Rhodium(I)-Catalyzed Allenic Carbocyclization Reaction Affording δ- and ε-Lactams

Abstract

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...

Dendralene auf dem Vormarsch: kreuzkonjugierte Oligoene ermöglichen den schnellen Aufbau molekularer Komplexität

“…Nach den wichtigen frühen Beobachtungen von Malacria et al [116] und Sato et al [117] und auf Basis von vereinzelten Beispielen mit niedrigen Ausbeuten, über die von Oh et al [118] und Livinghouse et al [119] berichtet wurde, erfolgte der Durchbruch 2002 mit einer Verçffentlichung von Brummond et al, [120] die Cyclisierung von Substraten zu Trienlactamen katalysieren kann, wenn die Allen-und Alkineinheiten durch eine überbrückende Amidgruppe verbunden sind. [124] Brummond und Yan demonstrierten auch die Synthese von fünf-und sechsgliedrigen cyclischen Trienonen (d. h. 159!160) und von fünf-, sechs-und siebengliedrigen cyclischen Trienamiden unter Verwendung des gleichen Katalysators. [125] Eine der grçßten Hürden bei dieser Reaktion ist die Entwicklung einer Mçglichkeit, selektiven Hydridtransfer von einem der beiden verschiedenen terminalen Allensubstituenten zu erreichen.…”

Skeletal and appendage diversity as design elements in the synthesis of a discovery library of nonaromatic polycyclic 5-iminooxazolidin-2-ones, hydantoins, and acylureas

“…16,21 Saponification of the methyl esters 1 { 1–2 } with lithium hydroxide, followed by HOBt/DMAP/EDCI mediated amidation with amines 2 { 1–6 } provided amides 5 { 1–2,1–6 } in yields ranging from 18–93% (Scheme 1, Table 1) for the two steps.…”

One-Pot Synthesis of 3-(Trimethylsilyl)propynamides

“…3-(Trimethylsilyl)propynoic acid amides are valuable intermediates in the synthesis of biologically important heterocyclic compounds, such as chiral 2-trimethylsilyldihydro-1,3-oxazoles [1], trimethylsilylidenehydantoins [2], 1,5-trisubstituted 1H-1,2,3-triazoles [3], indoloquinolines [key compounds in the total synthesis of alkaloids (±)-lysergic acid and (±)-LSD] [4], as well as in the regio-and stereocontrolled synthesis of 3-carbamoylcyclopentenones as chiral synthetic intermediates or ligands [5], tetra-(hexa)hydrofuro [3,4-e]isoindol-6-ones as intermediate products in the synthesis of antibiotic lactonamycin [6], and unsaturated γ- [7] and δ-lactams [8].…”

“…The presence of a trimethylsilyl group at the triple bond favors stabilization of carbofunctional acetylene derivatives and their adducts, deactivates the triple bond toward nucleophiles [9], and ensures regioselective cycloaddition of azides at the triple of bond of various trimethylsilylalkynes with formation of the corresponding 4-trimethylsilyl-1H-1,2,3-triazoles [3,10] and cycloaddition of norbornadiene to the Co 2 (CO) 8 complex with (trimethylsilylpropynoyl)oxazolidine or sultam according to the Pauson-Khand reaction [5].…”