Dyotropic Rearrangements Research Articles

Dyotropic Rearrangement of β‐Lactams: Reaction Development, Mechanistic Study, and Application to the Total Syntheses of Tricyclic Marine Alkaloids

An unprecedented dyotropic rearrangement of β‐lactams has been developed, which provides an enabling tool for the synthesis of structurally diverse γ‐butyrolactams. Unlike the well‐established dyotropic rearrangements of β‐lactones, the present reaction probably proceeds through a dual‐activation mode, and thus displays unusual reactivity and chemoselectivity. The combined computational and experimental results suggest that the dyotropic rearrangement of β‐lactams may proceed through different mechanisms depending on the nature of migrating groups (H, alkyl, or aryl). Hinging on a chemoselective H‐migration dyotropic rearrangement of β‐lactams, we have completed the divergent synthesis of tricyclic marine alkaloids (–)‐lepadiformine A, (+)‐cylindricine C, and (–)‐fasicularin within 11‐12 longest linear steps.

Dyotropic Rearrangement of β-Lactams: Reaction Development, Mechanistic Study, and Application to the Total Syntheses of Tricyclic Marine Alkaloids.

An unprecedented dyotropic rearrangement of β-lactams has been developed, which provides an enabling tool for the synthesis of structurally diverse γ-butyrolactams. Unlike the well-established dyotropic rearrangements of β-lactones, the present reaction probably proceeds through a dual-activation mode, and thus displays unusual reactivity and chemoselectivity. The combined computational and experimental results suggest that the dyotropic rearrangement of β-lactams may proceed through different mechanisms depending on the nature of migrating groups (H, alkyl, or aryl). Hinging on a chemoselective H-migration dyotropic rearrangement of β-lactams, we have completed the divergent synthesis of tricyclic marine alkaloids (-)-lepadiformine A, (+)-cylindricine C, and (-)-fasicularin within 11-12 longest linear steps.

Dyotropic Rearrangements in Organic Solvents, in the Gas Phase, and in Enzyme Catalysis

AbstractThis short historical account outlines how Helmut Schwarz and Manfred T. Reetz first met almost half a century ago and remained personal friends ever since. It began by collaborations on dyotropic rearrangements and other transformations in the gas phase. Although their chemical interests diverged considerably over decades, which are briefly mentioned in this account, both were always driven by curiosity. Another common feature was the fact that they both collaborated with Israeli chemists in various projects up to the present day. They also contributed to the celebration in 2015 commemorating 50 years of diplomatic relationship between Israel and Germany.

Synthesis of Hydrofluoroolefin-Based Iodonium Reagent via Dyotropic Rearrangement and Its Utilization in Fluoroalkylation.

[1,2]‐shift of atoms in alkyl fragments belongs to the class of dyotropic rearrangements. Various atoms, including halogens can be involved in the migration, however participation of iodine is unprecedented. Herein, we report our experimental and DFT studies on the oxidation triggered dyotropic rearrangement of iodo and chloro functions via butterfly‐type transition state to demonstrate the migrating ability of λ3‐iodane centre. With the exploitation of dyotropic rearrangement we designed and synthesized a novel fluoroalkyl iodonium reagent from industrial feedstock gas HFO‐1234yf. We demonstrated that the hypervalent reagent serves as an excellent fluoroalkylation agent for various amines and nitrogen heterocycles.

Synthesis of Hydrofluoroolefin‐Based Iodonium Reagent via Dyotropic Rearrangement and Its Utilization in Fluoroalkylation

Abstract[1,2]‐shift of atoms in alkyl fragments belongs to the class of dyotropic rearrangements. Various atoms, including halogens can be involved in the migration, however participation of iodine is unprecedented. Herein, we report our experimental and DFT studies on the oxidation triggered dyotropic rearrangement of iodo and chloro functions via butterfly‐type transition state to demonstrate the migrating ability of λ3‐iodane centre. With the exploitation of dyotropic rearrangement we designed and synthesized a novel fluoroalkyl iodonium reagent from industrial feedstock gas HFO‐1234yf. We demonstrated that the hypervalent reagent serves as an excellent fluoroalkylation agent for various amines and nitrogen heterocycles.

Elucidating the selectivity of dyotropic rearrangements of β-lactones: a computational survey

A comprehensive computational study on dyotropic rearrangements of β-lactones has been performed for the first time, which provides a valuable guidance for predicting and controlling the selectivity of the reactions.

Tailored Synthesis of Skeletally Diverse Stemona Alkaloids through Chemoselective Dyotropic Rearrangements of β-Lactones.

The collective synthesis of skeletally diverse Stemona alkaloids featuring tailored dyotropic rearrangements of β-lactones as key elements is described. Specifically, three typical 5/7/5 tricyclic skeletons associated with stemoamide, tuberostemospiroline and parvistemonine were first accessed through chemoselective dyotropic rearrangements of β-lactones involving alkyl, hydrogen, and aryl migration, respectively. By the rational manipulation of substrate structures and reaction conditions, these dyotropic rearrangements proceeded with excellent efficiency, good chemoselectivity and high stereospecificity. Furthermore, several polycyclic Stemona alkaloids, including saxorumamide, isosaxorumamide, stemonine and bisdehydroneostemoninine, were obtained from the aforementioned tricyclic skeletons through late-stage derivatizations. A novel visible-light photoredox-catalyzed formal [3+2] cycloaddition was also developed, which offers a valuable tool for accessing oxaspirobutenolide and related scaffolds.

Tailored Synthesis of Skeletally Diverse Stemona Alkaloids through Chemoselective Dyotropic Rearrangements of β‐Lactones

AbstractThe collective synthesis of skeletally diverse Stemona alkaloids featuring tailored dyotropic rearrangements of β‐lactones as key elements is described. Specifically, three typical 5/7/5 tricyclic skeletons associated with stemoamide, tuberostemospiroline and parvistemonine were first accessed through chemoselective dyotropic rearrangements of β‐lactones involving alkyl, hydrogen, and aryl migration, respectively. By the rational manipulation of substrate structures and reaction conditions, these dyotropic rearrangements proceeded with excellent efficiency, good chemoselectivity and high stereospecificity. Furthermore, several polycyclic Stemona alkaloids, including saxorumamide, isosaxorumamide, stemonine and bisdehydroneostemoninine, were obtained from the aforementioned tricyclic skeletons through late‐stage derivatizations. A novel visible‐light photoredox‐catalyzed formal [3+2] cycloaddition was also developed, which offers a valuable tool for accessing oxaspirobutenolide and related scaffolds.

Strain-Driven Dyotropic Rearrangement: A Unified Ring-Expansion Approach to α-Methylene-γ-butyrolactones.

An unprecedented strain-driven dyotropic rearrangement of α-methylene-β-lactones has been realized, which enables the efficient access of a wide range of α-methylene-γ-butyrolactones displaying remarkable structural diversity. Several appealing features of the reaction, including excellent efficiency, high stereospecificity, predictable chemoselectivity and broad substrate scope, render it a powerful tool for the synthesis of MBL-containing molecules of either natural or synthetic origin. Both experimental and computational evidences suggest that the new variant of dyotropic rearrangements proceed in a dualistic pattern: while an asynchronous concerted mechanism most likely accounts for the reactions featuring hydrogen migration, a stepwise process involving a phenonium ion intermediate is favored in the cases of aryl migration. The great synthetic potential of the title reaction is exemplified by its application to the efficient construction of several natural products and relevant scaffolds.

Strain‐Driven Dyotropic Rearrangement: A Unified Ring‐Expansion Approach to α‐Methylene‐γ‐butyrolactones

AbstractAn unprecedented strain‐driven dyotropic rearrangement of α‐methylene‐β‐lactones has been realized, which enables the efficient access of a wide range of α‐methylene‐γ‐butyrolactones displaying remarkable structural diversity. Several appealing features of the reaction, including excellent efficiency, high stereospecificity, predictable chemoselectivity and broad substrate scope, render it a powerful tool for the synthesis of MBL‐containing molecules of either natural or synthetic origin. Both experimental and computational evidences suggest that the new variant of dyotropic rearrangements proceed in a dualistic pattern: while an asynchronous concerted mechanism most likely accounts for the reactions featuring hydrogen migration, a stepwise process involving a phenonium ion intermediate is favored in the cases of aryl migration. The great synthetic potential of the title reaction is exemplified by its application to the efficient construction of several natural products and relevant scaffolds.

Designing Reactions with Post-Transition-State Bifurcations: Asynchronous Nitrene Insertions into C–C σ Bonds

Summary Discoveries of chemical reactions with potential energy surfaces with post-transition-state bifurcations are increasing in frequency. Although such potential energy surface features are often discovered accidentally, we demonstrate here that they can be designed rationally. We describe a process for designing such reactions and apply it to the design of a nitrene addition/alkyl-shift reaction with a post-transition state bifurcation. We examine substituent effects on this reaction and propose a dynamics-based model for selectivity control.

Stereospecific Ring Contraction of Bromocycloheptenes through Dyotropic Rearrangements via Nonclassical Carbocation–Anion Pairs

Experimental and theoretical evidence is reported for a rare type I dyotropic rearrangement involving a [1,2]-alkene shift, leading to the regio- and stereospecific ring contraction of bromocycloheptenes. This reaction occurs under mild conditions, with or without a Lewis acid catalyst. DFT calculations show that the reaction proceeds through a nonclassical carbocation–anion pair, which is crucial for the low activation barrier and enantiospecificity. The chiral cyclopropylcarbinyl cation may be a transition state or an intermediate, depending on the reaction conditions.

A Maze of Dyotropic Rearrangements and Triple Shifts: Carbocation Rearrangements Connecting Stemarene, Stemodene, Betaerdene, Aphidicolene, and Scopadulanol.

Results of quantum chemical investigations shed new light on the mechanisms of formation of the stemarene, stemodene, betaerdene, aphidicolene, and scopadulanol diterpenes from syn-copalyl diphosphate ( syn-CPP). These terpenes are shown to be connected by a complex network of reaction pathways involving concerted but asynchronous dyotropic rearrangements and triple shift rearrangements. The interconnection of these pathways leads to multiple routes for formation of each diterpene, which could lead to different origins for some carbon atoms in a given diterpenes under different conditions.

Daniel Romo

Angewandte Chemie International EditionVolume 56, Issue 39 p. 11682-11682 Author ProfileFree Access Daniel Romo First published: 06 June 2017 https://doi.org/10.1002/anie.201703689AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract “I celebrate success by giving thanks to God and “chillin” with my family. The best advice I have ever been given is “Romo, when you begin your independent career, be sure to do some chemistry that will become associated with your name” (A. I. Meyers). ...” This and more about Daniel Romo can be found on page 11682. Daniel Romo The author presented on this page has published 10 articles in Angewandte Chemie in the last 10 years: “Asymmetric Organocatalysis: The Emerging Utility of α,β-Unsaturated Acylammonium Salts”: S. Vellalath, D. Romo, Angew. Chem. Int. Ed. 2016, 55, 13934; Angew. Chem. 2016, 128, 14138. The work of D. Romo has been featured on the cover of Angewandte Chemie: “Total Synthesis of (+)-Omphadiol”: G. Liu, D. Romo, Angew. Chem. Int. Ed. 2011, 50, 7537; Angew. Chem. 2011, 123, 7679. Date of birth: November 30, 1964 Position: Schotts Professor of Chemistry, Baylor University E-mail: Daniel_Romo@baylor.edu Homepage: http://www.danielromogroup.com/ ORCID: 0000-0003-3805-092X Education: 1986 BA in chemistry/biology, Texas A&M University 1991 PhD supervised by Prof. Albert I. Meyers, Colorado State University 1991–1993 postdoc with Prof. Stuart L. Schreiber, Harvard University Awards: 2001 Pfizer Award for Creativity in Organic Chemistry; 2009 NIH MERIT Award; 2013 Fellow of the Royal Society of Chemistry Current research interests: Synthesis and biology of β-lactones; total synthesis/mode of action studies of natural products; organocascade catalysis Hobbies: Christian apologetics, Aggie sports (college sports), science–faith intersection, fishing I celebrate success by giving thanks to God and “chillin” with my family. The best advice I have ever been given is “Romo, when you begin your independent career, be sure to do some chemistry that will become associated with your name” (A. I. Meyers). My favorite quote is “never, never, never give up!” (Winston Churchill). The most important thing I learned from my parents is you can accomplish anything you can dream and hard work pays off; demonstrated through example rather than words. My favorite place on earth is next to my wife Laura, enjoying a good show with a bowl of popcorn. I chose chemistry as a career because of excellent chemistry teachers from high school to college. My best investment was/is the time, energy, love, and finances poured into our children (five boys) since they will be our true legacy. If I were not a scientist, I would be a professional fisherman who spends weekends running fishing tours while collecting specimens for isolation chemists and serving sashimi on deck! My worst nightmare is a reoccurring one involving forgetting I signed up for an undergraduate course until finals week! The most exciting thing about my research is when my students share an unexpected finding with me and I see their excitement and desire to dig deeper into the generality of the observation. I lose track of time when getting into a groove toward completing a manuscript or grant application. My 5 top papers: References 1“Intramolecular Nucleophile-Catalyzed Aldol-Lactonization (NCAL) Reactions: Catalytic, Asymmetric Synthesis of Bicyclic β-Lactones”: G. S. Cortez, R. L. Tennyson, D. Romo, J. Am. Chem. Soc. 2001, 123, 7945. (Early β-lactone paper by Reggie and Guillermo, building on elegant work of Wynberg.) 2“Inhibition of Eukaryotic Translation Initiation by the Marine Natural Product Pateamine A”: W.-K. Low, Y. Dang, T. Schneider-Poetsch, Z. Shi, N. S. Choi, W. C. Merrick, D. Romo, J. O. Liu, Mol. Cell 2005, 20, 709. (Culmination of synthesis/mode of action studies of PatA initiated by one of my first grads, Robert Rzasa.) 3“Concise Synthesis of Spirocyclic, Bridged γ-Butyrolactones via Stereospecific, Dyotropic Rearrangements of β-Lactones Involving 1,2-acyl and δ-Lactone Migrations”: V. C. Purohit, A. S. Matla, D. Romo, J. Am. Chem. Soc. 2008, 130, 10478. (Extension of a known, but intriguing transformation of β-lactones by Vikram.) 4“Enantioselective Total Synthesis of the Marine Toxin (−)-Gymnodimine Employing a Barbier-Type Macrocyclization”: K. Kong, C. S. Lee, D. Romo, Angew. Chem. Int. Ed. 2009, 48, 7402; Angew. Chem. 2009, 121, 7538. (Ke's fearlessness in adding tBuLi at room temperature to an advanced intermediate was critical for the key macrocyclization!) 5“Rapid assembly of complex cyclopentanes employing chiral α,β-unsaturated acylammonium intermediates”: G. Liu, M. E. Shirley, K. N. Van, R. L. McFarlin, D. Romo, Nat. Chem. 2013, 5, 1049. (Gang took a rough idea from his advisor and “ran with it”.) Volume56, Issue39September 18, 2017Pages 11682-11682 ReferencesRelatedInformation

Dyotropic rearrangements in natural product total synthesis and biosynthesis.

Covering: up to January 2017This highlight article presents some recent examples of dyotropic rearrangements, which were applied in natural product total synthesis or proposed to occur in biosyntheses. The implementation of dyotropic reactions in the preparation of complex natural products has resulted in the development of elegant synthetic routes, and thereby highlights the utility of these powerful, yet relatively underrepresented, transformations.

ChemInform Abstract: Formal Dyotropic Rearrangements in Organometallic Transformations

AbstractReview: [recent developments and applications of formal dyotropic rearrangements involving both stoichiometric and catalytic amounts of transition metals; 37 refs.

Formal Dyotropic Rearrangements in Organometallic Transformations

AbstractA thorough understanding of the mechanistic steps that occur in organometallic processes is crucial to the development of new, increasingly sophisticated transformations. This microreview discusses an unusual class of organometallic reactions that occur through formal Type I dyotropic rearrangements, defined as processes involving the interchange of two groups along a stationary scaffold by breaking and reforming two σ bonds in which at least one σ bond is a M–X bond. Examples are subdivided into two categories – stoichiometric and catalytic – and further classified by the number of atoms across which the migrating groups interchange positions. The metal can either serve as the migrating group or function as part of the stationary scaffold. Furthermore, these rearrangements can proceed through a wide variety of different mechanisms that include oxidative insertion/reductive elimination, radical processes, or pathways in which the metal does not change oxidation state.

Computational and experimental investigations of the formal dyotropic rearrangements of Himbert arene/allene cycloadducts.

The fascinating intramolecular arene/allene cycloaddition discovered by Himbert affords dearomatized, polycyclic intermediates with sufficient strain energy to drive rearrangement processes of the newly formed ring system. We disclose a detailed examination of a thermally induced stepwise dyotropic skeletal rearrangement of these cycloadducts, a reaction also first described by Himbert. We offer computational evidence for a two-stage mechanism for this formal dyotropic rearrangement and provide rationalizations for the significant substitution-dependent rate differences observed in experiments. These investigations led to the development of a Lewis-acid-catalyzed rearrangement of precursors that were unreactive under simple thermal instigation. The isolation of the product of an "interrupted" rearrangement under Lewis acidic conditions provides further support for the proposed stepwise mechanism. Computational results also matched experiments in terms of regiochemical preferences in unsymmetrical rearrangement precursors and explained why lactam O-, S-, and C-heterologues do not easily undergo this rearrangement.

Correction to “Dyotropic Rearrangements of Fused Tricyclic β-Lactones: Application to the Synthesis of (−)-Curcumanolide A and (−)-Curcumalactone”

Correction to “Dyotropic Rearrangements of Fused Tricyclic β-Lactones: Application to the Synthesis of (−)-Curcumanolide A and (−)-Curcumalactone”

Reaction mechanisms: pericyclic reactions

This is a review of forty five articles on pericyclic reactions published in 2012. Reviewed here are cycloadditions ([2+2], [3+2], [4+2], [4+3], [5+2], and [8+2]), sigmatropic reactions ([1,5]-, [2,3]-, [3,3]-, and [3,5]-shifts), as well as group transfer reactions, dyotropic rearrangements, cycloaromatization, and cascade reactions. Many of these pericyclic reactions were purely “organic”, while some eight used metal catalysts.