We
have designed
and realized an efficient and operationally simple
single-flask synthesis of imidodiphosphate-based Brønsted acids.
The methodology proceeds
via
consecutive chloride
substitutions of hexachlorobisphosphazonium salts, providing rapid
access to imidodiphosphates (IDP), iminoimidodiphosphates (
i
IDP), and imidodiphosphorimidates (IDPi). These privileged
acid catalysts feature a broad acidity range (p
K
a
from ∼11 to <2 in MeCN) and a readily tunable confined
active site. Our approach enables access to previously elusive catalyst
scaffolds with particularly high structural confinement, one of which
catalyzes the first highly enantioselective
(>95:5 er) sulfoxidation of methyl
n
-propyl sulfide.
Furthermore, the methodology delivers a novel, rationally designed
super acidic catalyst motif, imidodiphosphorbis(iminosulfonylimino)imidate
(IDPii), the extreme reactivity of which exceeds commonly employed
super-Brønsted acids, such as trifluoromethanesulfonic acid.
The unique reactivity of one such IDPii catalyst has been demonstrated
in the first α-methylation of a silyl ketene acetal with methanol
as the electrophilic alkylating reagent.
Since early 2020, scientists have strived to find an effective solution to fight SARS‐CoV‐2, in particular by developing reliable vaccines that inhibit the spread of the disease and repurposing drugs for combatting its effects on the human body. The antiviral prodrug Remdesivir is still the most widely used therapeutic during the early stages of the infection. However, the current synthetic routes rely on the use of protecting groups, air‐sensitive reagents, and cryogenic conditions, thus impeding a cost‐efficient supply to patients. We have, therefore, focused on the development of a straightforward, direct addition of (hetero)arenes to unprotected sugars. Here we report a silylium‐catalyzed and completely stereoselective C‐glycosylation that initially yields the open‐chain polyols, which can be selectively cyclized to provide either the kinetic α‐furanose or the thermodynamically favored β‐anomer. The method significantly expedites the synthesis of Remdesivir precursor GS‐441524 after a subsequent Mn‐catalyzed C−H oxidation and deoxycyanation.
We disclose a new Brønsted acid promoted quinoline synthesis, proceeding via homo-diaza-Cope rearrangement of N-aryl-N'-cyclopropyl hydrazines. Our strategy can be considered a homologation of Fischers classical indole synthesis and delivers 6-membered N-heterocycles, including previously inaccessible pyridine derivatives. This approach can also be used as a pyridannulation methodology toward constructing polycyclic polyheteroaromatics. A computational analysis has been employed to probe plausible activation modes and to interrogate the role of the catalyst.
Derivatives of cationic six-membered N-heterocyclic carbene G with a quinazolinium scaffold are easily obtained by abstraction of an alcoholate group from related neutral precursors which are easily accessible. On the basis of this route, chalcogene adducts and metal complexes of G, which is a benzo-anellated pyrimidiniumylidene, could be prepared. Evaluation of the ligand properties by IR and 77 Se NMR spectroscopy indicate that cationic carbene G is a much more powerful π-acceptor (δ( 77 Se): 768 ppm) and a significantly weaker overall donor (TEP: 2073 cm −1 ) than related neutral carbene 4 (361 ppm, 2054 cm −1 ). DFT calculations provide a rationale for these experimental observations. AuCl complexes of both carbenes were used as catalysts for the cyclization of a propargylamide to a methyleneoxazoline. The complex containing the cationic carbene featured a much higher activity.
We disclose a highly regioselective, catalytic one‐step dehydrogenation of α‐substituted cyclic ketones in the presence of 2,3‐dichlorobenzo‐5,6‐dicyano‐1,4‐benzoquinone (DDQ). The high regioselectivity originates from a phosphoric acid‐catalyzed enolization, selectively affording the thermodynamically preferred enol, followed by the subsequent oxidation event. Our method provides reliable access to several α‐aryl and α‐alkyl substituted α,β‐unsaturated ketones.
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