processes in terms of synthetic efficiencya nd sustainability.A saresult, the field of asymmetric organocatalytic domino reactions has witnessed tremendous progress in recent years.T his review attempts to summarize the latest developments in asymmetric organocatalyzed domino reactions since 2012, with the emphasis on the catalysts andr eactionm odes.D iscussions on the reactionm echanismsa nd the applications of the developed domino reactionm ethodsi nt he synthesis of biologically active molecules and natural products are also includedwhen appropriate.

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Section: Esters As Substratesmentioning

confidence: 99%

Recent Progress in Organocatalytic Asymmetric Domino Transformations

2017

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“…21 This resulted in the formation of a single diastereoisomer of epoxide 52, containing four contiguous stereocentres (Scheme 10). The relative and absolute stereochemistry of 52 was confirmed through X-ray crystallography.…”

Section: Derivatisation Of the Dihydropyridinone Corementioning

confidence: 99%

“…20 While all attempts at homo-or heterogeneous hydrogenation of the C-5,6 double bond in 8 to form the 2-piperidone returned only starting material, epoxidation was successful with m-CPBA. 21 This resulted in the formation of a single diastereoisomer of epoxide 52, containing four contiguous stereocentres (Scheme 10). The relative and absolute stereochemistry of 52 was confirmed through X-ray crystallography.…”

Section: Derivatisation Of the Dihydropyridinone Corementioning

confidence: 99%

Exploring the scope of the isothiourea-mediated synthesis of dihydropyridinones

et al. 2015

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The exploration and expansion of the scope of the isothiourea-mediated synthesis of dihydropyridinones is presented. The use of ketimines derived from α,β-unsaturated γ-ketoesters as the Michael acceptor in a Michael addition / lactamisation cascade gives access to a range of dihydropyridinones with high enantioselectivity. The nature of the N-sulfonyl group present on the ketimine is extensively investigated, with further studies into derivatisation of the dihydropyridinone core also reported. IntroductionThe direct organocatalytic asymmetric functionalisation of readily available, bench-stable carboxylic acids 1 towards valueadded products has received much attention since the seminal report by Romo and co-workers in 2001 on the intramolecular nucleophile-catalysed aldol / lactonisation (NCAL) reaction (Scheme 1). 2 Further work from the Romo group has demonstrated the utility of ammonium and isothiouronium enolates generated from carboxylic acids in the stereoselective synthesis of β-lactones, 3 including the application to the total synthesis of (+)-omphadiol 3j 1 and (−)-curcumalactone 2 (Scheme 1), amongst others. 3l Scheme 1 Romo and co-wokers' intramolecular NCAL reaction 2 and select examples of natural products accessed using this reaction. 3j,3lWe have previously explored the scope of the intramolecular reactions of ammonium and isothiouronium enolates, 4 allowing access to dihydrobenzofurans, 5 2H-indenes, 5a THFs, 5b as well as pyrrolidines. Our previous synthesis of dihydropyridinones reacted isothiouronium enolates generated from carboxylic acids with N-tosyl chalcone-derived ketimines in a Michael addition / lactamisation cascade (Scheme 2a). 9 This afforded a range of dihydropyridinones in high yields and excellent stereoselectivity. In this methodology the N-tosyl substituent was employed exclusively in the ketimine Michael acceptor. Furthermore, the use of chalcones as the backbone of the ketimine, alongside the requirement for aryl or heteroaryl acetic acids, resulted in dihydropyridinones furnished with three (hetero)aryl substituents thereby constraining the scope of the hetercyclic products. To extend these studies, alternative ketimine backbones incorporating more versatile functional handles, whilst maintaining the reactivity of the Michael acceptor were explored. Herein we report the successful incorporation of ketimines derived from α,β-unsaturated γ-ketoesters within this ARTICLE Journal Name 2 | J. Name., 2012, 00, 1-3 This journal is © The Royal Society of Chemistry 2012Scheme 2 Organocatalytic synthesis of dihydropyridinones methodology, 10,13 affording dihydropyridinone products containing ester substituents as functional handles (Scheme 2b). Extensive exploration of the sulfonyl substituent and the potential for derivatisation of the dihydropyridinone core is also described. Results and Discussion OptimisationInitial studies showed that α,β-unsaturated γ-ketimine ester 6 was a competent electrophile for intermolecular Michael addition / lactamisation with the isothiouronium en...

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“…Enolate chemistry, on the other hand, is favoured by triazolium precatalysts in combination with weak bases 3,4. Azolium enolates have been generated by the combination of NHCs with ketenes,13 aldehydes,3a,14 and esters 15. Reactions proceeding via the azolium enolate pathway have been used to provide β-lactams,13b,c β-lactones,13d,e unsaturated δ-lactams,14b,f,15b,c and unsaturated δ-lactones 14a,14e–g,15c…”

Section: Introductionmentioning

confidence: 99%