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Related Concept Videos

¹H NMR: Long-Range Coupling01:27

¹H NMR: Long-Range Coupling

2.9K
The coupling interactions of nuclei across four or more bonds are usually weak, with J values less than 1 Hz. While these are usually not observed in spectra, the presence of multiple bonds along the coupling pathway can result in observable long-range coupling.
In alkenes, spin information is communicated via σ–π overlap, as seen in allylic (four-bond) and homoallylic (five-bond) couplings. These coupling interactions are stronger when the σ bond is parallel to the alkene...
2.9K
Spin–Spin Coupling: Two-Bond Coupling (Geminal Coupling)01:20

Spin–Spin Coupling: Two-Bond Coupling (Geminal Coupling)

1.9K
Two NMR-active nuclei bonded to a central atom can be involved in geminal or two-bond coupling. Geminal coupling is commonly seen between diastereotopic protons in chiral molecules and unsymmetrical alkenes, among others.
The central atom need not be NMR-active because its electrons are affected by the electron polarization of the spin-active atoms. However, spin information is transmitted less effectively than in one-bond coupling, and 2J values are usually weaker than 1J values. The energy of...
1.9K
¹H NMR: Pople Notation01:09

¹H NMR: Pople Notation

2.8K
The Pople nomenclature system classifies spin systems based on the difference between their chemical shifts. Coupled spins are denoted by capital letters with subscripts indicating the number of equivalent nuclei. When the coupled nuclei have well-separated chemical shifts, they are assigned letters that are far apart in the alphabet, such as A and X. When the difference in chemical shifts is small, coupled nuclei are named using adjacent letters of the alphabet (AB, MN, or XY).
A proton...
2.8K
Spin–Spin Coupling: Three-Bond Coupling (Vicinal Coupling)01:22

Spin–Spin Coupling: Three-Bond Coupling (Vicinal Coupling)

1.7K
Vicinal or three-bond coupling is commonly observed between protons attached to adjacent carbons. Here, nuclear spin information is primarily transferred via electron spin interactions between adjacent C‑H bond orbitals. This generally favors the antiparallel arrangement of spins, so 3J values are usually positive.
The extent of coupling depends on the C‑C bond length, the two H‑C‑C angles, any electron-withdrawing substituents, and the dihedral angle between the involved orbitals. The...
1.7K
¹H NMR: Complex Splitting01:13

¹H NMR: Complex Splitting

2.1K
A proton M that is coupled to a proton X results in doublet signals for M. However, NMR-active nuclei can be simultaneously coupled to more than one nonequivalent nucleus. When M is coupled to a second proton A, such as in styrene oxide, each peak in the doublet is split into another doublet.
Splitting diagrams or splitting tree diagrams are routinely used to depict such complex couplings. While drawing splitting diagrams, the splitting with the larger coupling constant is usually applied...
2.1K
π Molecular Orbitals of 1,3-Butadiene01:24

π Molecular Orbitals of 1,3-Butadiene

12.6K
Conjugated dienes have lower heats of hydrogenation than cumulated and isolated dienes, making them more stable. The enhanced stabilization of conjugated systems can be understood from their π molecular orbitals.
The simplest conjugated diene is 1,3-butadiene: a four-carbon system where each carbon is sp2-hybridized and has an unhybridized p orbital that contains an unpaired electron. According to molecular orbital theory, atomic orbitals combine to form molecular orbitals such that the number...
12.6K

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Related Experiment Video

Updated: Mar 27, 2026

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions
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Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions

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Aligning Catalyst Structure With Reactivity: Cross-Coupling of Neopentyl Centers.

Kyle D Passley1, Philip Eckert1, James Craig Ruble2

  • 1Centre for Catalysis Research and Innovation (CCRI), Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.

Chemistry (Weinheim an Der Bergstrasse, Germany)
|March 25, 2026
PubMed
Summary

Researchers developed a scalable method for synthesizing hindered nonnatural amino acids using palladium-N-heterocyclic carbene (Pd-NHC) catalysts. Chlorinated NHC backbones are crucial for coupling bulky neopentylalkylzinc reagents, enabling late-stage functionalization.

Keywords:
PEPPSIdrug discoveryneopentyl Negishi cross‐couplingnonnatural amino acidspeptides

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Retropinacol/Cross-pinacol Coupling Reactions - A Catalytic Access to 1,2-Unsymmetrical Diols
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A Simple and Efficient Protocol for the Catalytic Insertion Polymerization of Functional Norbornenes
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A Simple and Efficient Protocol for the Catalytic Insertion Polymerization of Functional Norbornenes

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Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions
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Retropinacol/Cross-pinacol Coupling Reactions - A Catalytic Access to 1,2-Unsymmetrical Diols
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A Simple and Efficient Protocol for the Catalytic Insertion Polymerization of Functional Norbornenes
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A Simple and Efficient Protocol for the Catalytic Insertion Polymerization of Functional Norbornenes

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Area of Science:

  • Organic Chemistry
  • Catalysis
  • Medicinal Chemistry

Background:

  • Cross-coupling reactions involving sterically hindered substrates are challenging.
  • Palladium-N-heterocyclic carbene (Pd-NHC) complexes are effective catalysts, with bulkier catalysts often showing increased proficiency.
  • Deactivated amines, sulfides, and aryls require specific catalytic conditions for efficient coupling.

Purpose of the Study:

  • To systematically investigate the effect of substrate bulk and catalyst structure on cross-coupling reactions.
  • To develop a general and scalable method for synthesizing sterically hindered α-heteroarylmethyl nonnatural amino acids.
  • To explore the applicability of the developed method to challenging neopentylzinc substrates.

Main Methods:

  • Systematic pairing of neopentylalkylzinc building blocks with a series of Pd-NHC complexes.
  • Evaluation of catalyst performance based on substrate bulk and NHC ligand structure (specifically N-aryl ortho substituents and backbone chlorination).
  • Application of the optimized conditions for late-stage functionalization of complex molecules.

Main Results:

  • Identified that N-aryl ortho substituents on Pd-NHC catalysts can be no larger than isopropyl for coupling hindered alkylzincs.
  • Determined that chlorination of the NHC-core backbone (e.g., Pd-PEPPSI-IPrCl) is essential for high reactivity with these hindered substrates.
  • Demonstrated the method's broad applicability to challenging neopentylzincs, including those with coordinating groups (esters) and secondary substrates.

Conclusions:

  • A general, scalable synthetic route to sterically hindered, biomedically important α-heteroarylmethyl nonnatural amino acids has been established.
  • The study highlights the critical role of catalyst design, specifically NHC backbone chlorination and controlled steric bulk, in enabling challenging cross-coupling reactions.
  • The developed methodology offers a valuable tool for late-stage functionalization and the synthesis of complex organic molecules.