BNAH-mediated free radical addition to aromatic imines

Article abstract of DOI:10.1016/S0040-4039(00)01217-X

Benzyl radical is added regioselectively to the carbon-nitrogen double bond of aromatic imines by UV irradiation (λ > 300 nm) of a ternary mixture of benzyl bromide/aromatic imines/1-benzyl-1,4-dihydronicotinamide (BNAH) in acetonitrile via a BNAH-mediated photoinduced electron transfer mechanism. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01217-X

Tetrahedron Letters 41 (2000) 7357±7360
BNAH-mediated free radical addition to aromatic imines
Meizhong Jin, Dong Zhang, Li Yang, Youcheng Liu and Zhongli Liu*
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China
Received 16 June 2000; accepted 14 July 2000
Abstract
Benzyl radical is added regioselectively to the carbon±nitrogen double bond of aromatic imines by UV
irradiation (l>300 nm) of a ternary mixture of benzyl bromide/aromatic imines/1-benzyl-1,4-dihydro-
nicotinamide (BNAH) in acetonitrile via a BNAH-mediated photoinduced electron transfer mechanism.
# 2000 Elsevier Science Ltd. All rights reserved.
Keywords: photoinduced electron transfer; regioselective free radical addition.
In contrast to extensive studies on free radical addition reactions onto CˆC bonds, free radical
addition onto CˆN bonds has received much less scrutiny until recently.1 An early example of an
intramolecular aryl radical addition onto an imine bond was reported by Takano and co-workers2
in 1990. Similar aryl radical addition reactions to the CˆN bond of imines were reported latter by
Takano and co-workers,3 Warkentin and Tomaszewiski,4 Leardini and co-workers,5 and Bowman
and co-workers.6 Recently, Ryu et al.7 reported vinyl radical addition to aldimines. All of these
reactions were accomplished by using tin hydride-mediated radical reaction to generate primary
carbon-centered radicals from aryl halides,3 5 vinyl halides7 or from phenyl selenides.6 We wish
to report herein an alternative photochemical approach to generate free radicals for radical
addition to aromatic imimes. This reaction was mediated by 1-benzyl-1,4-dihydronicotinamide
(BNAH, an NADH model molecule). To the best of our knowledge, this is the ®rst photoinduced
radical addition reaction to imines.8
Aromatic imine 1, benzyl bromide 2 and BNAH were dissolved in dry acetonitrile and irradiated
with a 500-W high pressure mercury lamp in a Pyrex bottle (l>300 nm) under argon atmosphere
at ambient temperature. The reaction was monitored by thin layer chromatography. After irradiation,
the solvent was removed under reduced pressure and the products were isolated by column
chromatography with neutral alumina. The nitrogen-addition product, tert-amine 3, and/or the
carbon-addition product, sec-amine 4, were obtained in good yield (Scheme 1). The results are
summarized in Table 1.
* Corresponding author. Fax: +86-931-8625657; e-mail: liuzl@lzu.edu.cn
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01217-X

7358
Scheme 1.
Table 1
BNAH-mediated photoinduced benzyl radical addition of aromatic imines
It is seen from Table 1 that the benzyl group added exclusively to the nitrogen atom in 1 giving
tert-amine 3 in the case of 1a±e and 1g. However, when a strongly electron-donating group was
attached to the Ar2 moiety (1f) or a strongly electron-withdrawing group was attached to the Ar1
moiety (1h), the carbon-addition products 4f and 4h were also obtained. This is understood
because the benzyl radical is electrophilic due to the delocalization of the unpaired electron to the
phenyl ring; it preferentially attacks the electronegative nitrogen atom of the CˆN bond of 1. It
has been found previously that, in the intramolecular free radical addition reaction of imines, aryl
radicals could add to either the nitrogen or carbon atom depending on the combination of both
kinetic and thermodynamic factors coupled with relative radical stability and substituent
e€ect.1b,2 5 Our result demonstrates clearly that, in the present case, the polar e€ect is the
predominant factor which governs the regioselectity of the reaction.
It was found that BNAH was oxidized to the corresponding pyridinium salt (BNA+Br^) and a
small amount of toluene (yields range from 1 to 4% in all cases) was generated during the reac-
tion as evidenced by gas chromatography. No reaction took place either in the dark or under
irradiation in the absence of benzyl bromide. This is consistent with previous reports that imines
are not reduced by BNAH thermally or photochemically unless the imine is activated by coordinating
with a proton, an alkyl group or a metal ion.9 Therefore, photoinduced electron transfer between
BNAH and benzyl bromide is clearly the initiating step for the reaction, as outlined in Scheme 2.
The oxidation potential and the excitation energy of BNAH are 0.57 V versus SCE and 3.17 eV,
respectively,10 and the reduction potential of benzyl bromide is ca. ^1.11 V versus Ag/AgBr
electrode.11 Therefore, the photoinduced electron transfer between BANH and benzyl bromide is
energetically feasible.12 It is well known that carbon±halogen bonds in the radical anion of alkyl
halides are extremely weak and the bond breaking may occur concertedly with electron transfer
via the so-called mesolytic cleavage process,13 generating alkyl radical as the vital intermediate. In

7359
Scheme 2.
the present case, the benzyl radical thus formed attacks the CˆN bond in imines, producing a
new carbon-centered and/or nitrogen-centered radical. The latter abstracts a hydrogen from
BANH giving 3 and/or 4 and BNAÁ radical. This radical may transfer an electron to another
molecule of benzyl bromide, giving BNA+ as the ®nal product and generating the radical anion of
benzyl bromide to continue the radical chain reaction.10 The by-product toluene may be formed
by the free radical chain reaction between benzyl radical and BNAH, as reported previously.10,14
In conclusion, this work provides a new approach to initiate free radical addition reactions,
which may be extended to other synthetically useful reactions, such as intramolecular radical
cyclizations.
Acknowledgements
We thank the National Natural Science Foundation of China for ®nancial support (Grant No.
29972018).
References
1. (a) Motherwell, W. B.; Crich, D. Free Radical Chain Reactions in Organic Synthesis; Academic Press: London,
1992. (b) Fallis, A. G.; Brinza, I. M. Tetrahedron 1997, 53, 17543. (c) Yet, L. Tetrahedron 1999, 55, 9349.
2. Takano, S.; Suzuki, M.; Kijima, A.; Ogasawara, K. Chem. Lett. 1990, 315.
3. Takano, S.; Suzuki, M.; Kijima, A.; Ogasawara, K. Heterocycles 1994, 37, 149.
4. (a) Tomaszewski, M. J.; Warkentin, J. Tetrahedron Lett. 1992, 33, 2123. (b) Tomaszewski, M. J.; Warkentin, J.
J. Chem. Soc., Chem. Commun. 1993, 966. (c) Tomaszewski, M. J.; Warkentin, J.; Werstiuk, N. H. Aust. J. Chem.
1995, 48, 291.
5. (a) Leardini, R.; Lucarini, M.; Nanni, A.; Nanni, D.; Pedulli, G. F.; Tundo, A.; Zanardi, G. J. Org. Chem. 1993,
58, 2419. (b) Gioanola, M.; Leardini, R.; Nanni, D.; Pareschi, P.; Zanardi, G. Tetrahedron 1995, 51, 2039.
6. (a) Bowman, W. R.; Stephenson, P. T.; Terrett, N. K.; Young, A. R. Tetrahedron Lett. 1994, 35, 6369.
(b) Bowman, W. R.; Stephenson, P. T.; Terrett, N. K.; Young, A. R. Tetrahedron 1995, 51, 7959.
7. Ryu, I.; Ogura, S.; Minaka, S.; Komatsu, M. Tetrahedron Lett. 1999, 55, 1515.
8. Chen et al. reported a photoinduced reaction of chloranil with aromatic imines, but the CˆN bond was intact. See
Chen, C.-F.; Zhang, Z.-G.; Yan, B.-Z.; Xu, J.-H. Tetrahedron Lett. 1994, 49, 9221.

7360
9. (a) Singh, S.; Sharma, V. K.; Gill, S.; Sahota, R. I. K. J. Chem. Soc., Perkin Trans. 1 1985, 437. (b) Shinkai, S.;
Shiraishi, S.; Kunitake, T. Bull. Chem. Soc. Jpn. 1976, 49, 3656. (c) Steevens, J. B.; Pandit, U. K. Tetrahedron
1983, 39, 1395.
10. Fukuzumi, S.; Tanaka, T. In Photoinduced Electron Transfer, Part C; Fox, M. A.; Chanon, M., Eds.; Elsevier:
New York, 1988; p. 578.
11. Tanner, D. D.; Plambeck, J. A.; Reed, D. W.; Mojelsky, T. W. J. Org. Chem. 1980, 45, 5177.
12. ÁG0 is approximately ^32.5 kcal mol^1 as calculated by using Rehm±Weller equation (Isr. J. Chem. 1970, 8, 259).
13. (a) Jin, M. Z.; Yang, L.; Wu, L. M.; Liu, Y. C.; Liu, Z. L. Chem. Commun. 1998, 2541. (b) Maslak, P.; Narvaez,
N. Angew. Chem., Int. Ed. Engl. 1990, 29, 283.
14. Fukuzumi, S.; Hironaka, K.; Tanaka, T. J. Am. Chem. Soc. 1983, 105, 4722.