Significant advances have been achieved
for the construction of
chiral skeletons containing 1,2,3-triazoles via transition-metal-catalyzed
asymmetric azide–alkyne cycloaddition; however, most of them
have been limited to terminal alkynes in the synthesis of central
chirality via desymmetrization and dynamic/dynamic kinetic resolution.
Enantioselective transition-metal-catalyzed azide-internal-alkyne
cycloaddition is extremely limited. Moreover, the construction of
a challenging five-membered (hetero)biaryl axially chiral molecule
via transition-metal-catalyzed asymmetric azide-internal-alkyne cycloaddition
is still underexplored. Herein, we first report an atroposelective
and atom-economical synthesis of axially chiral 1,4,5-trisubstituted
1,2,3-triazoles, directly acting as core chiral units of challenging
five-membered atropisomers, via the enantioselective Rh-catalyzed
azide–alkyne cycloaddition (E-RhAAC) of internal alkynes and
azides. The reaction demonstrates excellent functional group tolerance,
forging a variety of C–C axially chiral 1,2,3-triazoles under
mild conditions with moderate to excellent yields (up to 99% yield)
and generally high to excellent enantioselectivities (up to 99% ee)
along with specific regiocontrol. The origin of regio- and enantioselectivity
control is disclosed by density functional theory (DFT) calculations,
providing new guidance for the facile construction of axially chiral
compounds.
of main observation and conclusion An efficient NaBAr F 4 -catalyzed oxidative cyclization of readily available 1,5-and 1,6-diynes has been developed. Importantly, this transition metal-free oxidative catalysis proceeds via a presumable Lewis acid-catalyzed S N 2' pathway, which is distinct from the relevant oxidative rhodium and gold catalysis. This method leads to the facile and practical construction of a diverse range of synthetically useful γand δ-lactams in mostly good to excellent yields with broad substrate scope.
Scheme 1 Known knowledge and conceptual advance of this contribution
Results and DiscussionWe set out to screen different conditions for this reaction by Chin.
Herein, an I 2 -catalyzed unprecedented cycloisomerization of ynamides is developed, furnishing various functionalized bis(indole) derivatives in generally good to excellent yields with wide substrate scope and excellent atom-economy. This protocol not only represents the first molecular-iodine-catalyzed tandem complex alkyne cycloisomerizations, but also constitutes the first chemoselective cycloisomerization of tryptamine-ynamides involving distinctively different C-(sp 3 )À C(sp 3 ) bond cleavage and rearrangement. Moreover, chiral tetrahydropyridine frameworks containing two stereocenters are obtained with moderate to excellent diastereoselectivities and excellent enantioselectivities. Meanwhile, cycloisomerization and aromatization of ynamides produce pyrrolyl indoles with high efficiency enabled by I 2 . Additionally, control experiments and theoretical calculations reveal that this reaction probably undergoes a tandem 5-exo-dig cyclization/rearrangement process.
An efficient gold-catalyzed cascade cyclization of alkenyl diynes involving alkyne oxidation, carbene-alkyne metathesis and cyclopropanation has been developed, furnishing a series of tetracyclic γ-lactams bearing one quaternary carbon center and...
Transition-metal-catalyzed alkyne hydration reaction has attracted considerable interest in the past decades because this approach would lead to the facile and efficient formation of synthetically useful carbonyls. However, transition-metal-catalyzed alkyne hydration-initiated tandem reactions have seldom been explored because their metal enolate intermediates generally undergo facile protodemetallation rather than further trapped by other types of electrophiles. Described herein is an efficient coppercatalyzed tandem alkyne hydration/intramolecular Mannich reaction of imine-ynamides with water. This method allows efficient and diastereodivergent synthesis of valuable 3,4-dihydro-2-quinolones with high regio-, diastereo-, and enantioselectivity. Moreover, this hydrative cyclization can also be applicable to the hydrative aldol reaction of carbonyl-ynamides with water to form 3,4-dihydro-2-quinolones regio-and diastereoselectively by employing zinc as the catalyst.
Herein, an unprecedented non-noble-metal-catalyzed oxidation/cyclization of ene-ynamides is developed, allowing the synthesis of diversely functionalized lactams in moderate to good yields with excellent diastereoselectivities without the observation of typical cyclopropanation products. In combination with Ellman's tert-butylsulfinimine chemistry, chiral γ-lactams containing three contiguous stereocenters are obtained with high diastereo-and enantioselectivity. Moreover, density functional theory (DFT) calculations indicate that this protocol probably undergoes a carbon cation or proton transfer process.Letter pubs.acs.org/OrgLett
A novel copper-catalyzed tandem cyclization/direct C-(sp 2 )−H annulation of phenyl azide−ynamides via α-imino copper carbenes has been developed, which provides a concise and flexible approach for the construction of a range of valuable azepino[2,3-b:4,5-b′]diindoles in mostly good to excellent yields with high chemoselectivities. This tandem reaction also exhibits a broad substrate scope, excellent functional group tolerance, simple operation, and mild reaction conditions.
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