A new high-load, soluble oligomeric dichlorotriazine (ODCT) reagent derived from ring-opening metathesis polymerization (ROMP) is reported as an effective coupling reagent, scavenger of nucleophilic species and activator of DMSO for the classic Swern oxidations. Two variants of this reagent 2GODCT 4 and 1GODCT 16, possessing theoretical loads of 5.3 mmol/g and 7.3 mmol/g, respectively, have been synthesized. Preparation was accomplished via simple synthetic protocols affording free flowing powders, amenable for large-scale production. Removal of the spent oligomeric reagent was achieved via either precipitation of the spent reagent or simple filtration utilizing a silica SPE, followed by solvent removal, to deliver products in excellent yield and purity. In addition, the corresponding norbornenyl monomer 3 was successfully demonstrated in a couple-ROMP-filter protocol utilizing in-situ polymerization, achieving comparable results versus the corresponding oligomeric variant.
This communication extends the scope of the rhodium(I)-catalyzed allenic Alder-ene carbocyclization reaction to the preparation of δ-and ε-lactams from amides. A variety of allenic propiolamides were cycloisomerized to give a number of unsaturated δ-lactams. In addition, allenic propargylamides give good yields of the corresponding ε-lactams. Formation of lactams possessing these ring sizes has rarely been accomplished via transition-metal catalyzed carboncarbon bond forming strategies. Thus, this approach provides an alternative strategy for synthesizing these substructures.Discovery of new and biologically significant compounds from nature provides a remarkable collection of structurally complex targets. Thus, there is a continual need for the development of new, more robust strategies for stitching atoms together. Expanding the synthetic toolbox to include under-utilized functional groups can serve as a springboard for these investigations. Our group is involved in examining transition metal catalyzed reactions of allenes, and these investigations have led to useful arrays of functionality via novel cyclocarbonylation and carbocyclization reactions. For example, we have previously demonstrated that the Rh(I)-catalyzed Alder-ene carbocyclization process affords crossconjugated trienes in high yields and is tolerant of a wide array of functionality. 1 Moreover, the resulting trienes can be used in a variety of ways, including tandem transition metal catalyzed carbon-carbon bond forming reactions 2 and DOS strategies. 3 It was upon consideration of these triene products that inspired us to explore the formal Alder-ene reaction of alkynyl allenes possessing amide tethers as a method for preparing highly unsaturated lactams. 4 Lactams are most commonly obtained via cyclodehydration reactions of amino acids, from ketones using either the Schmidt or Beckmann rearrangement reactions or cyclization of the amide nitrogen onto an alkene, alkyne or allene. 5 It is much less common to access amides via carbon-carbon bond forming reactions. 6 There are a handful of reports demonstrating the feasibility of an amide tether in carbocyclization reactions but these protocols have been limited to the preparation of γ-lactams. 7 Moreover, the reaction conditions are not generally tolerant of an unprotected amide, which is typically attributed to a disfavored rotamer population of the amide bond. 8 We would now like to report on our kbrummon@pitt.edu. Supporting Information Available. Characterization data and full experimental procedures are provided for all compounds in Tables 1 and 2 and Schemes 1, 2 and 3. This material is available free of charge via the internet at http://pubs.acs.org. progress towards extending the scope of the allenic Alder-ene carbocyclization reaction to amides for the formation of δ-and ε-lactams. 9
NIH Public AccessAllenic amino ester 1a was prepared as a single diasteromer using a Claisen rearrangment protocol developed in the Kazmaier laboratories. 10 Allenic amino esters 1b and 1c were obta...
A library of 90 carboxamide-containing oxepines and pyrans was synthesized. A dual-branching strategy was used where a common intermediate, an allenyl-hydroxy ester, was either allylated or propargylated then subjected to rhodium(I)-catalyzed carbocyclization reaction conditions to afford an oxepine- or triene-containing pyran, respectively. The oxepines were selectively reduced to afford two functionally unique scaffolds using complementary hydrogenation conditions. Diversification of the oxepines and pyrans involved conversion of the methyl carboxylate group to a carboxamide via either a microwave-assisted amidation using polymer-bound carbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) or a NaCN-catalyzed aminolysis. The scope of a rarely used carbonyl-yne reaction was expanded to the preparation of 10 new allenyl-hydroxy esters using microwave irradiation. Finally, a cell-based diversity analysis using BCUT (Burden (B) CAS (C) Pearlman at the University of Texas (UT)) metrics calculations and two-dimensional fingerprint similarity approaches shows that when compared to the 100,000 Pittsburgh Molecular Library Screening Center (PMLSC) compound database and PubChem the new compound library occupies a unique chemical space.
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