Organic Letters
Letter
the presence of SmI2/H2O/Et3N to furnish secondary alkyl-
amine 9 in 80% yield with 96% ee (Scheme 6d).16 Moreover, the
C−C triple bond could be reduced with diisobutylaluminum
hydride (DIBAL-H) to deliver the (Z)-alkene in 94% yield with
95% ee (Scheme 6e).17
More importantly, the aminoalkynylation products could be
converted into various chiral heterocyclic motifs that commonly
exist in therapeutics and natural products (Scheme 7). Upon
Further applications of this strategy are still in progress in our
laboratory.
ASSOCIATED CONTENT
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sı
* Supporting Information
The Supporting Information is available free of charge at
General considerations, synthesis and characterization of
alkynyl silanes and N−F reagents, general procedure for
the asymmetric aminoalkynylation of alkenes, further
transformations of products, new compound character-
ization, and single-crystal X-ray diffraction data for 3d
a
Scheme 7. Synthetic Applications
NMR spectra of substrates and products and HPLC
analysis of products (PDF)
FAIR data, including the primary NMR FID files, for
compounds 2c, 2d, 3a−z, 3aa, 4s, 5a−t, 6−15, and NFAS-
Accession Codes
CCDC 2010759 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, U.K.; fax: +44 1223 336033.
AUTHOR INFORMATION
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a
Reaction conditions: (a) Conc. HCl in MeCN, rt, 2 h. (b) NH4F (8
Corresponding Authors
equiv) in MeOH, rt, 12 h. (c) AgOAc (10 mol %) in CH2Cl2, 40 °C,
18 h. (d) AgNO3 (10 mol %), NBS (1.2 equiv), and H2O (3 equiv) in
acetone, rt, 2 h. (e) Hg(OTf)2 (20 mol %), H2O (3.0 equiv), rt, 18 h.
(f) I2 (3 equiv), K2CO3 (3 equiv), and AgOAc (3 equiv) in CH3CN, 0
°C, 12 h. (g) TBD (20 mol %) in THF, rt, 48 h.
Guosheng Liu − State Key Laboratory of Organometallic
Chemistry and Shanghai−Hong Kong Joint Laboratory in
Chemical Synthesis, Center for Excellence in Molecular
Synthesis, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, China; orcid.org/
Weiguo Cao − Department of Chemistry, Innovative Drug
Research Center, Shanghai University, Shanghai 200444,
treatment of 5s with concentrated hydrochloric acid, the
methoxymethyl (MOM) N-protecting group could be easily
removed togive secondary sulfonamide 4sin 95% yield with 94%
ee. Sulfonamide 5d could be transformed into 2,3-dihydropyr-
role 11 in 85% overall yield over three steps with 96% ee through
sequential MOM deprotection, desilylation, and silver(I)-
catalyzed cyclization.18 After MOM deprotection of 5q, direct
bromination of the alkynyl-TMS group using N-bromosuccini-
mide (NBS) enabled access to 12 in 90% yield with 94% ee. In
the presence of Hg(OTf)2 and water, 12 could be readily
transformed into lactam 13 in 88% yield with 92% ee.19 In
addition, iodocyclization of sulfonamide 4s led to the formation
of iodopyrroline 14 in 83% yield with 96% ee.20 Moreover, 4s
could be isomerized to allene 15 in 96% yield with 88% ee by the
use of triazabicyclodecene (TBD) as a catalyst.21
In conclusion, we have developed the first copper-catalyzed
enantioselective intermolecular aminoalkynylation of styrenes
via a radical relay process, which provides easy access to 2-
alkynylethylamines in good yields with excellent enantioselec-
tivities. The reaction displays a wide substrate scope, high
functional group tolerance, and mild conditions. In addition, the
aminoalkynylation products can be easily converted into a wide
variety of synthetically useful chiral synthons, such as terminal
alkynes, (Z)-alkenes, allenes, amines, bromoalkynes, carboxylic
acids, and heterocycles, making the method particularly useful.
Authors
Zhoumi Hu − Department of Chemistry, Innovative Drug
Research Center, Shanghai University, Shanghai 200444,
China
Liang Fu − State Key Laboratory of Organometallic Chemistry
and Shanghai−Hong Kong Joint Laboratory in Chemical
Synthesis, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
Pinhong Chen − State Key Laboratory of Organometallic
Chemistry and Shanghai−Hong Kong Joint Laboratory in
Chemical Synthesis, Center for Excellence in Molecular
Synthesis, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, China
Complete contact information is available at:
Notes
The authors declare no competing financial interest.
D
Org. Lett. XXXX, XXX, XXX−XXX