Joshua N. Payette

Bio: Joshua N. Payette is an academic researcher from University of Chicago. The author has contributed to research in topics: Enantioselective synthesis & Diels–Alder reaction. The author has an hindex of 5, co-authored 11 publications receiving 355 citations.

Enantioselective Route to Platensimycin: An Intramolecular Robinson Annulation Approach

Abstract: An enantioselective route to the tetracyclic core structure of the novel antibiotic lead compound platensimycin is accomplished in 10 steps from simple commercially available starting materials. Highlights of this synthesis include (1) a regio- and enantioselective Diels−Alder reaction between methyl acrylate and methyl cyclopentadiene to give adduct 2 with essentially complete regio-, diastereo-, and enantiocontrol; (2) oxidative decarboxylation of ester 2 using nitrosobenzene; (3) a one-pot reductive cyanation of lactone 4; (4) a stereoselective intramolecular Michael addition between an α-branched aldehyde moiety and a β-substituted enone part of 8, followed by aldol dehydration in one pot to give the Robinson annulation product 9.

Regioselective and Asymmetric Diels−Alder Reaction of 1- and 2-Substituted Cyclopentadienes Catalyzed by a Brønsted Acid Activated Chiral Oxazaborolidine

Abstract: Cationic oxazaborolidine 2 affords Diels−Alder adducts of ethyl acrylate and 2-substituted cyclopentadienes, derived from the corresponding mixture of regioisomers, as single isomers in excellent yields and enantioselectivities. Furthermore, Diels−Alder adducts of 1-substituted cyclopentadienes are obtained through a one-pot procedure whereby ethyl acrylate is initially employed to consume all 2-substituted cyclopentadiene. Subsequently, various 2,5-disubstituted benzoquinones are added to react with remaining 1-substituted cyclopentadiene. Remarkably, reaction occurs selectively at the double bond coordinated anti to catalyst 2 to provide adducts containing adjacent all-carbon quaternary stereocenters in high yields and excellent enantioselectivities.

Nitrosobenzene-mediated C-C bond cleavage reactions and spectral observation of an oxazetidin-4-one ring system.

Abstract: While bond formation processes have traditionally garnered the attention of the chemical community, methods facilitating bond breaking remain relatively undeveloped. We report a novel, transition-metal-free oxidative C−C bond cleavage process for a broad range of ester and dicarbonyl compounds involving carbanion addition to nitrosobenzene. ReactIR experiments on the nitrosobenzene-mediated oxidative decarboxylation of esters indicate the reaction proceeds via fragmentation of a previously unobserved oxazetidin-4-one heterocycle, characterized by an intense IR stretching frequency at 1846 cm−1. These mechanistic studies have allowed further expansion of this protocol to ketone cleavage reactions of a diverse array of β-ketoester and 1,3-diketone substrates. The conceptual and mechanistic insights offered by this study are likely to provide a platform for further development of bond-breaking methodologies.

Cationic-Oxazaborolidine-Catalyzed Enantioselective Diels–Alder Reaction of α,β-Unsaturated Acetylenic Ketones†

Abstract: Cationic oxazaborolidine 1 affords Diels-Alder adducts of α,β-unsaturated acteylenic ketones with cyclic and acyclic dienes in excellent yields and enantioselectivities. Importantly, dienophiles lacking the typical hydrogen bonding motif as required for other oxazaborolidinium mediated reactions also provide uniformly high levels of asymmetric induction. Subsequently, mechanistic studies of this reaction were undertaken through X-ray crystallographic and computational studies of BF3-acetylene complexes which both indicate a strong preference for syn-coordination geometry of the Lewis acid relative to the alkyne. Thus, we postulate syn-coordination of the acetylene by 1 is operative, which precludes the necessity for hydrogen bonding and maintains close proximity of the reactive sp carbon centers to the chiral environment of the catalyst, ensuring high enantioselectivities.

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

Abstract: : The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Quantum Mechanical Investigations of Organocatalysis: Mechanisms, Reactivities, and Selectivities

Abstract: Organocatalysis has captured the imagination of a significant group of synthetic chemists. Much of the mechanistic understanding of these reactions has come from computational investigations or studies involving both experimental and complementary computational explorations. As much as any other area of chemistry, organocatalysis has advanced because of both empirical discoveries and computational insights. Quantum mechanical calculations, particularly with density functional theory (DFT), can now be applied to real chemical systems that are studied by experimentalists; this review describes the quantum mechanical studies of organocatalysis. The dramatic growth of computational investigations on organocatalysis in the last decade reflects the great attention focused on this area of chemistry since the discoveries of List, Lerner, and Barbas of the proline-catalyzed intermolecular aldol reaction, and by MacMillan in the area of catalysis by chiral amino-acid derived amines. The number of reports on the successful applications of organocatalysts and related mechanistic investigations for understanding the origins of catalysis and selectivities keep growing at a breathtaking pace. Literature coverage in this review is until October 2009, except for very recent discoveries that alter significantly the conclusions based on older literature. 1.1 Computational methods for organocatalysis Over the last two decades, DFT has become a method of choice for the cost-effective treatment of large chemical systems with high accuracy.1 Most of the studies reported in this review were carried out using the B3LYP functional with the 6-31G(d) basis set, which is a standard in quantum mechanical calculations. Nevertheless, DFT is experiencing continuing developments of new functionals and further improvements. The availability of many new functionals and, in particular, the rapidly evolving performance issues of B3LYP have stimulated extra efforts on benchmarking DFT methods for the prediction of key classes of organic reactions.2 The well-documented deficiencies of B3LYP include the failure to adequately describe medium-range correlation and photobranching effects,3,4 delocalization errors causing significant deviations in π→σ transformations,2b,5 and incorrect description of non-bonding and long-range interactions,6 which are likely to be key factors in determining stereoselectivities. Benchmark results also show that newer functionals considerably improve some of the underlying issues.2–7 Recent advances, especially in the treatment of dispersion effects, now offer more reliable models of the reaction profiles and stereoselectivities. Most benchmarks focus on energetics rather than stereoselectivities. Systematic benchmarking for stereoselectivities requires more sophisticated techniques and averaging over conformations. To date, such benchmarking based upon stereoselectivity is available for only three reactions,8 and even there only various basis sets with B3LYP, as well as comparisons of results predicted using enthalpies and free energies. It is not possible to assign error bars for stereoselectivities for the majority of reports discussed in this review. Because stereoisomeric transition structures are very similar species, their relative energies are likely to be calculated accurately, as shown by the good agreement between calculated and experimental values. More recently Harvey (Harvey, 2010, faraday discussions) has studied two typical organic reactions of polar species (Wittig and Morita-Baylis-Hillman reactions) at different levels of theory.2i He showed that many standard computational methods, involving B3LYP, are qualitatively useful, but the energetics may be misleading for larger reactive partners; the quantitative prediction of rate constants remains difficult. These studies suggest that although B3LYP provides valuable qualitative insight into the reaction mechanisms and selectivities, the energetics may require testing with higher accuracy methods for complex organic systems. On the other hand, Simon and Goodman found B3LYP to be “only slightly less accurate” than newer methods, and recommended its use for organic reaction mechanisms.9

Brønsted acid catalyzed, conjugate addition of β-dicarbonyls to in situ generated ortho-quinone methides--enantioselective synthesis of 4-aryl-4H-chromenes.

Abstract: We describe herein a catalytic, enantioselective process for the synthesis of 4H-chromenes which are important structural elements of many natural products and biologically active compounds. A sequence comprising a conjugate addition of β-diketones to in situ generated ortho-quinone methides followed by a cyclodehydration reaction furnished 4-aryl-4H-chromenes in generally excellent yields and high optical purity. A BINOL-based chiral phosphoric acid was employed as a Bronsted acid catalyst which converted ortho-hydroxy benzhydryl alcohols into hydrogen-bonded ortho-quinone methides and effected the carbon-carbon bond-forming event with high enantioselectivity.