Catalytic Asymmetric Hydroalkoxylation and Formal Hydration and Hydroaminoxylation of Conjugated Dienes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 3915 - 3925

Published: Feb. 10, 2023

The straightforward construction of stereogenic centers bearing unprotected functional groups, as in nature, has been a persistent pursuit synthetic chemistry. Abundant applications free enantioenriched allyl alcohol and hydroxylamine motifs have made the asymmetric hydration hydroaminoxylation conjugated dienes from water hydroxylamine, respectively, intriguing efficient routes that have, however, unachievable thus far. A fundamental challenge is failure to realize transition-metal-catalyzed enantioselective C–O bond constructions via hydrofunctionalization dienes. Here, we perform comprehensive study toward stereoselective formal by synthesizing set new P,N-ligands identifying an aryl-derived oxime surrogate for both hydroxylamine. Asymmetric hydroalkoxylation with also elucidated. Furthermore, versatile derivatizations following provide indirect but concise hydrophenoxylation, hydrofluoroalkoxylation, hydrocarboxylation unreported Finally, ligand-to-ligand hydrogen transfer process proposed based on results preliminary mechanistic experiments.

Language: Английский

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Palladium‐Catalyzed Inverse and Normal Dehydrogenative Aza‐Morita–Baylis–Hillman Reactions with γ,δ‐Unsaturated Compounds

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(23)

Published: April 3, 2023

σ-Lewis base-catalyzed regio- and enantioselective aza-Morita-Baylis-Hillman (MBH) reaction of α,β,γ,δ-unsaturated systems remains a challenge due to the intrinsic covalent activation mode. Here we demonstrate that Pd0 complex can mediate dehydrogenative γ,δ-unsaturated compounds give corresponding electron-poor dienes, which further undergo δ-regioselective umpolung Friedel-Crafts-type addition imines via auto-tandem -π-Lewis base catalysis. After β-H elimination in situ formed PdII -complexes, unprecedented chemically inverse aza-MBH-type adducts are finally furnished with fair outstanding enantioselectivity, diversity functional groups both ketimine aldimine acceptors be well tolerated. Moreover, switchable α-regioselective normal also realized by tuning catalytic conditions, whereas moderate good enantioselectivity low excellent Z/E-selectivity is attained.

Language: Английский

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Ligand‐Dictated Regiodivergent Allylic Functionalizations via Palladium‐Catalyzed Remote Substitution

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(28)

Published: March 15, 2023

Different from classical allylic substitutions that require a vicinal leaving group, an olefin bearing remote group is scarcely viewed as potential allylation substrate. Herein, we describe feasible protocols to achieve regiodivergent C-H functionalizations via palladium-catalyzed substitution, which provides novel strategy for the seldomly studied migratory Tsuji-Trost reaction. Dictated by suitable ligand, process involved 4,3-hydrofunctionalization of generated conjugated diene intermediate metal walking observed in generally >20 : 1 regioselectivity. Unexpectedly, related 1,4-hydrofunctionalization pathway found be major route with newly synthesized electron-rich bisphosphine challenges conventional viewpoint on regioselectivity hydrofunctionalizations linear internal dienes η3 -substitution. A series deuterium experiments and kinetic studies provide preliminary insight into catalytic cycle.

Language: Английский

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Enantioselective Palladium‐Catalyzed Directed Migratory Allylation of Remote Dienes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(34)

Published: June 30, 2023

Chain walking has been an efficient route to realize the functionalization of inert C(sp3 )-H bonds, but this strategy is limited mono-olefin migration and functionalization. Herein, we demonstrate feasibility tandem directed simultaneous migrations remote olefins stereoselective allylation for first time. The adoption palladium hydride catalysis secondary amine morpholine as solvent critical achieving high substrate compatibility stereochemical control with method. protocol also applicable three vicinal bonds thus construct continuous stereocenters along a propylidene moiety via short synthetic process. Preliminary mechanistic experiments corroborated design dienes.

Language: Английский

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Chemodivergent Tandem Hydroalkylation and Hydroalkenoxylation of Conjugated Enynes

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(13), P. 9742 - 9751

Published: June 14, 2024

Due to the instability and weak O-nucleophilicity of enol, carbonyl compounds prefer function as C-nucleophiles instead O-nucleophiles in extensively studied transition metal-catalyzed hydrofunctionalizations unsaturated bonds. The corresponding hydroalkenoxylation reaction has thus long been unexplored. Here, we describe a chemodivergent protocol for challenging reactions. Dictated by Pd catalyst bearing different ligands, both 5-exo-trig 6-endo-trig processes are demonstrated be feasible between 1,3-enynes ketoesters, polysubstituted hydrofurans hydropyrans achieved good yields excellent chemoselectivities. In addition, enantioselective is also explored under an Rh moderate efficiency but with high stereoselectivities. Mechanistic studies corroborate designed tandem hydroalkylation uncover that ligand-to-ligand hydrogen transfer process might involved turnover-limiting step hydroalkenoxylation.

Language: Английский

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Asymmetric formal sp2-hydrocarbonations of dienes and alkynes via palladium hydride catalysis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 9, 2023

Abstract Transition metal-catalyzed asymmetric hydrofunctionalizations of unsaturated bonds via π-ƞ 3 substitution have emerged as a reliable method to construct stereogenic centers, and mainly rely on the use heteroatom-based or carbon nucleophiles bearing acidic C-H bonds. In comparison, sp 2 are generally not under consideration because enormous challenges in cleaving corresponding inert Here, we report protocol achieve formal hydrocarbonations, including hydroalkenylation, hydroallenylation hydroketenimination both 1,3-dienes alkynes hydroalkylation Wittig reaction cascade. A series unachievable motifs hydrofunctionalizations, such di-, tri- tetra-substituted alkenes, allenes, tri-substituted ketenimines allyl skeletons all facilely constructed high regio-, diastereo- enantioselectivities with this cascade design. Stereodivergent synthesis four stereoisomers 1,4-diene stereocenter Z/E-controllable olefin unit highlights power present protocol. An interesting mechanistic feature is revealed that alkyne actually undergoes hydrocarbonation formation conjugated diene intermediate, different from conventional viewpoint hydrofunctionalization only involves allene species.

Language: Английский

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Copper/ruthenium relay catalysis enables 1,6-double chiral inductions with stereodivergence

Chemical Science, Journal Year: 2024, Volume and Issue: 15(26), P. 10135 - 10145

Published: Jan. 1, 2024

A stereodivergent synthesis of chiral ζ-hydroxy amino esters containing 1,6-stereocenters and a unique β,γ-unsaturation was developed through asymmetric Cu/Ru relay catalysis to conduct the borrowing hydrogenation/1,6-Michael addition protocol.

Language: Английский

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Transition Metal-Catalyzed Asymmetric Migratory Allylic C—H Functionalization of Remote Dienes

Chinese Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 45(2), P. 592 - 592

Published: Jan. 1, 2025

Language: Английский

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Enantioselective Synthesis of Bicyclo[3.2.1]octadienes via Palladium‐Catalyzed Intramolecular Alkene‐Alkyne Coupling Reaction

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(51)

Published: Nov. 3, 2023

Bicyclo[3.2.1]octadiene compounds and derivatives exist in a number of natural products bioactive compounds. Nevertheless, catalytic enantioselective protocols for the synthesis these skeletons have not been disclosed. Herein we reported palladium-catalyzed asymmetric intramolecular alkene-alkyne coupling alkyne-tethered cyclopentenes, affording library enantionenriched bicyclo[3.2.1]octadienes excellent yields enantioselectivities (mostly >99 % ee). Moreover, could undergo an unusual iodination-induced 1,2-acyl migration, forming iodinated with three vicinal stereocenters. The enone isolated olefin motifs embedded provide useful handles downstream elaboration.

Language: Английский

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Nickel-catalyzed direct stereoselective α-allylation of ketones with non-conjugated dienes

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 22, 2023

The development of efficient and sustainable methods for the construction carbon-carbon bonds with simultaneous stereoselective generation vicinal stereogenic centers is a longstanding goal in organic chemistry. Low-valent nickel(0) complexes which promote α-functionalization carbonyls leveraging its pro-nucleophilic character conjunction suitable olefin acceptors are scarce. We report Ni(0)NHC catalyst selectively converts ketones non-conjugated dienes to synthetically highly valuable α-allylated products. directly activates α-hydrogen atom carbonyl substrate transferring it acceptor. transformation creates adjacent quaternary tertiary diastereoselective enantioselective manner. Computational studies indicate ability trigger ligand-to-ligand hydrogen transfer process from ketone substrate, setting selectivity process. shown selective functionalization α-C-H bond groups by opens up new opportunities exploit 3d-metal catalysis access chiral building blocks.

Language: Английский

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