1 3
Topics in Current Chemistry (2019) 377:38
as the transformation of the alcohol to an acetate or halide. Later, List et al. [15]
employed the more challenging branched aldehydes for similar chemical transformation providing the corresponding product in high yield and with excellent
enantioselectivity. The catalytic reaction was proposed to proceed via the formation of the combined enamine and allylic intermediate IV (Scheme 7) [30].
The employment of allylic alcohols in the α-allylic alkylation by combined catalysis (enamine and transition metal catalysis) has also been expanded by several other
groups [31]. For example, Bandini et al. [32] used gold as the co-catalyst, Yasuda
et al. [33] and Yoshida et al. [34, 35] used palladium as co-catalyst, and Zhou et al.
[36] employed β-ketocarbonyl compounds as substrates.
The strategy of combined catalysis serves as a powerful tool allowing the stereodivergent synthesis (diastereo- and enantiodivergent catalyzed reactions) of various
valuable compounds with multiple stereocenters, and further expands and diversify
the chemical space [37, 38]. In this context, Carreira’s group disclosed an elegant
strategy for the stereodivergent preparation of α-allylated aldehydes 34 by the concurrent combined activation of the nucleophile and electrophile using distinct catalysts. Remarkably, by simple alteration of the employed catalyst combinations, various aldehydes 34 could be generated with excellent stereoselectivities and efficiency
(Scheme 8) [39]. The allylic alcohols 30 were activated by the chiral iridium complex catalyst (Ir/olefin), which was combined with a Brønsted acid promoter, and
the branched aldehydes 27 by the chiral cinchona-alkaloid-derived primary amine
30
H
O
Ph +
Ph
OH
[Ir(cod)Cl] 2 (2 mol%), (R)-33 or (S)-33 (8 mol%)
31 or 32 (10 mol%), Cl 3 CCO 2 H (50 mol%)
1,2-dichloroethane (0.5 M), R.T., 24 h
O
O
P N
(S)-33
N
NH 2
N
31
N
NH 2
N
32
27
H
O
(R,S)-34
78% yield
>99% ee
15:1 d.r.
Ph
Ph
H
H
O
(R,R)-34
77% yield
>99% ee
20:1 d.r.
Ph
Ph
H
H
O
(S,S)-34
71% yield
>99% ee
20:1 d.r.
Ph
Ph
H
H
O
(S,R)-34
80% yield
>99% ee
20:1 d.r.
Ph
Ph
H
31
(S)-33
32 (S)-33
32
(R)-33
31 (R)-33
O
O
P N
(R)-33
Scheme 8 Combined enamine and transition metal catalysis for highly efficient and selective stereodivergent synthesis
Reprinted from the journal
7
Topics in Current Chemistry (2019) 377:38
as the transformation of the alcohol to an acetate or halide. Later, List et al. [15]
employed the more challenging branched aldehydes for similar chemical transformation providing the corresponding product in high yield and with excellent
enantioselectivity. The catalytic reaction was proposed to proceed via the formation of the combined enamine and allylic intermediate IV (Scheme 7) [30].
The employment of allylic alcohols in the α-allylic alkylation by combined catalysis (enamine and transition metal catalysis) has also been expanded by several other
groups [31]. For example, Bandini et al. [32] used gold as the co-catalyst, Yasuda
et al. [33] and Yoshida et al. [34, 35] used palladium as co-catalyst, and Zhou et al.
[36] employed β-ketocarbonyl compounds as substrates.
The strategy of combined catalysis serves as a powerful tool allowing the stereodivergent synthesis (diastereo- and enantiodivergent catalyzed reactions) of various
valuable compounds with multiple stereocenters, and further expands and diversify
the chemical space [37, 38]. In this context, Carreira’s group disclosed an elegant
strategy for the stereodivergent preparation of α-allylated aldehydes 34 by the concurrent combined activation of the nucleophile and electrophile using distinct catalysts. Remarkably, by simple alteration of the employed catalyst combinations, various aldehydes 34 could be generated with excellent stereoselectivities and efficiency
(Scheme 8) [39]. The allylic alcohols 30 were activated by the chiral iridium complex catalyst (Ir/olefin), which was combined with a Brønsted acid promoter, and
the branched aldehydes 27 by the chiral cinchona-alkaloid-derived primary amine
30
H
O
Ph +
Ph
OH
[Ir(cod)Cl] 2 (2 mol%), (R)-33 or (S)-33 (8 mol%)
31 or 32 (10 mol%), Cl 3 CCO 2 H (50 mol%)
1,2-dichloroethane (0.5 M), R.T., 24 h
O
O
P N
(S)-33
N
NH 2
N
31
N
NH 2
N
32
27
H
O
(R,S)-34
78% yield
>99% ee
15:1 d.r.
Ph
Ph
H
H
O
(R,R)-34
77% yield
>99% ee
20:1 d.r.
Ph
Ph
H
H
O
(S,S)-34
71% yield
>99% ee
20:1 d.r.
Ph
Ph
H
H
O
(S,R)-34
80% yield
>99% ee
20:1 d.r.
Ph
Ph
H
31
(S)-33
32 (S)-33
32
(R)-33
31 (R)-33
O
O
P N
(R)-33
Scheme 8 Combined enamine and transition metal catalysis for highly efficient and selective stereodivergent synthesis
Reprinted from the journal
7