1 3
Topics in Current Chemistry (2019) 377:38
catalysis (ACDC) based on their proposed mechanism of action, where the electrophilic palladium species is charged, and a chiral counter anion surrounding the
species promotes the selective attack of an achiral enamine.
Furthermore, Saicic et al. employed the strategy of merging the enamine and
metal catalysis for the preparation of five- and six membered rings by using either
palladium [16] or iridium [17] catalysts (Scheme 4). The applicability of the intramolecular α-allylic alkylation stratagem was demonstrated for the stereoselective
synthesis of the natural product (+)-allokainic acid [18]. Afterwards, Dixon et al.
[19] disclosed the stereoselective intramolecular α-allylic alkylation using aldehyde
and ketone-linked allenes. After a thorough optimization study based on several
parameters such as amine and palladium catalysts, solvent and reaction time, the carbocyclic product 20 could be afforded in high yields and diastereoselectivities, and
with up to 82% ee (Scheme 5). Later, several other groups employed allene-based
substrates successfully in combination with gold- and enamine catalysis [20, 21].
All these reactions opened up new avenues and sparked great interest in the field,
leading to the invention of a plethora of various α-allylic alkylation transformations
(R)-(BINAP)Pd (7 mol%)
Pyrrolidine 14
Et 3 N, THF
–20
o C, 4 h, 40% yield, 91% ee
O
O
P N
Ph
17
Br
O
H
CO 2 Et
EtO 2 C
N
H
CO 2 Et
EtO 2 C
H
O
13
15
14
[Ir(cod)Cl] 2 (5 mol%)
16 (0.5 eq.), 17 (10 mol%)
DIPEA (1.0 eq.
CH 3 CN, 0
o
C)
98% yield
Br
O
H
CO 2 Et
EtO 2 C
CO 2 Et
EtO 2 C
H
O
13
15
H
N
16
Scheme 4 Selected examples from the integrated enamine and metal catalysts for the preparation of fiveand six membered cyclization products, where the metal could be either palladium or iridium catalyst
19 (30 mol%)
Pd(OAc) 2 (5 mol%)
toluene, 60
o
C
Ar = 3,5-(CF 3 ) 2 -C 6 H 3
O
H
CO 2 Me
MeO 2 C
CO 2 Et
EtO 2 C
H
O
18
20
N
H
Ar
OTIPS
Ar
72% yield, 13:1 dr, 82% ee
Scheme 5 Example of the stereoselective intramolecular α-allylic alkylation using aldehyde-linked
allenes providing carbocycle 20
Reprinted from the journal
5
Topics in Current Chemistry (2019) 377:38
catalysis (ACDC) based on their proposed mechanism of action, where the electrophilic palladium species is charged, and a chiral counter anion surrounding the
species promotes the selective attack of an achiral enamine.
Furthermore, Saicic et al. employed the strategy of merging the enamine and
metal catalysis for the preparation of five- and six membered rings by using either
palladium [16] or iridium [17] catalysts (Scheme 4). The applicability of the intramolecular α-allylic alkylation stratagem was demonstrated for the stereoselective
synthesis of the natural product (+)-allokainic acid [18]. Afterwards, Dixon et al.
[19] disclosed the stereoselective intramolecular α-allylic alkylation using aldehyde
and ketone-linked allenes. After a thorough optimization study based on several
parameters such as amine and palladium catalysts, solvent and reaction time, the carbocyclic product 20 could be afforded in high yields and diastereoselectivities, and
with up to 82% ee (Scheme 5). Later, several other groups employed allene-based
substrates successfully in combination with gold- and enamine catalysis [20, 21].
All these reactions opened up new avenues and sparked great interest in the field,
leading to the invention of a plethora of various α-allylic alkylation transformations
(R)-(BINAP)Pd (7 mol%)
Pyrrolidine 14
Et 3 N, THF
–20
o C, 4 h, 40% yield, 91% ee
O
O
P N
Ph
17
Br
O
H
CO 2 Et
EtO 2 C
N
H
CO 2 Et
EtO 2 C
H
O
13
15
14
[Ir(cod)Cl] 2 (5 mol%)
16 (0.5 eq.), 17 (10 mol%)
DIPEA (1.0 eq.
CH 3 CN, 0
o
C)
98% yield
Br
O
H
CO 2 Et
EtO 2 C
CO 2 Et
EtO 2 C
H
O
13
15
H
N
16
Scheme 4 Selected examples from the integrated enamine and metal catalysts for the preparation of fiveand six membered cyclization products, where the metal could be either palladium or iridium catalyst
19 (30 mol%)
Pd(OAc) 2 (5 mol%)
toluene, 60
o
C
Ar = 3,5-(CF 3 ) 2 -C 6 H 3
O
H
CO 2 Me
MeO 2 C
CO 2 Et
EtO 2 C
H
O
18
20
N
H
Ar
OTIPS
Ar
72% yield, 13:1 dr, 82% ee
Scheme 5 Example of the stereoselective intramolecular α-allylic alkylation using aldehyde-linked
allenes providing carbocycle 20
Reprinted from the journal
5