Sequential catalysis: exploiting a single rhodium(i) catalyst to promote an alkyne hydroacylation–aryl boronic acid conjugate addition sequence

Abstract

We demonstrate that a single Rh(i) complex can promote two mechanistically distinct C–C bond-forming reactions – alkyne hydroacylation and aryl boronic acid conjugate addition – to deliver substituted ketone products from the controlled assembly of three readily available fragments.

Chiral Diene Ligands in Asymmetric Catalysis

“…The sequential hydroacylation of alkynes and asymmetric conjugate addition of boronic acids to provide enantioenriched β-substituted ketones has also been reported (Scheme 43b). 207 High enantioselectivity (up to >99% ee) was achieved using two rhodium catalysts, one of which was achiral rhodium complex ([Rh(dcpm)(C 6 H 5 F)]BAr F ) for the hydroacylation and the other of which was a chiral diene complex ([Rh(L11h)- (MeCN) 2 ]BAr F ) for the asymmetric conjugate addition. In the presence of both rhodium complexes, the hydroacylation of alkyne with 2-aminobenzaldehyde 177 took place, producting α,β-unsaturated ketone 178.…”

α‐Amidoaldehydes as Substrates in Rhodium‐Catalyzed Intermolecular Alkyne Hydroacylation: The Synthesis of α‐Amidoketones

“…Alternative wide bite angle ligands, such as BINAP,D PEphosa nd Xantphos were not effective (entries 5-7). Havinge stablished dppe as the most effective ligand for the reaction, we next evaluated ap reformed catalyst [Rh(dppe)(C 6 H 5 F)][BAr F 4 ], [17] with the aim of achieving good reactivity with ad ecreased catalyst loading. Pleasingly, full conversion (80 %i solated yield) and increased regioselectivity (7:1 to 10:1) wasa chieved using 5mol %c atalyst (entry 8), and importantly,the reaction could be performed at 40 8Ci nC H 2 Cl 2 ,c ompared to 80 8Cn eeded in the originalr eaction.…”

Enantioselective Three-Component Assembly of β′-Aryl Enones Using a Rhodium-Catalyzed Alkyne Hydroacylation/Aryl Boronic Acid Conjugate Addition Sequence

“…Our design relies on three key operations: (i) rhodium-catalyzed hydroacylative union of an alkyne and a β-substituted alkyl aldehyde to provide β′-substituted enone A ; (ii) rhodium-catalyzed enantioselective addition of an aryl boronic acid to enone A ; and (iii) elimination of the β-substituent X to provide the target compounds. We have recently established the synthetic utility of combining rhodium-catalyzed hydroacylation and conjugate addition reactions in one-pot cascade sequences and, as such, speculated that the targeted route, which employs three readily available starting materials, could be achieved in an efficient and selective manner.…”

“…Accordingly, we selected a variety of β- S -substituted octenal derivatives as our evaluation substrates and explored their addition to octyne as the first step of our planned sequence (Table ). Based on earlier studies, we selected the small bite angle ligand dppm as the ligand of choice for use in the hydroacylation step and diene ligand L1 for the conjugate addition . Although we could achieve efficient hydroacylation reactions for aldehydes bearing Et-, i -Pr-, and t -Bu-sulfide substituents, it was only with the sterically demanding t -BuS-substituted example that efficient conjugate addition took place (Table , entries 1–3) .…”