Gram‐Scale Enantioselective Formal Synthesis of Morphine through an <i>ortho</i>–<i>para</i> Oxidative Phenolic Coupling Strategy

Tissot, Matthieu; Phipps, Robert J.; Lucas, Catherine L.; León, Rafael; Pace, R. D.; Ngouansavanh, Tifelle; Gaunt, Matthew J.

doi:10.1002/ange.201408435

Cited by 15 publications

(2 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous bioactive compounds, natural products, and drugs, such as the analgesic morphine 6–8 , the broad-spectrum antibiotic doxycycline 9 and the antiviral drug oseltamivir (Tamiflu) 10–12 , have been synthesized utilizing dearomatization as a key step. Despite their strategic and widespread use, most dearomative strategies do not result in the introduction of additional functionality.…”

mentioning

confidence: 99%

Dearomative dihydroxylation with arenophiles

et al. 2016

View full text Add to dashboard Cite

Aromatic hydrocarbons are some of the most elementary feedstock chemicals, produced annually on a million metric ton scale, and are used in the production of polymers, paints, agrochemicals and pharmaceuticals. Dearomatization reactions convert simple, readily available arenes into more complex molecules with broader potential utility, however, despite substantial progress and achievements in this field, there are relatively few methods for the dearomatization of simple arenes that also selectively introduce functionality. Here we describe a new dearomatization process that involves visible-light activation of small heteroatom-containing organic molecules—arenophiles—that results in their para-cycloaddition with a variety of aromatic compounds. The approach uses N–N-arenophiles to enable dearomative dihydroxylation and diaminodihydroxylation of simple arenes. This strategy provides direct and selective access to highly functionalized cyclohexenes and cyclohexadienes and is orthogonal to existing chemical and biological dearomatization processes. Finally, we demonstrate the synthetic utility of this strategy with the concise synthesis of several biologically active compounds and natural products.

show abstract

mentioning

confidence: 99%

Dearomative dihydroxylation with arenophiles

et al. 2016

View full text Add to dashboard Cite

show abstract

“…33 The effort began with a seven step sequence highlighted by a Noyori transfer hydrogenation to give chiral aldehyde (−)-22 from isovanillin (21). A PhI(OAc) 2 mediated, intramolecular oxidative coupling was followed by Michael addition to give enone (+)-24.…”

Section: The Opiatesmentioning

confidence: 99%

The DARK Side of Total Synthesis: Strategies and Tactics in Psychoactive Drug Production

Chambers

DeSousa

Huseman

et al. 2018

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Humankind has used and abused psychoactive drugs for millennia. Formally, a psychoactive drug is any agent that alters cognition and mood. The term “psychotropic drug” is neutral and describes the entire class of substrates, licit and illicit, of interest to governmental drug policy. While these drugs are prescribed for issues ranging from pain management to anxiety, they are also used recreationally. In fact, the current opioid epidemic is the deadliest drug crisis in American history. While the topic is highly politicized with racial, gender, and socioeconomic elements, there is no denying the toll drug mis- and overuse is taking on this country. Overdose, fueled by opioids, is the leading cause of death for Americans under 50 years of age, killing ca. 64,000 people in 2016. From a chemistry standpoint, the question is in what ways, if any, did organic chemists contribute to this problem? In this targeted review, we provide brief historical accounts of the main classes of psychoactive drugs and discuss several foundational total syntheses that ultimately provide the groundwork for producing these molecules in academic, industrial, and clandestine settings.

show abstract

Synthesis of ent‐Ketorfanol via a C–H Alkenylation/Torquoselective 6π Electrocyclization Cascade

et al. 2015

View full text Add to dashboard Cite

The asymmetric synthesis of ent‐ketorfanol from simple and commercially available precursors is reported. A RhI‐catalyzed intramolecular CH alkenylation/torquoselective 6π electrocyclization cascade provides a fused bicyclic 1,2‐dihydropyridine as a key intermediate. Computational studies were performed to understand the high torquoselectivity of the key 6π electrocyclization. The computational results demonstrate that a conformational effect is responsible for the observed selectivity. The ketone functionality and final ring are introduced in a single step by a redox‐neutral acid‐catalyzed rearrangement of a vicinal diol to give the requisite carbonyl, followed by intramolecular Friedel–Crafts alkylation.

show abstract

Gram‐Scale Enantioselective Formal Synthesis of Morphine through an ortho–para Oxidative Phenolic Coupling Strategy

Cited by 15 publications

References 60 publications

Dearomative dihydroxylation with arenophiles

Dearomative dihydroxylation with arenophiles

The DARK Side of Total Synthesis: Strategies and Tactics in Psychoactive Drug Production

Synthesis of ent‐Ketorfanol via a C–H Alkenylation/Torquoselective 6π Electrocyclization Cascade

Contact Info

Product

Resources

About