Highly (<i>E</i>)-Selective Trisubstituted Alkene Synthesis by Low-Valent Titanium-Mediated Homolytic Cleavage of Alcohol C–O Bond

Suga, Tetsuya; Takada, Ryusei; Shimazu, Shoma; Sakata, Mizuki; Ukaji, Yutaka

doi:10.1021/acs.joc.2c00246

Cited by 9 publications

(4 citation statements)

References 43 publications

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“…Based on the above results and previous reports, [ 64‐69 ] we proposed two mechanisms depicted in Figure 6 for this divergent deoxygenative coupling of alcohols with trifluoromethyl alkenes. Cp*TiCl 3 was reduced by Zn to generate active Cp*TiCl 2 species.…”

Section: Resultssupporting

confidence: 73%

“…[ 51‐61 ] In this context, as one of the cheapest and nontoxic transition metals, [ 62 ] titanium has displayed distinct reactivity for radical dehydroxylation of alcohols due to their strong oxophilicity and high reduction potential. Some elegant reports by Zheng, [ 63 ] Suga/Ukaji, [ 64‐67 ] Shu [ 68‐71 ] and others [ 72‐74 ] have disclosed titanium‐mediated (catalyzed), directly activated free alcohols and application in the efficient cross‐coupling reactions (Figure 1d), showing the great potential to generate highly active alkyl radicals from free alcohols using Ti complexes.…”

Section: Background and Originality Contentmentioning

confidence: 99%

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Divergent Synthesis of Organofluorinated Molecules from Titanium Mediated Deoxygenation of Free Alcohols

et al. 2023

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Comprehensive Summary Alcohols as among the most widely occurring organic compounds known, deoxygenative transformations of free alcohols as partners in radical addition reactions remain formidable challenges with great opportunities to achieve new and useful transformations. Herein, we report a protocol via C—O bond cleavage and C—C bond‐forming reaction of trifluoromethyl alkenes with free alcohols assisted by titanium reagents via a deoxygenative radical strategy, enabling the divergent synthesis for functional‐group‐rich organofluorinated compounds in high efficiencies. In this transformation, tertiary alcohols by Ti‐catalysis could be converted to trifluoromethyl alkanes without defluorination in acidic conditions, while benzyl alcohols are employed by Ti‐mediated activation to supply the gem‐difluoroalkenes with defluorination in the presence of a base. This protocol is applicable for a broad range of trifluoromethyl alkenes with good functional group tolerance and a variety of tertiary alcohols and benzyl alcohols (including primary, secondary, and tertiary alcohols), and is scalable to the gram level. Remarkably, the utility of this protocol is demonstrated by several derivatizations and late‐stage functionalization of drug molecules. The successful applications in scale up reactions and late‐stage functionalization of several drug molecules demonstrate its potential synthetic value in drug discovery settings.

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Section: Resultssupporting

confidence: 73%

Section: Background and Originality Contentmentioning

confidence: 99%

Divergent Synthesis of Organofluorinated Molecules from Titanium Mediated Deoxygenation of Free Alcohols

et al. 2023

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“…Titanium has been frequently explored as a catalyst for the activation of alcohols, with early reports on stoichiometric activation published by von Tamelyn in the 1960s , being revisited by the Barrero group in recent years, , wherein titanium is proposed to induce homolytic cleavage of the C–O bond. More recently, the Ukaji group has explored the use of low-valent titanium reagents in the coupling of alcohols with unsaturated carbon compounds , (Scheme a); while these methods are stoichiometric in titanium, they serve as key precedent for the development of methods using catalytic titanium to facilitate alcohol functionalization through related radical mechanisms. , In 2013, Li and co-workers disclosed a palladium/titanium cocatalytic system for the coupling of allyl alcohols with terminal alkynes, providing access to 1,4-enynes (Scheme b) . The authors proposed that titanium first coordinates to the alcohol through a Lewis acid–base interaction, sufficiently weakening the C–O bond such that it can undergo oxidative addition with palladium.…”

Section: Deoxygenative Functionalizationmentioning

confidence: 99%

Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

Cook,

Newman

2024

Chem. Rev.

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Alcohols are abundant and attractive feedstock molecules for organic synthesis. Many methods for their functionalization require them to first be converted into a more activated derivative, while recent years have seen a vast increase in the number of complexity-building transformations that directly harness unprotected alcohols. This Review discusses how transition metal catalysis can be used toward this goal. These transformations are broadly classified into three categories. Deoxygenative functionalizations, representing derivatization of the C−O bond, enable the alcohol to act as a leaving group toward the formation of new C−C bonds. Etherifications, characterized by derivatization of the O−H bond, represent classical reactivity that has been modernized to include mild reaction conditions, diverse reaction partners, and high selectivities. Lastly, chain functionalization reactions are described, wherein the alcohol group acts as a mediator in formal C−H functionalization reactions of the alkyl backbone. Each of these three classes of transformation will be discussed in context of intermolecular arylation, alkylation, and related reactions, illustrating how catalysis can enable alcohols to be directly harnessed for organic synthesis.

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“…In 2022, the group of Suga and Ukaji used a stoichiometricamount of TiCl 4 (col) (col = 2,4,6‐collidine) and Mn powder to achieve the allylation reaction of benzylic alcohols with 2‐carboxyallyl acetates (Scheme 7). [ 18 ] In these reactions, benzyl radical adds to 2‐carboxyallyl acetates, and the formed enolate undergoes elimination of the acetoxy group to yield the desired products. The reactions worked with various benzylic alcohols and afforded α , β ‐unsaturated carbonyl compounds with an exclusive ( E )‐stereoselectivity.…”

Section: Ti‐catalyzed Reductive Dehydroxylative Functionalization Of ...mentioning

confidence: 99%

Reductive Deoxygenative Functionalization of Alcohols by First‐Row Transition Metal Catalysis

Pang

Shu

2023

Chin. J. Chem.

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Xiaobo Pang received her Master's and Ph.D. degrees from Lanzhou University. She is currently a postdoctoral researcher at Lanzhou University in Professor Shu's group. She is working on asymmetric reductive cross-coupling reactions. Xing-Zhong Shu received his Ph.D. degree from Lanzhou University in 2010. He then moved to the University of Wisconsin-Madison to conduct postdoctoral research with Professor Weiping Tang. In 2012, he joined F. Dean Toste's group at the University of California-Berkeley as a postdoctoral researcher. He was appointed at Lanzhou University (China) in 2015, where he is a Full Professor of chemistry. Contents 1. Introduction 1638 2. Ti-Catalyzed Reductive Dehydroxylative Functionalization of Alcohols 1638 2.1. Short background of Ti(III) catalysts 1638 2.2. Ti-catalyzed dehydroxylative functionalization of alcohols 1639 2.

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Highly (E)-Selective Trisubstituted Alkene Synthesis by Low-Valent Titanium-Mediated Homolytic Cleavage of Alcohol C–O Bond

Cited by 9 publications

References 43 publications

Divergent Synthesis of Organofluorinated Molecules from Titanium Mediated Deoxygenation of Free Alcohols

Divergent Synthesis of Organofluorinated Molecules from Titanium Mediated Deoxygenation of Free Alcohols

Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

Reductive Deoxygenative Functionalization of Alcohols by First‐Row Transition Metal Catalysis

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