Browsing by Subject "Carbonyl addition"

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Carbon-carbon bond formation via transition metal-catalyzed transfer hydrogenative carbonyl addition
(2022-11-28) Spinello, Brian Joseph; Krische, Michael J.; Liu, Hung-Wen; Hull, Kami; Whitman, Christian P
Carbonyl addition persists as one of the most broadly utilized methods for the construction of carbon-carbon bonds. However, classical methods for carbonyl addition require preformed organometallic reagents, which are often highly basic, moisture sensitive, and hazardous. To circumvent these issues, novel synthetic methods have been developed for the construction of carbon-carbon bonds via metal-catalyzed transfer hydrogenative carbonyl reductive coupling, which avoid the use of stoichiometric organometallic reagents. Three methods for ketone formation are described that involve rhodium-catalyzed carbonyl reductive coupling to deliver allylic or homoallylic alcohols, which undergo immediate redox-isomerization to generate saturated ketones products. Additionally, the use of a novel iodide-bound ruthenium-JOSIPHOS catalyst system catalyzes anti-diastereo- and enantioselective carbonyl crotylations of primary alcohols mediated by methylallene and butadiene. Finally, π-allyliridium C,O-benzoate complexes catalyze enantioselective electrophilic allylation of α,α-disubstituted nitronates providing entry to β-stereogenic α-quaternary primary amines after zinc-mediated nitroalkane reduction.
Commodity chemicals in enantioselective iridium-catalyzed carbonyl allylation
(2023-04-13) Meyer, Cole Christian; Krische, Michael J.; Hull, Kami L; Sessler, Jonathan L; Whitman, Christian P
A principal characteristic of a scalable synthetic method is its ability to facilitate the formation of C-C bonds between inexpensive, abundant commodity chemicals without producing stoichiometric metallic byproducts. To this end, a suite of enantioselective iridium-catalyzed reactions for the direct transformation of commodity chemicals to value-added products is described. The reductive couplings discussed herein utilize alcohols as terminal reductants, and therefore do not produce stoichiometric metallic byproducts. The work presented in this dissertation includes 1) a review on couplings of methanol, ethanol, and formaldehyde with π-unsaturated pronucleophiles, and primary research articles describing enantioselective iridium-catalyzed carbonyl allylations involving commodity chemicals 2) allene gas, a petrochemical feedstock, 3) ethanol, a biorenewable C2 feedstock, 4) oxetan-3-one and azetidin-3-ones, abundant building blocks deployed in medicinal chemistry, 5) allyl alcohol, a reliably-sourced acrolein proelectrophile, and its application to the total synthesis of three amphidinolide natural products, and 6) acetyl 1,3-propanediol, a derivative of 1,3-propanediol, as an improved acrolein proelectrophile.
Controlling selectivity in novel transition metal catalyzed carbon-carbon bond forming hydrogenations
(2012-05) Zbieg, Jason Robert; Krische, Michael J.; Anslyn, Eric V.; Siegel, Dionicio R.; Brodbelt, Jennifer S.; Liu, Hung-Wen
The focus of my graduate research in the Krische group has been the development of catalytic carbon-carbon bond forming reactions with an emphasis on controlling diastereo- and enatio-selectivity in transfer hydrogenative couplings. The broad goal of our research program has been the development and implementation of efficient green methods for carbonyl addition employing [pi]-unsaturates as surrogates to preformed organometallic reagents, thus enabling byproduct free variants of traditional carbanion chemistry. This dissertation shows the new reactions that I have developed toward this goal. These reactions includes new metal catalyzed approaches for carbonyl crotylation, aminoallylation, and vinylogous reformatsky aldol reactions.
Transition metal catalyzed C-C bond formation : advances in carbonyl addition
(2017-08) Garza, Victoria J.; Krische, Michael J.; Anslyn, Eric V; Martin, Stephen F; Keatinge-Clay, Adrian T; Rose, Michael J
Transition metal catalyzed transfer hydrogenative methods for carbon-carbon bond construction are attractive alternatives to tradition carbonyl addition protocols. By generating carbonyl and organometallic species in-situ, these redox-triggered reactions remove the need for preactivation of reactive partners. This affords a more atom and step economic, and ultimately more efficient approach to carbonyl addition. Efforts have been focused on the development of ruthenium and iridium catalyzed coupling reactions of primary alcohols and aldehydes to a variety of unsaturates. To produce highly stereoselective transformations, investigation into the selectivity in iridium catalyzed couplings was undertaken. Improving upon methods for carbonyl addition can provide access to new areas in synthetic organic methodology.
Transition metal-catalyzed carbon-carbon bond formation utilizing transfer hydrogenation
(2015-05) Montgomery, Timothy Patrick; Krische, Michael J.; Anslyn, Eric V; Dong, Guangbon; Brodbelt, Jennifer S; Liu, Hung-wen
A central tenant of organic synthesis is the construction of carbon-carbon bonds. One of the traditional methods for carrying out such transformations is that of carbonyl addition. Unfortunately, traditional carbonyl addition chemistry suffers various drawbacks: preactivation, moisture sensitivity, and the generation of stoichiometric organometallic waste. The research presented in this dissertation focuses on the development of methods that make use of nucleophile-electrophile pairs generated in situ via transfer hydrogenation, which allow the formation of carbonyl or imine addition products from the alcohol or amine oxidation level; streamlining the construction of complex molecules from simple, readily available starting materials. Additionally, studies toward the total synthesis of the fibrinogen receptor inhibitor tetrafibricin, utilizing the methods developed in catalytic carbon-carbon bond formation through the addition, transfer or removal of hydrogen, are presented.
Transition-metal catalyzed redox triggered C-C bond forming reactions via carbonyl addition
(2019-05) Zhang, Wandi; Krische, Michael J.
Carbon-carbon (C–C) bonds construct the skeleton of all organic molecules. Hence, the development of new efficient methods of C–C bond formation is of great significance in organic chemistry. Since the discovery of the Grignard reaction, carbonyl addition has been an established method for C–C bond formation. In classical carbonyl additions, premetalated reagents or stoichiometric metallic reductants are required. By taking advantage of the native reducing capability of alcohols, our lab has developed methods that exploit alcohols and π-unsaturates to generate transient electrophile-nucleophile pairs to directly convert lower alcohols to higher alcohol. Efforts have been focused on the development of transition metal-catalyzed redox-triggered coupling reactions of primary alcohols and aldehydes to π-unsaturates as well as aryl iodides. Modern methods to construct new C-C bonds in highly selective manner via carbonyl addition were undertaken.