Palladium-catalysed formation of vicinal all-carbon quaternary centres via propargylation

Abstract

Construction of two vicinal all-carbon quaternary carbon centres is of great importance due to the common presence of such units in natural and unnatural molecules with attractive functions. However, it remains a significant challenge. Here, we have developed a palladium-catalysed general coupling for the efficient connection of two tertiary carbon atoms: Specifically, propargylic carbonate has been treated with a fully loaded soft functionalized nucleophile to connect such two fully loaded carbon atoms with a simple palladium catalyst. It is observed that the central chirality in the optically active tertiary propargylic carbonates has been remembered and transferred into the products with very high efficiency. The triple bond and the functional groups such as ester, cyano and unsaturated C–C bonds make this method a relatively general solution for such a purpose due to their high synthetic versatility.

Transition‐Metal‐Catalyzed Propargylic Substitution of Propargylic Alcohol Derivatives Bearing an Internal Alkyne Group

“…In 2016, Ma and co-workers demonstrated the palladiumcatalyzed propargylic substitution of internal alkyne-containing propargylic carbonates with malononitrile derivatives for the formation of vicinal all-carbon quaternary centers. [21] In this study, the authors showed that the stereospecific propargylic alkylation of the propargylic carbonates with malononitriles also proceeded under the palladium catalysis to give the chiral alkylation products bearing two vicinal all-carbon quaternary centers in 79-90% yields without loss of enantiomeric purity of the starting materials (Scheme 10).…”

“…As we mentioned in section 2.2.2, Ma and co-workers reported the palladium-catalyzed propargylic substitution of internal-alkyne substituted propargylic carbonates with soft carbon nucleophiles including its stereospecific variants. [21] The authors showed the scope of the non-asymmetric propargylic alkylation of the propargylic carbonates as shown in Scheme 45. A broad range of the tertiary propargylic carbonates and malononitrile derivatives engaged in the palladium catalysis, producing the desired alkylation products bearing vicinal allcarbon quaternary centers in up to 99% yield.…”

Ruthenium-Catalyzed Propargylic Reduction of Propargylic Alcohols with Hantzsch Ester

“…In 2000, thiolate-bridged diruthenium complexes as bioinspired catalysts were reported to catalytically promote propargylic substitution reactions of propargylic alcohols bearing a terminal alkyne moiety with various carbon- and heteroatom-centered nucleophiles to give the corresponding propargylic substituted products in good to high yields with complete selectivity. In this reaction system, ruthenium–allenylidene complexes were found to work as key reactive intermediates. , After our milestone work, a variety of transition-metal-catalyzed propargylic substitution reactions of propargylic alcohol derivatives were reported by many research groups. , …”

Collective synthesis of acetylenic pharmaceuticals via enantioselective Nickel/Lewis acid-catalyzed propargylic alkylation

“…Recently, Kawatsura et al made seminal contribution in their design of nickel-catalyzed asymmetric Friedel-Crafts propargylation of 3-substituted indoles with propargylic carbonates 25 . However, efficient methods that achieve enantioselective control of the formation of C(sp 3 )-C(sp 3 ) bonds adjacent to internal alkynes with malonate derivatives have not been identified [26][27][28][29][30][31][32] . In light of the synthetic value of the reaction products, we embarked on the study to address the synthetic challenge and accomplish the enantioselective collective synthesis.…”