1 Introduction
Enamines and enamides are widely present as key structural motifs in a large number
of natural products of great biological and medicinal importance such as the antibiotics and antitumor cyclopeptide alkaloids outlined in Fig. 1 [1]. Besides, they have
found numerous applications as highly versatile intermediates in organic synthesis
[2, 3] being found of utmost significance in Heck reactions [4–6], 1,3-dipolar
cycloadditions [7], C–H activation processes [8–13], asymmetric fluorinations [14],
and ring-closing metathesis [15, 16]. Furthermore, they are established as powerful
nucleophiles in asymmetric Michael addition reactions [17] and other valuable
stereoselective C–C [18] and C–N bond forming processes [19].
On one hand, conventional approaches for the preparation of enamines involve
acid-catalyzed condensations of secondary amines with carbonyl compounds [20, 21].
However, the commonly required severe reaction conditions imply low functional
group tolerance and lack of stereoselectivity. Other alternative routes include
the hydroamination of alkynes [22, 23], and dehydrogenation of tertiary [24] and
secondary amines [25]. On the other hand, numerous methods for the preparation
of enamide-type compounds have been devised including ruthenium-[26–28]
and rhenium-catalyzed amidation of alkynes [29], metal-catalyzed isomerizations of
N-allylamides [30–32], ruthenium-catalyzed co-oligomerizations of N-vinylamides
and alkenes or alkynes [33], reductive acylations of oximes [34, 35], N-acylations of
imines [16], Wittig olefinations of N-formylimides [36], and Pd-catalyzed chloroallylation of ynamides [37], among others.
HN
NH
O
N
OMe
O O
Me
Me
paliurine F
O
HN
O
Me
Me
Me 2 N
Me
Me
NH
NH
HN
Me
R
MeO
NH
O
Me
Me
O
Me
Me
O
R = H, abyssenine A
R = OMe, mucronine E
N
NH
O
N
OMe
O O
ziziphine N
O
HN
O
Me
Me 2 N
Me
Me
Me
O
OH
O
OH
O
OH
H
N
O
N
OMe
CJ-12,950
O
OH
Me
O
OH
O
CH 2 R
O
H
N
O
N
MeO
R = H, lobatamide C
R = OH, lobatamide F
Fig. 1 Important compounds bearing enamide backbone
56
A. Correa and C. Bolm
Enamines and enamides are widely present as key structural motifs in a large number
of natural products of great biological and medicinal importance such as the antibiotics and antitumor cyclopeptide alkaloids outlined in Fig. 1 [1]. Besides, they have
found numerous applications as highly versatile intermediates in organic synthesis
[2, 3] being found of utmost significance in Heck reactions [4–6], 1,3-dipolar
cycloadditions [7], C–H activation processes [8–13], asymmetric fluorinations [14],
and ring-closing metathesis [15, 16]. Furthermore, they are established as powerful
nucleophiles in asymmetric Michael addition reactions [17] and other valuable
stereoselective C–C [18] and C–N bond forming processes [19].
On one hand, conventional approaches for the preparation of enamines involve
acid-catalyzed condensations of secondary amines with carbonyl compounds [20, 21].
However, the commonly required severe reaction conditions imply low functional
group tolerance and lack of stereoselectivity. Other alternative routes include
the hydroamination of alkynes [22, 23], and dehydrogenation of tertiary [24] and
secondary amines [25]. On the other hand, numerous methods for the preparation
of enamide-type compounds have been devised including ruthenium-[26–28]
and rhenium-catalyzed amidation of alkynes [29], metal-catalyzed isomerizations of
N-allylamides [30–32], ruthenium-catalyzed co-oligomerizations of N-vinylamides
and alkenes or alkynes [33], reductive acylations of oximes [34, 35], N-acylations of
imines [16], Wittig olefinations of N-formylimides [36], and Pd-catalyzed chloroallylation of ynamides [37], among others.
HN
NH
O
N
OMe
O O
Me
Me
paliurine F
O
HN
O
Me
Me
Me 2 N
Me
Me
NH
NH
HN
Me
R
MeO
NH
O
Me
Me
O
Me
Me
O
R = H, abyssenine A
R = OMe, mucronine E
N
NH
O
N
OMe
O O
ziziphine N
O
HN
O
Me
Me 2 N
Me
Me
Me
O
OH
O
OH
O
OH
H
N
O
N
OMe
CJ-12,950
O
OH
Me
O
OH
O
CH 2 R
O
H
N
O
N
MeO
R = H, lobatamide C
R = OH, lobatamide F
Fig. 1 Important compounds bearing enamide backbone
56
A. Correa and C. Bolm