Browsing by Subject "Allylation"
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Item Carbon-carbon bond formation via catalytic hydrogenation and transfer hydrogenation : application in the total synthesis of bryostatin 7(2012-08) Lu, Yu, active 2012; Krische, Michael J.Under the conditions of transfer hydrogenation employing ortho-cyclometallated iridium C,O-benzoate catalysts, two protocols of iterative chain elongation of 1,3-diols to furnish 1,3-polyols were developed. First, one-directional chain elongation employing mono-protected 1,3-diols as starting materials was achieved. In all cases, high levels of catalyst-directed enantioselectivity and diastereoselectivity were observed. Then, double asymmetric allylation of 1,n-glycols to deliver C₂-symmetric adducts with exceptional level of enantioselectivity was devised. Iterative two-directional elongation of 1,3-diols to furnish 1,3-polyols with high level of catalyst-directed diastereoselectivity was then achieved. Implementation of this methodology and other hydrogenative C-C bond formations proved to be effective means for the preparation of a known bryostatin A-ring fragment and the total synthesis of bryostatin 7.Item Formation of C-C bonds via transfer hydrogenation : from methodology development to natural product synthesis(2013-08) Gao, Xin, active 2013; Krische, Michael J.Under the conditions of transfer hydrogenation employing ortho-cyclometallated iridium C,O-benzoate catalysts, selective silylallylation and CF₃-allylation were developed. In both cases, high levels of catalyst-directed enantioselectivity and diastereoselectivity were observed. Column chromatography was then tested as a new protocol to purify the iridium precatalyst; this single component precatalyst was proved to be more efficient to promote carbonyl crotylation reactions, both diastereo- and enantioselectivity were increased. Then, double asymmetric crotylation of 1,3-diols to deliver (pseudo-)C₂-symmetric adducts with exceptional level of enantioselectivity was devised. Implementation of this methodology and other hydrogenative C-C bond formations proved to be effective means for the preparation of two known polypropionate natural product fragments of C19-C25 of scytophycin C, C19-C27 of rifamycin S and the total synthesis of 6-deoxyerythronolide B.Item Regio- and enantioselective C-C and C-N bond formations catalyzed by amphiphilic [pi]-allyliridium C,O-benzoate complexes(2022-05-02) Jung, Woo-Ok; Krische, Michael J.; Liu, Hung-Wen; Hull, Kami L; Rose, Michael J; Whitman, Christian PEnantioselective nucleophilic and electrophilic allylations mediated by racemic branched allylic acetates and catalyzed by π-allyliridium C,O-benzoate complexes are described. The π-allyliridium C,O-benzoate-catalyzed reductive coupling of the commodity chemical allyl acetate with acetylenic ketones mediated by 2-propanol to form enantiomerically enriched tertiary propargyl alcohols was developed. The same π-allyliridium C,O-benzoate complexes were found to be competent catalysts for the enantioselective electrophilic allylations of secondary amines and α,α-disubstituted nitronates, delivering tertiary allylic amines and (after zinc-mediated reduction of the nitroalkane) β‑stereogenic α‑quaternary primary amines, respectively. These processes form hindered C-C and C-N bonds with complete levels of branched regioselectivity. Attempted use of linear allyl acetates in the aforesaid processes provided products hydroamination instead of the expected products of Tsuji-Trost-type allylation. As revealed by deuterium labelling studies, chelation of the iridium catalyst to the internal olefin and the acetate carbonyl played a key role in partitioning the hydroamination vs allylation pathways and directing the regioselectivity of hydroamination.Item Transition metal catalyzed carbonyl additions under the conditions of transfer hydrogenation(2011-05) Patman, Ryan Lloyd; Krische, Michael J.; Anslyn, Eric V.; Siegel, Dionicio R.; Brodbelt, Jennifer S.; Kerwin, Sean M.The efficient construction of complex organic molecules mandates that an assortment of methods for forming C-C bonds be available to the practicing synthetic chemist. The addition of carbon based nucleophiles to carbonyl compounds represents a broad class of reactions used to achieve this goal. Traditional methodology requires the use of stoichiometrically preformed organometallic reagents as nucleophiles in this type of reaction. However, due to the moisture sensitivity, excessive preactivation and inevitable generation of stoichiometric waste required for the use of these reagents, alternative methods have become a focus of the synthetic organic community. The research presented in this dissertation describes a new class of C-C bond forming reactions enabled through catalytic transfer hydrogenation. Here, the development and implementation of efficient green methods for carbonyl addition employing π-unsaturates as surrogates to preformed organometallic reagents is described. Additionally, this research describes the first systematic studies toward using alcohols as electrophiles in carbonyl allylation, propargylation and vinylation reactions.Item Transition metal-catalyzed reductive C-C bond forming hydrogenation/transfer hydrogenation and applications in the total synthesis of (+)-roxaticin(2010-12) Han, Soo Bong, 1975-; Krische, Michael J.; Magnus, Philip D.; Cowley, Alan H.; Kerwin, Sean M.; Siegel, Dionicio R.By simply hydrogenating enones in the presence of aldehydes at ambient temperature and pressure, aldol adducts are generated under neutral conditions in the absence of any stoichiometric byproducts. Using cationic rhodium complexes modified by tri(2-furyl)phosphine, highly syn-diastereoselective reductive aldol additions of vinyl ketones are achieved. Finally, using novel monodentate TADDOL-like phosphonite ligands, the first highly diastereo- and enantioselective reductive aldol couplings of vinyl ketones were devised. These studies, along with other works from our laboratory, demonstrate that organometallics arising transiently in the course of catalytic hydrogenation offer byproduct-free alternatives to preformed organometallic reagents employed in classical carbonyl addition processes. Existing methods for enantioselective carbonyl allylation, crotylation and tert-prenylation require stoichiometric generation of pre-metallated nucleophiles, and often employ stoichiometric chiral modifiers. Under the conditions of transfer hydrogenation employing an ortho-cyclometallated iridium C,O-benzoate catalyst, enantioselective carbonyl allylations, crotylations and tert-prenylations are achieved in the absence of stoichiometric metallic reagents or stoichiometric chiral modifiers. Moreover, under transfer hydrogenation conditions, primary alcohols function dually as hydrogen donors and aldehyde precursors, enabling enantioselective carbonyl addition directly from the alcohol oxidation level.