CuH-Catalyzed Olefin Functionalization: From Hydroamination to Carbonyl Addition

Accounts of Chemical Research, Journal Year: 2020, Volume and Issue: 53(6), P. 1229 - 1243

Published: May 13, 2020

ConspectusIn organic synthesis, ligand-modified copper(I) hydride (CuH) complexes have become well-known reagents and catalysts for selective reduction, particularly toward Michael acceptors carbonyl compounds. Recently, our group others found that these undergo migratory insertion (hydrocupration) with relatively unactivated electronically unpolarized olefins, producing alkylcopper intermediates can be leveraged to forge a variety of useful bonds. The resulting formal hydrofunctionalization reactions formed the basis resurgence research in CuH catalysis. This Account chronicles development this concept group, highlighting its origin context asymmetric hydroamination, evolution more general C–X bond-forming reactions, applications addition olefin-derived nucleophiles derivatives.Hydroamination, an olefin into N–H bond amine, is process significant academic industrial interest, due potential transform widely available alkenes alkynes valuable complex amines. We developed polarity-reversed strategy catalytic enantioselective hydroamination relying on reaction olefins generate chiral organocopper intermediates, which are intercepted by electrophilic amine reagents. By engineering auxiliary ligand, electrophile, conditions, scope method has since been extended include many types including challenging internal olefins. Further, expanded enable synthesis primary, secondary, tertiary amines as well amides, N-alkylated heterocycles, anilines. All exhibit high regio- stereoselectivity and, mild conditions required, excellent tolerance heterocycles polar functional groups.Though generation species from was originally devised means solve problem, we soon could react efficiently unexpectedly broad range electrophiles, alkyl halides, silicon reagents, arylpalladium species, derivatives. ability function precursors nucleophilic proved advantageous because it overcomes disadvantages associated traditional organometallic removing need pregeneration nucleophile separate operation, CuH-catalyzed feature improved step economy, enhanced tolerance, catalyst control over stereoselectivity. Following paradigm, feedstock such allene, butadiene, styrene employed alkylation ketones, imines, aldehydes.

Language: Английский

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Copper-Catalyzed Functionalization of 1,3-Dienes: Hydrofunctionalization, Borofunctionalization, and Difunctionalization

ACS Catalysis, Journal Year: 2019, Volume and Issue: 10(2), P. 1485 - 1499

Published: Dec. 18, 2019

The catalytic conversion of chemical feedstocks into products medicinal and agricultural value is a key theme across modern synthetic chemistry. As 1,3-dienes are readily available from industrial cracking processes, there great interest in the development sustainable methods for functionalization these simple molecules. Although initial developments this field have required precious-transition-metal catalysts, has been push toward use inexpensive, nontoxic, more abundant copper catalysts to promote functionalization. This Perspective covers many area copper-catalyzed 1,3-dienes, particular hydrofunctionalization, borofunctionalization, difunctionalization (e.g., diamination).

Language: Английский

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Three-Component, Interrupted Radical Heck/Allylic Substitution Cascade Involving Unactivated Alkyl Bromides

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(22), P. 10173 - 10183

Published: May 7, 2020

Developing efficient and selective strategies to approach complex architectures containing (multi)stereogenic centers has been a long-standing synthetic challenge in both academia industry. Catalytic cascade reactions represent powerful means of rapidly leveraging molecular complexity from simple feedstocks. Unfortunately, carrying out Heck-type involving unactivated (tertiary) alkyl halides remains an unmet owing unavoidable β-hydride elimination. Herein, we show that modular, practical, general palladium-catalyzed, radical three-component coupling can indeed overcome the aforementioned limitations through interrupted Heck/allylic substitution sequence mediated by visible light. Selective 1,4-difunctionalization 1,3-dienes, such as butadiene, achieved employing different commercially available nitrogen-, oxygen-, sulfur-, or carbon-based nucleophiles bromides (>130 examples, mostly >95:5 E/Z, >20:1 rr). Sequential C(sp3)–C(sp3) C–X (N, O, S) bonds have constructed efficiently with broad scope high functional group tolerance. The flexibility versatility strategy illustrated gram-scale reaction streamlined syntheses ether, sulfone, tertiary amine products, some which would be difficult access via currently established methods.

Language: Английский

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Catalytic Enantio- and Regioselective Addition of Nucleophiles in the Intermolecular Hydrofunctionalization of 1,3-Dienes

ACS Catalysis, Journal Year: 2019, Volume and Issue: 10(2), P. 1060 - 1076

Published: Dec. 12, 2019

Catalytic enantioselective synthesis of small-molecule building blocks with allylic stereogenic centers is an important objective in organic synthesis, but preparing this motif wherein the adjacent olefin 1,2-disubstituted a single step tremendous challenge. Late-transition-metal-catalyzed intermolecular couplings nucleophiles and 1,3-dienes hydrofunctionalization reactions have quickly emerged as compelling approach to these related compounds. In Perspective, we illustrate how diene hydrofunctionalizations provided avenue complex, highly desirable chemical space that not readily accessed by other technologies. We also aim provide some insight into varying mechanistic pathways nuances myriad help inform future reaction catalyst design.

Language: Английский

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Synergistic Pd/Amine-Catalyzed Stereodivergent Hydroalkylation of 1,3-Dienes with Aldehydes: Reaction Development, Mechanism, and Stereochemical Origins

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(29), P. 10948 - 10962

Published: July 15, 2021

Metal-hydride-catalyzed hydroalkylation of 1,3-dienes with enolizable carbonyl compounds is an atom- and step-economical method for preparing chiral molecules allylic stereocenters. Although high diastereo- enantioselectivities have been achieved many coupling partners, aldehydes not yet used this purpose because they are less stable than other under basic conditions the potential to rapidly epimerize at α-position. Moreover, stereodivergent reactions access complementary diastereomers vicinal stereocenters challenging. Herein, we describe a synergistic palladium/amine catalyst system that allowed us achieve first aldehydes. By choosing appropriate combination palladium amine catalysts, could obtain either syn or anti products, therefore provides highly enantioselective α,β-vicinal Density functional theory calculations revealed mechanism involving PdH formation migratory insertion into alkene, followed by C–C bond formation. The origin stereoselectivities was investigated means distortion/interaction analysis.

Language: Английский

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Catalytic Allylation of Aldehydes Using Unactivated Alkenes

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(28), P. 12374 - 12381

Published: July 1, 2020

Simple feedstock organic molecules, especially alkenes, are attractive starting materials in synthesis because of their wide availability. Direct utilization such bulk, inert molecules for practical and selective chemical reactions, however, remains limited. Herein, we developed a ternary hybrid catalyst system comprising photoredox catalyst, hydrogen-atom-transfer chromium complex enabling catalytic allylation aldehydes with simple including lower alkenes. The reaction proceeded under visible-light irradiation at room temperature high functional group tolerance. was extended to an asymmetric variant by employing chiral catalyst.

Language: Английский

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Highly Selective and Catalytic Generation of Acyclic Quaternary Carbon Stereocenters via Functionalization of 1,3-Dienes with CO₂

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(47), P. 18825 - 18835

Published: Nov. 8, 2019

The catalytic asymmetric functionalization of readily available 1,3-dienes is highly important, but current examples are mostly limited to the construction tertiary chiral centers. generation acyclic products containing all-carbon quaternary stereocenters from substituted represents a more challenging, desirable, synthetic process for which there very few examples. Herein, we report selective copper-catalyzed via with CO2. A variety 1,1-disubstituted 1,3-dienes, as well 1,3,5-triene, undergo reductive hydroxymethylation high chemo-, regio-, E/Z-, and enantioselectivities. reported method features good functional group tolerance, scaled up at least 5 mmol starting diene, generates that useful building blocks further derivatization. Systemic mechanistic investigations using density theory calculations were performed provided first theoretical investigation an transformation involving These computational results indicate 1,2-hydrocupration 1,3-diene proceeds π-facial selectivity generate (S)-allylcopper intermediate, induces chirality carbon center in final product. 1,4-addition internal allylcopper complex, differs previous reports terminal allylmetallic intermediates, CO2 kinetically determines E/Z- regioselectivity. rapid reduction copper carboxylate intermediate corresponding silyl-ether presence Me(MeO)2SiH provides exergonic impetus leads chemoselective rather than carboxylation. provide new insights guiding development C-C bond formations

Language: Английский

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Palladium-Catalyzed Regio- and Enantioselective Hydrosulfonylation of 1,3-Dienes with Sulfinic Acids: Scope, Mechanism, and Origin of Selectivity

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(37), P. 15860 - 15869

Published: Aug. 19, 2020

Chiral sulfones are important structural motifs in organic synthesis because of their widespread use pharmaceutical chemistry. In particular, chiral allylic have drawn particular interest synthetic utility. However, enantioselective 1,3-disubstituted unsymmetrical remains a challenge. this article, we report protocol for (R)-DTBM-Segphos/Pd-catalyzed regio- and hydrosulfonylation 1,3-dienes with sulfinic acids, which provides atom- step-economical access to sulfones. The reaction occurs under mild conditions has broad substrate scope. Combined experimental computational studies suggest that the is initiated by ligand-to-ligand hydrogen transfer followed C–S bond reductive elimination via six-membered transition state. Steric repulsion between olefinic C–H tert-butyl group (R)-DTBM-Segphos was found be key factor enantiocontrol.

Language: Английский

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Electroreductive Olefin–Ketone Coupling

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(50), P. 20979 - 20986

Published: Dec. 1, 2020

A user-friendly approach is presented to sidestep the venerable Grignard addition unactivated ketones access tertiary alcohols by reversing polarity of disconnection. In this work a ketone instead acts as nucleophile when adding simple olefins accomplish same overall transformation. The scope coupling broad enabled using an electrochemical approach, and reaction scalable, chemoselective, requires no precaution exclude air or water. Multiple applications demonstrate simplifying nature on multistep synthesis, mechanistic studies point intuitive mechanism reminiscent other chemical reductants such SmI2 (which cannot reaction).

Language: Английский

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Ni-Catalyzed Enantioselective Intermolecular Hydroamination of Branched 1,3-Dienes Using Primary Aliphatic Amines

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(37), P. 14814 - 14822

Published: Aug. 22, 2019

A Ni-catalyzed intermolecular enantioselective hydroamination of branched 1,3-dienes is reported. The method broadly applicable, highly regio-, chemo-, and enantioselective, provides direct access to valuable chiral allylic amines starting from linear or α-branched aliphatic primary secondary amines. Mechanistic studies have been conducted using 31P NMR spectroscopy for reaction progress monitoring, isotopic labeling experiments (2H), kinetic analysis. resting state the catalyst a Ni−π-allyl complex, outer-sphere nucleophilic attack H-bonded amine aggregates proposed be rate-determining step. This hypothesis guided identification an improved set conditions 1,3-dienes.

Language: Английский

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