Categories: C-C Bond Formation > Amines, Alkynes >
Synthesis of propargylamines and amides
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A copper(I) complex of i-Pr-pybox-diPh efficiently catalyzes the
enantioselective one-pot three-component synthesis of propargylamines from
aromatic aldehydes, anilines, and alkynes. A transition-state model has been
proposed.
A. Bisai, V. K. Singh, Org. Lett.,
2006,
8, 2405-2408.
π-Stacking can be used to increase the barrier to rotation in chiral atropisomers. Using this concept, an imidazole-based biaryl P,N-ligand has been designed and
prepared as a single enantiomer. This ligand performs exceptionally well in the
enantioselective A3-coupling.
F. S. P. Cardoso, K. Abboud, A. Aponick, J. Am. Chem. Soc., 2013,
135, 14548-14551.
A wide range of chiral propargylamines can be prepared in a one-pot
three-component reaction between an alkyne, an aldehyde and a secondary amine at
room temperature in the presence of CuBr and (R)-quinap in good yield and
good enantioselectivity. Remarkably, the copper-catalyzed reaction is highly diastereoselective if a
chiral amine or aldehyde is used.
N. Gommermann, C. Koradin, K. Polborn, P. Knochel, Angew. Chem. Int. Ed., 2003,
42, 5763-5766.
Coupling of an available pool of Brønsted acids, namely, amino acid derivatives,
with tunable ligands on copper catalysts can be used to generate many different
chiral environments simply by changing the amino acid or ligand employed and
provides a scaffold for rapid screening for high enantioselectivity. The latter
is illustrated in the copper-catalyzed alkynylation of imines in up to 99% ee.
. Lu, T. C. Johnstone, B. A. Arndtsen, J. Am. Chem. Soc., 2009,
131, 11284-11285.
A metal-free decarboxylative three-component coupling reaction was developed.
When alkynyl carboxylic acids, paraformaldehyde, and amines were reacted in
CH3CN at 65 °C for 3 h, the desired propargylamines were obtained in good yields.
This coupling reaction also showed good yield in water solvent. This reaction
showed higher selectivity toward alkynyl carboxylic acids than a terminal alkyne.
K. Park, Y. Heo, S. Lee, Org. Lett., 2013,
15, 3322-3325.
A copper-based system enables methylene insertion between an amine and an
alkyne counterpart, via C-N bond cleavage of N,N-dimethylacetamide. The
method gives an expedient access to a broad range of propargylic amines in good
yields.
A. Rahaman, R. D. Shinde, S. Bhadra, J. Org. Chem., 2023, 88,
1884-1889.
A single Cu(II) catalyst couples a diverse range of nitrogen sources with
various alkynes and aldehydes without the addition of ligand or base.
Copper-catalyzed alkynylation involving p-toluenesulfonamide provides
high yields of N-Ts-protected propargylamines. The superior activity of
copper(II) triflate also allows this three-component alkynylation to incorporate
a ketone.
C. E. Meyet, C. J. Pierce, C. H. Larsen, Org. Lett., 2012,
14, 964-967.
A highly efficient gold-catalyzed three-component-coupling of aldehydes,
alkynes, and amines in water was developed. Excellent yields of the
corresponding propargylamines were obtained in most cases for both aromatic
and aliphatic aldehydes and various amines.
V. K.-Y. Lo, Y. Liu, M.-K. Wong, C.-M. Che, Org. Lett.,
2006,
8, 1529-1532.
A BF3-mediated in situ generation of alkynyl imines followed by
alkynylation or allylation with boronic esters enables an efficient synthesis of
α-alkynyl- or α-allyl-substituted N-Boc-propargylic amines in good yields
under mild conditions.
K. Yasumoto, T. Kano, K. Maruoka,
Org. Lett., 2019, 21, 3214-3217.
The addition of dimethylalkynylaluminum reagents derived from terminal alkynes
and trimethylaluminum to various N-activated α-amido sulfones provides
the corresponding propargylamines in good yields. The use of stable, N-activated
α-amido sulfone avoids the preparation and isolation of relatively unstable N-activated
imines.
J.-H. Lee, S.-H. Lee, Synthesis, 2022, 54,
2233-2241.
Merging photoredox with copper catalysis enables an efficient decarboxylative
alkynylation of N-(acetoxy)phthalimides of α-amino acids with terminal
alkynes at room temperature to provide valuable propargylamines in very good
yields. This [Ru(bpy)3]Cl2/CuI catalyzed simple protocol
offers mild reaction conditions and high efficiency.
H. Zhang, P. Zhang, M. Jiang, H. Yang, H. Fu, Org. Lett.,
2017, 19, 1016-1019.
9,10-Dicyanoanthracene as the photoredox catalyst enables a metal-free,
visible-light-induced photocatalytic decarboxylative alkynylation of a broad
scope of α-amino acids, α-oxo acids, and α-keto acids at room temperature under
an atmosphere of argon.
C. Yang, J.-D. Yang, Y.-H. Li, X. Li, J.-P. Chen, J. Org. Chem.,
2016, 81, 12357-12363.
The reaction between N-Boc-aminals and organomagnesium reagents provides
previously inaccessible N-Boc-protected propargylic and allylic amines
via in situ generated N-Boc-imine intermediates. The obtained N-Boc-propargylic
amines could be readily converted into unprecedented N-Boc-ketimines by
oxidation with manganese dioxide.
T. Kano, R. Kobayashi, K. Maruoka, Org. Lett., 2016, 18,
276-279.
A novel InBr3-Et3N reagent system promotes the alkynylation of
not only a variety of aromatic/heterocyclic or bulky aliphatic aldehydes but
also N,O- or N,S-acetals. The reaction of N-silyl-N,O-acetals
with
1-alkynes gives primary propargylic amines in
good yields.
N. Sakai, R. Kanada, M. Hirasawa, T. Konakahara, Tetrahedron, 2005,
61, 9298-9304.
Copper-catalyzed Mannich reactions of terminal alkynes and secondary amines with
aqueous formaldehyde is accelerated by the use of a catalytic amount of an
imidazole ligand carrying a long alkyl chain.
T. Okamura, K. Asano, S. Matsubara, Synlett, 2010,
3053-3056.
N. Sakai, R. Kanada, M. Hirasawa, T. Konakahara, Tetrahedron, 2005,
61, 9298-9304.
Mediated by copper/diethyl azodicarboxylate, regioselective alkynylation of
unactivated aliphatic tertiary methylamine with terminal alkyne was successfully
established. The alkynylation reaction described here has the advantage of
simple operation, mild reaction conditions, good to excellent yields, and no
need to exclude air and moisture.
X. Xu, X. Li, Org. Lett., 2009,
11, 1027-1029.
A one-pot reaction for the transformation of common secondary amides into amines
with C-C bond formation consists of in situ amide activation with Tf2O
followed by partial reduction and addition of C-nucleophiles. The method is
general in scope and allows the use of both hard nucleophiles (RMgX, RLi) and
soft nucleophiles, as well as enolates. With soft nucleophiles the presence of
ester, cyano, nitro, and tertiary amide groups are tolerated.
P.-Q. Huang, Y.-H. Huang, K.-J. Xiao, Y. Wang, X.-E. Xia, J. Org. Chem.,
2015,
80, 2861-2868.
A simple and effective copper-catalyzed oxidative cross-coupling of
dimethylanilines with alkynes in the presence of tert-BuOOH allows
the construction of propargylamines via a combination of sp3 C-H
bond and sp C-H bond activations followed by C-C bond formation.
Z. Li, C.-J. Li, J. Am. Chem. Soc.,
2004,
126, 11810-11811.
Highly enantioselective direct alkyne-imine additions catalyzed by Cu(I)OTf
and Evan's pybox ligands were developed in water and in toluene. The process
is simple and allows the synthesis of various propargylic amines in high ees
and good yields.
C. Wei, C.-J. Li, J. Am. Chem. Soc., 2002,
124, 5638-5639.
An economical and efficient Cu(I)-catalyzed one-pot reaction of enaminones
with terminal alkynes provides symmetrical and asymmetrical 3-amino diynes in
good yield under mild conditions.
C. Zhang, H. Guo, L. Chen, J. Zhang, M. Guo, X. Zhu, C. Shen, Z. Li, Org. Lett., 2021, 23,
8169-8173.
Propargylamines have been synthesized by a gold(III) salen complex-catalyzed
three-component coupling reaction of aldehydes, amines, and alkynes in water
in excellent yields at 40°C. With chiral prolinol derivatives as the amine
component, excellent diastereoselectivities have been attained.
V. K.-Y. Lo, Y. Liu, M.-K. Wong, C.-M. Che, Org. Lett.,
2006,
8, 1529-1532.
MgI2 as an additive enables a dramatic improvement in the [IrCl(COD)]2-catalyzed
addition reaction of silylacetylenes and imines. This general and convenient
reaction provides various amine products in excellent yields and can be
conducted in THF as well as in the absence of solvent.
C. Fischer, E. M. Carreira, Synthesis, 2004,
1497-1503.
A highly enantioselective, catalytic three-component coupling of aldehydes,
alkynes, and 4-piperidone hydrochloride hydrate affords the corresponding
tertiary propargylamines in useful yields. A selective cleavage of the
piperidone protecting group is possible using either ammonia/EtOH or a
polymer-supported scavenger amine.
P. Aschwanden, C. R. J. Stephenson, E. M. Carreira, Org. Lett.,
2006,
8, 2437-2440.
A Zn(OTf)2-mediated solvent-free synthesis of propargylamines
proceeds effectively via A3 coupling of aldehydes, amines, and phenylacetylene.
The protocol tolerates a broad range of substituted benzaldehydes, enolizable
aldehydes, and formaldehyde. Recyclability of the catalyst, low catalyst loading,
and use of inexpensive catalyst are the key features.
P. B. Sarode, S. P. Bahekar, H. S. Chandak,
Synlett, 2016, 27, 2209-2212.
A three-component coupling between an aldehyde, alkyne and amine is
catalyzed by silver iodide to generate propargylic amines in high yields in
water without cocatalyst or activator. This method is especially effective for
reactions involving aliphatic aldehydes.
C. Wei, Z. Li, C.-J. Li, Org. Lett., 2003,
5, 4473-4475.
Treatment of various aromatic and aliphatic aldimines with a mixture of a
terminal alkynes and dimethylzinc solution in toluene yields the
corresponding protected propargylic amines in moderate to excellent yields.
A three-component synthesis of propargylic amines with an aldehyde, ortho-methoxyaniline
and phenylacetylene through in situ formation of the corresponding imine in
the presence of dimethylzinc was developed.
L. Zani, S. Alesi, P. G. Cozzi, C. Bolm, J. Org. Chem.,
2006, 71, 1558-1562.
A copper(I)-catalyzed direct three-component coupling of ethyl glyoxylate, p-anisidine,
and terminal alkynes provides β,γ-alkynyl α-amino acid derivatives in good
yields.
Z. Shao, A. S. C. Chan, Synthesis, 2008,
2868-2870.
A modified binaphthol catalyzes an asymmetric conjugate alkynylation of
β-enaminones with potassium alkynyltrifluoroborates via in situ generated
organodifluoroboranes. Mechanistic studies revealed the impact of molecular
sieves on efficiency and stereocontrol. Additional functionalization provides a
diverse set of valuable β-alkynyl-β-amino carbonyl scaffolds.
J.-F. Wang, X. Meng, C.-H. Zhang, C.-M. Yu, B. Mao,
Org. Lett., 2020, 22, 7424-7426.
L. Zani, S. Alesi, P. G. Cozzi, C. Bolm, J. Org. Chem.,
2006, 71, 1558-1562.
A copper-catalyzed coupling of imines with alkynes and acid chlorides provides
an efficient and general three-component coupling method to prepare
propargylamides. The coupling can also be diversified to allow the formation of
N-carbamate-protected propargylamines with the use of chloroformates.
D. A. Black, B. A. Arndtsen, Org. Lett., 2004, 6, 1107-1110.
A mild, copper(I)/Quinap-catalyzed addition of functionalized alkynes to
enamines in high yields and with up to 90% ee is reported. Some selective
transformations of the propargylamine products show the potential synthetic
utility of this method.
C. Koradin, K. Polborn, P. Knochel, Angew. Chem. Int. Ed., 2002,
41, 2535-2538.
An expeditious and convenient method gives γ-amino-ynamides via nucleophilic
addition of lithiated ynamides to aryl imines. This work also features an
aza-variant of a Meyer–Schuster rearrangement of γ-amino-ynamides and their
synthetic utility in intramolecular ketenimine [2+2] cycloadditions.
R. Qi, X.-N. Wang, K. A. DeKorver, Y. Tang, C.-C. Wang, Q. Li, H. Li, M.-C. Lv,
Q. Yu, R. P. Hsung, Synthesis, 2013, 45,
1749-1758.
