Tetrahedron Letters
Visible-light promoted allylation of N-substituted
tetrahydroisoquinoline using riboflavin tetra-acetate as photocatalyst
a,b
a
a
a
a
a
a,
⇑
Yunfei Song , Xinhao Wang , Lin Wang , Zhuang Dong , Shulin Fan , Pilin Huang , Jianguo Zeng ,
Pi Cheng
a
a,
⇑
Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan 410128, China
Guilin Layn Natural Ingredients Corporation, Guilin, Guangxi 541199, China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Riboflavin (RF) and relative derivatives are important coenzyme of some redox enzymes controlling the
growing development of plants by harvesting light. The unique isoalloxazine structure unit with special
photoredox capacity makes it applicable to induce single electron transfer (SET) oxidation of organic
molecules. We report here that riboflavin tetra-acetate (RFTA) catalyzed the oxidation of N-phenyl
Received 14 May 2021
Revised 6 July 2021
Accepted 12 July 2021
Available online 24 July 2021
tetrahydroisoquinoline to
a-amino C-radical which subsequently undergoes radical type Michael addi-
tion to C@C double bond of allylsulfone to access 1-allylated N-phenyl tetrahydroisoquinoline.
Ó 2021 Elsevier Ltd. All rights reserved.
Keywords:
Riboflavin
Photoredox catalysis
N-phenyl tetrahydroisoquinoline
Allylation
3
Riboflavin(RF) was first described in 1879 as a yellow pigment
isolated from milk, named lactochrome [1], and found afterwards
several times from different sources [2]. Riboflavin, also known
plet states intermediate RF [10] (E
0
= 1.77 V) with the strong oxi-
dization ability [11] by intersystem crossing (ISC) (Scheme 1). The
different redox states are easily distinguished by UV/Vis spec-
troscopy [12]. Based on the oxidation power of RF, the riboflavin
3
as vitamin B
2
[3], are the coenzyme of some redox enzymes in
the secondary metabolic pathway (such as flavoproteins redox
enzymes) and also the chromophores of some light-sensitive pro-
tein (such as cryptochrome) with photo-harvesting capability. This
photo-harvesting chromophores plays a key role in the electron
transfer process of enzymatic reaction [4]. For example, flavin ade-
nine dinucleotide (FAD) and it’s homologue flavin mononucleotide
photocatalytic model based on isoalloxazine has been applied to
develop novel synthetic methodology in recent years.
The RF derivative riboflavin tetra-acetate (RFTA) (Scheme 1) is a
promising and versatile photoredox catalyst compared to transi-
tion-metal complexes (based on Ru and Ir) [13] featuring cheap
price and environmentally friendly property. RFTA has been used
in the single-electron transfer (SET) oxidation of the methylben-
zene [14], benzyl alcohols [15], benzyl amine [16], sulphides
(FMN) are the representative light harvesting chromophores [5]
Scheme 1) which are the key functional molecules for some pho-
(
tosensitive proteins in plants to feel blue light from environment.
These photosensitive proteins regulate growing development of
plants by feeling the power and cycle of blue light [6].
Without light irradiation, FAD and FMN usually participate in
the covalent oxidation of CAH bond of substrate, such as the for-
mation of CAO bond [7] and dehydrogenation [8]. When excited
by light, the chemical properties of FAD and FMN changed signifi-
cantly. Under the blue light’s irradiation (455 nm), reboflavin
which contains unique isoalloxazines structure unit [9] (Scheme 1)
was excited to singlet state 1RF*. 1RF* was converted into the tri-
[17], benzaldehyde [18], carboxylic acid [10a,19], [2 + 2]
cycloadditions [20] and E to Z isomerization of polarized alkenes
[21] (Scheme 2). In the field of natural product derivatization, it
was reported that the SET oxidation of flavonoids mediated by
RFTA induced free radical polymerization of polyphenols [22].
Tetrahydroisoquinoline has a wide range of biological activities
such as anti-inflammatory [23] and anti-cancer [24]. The sub-
stituent on C-1 is significant for activities. Inspired by previous
works on RFTA, we reported here the RFTA mediated C-1 allylation
of N-phenyl tetrahydroisoquinoline under visible-light irradiation
without any other additive.
We explored the reaction of N-phenyl tetrahydroisoquinoline
1a) with allylsulfone (2) to give rise to 1-allylated N-phenyl
tetrahydroisoquinoline (3a) in acetonitrile under the irradiation
of 12 W blue LED at ambient temperature (Table 1). Among these
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(
0
040-4039/Ó 2021 Elsevier Ltd. All rights reserved.