Catalytic asymmetric functionalization of the N-H groups of indoles and carbazoles constitutes an important but less developed class of reactions. Herein, we describe a propargylation protocol involving the use of a lithium SPINOL phosphate as the chiral catalyst and our recently developed C-alkynyl N,O-acetals as propargylating reagents. The direct asymmetric N-propargylation of indoles and carbazoles provides hitherto inaccessible Nfunctionalized products. Notably, the efficiency of the system allows reactions to be run at a very low catalyst loading (as low as 0.1 mol%). Mechanistic information about the titled reaction is also disclosed. This study represents an advance in the direct asymmetric functionalization of the N-H bonds of indoles and carbazoles, and additionally expands on the application of chiral alkali metal salts of chiral phosphoric acids in asymmetric catalysis.
Axially
chiral indole-based frameworks occur in natural products,
bioactive molecules, and chiral ligands. Thus, the development of
catalytic asymmetric atroposelective approaches for de novo construction
of these frameworks is highly valuable. Here, the atroposelective
organo/metal combined dual catalysis strategy for de novo construction
of valuable axially chiral indole frameworks has been developed. This
protocol utilized a catalyst system of two chiral phosphoric acids
(1 mol %) in combination with AgNO3 (1 mol %) and was based
on the unreported intermolecular cycloaddition–isomerization
reaction of our recently introduced C-alkynyl N,O-acetals and 2-naphthylamines.
An important class of hitherto inaccessible axially chiral indoles
with a C–N axis were obtained in good yields and enantioselectivities.
The axially chiral indoles obtained also provided a platform for the
catalyst-controlled atroposelective synthesis of axially chiral indoles
bearing two C–N axes, which are difficult to access by the
existing methods. This work is also an example of 2-naphthylamines
used as 1,3-dinucleophiles and three-atom (CCN) synthons in cycloadditions.
We
disclose an l-isoleucine-derived amide phosphine-catalyzed
trimerization of γ-aryl-3-butynoates, which undergo an isomerization
to allenoate, [3 + 2] cyclization, and Michael addition cascade. Exocyclopentene
derivatives bearing an all-carbon quaternary stereocenter were constructed
stereospecifically and enantioselectively. A wide variety of γ-aryl-3-butynoates
could be employed to deliver optically pure cyclopentene derivatives
in moderate to good yields with ee values of ≥95% and in most
cases ≥98%.
An efficient synthesis of Z-perfluoroalkyl-substituted enones by a multicomponent reaction strategy has been described. A variety of elusive perfluoroalkylated enones are furnished under mild reaction conditions in good yields with unique chemo- and stereoselectivity. A sequence of radical-mediated Kornblum-DeLaMare reaction, Michael addition, and HF elimination is proposed for the mechanism.
A SPINOL-CPA catalyzed asymmetric [2 + 3]-annulation of in situ generated alkynyl imines and 1,4-dithiane-2,5-diol has been developed to afford enantiopure α-alkynylated thiazolidones.
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