hydrogen atom donor, this method selectively delivered isotope incorporation to the
sp3 a-amino sites in 18 drug molecules (Scheme 21).
The reaction is proposed to operate via coupled photoredox and hydrogen atom
transfer (HAT) cycles (Scheme 22). The photoredox catalyst 66 is excited by the
Selected examples:
66 (2 mol%)
[87]
18 examples reported, inc.
modified systems for tritiation
R 1
N R 3
R 2
R 1
N R 3
R 2
D D
Ir
N
N
t Bu
t Bu
N
F
N
F
PF 6
(iPr) 3 Si SH (30 mol%)
D 2 O (50 equiv.), NMP, rt
34-W Blue LED
N
MeO
OMe
OMe
MeO
CN
[5]
[83]
[87]
HN
O
O
N
[85]
[85] [85]
O
N
F
NC
[53]
[91]
[82]
[82]
(+)-Verapamil
(+)-Escitalopram
[X] = %D in adjacent position
Scheme 21 Selected examples from MacMillan’s photoredox and hydrogen atom transfer (HAT)mediated alpha-selective sp
3 HIE process for drug-like amines
Scheme 22 Hypothesized mechanism for photoredox- and HAT-mediated HIE
288
M. Reid