Topics in Current Chemistry (2019) 377:37
1 3
4 Chiral Brønsted Acid Catalysis
In 2013, Knowles et  al. described an enantioselective aza-pinacol cyclization
reaction by means of the reductive coupling of ketones and hydrazones in an
intramolecular way [17]. With Ir(ppy) 2 (dtbpy)PF 6 as photocatalyst, blue LEDs
as light source and a chiral phosphoric acid as organocatalyst, this protocol proceeded smoothly through a proton-coupled electron transfer (PCET) process to
generate crucial ketyl radical intermediates (Scheme 15). Thus, the desired syn1,2-amino alcohol-derived compounds which were prevalent in pharmaceutical
agents, natural products and synthetic ligands and were produced in 45–96%
yields with 77–95% ee values. Initial mechanistic studies of this cyclization
OC-11
OC-11 (10 mol%)
PC-1 (1 mol%), m-DNB (1.2 eq)
CH 2 Cl 2 , rt, blue LEDs
up to 94% yield, 92% ee
O
H
R
1
N
R
2
H
Ar
N
R
2
Ar
O
R
1
N
N
N
O
Br
Br
Br
34
35
36
+
N
N
N
N
N
N
Ru
PC-1
(Cl
- ) 2
CO 2 H
O 2 N
NO 2
m-DNB
Scheme 13 Catalytic enantioselective α-acylation of N-aryltetrahydroisoquinolines
N Ph
H
PC-2 (2 mol%)
BrCCl 3 (2.0 eq), DCM, blue LEDs
then, OC-12(20 mol%)
K 2 CO 3 (1.0 eq), in dark
82% yield, 66% ee
N Ph
+
CHO
OHC
37
38
OC-12
N
O
N
OH
39
+
N
N
N
N
Ir
t-Bu
t-Bu
PC-2
PF 6
-
Scheme 14 Direct enantioselective C–H acroleination of THIQs
Reprinted from the journal
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