The palladium-catalyzed cross-coupling reaction of organoboron compounds with organic halides or pseudo-halides - the Suzuki-Miyaura reaction - is a remarkably useful tool in organic synthesis.
is a comprehensive online resource for synthetic organic chemists. Instead of offering coverage of millions of reactions, it uniquely focuses on 200,000+ of the most important and useful synthetic reactions. These reactions are reviewed and refined by trained chemists (rather than machine selected), resulting in a high quality, verified critical discussion of the use, selection, usability and repeatability of a given reaction.
Computer-Aided Design of Chiral Auxiliaries and Catalysts:Diastereo- and enantioselective chemical reactions are essential components for the efficient synthesis of complex chiral targets. We have generated several computational tools to assist researchers in designing and optimizing chiral catalysts including database searching and functionality mapping. In addition, we have developed semi-empirical quantum mechanical quantitative structure selectivity (QSSR) relationships for accurate and precise enantiomeric excess predictions of chiral catalysts. In one example, we correlated the structures of various beta-amino alcohol catalysts to their enantioselectivities in the asymmetric addition of diethylzinc to benzaldehyde. With our method the selectivities of new catalysts were also calculated. Subsequent chemical synthesis and analysis of the new catalysts indicated that the model was very useful and easily distinguished catalysts of low, moderate, and high selectivity.
The central theme of research in my laboratory is the rational design of new methods and catalysts for use in organic synthesis. As well as using traditional screening and development approaches, we employ several novel computational tools for the discovery and optimization of new reagents and catalysts. These new synthetic methods comprise the key steps in our total synthesis strategies to a variety of important pharmaceutical agents and natural products.
Thanks to the dedication of many chemists in this field, great advances of facile synthesis and wide utilization of alkynylboron compounds have been made with these versatile building blocks for diverse structures in organic synthesis.">
Efficient catalytic reactions that generate C–C bonds enantioselectively and those that produce trisubstituted alkenes diastereoselectively are central to research in chemistry. Transformations that accomplish these two tasks simultaneously in a single operation are prized, particularly if the catalysts, substrates and reagents are easily accessed at low cost and reaction conditions are mild. Here, we report a facile multicomponent catalytic process that begins with a chemo-, site- and diastereoselective copper–boron addition to a mon-substituted allene; the resulting boron-substituted organocopper intermediates then participate in a chemo-, site- and enantioselective allylic substitution. Products, which contain a stereogenic carbon center, a mono-substituted alkene and an easily modifiable Z-trisubstituted alkenylboron group, are obtained in up to 89% yield, with >98% branch- and stereoselectivity and >99:1 enantiomeric ratio. The copper-based catalyst is derived from a robust heterocyclic salt that can be prepared in multi-gram quantities from inexpensive starting materials and without costly purification procedures. Utility of the approach is showcased through enantioselective synthesis of gram quantities of natural products rottnestol (member of an antibiotic family) and herboxidiene/GEX1A (anti-tumor).
Thanks to the dedication of many chemists in this field, great advances of facile synthesis and wide utilization of alkynylboron compounds have been made with these versatile building blocks for diverse structures in organic synthesis.
Criegee intermediates: Research in the Lester laboratory is currently focused on the photo-induced chemistry of Criegee intermediates. Alkene ozonolysis is a primary oxidation pathway for alkenes emitted into the troposphere and an important mechanism for generation of atmospheric OH radicals, particularly in low light conditions, urban environments, and heavily forested areas. Alkene ozonolysis proceeds through Criegee intermediates, R1R2COO, which eluded detection until very recently. In the laboratory, the simplest Criegee intermediate, CH2OO, and methyl-substituted Criegee intermediates, CH3CHOO and (CH3)2COO, have now been generated by an alternative synthetic route and detected by VUV photoionization. This laboratory has further shown that UV excitation of the Criegee intermediates on a strong π*←π transition induces photochemistry, which involves multiple coupled excited state potentials and yields both O3P and O1D products. This group has also demonstrated that IR excitation of methyl-substituted Criegee intermediates in the CH stretch overtone region initiates unimolecular decay. The latter enables direct examination of the hydrogen transfer reaction leading to OH products, which is a key non-photolytic source of OH radicals in the atmosphere.
Mechanistic and synthetic organic photochemistry; NMR studies of through-space spin-spin coupling, magnetic anisotropy, substituent effects, and structural effects on spin relaxation rates.
Boron-substituted alkenes are widely used multipurpose functional groups. Single-catalyst/multi-substrate transformations that deliver multifunctional unsaturated organoboron compounds are therefore of great interest. In the first phase of our studies (), we found that chemoselective addition of (phosphine)Cu–B(pin) [B(pin) = (pinacolato)boron], derived from reaction of an in situ-generated (phosphine)Cu–alkoxide with B2(pin)2, to a mono-substituted allene (vs. aldehyde) affords 2-B(pin)-substituted allylcopper complex I, which then reacts with an aldehyde (vs. allene) to afford homoallylic alkoxide iii. An assortment of aldol-type products were obtained after oxidative treatment in up to >99:1 diastereomeric (d.r.) and 97:3 enantiomeric ratio (e.r.). Transformations with N-heterocyclic carbene (NHC) complexes of copper, while efficient, generated racemic products.
The central theme of the Molander group's research is the development of new synthetic methods and their application to the synthesis of organic molecules. The group's focus is to expand and improve the Suzuki coupling reaction for organoboron compounds. Robust, air- and water-stable potassium organotrifluoroborates (R-BF3K), are employed to carry out couplings under relatively mild conditions using non-toxic components.
The above reactions give 1,1-disubstituted alkenylboron units because of a second-stage γ addition (cf. ii), which causes the loss of a treasured attribute of the initially formed intermediate (i): a stereochemically defined and modifiable trisubstituted olefin. A multicomponent catalytic enantioselective process that preserves the trisubstituted alkenylboron group would have higher value. We thus envisioned a transformation involving chemo-, site- and stereoselective Cu–B(pin) addition to an allenyl substrate followed by chemo- and site-selective (branched vs. linear) cross-coupling of the resulting allylcopper species through enantioselective allylic substitution (EAS). The envisioned catalytic sequence would furnish multi-functional organoboron products v by a single operation; this would be in contrast to the existing strategies where each functional unit must be installed individually through extended and less efficient sequences, (for complete bibliography, see the ). Such a process would be a significant addition to an important but limited group of catalytic allyl–allyl reactions. Site- and enantioselective incorporation of allyl groups through catalytic EAS has been confined to simple fragments introduced via allylboron, allylmagnesium, or allylic alcohol compounds (see the for complete bibliography).