Thread by @ChrisSlootweg

@dad2420 @EricAnslyn @sksilverman I just finished teaching Physical Organic Chemistry in Amsterdam based on your awesome book. Sounds great that the 2nd edition is in preparation. I am very much looking forward to it! Some suggestions based on my teaching material: here’s a thread...👇

@dad2420 @EricAnslyn @sksilverman p7, going deeper: i always like to use pentaorganosilicates as an example to show that the formal negative charge is on the more electropositive Si atom, see e.g. @J_A_C_S doi.org/10.1021/ja0645…

@dad2420 @EricAnslyn @sksilverman @J_A_C_S p70, entropy: It’s fun to highlight that when reactants and products are in equilibrium, it’s possible to drive the reaction to completion by lowering the reaction temperature, and converting the reaction from endergonic at RT to exergonic at low T. E.g. doi.org/10.1002/anie.2…

@dad2420 @EricAnslyn @sksilverman @J_A_C_S p82, strain energy: To highlight that compounds can be highly strained, yet thermally stable I typically show my phospha[7]triangulane (SE = 224 kcal/mol; mp 168 C) doi.org/10.1021/ja0316… 🙂

@dad2420 @EricAnslyn @sksilverman @J_A_C_S p90, carbocations: the X-ray structure of the non-classical 2-norbornyl cation is a real treat! @sciencemagazine DOI:10.1126/science.1238849.

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine p112, Bredt’s rule: I always like highlighting these anti-Bredt olefins by illustrating Schleyer’s Olefin Strain, see e.g. doi.org/10.1002/anie.2… @angew_chem

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem and of course @brianstoltz70’s anti-Bredt (twisted) amide @nature doi:10.1038/nature04842

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature To illustrate alkyne strain, I love highlighting the copper-free click chemistry published by Wittig and Krebs in 1961!! See, e.g., doi.org/10.1021/ar2001… @CarolynBertozzi

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi Next to steric hindrance also steric attraction deserves to be highlighted, see the key review “London Dispersion in Molecular Chemistry—Reconsidering Steric Effects” by Peter Schreiner @prsgroupjlu doi.org/10.1002/anie.2… @angew_chem

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu p116, aromaticity: I love adding excited-state aromaticity, see e.g. @NatureChemistry doi.org/10.1038/nchem.…. This also makes it easy in Ch15 to explain the allowed photochemical [2+2] cycloaddition using the (excited-state) aromatic transition state theory.

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry Another great example is the aromatic P2N3 anion by @ccclabmit and @velianlab @science DOI:10.1126/science.aab0204, also illustrating solvent effects (31P NMR: 1 signal in acetonitrile and 2 in benzene)

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science p260, Brønsted acidity: The review “Basic Remarks on Acidiy” by Ingo Krossing @angew_chem doi.org/10.1002/anie.2… provides a great unified overview.

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science p271. To highlight that solvation is a major factor in controlling acid-base equilibria and that a free proton does not exist, Brookhart’s acid is a great example for nonaqueous solutions @Orgmet_ACS doi.org/10.1021/om0005…

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS A free hydroxide ion also does not exist, see e.g. Hoge’s water-stabilized hydroxide anion [OH(OH2)3] @angew_chem doi.org/10.1002/anie.2…

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS p264, pKa of water: it would be good to avoid confusing (15.7 or 14.0 for H2O, and -1.74 or 0.0 for H3O+), and also take the bulk solvent effects into account, see doi.org/10.1002/hlca.2….

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS p270, super acids: I love the fully characterized examples of protonated ketones/aldehydes by Gerken et al. doi.org/10.1002/anie.2… that also higlights solvation of the “free” proton by using two aldehydes.

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS More recent examples: protonated benzene by Riedel et al. @angew_chem doi.org/10.1002/anie.2…, protonated P4 by Mueller et al. @ChemicalScience
10.1039/C8SC03023E and protonated ferrocene by Meyer et al. doi.org/10.1002/anie.2…

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience p284, predicting acid strength, hybridization: super acidic protonated nitriles (nitrilium ions, see also @angew_chem doi.org/10.1002/anie.2…) are now also crystallographically characterized, see @DaltonTrans 10.1039/C6DT01301E

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert nicely illustrated the application of induction, resonance and aromaticity in the design of a potent chiral Brønsted acid catalyst. @sciencemagazine DOI: 10.1126/science.aad0591

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert p288, Lewis acids/bases: Dinitrogen is a poor Lewis acid/base, so only with very strong Lewis bases/acids its forms an adduct. With phenyl cations and phosphines N2 forms colorfull azophosphonium ions @angew_chem doi.org/10.1002/anie.2…

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert N2 can also be “trapped” by Lewis bases only. The intriguing donor-acceptor complex N2(PPh3)2 is kinetically stable, yet thermally unstable and decomposes into dinitrogen and phosphine above 215 C. @Jones_Research doi.org/10.1002/anie.2….

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research p290, HSAB: to deepen the concept of Hard and Soft Acids and Bases, I like Mayr’s “Farewell to the HSAB Treatment of Ambident Reactivity” @angew_chem doi.org/10.1002/anie.2… and in particular the ambident reactivity of the Cyanide Ion doi.org/10.1002/anie.2….

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research p322, Symmetry and Time Scale: I really like linking chirality with configurational stability. see, e.g. the four screenshots below.

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research In the design of chiral pentaorganosilicates, configurational stability/rigidity (hampering the Berry pseudorotation) as well as @fmbickelhaupt’s “ball-in-a-box” model is key. See doi.org/10.1021/ja8091… and doi.org/10.1021/acs.in….

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt For selectivity in catalysis also pentacoordinate intermediates should be rigid. See e.g. the design of sequence selectivity into a Ring-Opening Metathesis Polymerization Catalyst by Peter Chen @ETH_en doi.org/10.1021/acs.ac…

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en p455, solvent effects: The impact of solvation is nicely illustrated by Ken Houk for the Sn2 reaction @J_A_C_S doi.org/10.1021/ja0490…

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en Specific solvation effects: in the presence of 18-crown-6, KF is soluble in benzene and fluoride becomes a reactive nucleophile.

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en To highlight the importance of contact ion pairs in asymmetric catalysis, ACDC developed by @ListLaboratory is really elegant! @angew_chem doi.org/10.1002/anie.2…

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en @ListLaboratory p458, 8.4.4: Herbert Mayr’s “Philicities, Fugalities, and Equilibrium Constants” doi.org/10.1021/acs.ac… is a great review to add, which also highlights that the terms acidity and basicity are assigned to thermodynamic properties, while philicity and fugality refer to kinetics.

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en @ListLaboratory Much of the concepts of Physical Organic Chemistry are qualitative, hence I really enjoy including Mayr’s quantitative comparisons too, e.g. @angew_chem doi.org/10.1002/anie.2…

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en @ListLaboratory p507: Next to Brønsted acid-base Catalysis, I also included Lewis acid-base Catalysis, in particular the metal-free, frustrated Lewis pair catalysis developed by @FLPchemist!

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en @ListLaboratory @FLPchemist An awesome example of hydrogenation catalysis is:
doi.org/10.1002/anie.2… @angew_chem. After heterolytic H-H cleavage using the weak Lewis base diethyl ether, the strong Brønsted acid [H(OEt2)2][H-BCF] is formed that can protonate 1,1‐diphenylethylene forming a stable carbocat.

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en @ListLaboratory @FLPchemist In 1987, Lennart Eberson indicated that Organic Electron Transfer Theories come in Cycles. With, in particular, the advent of photoredox catalysis, single electron transfer/shift is a key concept not to forget.

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en @ListLaboratory @FLPchemist Armido Studer and Dennis Curran highlighted this concept with a seminal overview in @natchem entitled “The electron is a catalyst” @NatureChemistry doi.org/10.1038/nchem.… ...

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en @ListLaboratory @FLPchemist @natchem ...Very elegantly, they compared proton with electron catalysis and hole-catalysed with base-catalysed reactions.

@dad2420 @EricAnslyn @sksilverman @J_A_C_S @sciencemagazine @angew_chem @brianstoltz70 @nature @CarolynBertozzi @prsgroupjlu @NatureChemistry @ccclabmit @velianlab @science @Orgmet_ACS @ChemicalScience @DaltonTrans @TristanHLambert @Jones_Research @fmbickelhaupt @ETH_en @ListLaboratory @FLPchemist @natchem I hope this thread is of any use... At least I have thoroughly enjoyed adding this material to my PhysOrgChem lectures. 🙂