Kooperative Katalyse mit N‐heterocyclischen Carbenen

Abstract

Die Katalyse mit N‐heterocyclischen Carbenen (NHC) hat sich in der organischen Synthese zu einer leistungsfähigen Strategie entwickelt, um komplexe Moleküle hauptsächlich durch Umpolungsverfahren aufzubauen. Diese einzigartigen Lewis‐Basen wurden verwendet, um Acylanionen, Enolate und Homoenolate katalytisch zu generieren. Kürzlich wurde eine neue Strategie entwickelt, mit der die Anwendbarkeit der Carbenkatalyse bei Synthesen durch den wirksamen Einsatz zusätzlicher Aktivierungsarten erheblich erweitert werden konnte: die kooperative Katalyse. Durch die sorgfältige Auswahl von Cokatalysatoren können Reaktivitäten, Ausbeuten und Stereoselektivitäten verbessert werden. In einigen Fällen haben diese katalytischen Additive die Regioselektivität oder Diastereoselektivität verändert. In diesem Kurzaufsatz werden die neuesten Fortschritte bei der kooperativen Katalyse mit NHCs herausgestellt und die Gesamtentwicklung des Gebiets betrachtet.

Cooperative Catalysis for the Highly Diastereo‐ and Enantioselective [4+3]‐Cycloannulation of ortho‐Quinone Methides and Carbonyl Ylides

“…(3)]. Whereas the enantioselectivity of the latter reaction was virtually unchanged in comparison to the reaction with Rh 2 (OAc) 4 reported above, no enantioselectivity was observed with diphenyl phosphate as a Brønsted acid catalyst. Moreover, reaction of the stable ortho-quinone methide 1 q and 2 a in the presence of the chiral rhodium catalyst alone delivered dibenzooxacine 4 q in low yield and as a racemic mixture, indicating once again the critical role of the chiral phosphoric acid for the enantioselectivity of the process [Eq.…”

“…[3] The combination of a transition-metal catalyst and a Lewis acid or organocatalyst to activate two different substrates for a given reaction has attracted significant interest among synthetic organic chemists recently since it potentially enables highly efficient and/or unprecedented complex chemical transformations in a one-pot operation. [4] The success of this strategy relies upon the simultaneous activation of two reacting partners by two different catalysts that operate in concert in two distinct catalytic cycles. [4c] A prominent early example is the work of Hu, Gong, and co-workers on cooperative Rh-/chiral phosphoric acid catalyzed multicomponent reactions of a-diazoesters, alcohols, and imines, which were converted into a-hydroxy b-amino esters with excellent enantio-and diastereocontrol.…”

“…[14a,b] Very recently, the first example of a phosphoric acid catalyzed enantioselective reaction of o-QMs with 2indolylmethanols as 1,3-dipoles toward indolylbenzoxepins was established by Shi et al [14c] An interesting study by the Lautens group described a purely Brønsted acid catalyzed diastereoselective synthesis of oxa-bridged oxazocines through cycloaddition with isomünchnones. [14e] To test our hypothesis, we initiated our investigations with the model reaction between benzhydryl alcohol 1 a and adiazoester 2 a in the presence of 5 mol % of Rh 2 (OAc) 4 and chiral phosphoric acid PA1 (10 mol %) in CHCl 3 at room temperature. We were delighted to obtain the desired product 3 a in 77 % yield after 12 h with moderate diastereo-and enantioselectivity ( Table 1, entry 1).…”

“…Moreover, the products may be successfully manipulated to access valuable synthetic building blocks. The striking feature of this process is the separate catalytic activation of nucleophile and electrophile, with a chiral phosphoric acid enabling the formation of a transient hydrogen-bonded ortho-quinone methide and Rh 2 (OAc) 4 delivering the transient carbonyl ylide in a one-pot operation. Further extensions of this process are currently underway in our laboratory.…”

Dehydrative Allylation between Aldehydes and Allylic Alcohols through Synergistic N‐Heterocyclic Carbene/Palladium Catalysis

“…[2] The variety of nucleophilesi nd ehydrativea llylation is not yet sufficient,s ot heir expansion is highly desirable.Previously,w ed evelopedanewsynthetic strategy,t hat is, the direct use of aldehydes as umpolung acyl anion equivalents to reactw ith allylic carbonates, which was enabled by synergistic N-heterocyclic carbene (NHC)/palladiumc atalysis. [3] The reaction occurs through the formation of an ucleophilic Breslow intermediate [4][5][6][7][8] by the reactionb etween NHC and the aldehyde,f ollowed by its reactionw ith the p-allyl palladium species. We envisaged that, if this umpolung methodology could be applied to dehydrative reactions with allylic alcohols, an efficient and straightforward methodf or the synthesiso f b,g-unsaturated ketones,w hich are prominentm otifs in bioactive natural compounds, pharmaceuticals, and variouss ynthetic intermediates,w ould be possible.…”