We
present herein an unprecedented stereoselective synthesis
of bridged biaryls with defined axial and central chirality from readily
available starting materials. This N-heterocyclic carbene-catalyzed
method proceeds through propargylic substitution of azolium enolates
followed by two-directional cyclization, as supported by DFT calculation.
A range of benzofuran/indole-derived bridged biaryls bearing
an eight-membered lactone are accessed with uniformly high stereoselectivity
(>98:2 dr, mostly >98% ee).
The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic
N
-alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral
N
-aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis.
Presented herein is an unprecedented transition-metal-free propargylic substitution reaction with either azolium enolates or acyl anions, which are generated from aldehydes under N-heterocyclic carbene catalysis. This new catalytic activation operates on readily available cyclic propargylic carbamates through decarboxylation, and generates reactive allene intermediates that can undergo divergent cyclization pathways to deliver skeletally diverse polycyclic compounds with high levels of efficiency and excellent enantioselectivities.
Described is an unprecedented NHC-catalyzed (NHC=N-heterocyclic carbene), stereoselective ring opening of epoxy and cyclopropyl enals to deliver valuable compounds bearing multiple stereocenters. A straightforward three-step procedure involving two catalytic enantioselective transformations has been developed and leads to a regio- and stereodivergent synthesis of either 1,2-amino alcohols/diamines or 1,4-fluoro alcohols with excellent diastereo- and enantiopurity.
A Sonogashira experiment was transformed into a problem-based learning platform for third-year undergraduate students. Given a target that could be synthesized in a single step, students worked in groups to investigate which method was the best for large-scale production. Through this practical scenario, students learn to conduct a literature search, select procedures, practice their synthesis skills, and evaluate their results in a real-world context.
We report herein
an atroposelective N-acylation of sulfonamides
using a commercially available isothiourea catalyst, (S)-HBTM, with a simple procedure. The N-sulfonyl
anilide products can be obtained in good to high enantiopurity, which
represents a new axially chiral scaffold. The application of the product
as a chiral iodine catalyst is also demonstrated for the asymmetric
α-oxytosylation of propiophenone.
Presented herein is an unprecedented transitionmetal-free propargylic substitution reaction with either azolium enolates or acyl anions,w hich are generated from aldehydes under N-heterocyclic carbene catalysis.T his new catalytic activation operates on readily available cyclic propargylic carbamates through decarboxylation, and generates reactive allene intermediates that can undergo divergent cyclization pathwayst od eliver skeletally diverse polycyclic compounds with high levels of efficiency and excellent enantioselectivities.Scheme 1. Approaches of propargylic substitution. Ts = 4-toluenesufonyl.Scheme 2. Discovery of transition-metal-free fused indoline synthesis. Forthe X-ray crystal structures the thermal ellipsoidsa re shown at 25 %p robability. [22] Scheme 3. Indoline-fused cyclopentenone synthesis and derivatization. Forthe X-ray crystal structure the thermal ellipsoidsa re shown at 25 % probability. [22] Bz = benzoyl.
Angewandte ChemieCommunications 5715
Described is an unprecedented NHC-catalyzed (NHC = N-heterocyclic carbene), stereoselective ring opening of epoxy and cyclopropyl enals to deliver valuable compounds bearing multiple stereocenters.As traightforwardt hree-step procedure involving two catalytic enantioselective transformations has been developed and leads to ar egio-and stereodivergent synthesis of either 1,2-amino alcohols/diamines or 1,4-fluoro alcohols with excellent diastereo-and enantiopurity. Scheme 1. Divergentr eactions enabled by ad ual catalytic system. Boc = tert-butoxycarbonyl, Ts = 4-toluenesulfonyl. Scheme 6. Functionalization of fluoro allylic alcohols. DCM = dichloromethane, mCPBA = m-chloroperbenzoic acid.Scheme 7. Proposed mechanism and transition state (TS) for amination and fluorination of chiral epoxy enals.
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