Computational Insights into the Central Role of Nonbonding Interactions in Modern Covalent Organocatalysis Public Deposited

http://ir.library.oregonstate.edu/concern/articles/df65v9497

To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. This is the publisher’s final pdf. The published article is copyrighted by the American Chemical Society and can be found at:  http://pubs.acs.org/journal/achre4

Descriptions

Attribute NameValues
Creator
Abstract or Summary
  • Conspectus: The flexibility, complexity, and size of contemporary organocatalytic transformations pose interesting and powerful opportunities to computational and experimental chemists alike. In this Account, we disclose our recent computational investigations of three branches of organocatalysis in which nonbonding interactions, such as C–H···O/N interactions, play a crucial role in the organization of transition states, catalysis, and selectivity. We begin with two examples of N-heterocyclic carbene (NHC) catalysis, both collaborations with the Scheidt laboratory at Northwestern. In the first example, we discuss the discovery of an unusual diverging mechanism in a catalytic kinetic resolution of a dynamic racemate that depends on the stereochemistry of the product being formed. Specifically, the major product is formed through a concerted asynchronous [2 + 2] aldol-lactonization, while the minor products come from a stepwise spiro-lactonization pathway. Stereoselectivity and catalysis are the results of electrophilic activation from C–H···O interactions between the catalyst and the substrate and conjugative stabilization of the electrophile. In the second example, we show how knowledge and understanding of the computed transition states led to the development of a more enantioselective NHC catalyst for the butyrolactonization of acyl phosphonates. The identification of mutually exclusive C–H···O interactions in the computed major and minor TSs directly resulted in structural hypotheses that would lead to targeted destabilization of the minor TS, leading to enhanced stereoinduction. Synthesis and evaluation of the newly designed NHC catalyst validated our hypotheses. Next, we discuss two works related to Lewis base catalysis involving 4-dimethylaminopyridine (DMAP) and its derivatives. In the first, we discuss our collaboration with the Smith laboratory at St Andrews, in which we discovered the origins of the regioselectivity in carboxyl transfer reactions. We disclose how different Lewis base catalysts (NHC or DMAP) can lead to different regiomeric products as a result of differing magnitudes of aromatic and C–H···O interactions present in the respective transition states. In the second example, we discuss the mechanism and origins of the stereoselectivity of a reaction catalyzed by a planar-chiral 4-(pyrrolidino)pyridine derivative, namely, the coupling of ketenes with cyanopyrrole. We discovered that the chiral base mechanism is operative, in contrast to the originally proposed Brønsted acid mechanism. The selectivity is determined by the ease with which the major and minor TSs can realize strong stabilizing C–H···N interactions between the pyrrole cyano group and the catalyst. These interactions induce increased catalyst distortion in the minor TS, thereby leading to enantioselectivity. Finally, we discuss our computations related to amine-based organocatalysis in collaboration with the Carter laboratory at Oregon State. We probed the mechanism and stereoselectivity of a bifunctional amine thiourea-catalyzed Michael reaction. Our computations led to the design of an improved catalyst. However, synthesis and tests revealed that this catalyst was prone to degradation to side products that also catalyze the reaction, ultimately reducing the observed enantioselectivity. Lastly, we discuss our study of the mechanism and stereoselectivity of a proline sulfonamide-catalyzed Robinson annulation, in which we discovered that the enantioselectivity is controlled by the first Michael step but the diastereoselectivity is controlled by the following Mannich step.
Resource Type
DOI
Date Available
Date Issued
Citation
  • Walden, D. M., Ogba, O. M., Johnston, R. C., & Cheong, P. H. Y. (2016). Computational Insights into the Central Role of Nonbonding Interactions in Modern Covalent Organocatalysis. Accounts of Chemical Research, 49(6), 1279-1291. doi:10.1021/acs.accounts.6b00204
Series
Rights Statement
Funding Statement (additional comments about funding)
Publisher
Peer Reviewed
Language
Replaces
Additional Information
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2016-07-20T14:37:23Z (GMT) No. of bitstreams: 1 WaldenComputationalInsightsintotheCentral.pdf: 4418419 bytes, checksum: e1082cb45769a484bbfa6d21de1e82db (MD5)
  • description.provenance : Submitted by Patricia Black (patricia.black@oregonstate.edu) on 2016-07-20T14:36:44Z No. of bitstreams: 1 WaldenComputationalInsightsintotheCentral.pdf: 4418419 bytes, checksum: e1082cb45769a484bbfa6d21de1e82db (MD5)
  • description.provenance : Made available in DSpace on 2016-07-20T14:37:23Z (GMT). No. of bitstreams: 1 WaldenComputationalInsightsintotheCentral.pdf: 4418419 bytes, checksum: e1082cb45769a484bbfa6d21de1e82db (MD5) Previous issue date: 2016-06

Relationships

In Administrative Set:
Last modified: 07/26/2017

Downloadable Content

Download PDF
Citations:

EndNote | Zotero | Mendeley

Items