Enantioenriched 1,2- and 1,3-diamines with chiral α-branched
aliphatic amine motifs are important substructures in bioactive compounds
and related molecules and serve as privileged chiral ligands in both
organo- and transition-metal-catalysis. However, direct access to
such structural motifs remains a formidable challenge. Herein, a straightforward
method to access 1,n-diamines (n = 2, 3, 4) containing a chiral α-branched aliphatic amine
is achieved by Ni-catalyzed asymmetric hydroamination of unactivated
aliphatic alkenes. Facilitated by a remote weakly coordinating group,
the reaction is applicable to both terminal and internal unactivated
alkenes, delivering enantioenriched 1,2-, 1,3-, and 1,4-diamine precursors
in good yields and excellent enantioselectivities with diverse substitution
patterns. Unactivated aliphatic alkenes serve as secondary alkyl nucleophile
surrogates in the presence of Ni–H, forging the C–N
bond enantioselectively with aminating reagents. In addition, the
reaction proceeds at room temperature with excellent functional group
tolerance.
Direct
construction of fully alkyl-substituted tertiary chiral
centers remote to activating groups is highly challenging and desirable.
Herein, a Ni-catalyzed enantioselective hydroalkylation of unactivated
alkenes with unactivated alkyl halides at room temperature is reported,
providing a general and practical access to fully alkyl-substituted
tertiary stereogenic carbon centers not adjacent to activating groups.
This reaction undergoes the regio- and stereoselective hydrometalation
of unactivated alkenes with a nontrivial Markovnikov selectivity,
followed by the cross-coupling with unactivated alkyl electrophiles
to access trialkyl tertiary saturated stereogenic centers not adjacent
to activating groups. The mild and robust conditions enable the use
of terminal and internal unactivated alkenes and unactivated primary
and secondary alkyl, benzyl, and propargyl halides to construct diverse
trialkyl tertiary stereogenic carbon centers with broad functional
group tolerance. Moreover, experimental investigations support the
reaction undergoing irreversible and stereoselective hydrometalation
of alkenes. Density functional theory calculations provide further
insights into the reaction mechanism, suggesting a stereoselective
migration insertion of alkenes with Ni(II)–H species. Finally,
the origin of the regio- and enantioselectivities is also investigated.
Aryl and alkenyl iodides are important intermediates
for value-added
targets in organic synthesis and common motifs in natural products
and bioactive molecules. Thus, direct synthesis of aryl/alkenyl iodides
from easily available and cost-effective materials under mild conditions
is attractive. Herein, we reported a nickel-catalyzed Finkelstein
reaction under mild conditions. Notably, a wide range of aryl/alkenyl
bromides as well as chlorides could be transformed into corresponding
iodides with broad functional group tolerance.
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