Photo-Induced Atom-Transfer Radical Reactions Using Charge–Transfer Complex between Iodine and Tertiary Amine

Abstract

In the presence of charge–transfer complexes between iodine and tertiary amines, the aqueous-medium atom-transfer radical reactions proceeded under visible light irradiation without the typical photocatalysts.

The charge–transfer complex (CT complex) is formed by weak association of electron-donor and electron-acceptor. Particularly, the CT complexes between metal atoms and ligands are widely studied in inorganic chemistry.^1,2) In recent years, the metal-to-ligand charge transfer in transition metal photocatalysts has been applied to the synthetic organic chemistry.^3–5) Although the physical properties of organic CT complexes are investigated,^6–10) less is known about the utility of organic CT complexes in synthetic reactions.^11–15) In our studies on the radical reactions using Ru-catalyst or rhodamine B as a photocatalyst,^16–19) we found that the some reactions proceeded in the absence of these photocatalysts. Therefore, our laboratory is interested in developing a new method which doesn’t require the external photocatalysts. In this communication, we report the experiments to prove the utility of organic CT complexes between iodine (I₂) and tertiary amines in the aqueous-medium carbon–carbon bond-forming radical reactions.

Iodine is known to interact with amines to form the CT complexes, which have the two broader absorption bands at ca. 230–280 and 410–430 nm^20,21) (Chart 1). Therefore, we expected that the visible light irradiation of CT complex A in the ground state gives the excited state B, which may promote the single electron transfer (SET) from the donor amine to the acceptor iodine giving the iodine radical.^22–24)

Chart 1. Charge–Transfer Complex between Amine and Iodine

At first, we studied the effect of CT complexes derived from I₂ and several amines on the iodine atom-transfer radical reaction of alkene 1 with i-C₃F₇I (Table 1). In the presence of I₂ (0.1 eq) and trimethylamine (1.1 eq), the biphasic solution of 1 and i-C₃F₇I (5 eq) in H₂O was stirred for 1 h with white LED light (400–700 nm, 1000 lm) irradiation under Ar atmosphere (entry 1). In this reaction, 1.1 eq of trimethylamine were employed, because 1.0 eq of amine also acts as an electron-donor leading to C. As expected, the desired product 2 was obtained in 89% yield. In marked contrast, the reaction did not occur when MeCN was employed as solvent (entry 2). The use of (i-Pr)₂NEt as a tertiary amine led to enhancement in chemical yield (entry 3), although pyridine did not promote the reaction probably due to its low reactivity as an electron-donor (entry 4). The chemical yield of 2 dramatically decreased by using secondary amine such as (i-Pr)₂NH, owing to the oxidation of secondary amine by I₂ (entry 5).^25–27) Interestingly, in the absence of iodine, this transformation took place slowly by using (i-Pr)₂NEt (entry 6). Even in the absence of I₂, CT complex between (i-Pr)₂NEt and I₂ would be formed, because i-C₃F₇I is gradually decomposed to give I₂. However, in the absence of amine, the reaction using only iodine did not occur and the solubility of iodine also decreased without the association with amine (entry 7). Therefore, this CT complex-promoted reaction is differentiated from the reported iodine-mediated radical reactions.^28,29) Theoretical and computational studies on halogen bonding interactions have been a subject of current interest.^30,31) To understand the above results, we calculated the optimized structures of iodine complexes. The calculation shows that the noncovalent interaction between trimethylamine and I₂ is strong to form the stable CT complex, while pyridine weakly interacts with I₂. Additionally, we presume that the negligible interaction of MeCN solvent with I₂ may suppress the formation of CT complex.

Table 1. Iodine-Atom Transfer Reaction Using Charge–Transfer Complexes^a)

Entry	Amine	Solvent	Yield (%)b)
1	Me3N	H2O	89
2	Me3N	MeCN	NDd)
3	(i-Pr)2NEt	H2O	98
4	Pyridine	H2O	NDd)
5	(i-Pr)2NH	H2O	3
6c)	(i-Pr)2NEt	H2O	56
7	None	H2O	NDd)

a) Reactions of 1 (1 eq) with i-C₃F₇I (5 eq) were carried out in the presence of I₂ (0.1 eq) and amine (1.1 eq) under the LED light irradiation. The calculation studies were performed on density functional B3LYP 6–311+G** by using Spartan'10 (WAVEFUNCTION, INC.). b) Isolated yields. c) Reaction was carried out in the absence of I₂ for 4 h. d) The formation of product 2 was not detected.

We next explored the iodine atom-transfer radical reaction of various alkenes 3–8 with i-C₃F₇I under the optimized reaction conditions (Table 2). Except for styrene 8, alkenes 3–7 reacted with excellent chemical efficiencies and regioselectivities. It is important to note that the reactions of alkene 6 having bromine atom and alkene 7 having hydroxy group proceeded without any problems.

Table 2. Reaction of 3–8 with i-C₃F₇I^a)

a) Reactions of 3–8 (1 eq) with i-C₃F₇I (5 eq) were carried out in H₂O in the presence of I₂ (0.1 eq) and (i-Pr)₂NEt (1.1 eq) for 1 h under the LED light irradiation. b) Isolated yields. c) The formation of product was not detected.

To study the viability of the present method, n-C₃F₇I, ICH₂CN and CCl₃Br were next employed as carbon radical precursors (Chart 2). The reaction of 1 with n-C₃F₇I proceeded to give the product 14 in 81% yield. Although the reaction in MeCN did not occur (entry 2 in Table 1), ICH₂CN having cyano group worked as a radical precursor to give the adduct 15 in 43% yield. Moreover, the bromine atom-transfer radical reaction using CCl₃Br took place with moderate chemical efficiency.

Chart 2. Reaction with Other Carbon Radical Precursors

We finally investigated the radical addition-cyclization-trapping reaction of symmetrical substrates 17, 19 and 21 in aqueous media (Chart 3). When i-C₃F₇I was employed, the reaction of 17 was completed within 1 h to give the products cis-18a and trans-18a in 81% combined yield. Other radical precursors n-C₃F₇I and c-C₆F₁₁I worked well. Similarly, the reaction of 19 with i-C₃F₇I gave the products cis-20 and trans-20 in 82% combined yield. The reaction of 21 also proceeded effectively to give the product 22 in 98% yield with excellent cis-diastereoselectivity.

Chart 3. Cascade Radical Addition-Cyclization-Trapping Reaction

The possible reaction pathway for the generation of i-C₃F₇ radical is shown in Chart 4. The reaction is initiated by the visible light irradiation of CT complex A in the ground state to produce the excited state B. We presume the generation of an iodine radical via the single electron transfer from the donor amine to the acceptor iodine in the excited state B, which is evident from observation of the transient species generated in the photoexcitation of quinuclidine–I₂ and triethylenediamine–I₂ complexes by means of transient absorption spectroscopy,²²⁾ although it cannot be excluded that the excited state B acts as a reducing agent toward i-C₃F₇I. Finally, an iodine radical reacts with i-C₃F₇I to give i-C₃F₇ radical and the regenerated iodine.

Chart 4. Possible Reaction Pathway

In summary, we have demonstrated that CT complexes between iodine and tertiary amines have the potential to induce the atom-transfer radical reactions in aqueous media. In addition to typical photocatalysts, the CT complexes disclosed a broader utility of photo-induced radical reactions.

Acknowledgment

This work was supported by JSPS KAKENHI Grant-in-Aid for Scientific Research (C) Grant Number 16K08188 (to H.M.).

Conflict of Interest

The authors declare no conflict of interest.

References

• 1) Akimov A. V., Neukirch A. J., Prezhdo O. V., Chem. Rev., 113, 4496–4565 (2013).
• 2) Rondi A., Rodriguez Y., Feurer T., Cannizzo A., Acc. Chem. Res., 48, 1432–1440 (2015).
• 3) Tucker J. W., Stephenson C. R. J., J. Org. Chem., 77, 1617–1622 (2012).
• 4) Ischay M. A., Yoon T. P., Eur. J. Org. Chem., 2012, 3359–3372 (2012).
• 5) Shi L., Xia W., Chem. Soc. Rev., 41, 7687–7697 (2012).
• 6) Onda K., Yamochi H., Koshihara S., Acc. Chem. Res., 47, 3494–3503 (2014).
• 7) Wang C., Xu Q.-W., Zhang W.-N., Peng Q., Zhao C.-H., J. Org. Chem., 80, 10914–10924 (2015).
• 8) Geng Y., Pfattner R., Campos A., Hauser J., Laukhin V., Puigdollers J., Veciana J., Mas-Torrent M., Rovira C., Decurtins S., Liu S., Chem. Eur. J., 20, 7136–7143 (2014).
• 9) Haberhauer G., Gleiter R., Burkhart C., Chem. Eur. J., 22, 971–978 (2016).
• 10) Rosokha S. V., Kochi J. K., Acc. Chem. Soc., 41, 641–653 (2008).
• 11) Koshima H., Ding K., Chisaka Y., Matsuura T., Ohashi Y., Mukasa M., J. Org. Chem., 61, 2352–2357 (1996).
• 12) González-Béjar M., Stiriba S.-E., Miranda M. A., Pérez-Prieto J., Org. Lett., 9, 453–456 (2007).
• 13) Arceo E., Jurberg I. D., Álvarez-Fernández A., Melchiorre P., Nat. Chem., 5, 750–756 (2013).
• 14) Kandukuri S. R., Bahamonde A., Chatterjee I., Jurberg I. D., Escudero-Adán E. C., Melchiorre P., Angew. Chem. Int. Ed., 54, 1485–1489 (2015).
• 15) Woźniak Ł., Murphy J. J., Melchiorre P., J. Am. Chem. Soc., 137, 5678–5681 (2015).
• 16) Yoshioka E., Kohtani S., Tanaka E., Miyabe H., Synlett, 24, 1578–1582 (2013).
• 17) Yoshioka E., Kohtani S., Tanaka E., Hata Y., Miyabe H., Tetrahedron, 71, 773–781 (2015).
• 18) Yoshioka E., Kohtani S., Jichu T., Fukazawa T., Nagai T., Takemoto Y., Miyabe H., Synlett, 26, 265–270 (2015).
• 19) Yoshioka E., Kohtani S., Jichu T., Fukazawa T., Nagai T., Kawashima A., Takemoto Y., Miyabe H., J. Org. Chem., 81, 7217–7229 (2016).
• 20) Nagakura S., J. Am. Chem. Soc., 80, 520–524 (1958).
• 21) Yada H., Tanaka J., Nagakura S., Bull. Chem. Soc. Jpn., 33, 1660–1667 (1960).
• 22) Halpern A. M., Weiss K., J. Phys. Chem., 72, 3863–3870 (1968).
• 23) Lenderink E., Duppen K., Everdij F. P. X., Mavri J., Torre R., Wiersma D. A., J. Phys. Chem., 100, 7822–7831 (1996).
• 24) DeBoer G., Burnett J. W., Fujimoto A., Young M. A., J. Phys. Chem., 100, 14882–14891 (1996).
• 25) Ishihara M., Togo H., Synlett, 2006, 227–230 (2006).
• 26) Shie J.-J., Fang J.-M., J. Org. Chem., 72, 3141–3144 (2007).
• 27) Lin C., Lai P.-T., Liao S. K.-S., Hung W.-T., Yang W.-B., Fang J.-M., J. Org. Chem., 73, 3848–3853 (2008).
• 28) Usami K., Nagasawa Y., Yamaguchi E., Tada N., Itoh A., Org. Lett., 18, 8–11 (2016).
• 29) Lin Y., Lu G., Cai C., Yi W., Org. Lett., 17, 3310–3313 (2015).
• 30) Kolář M. H., Hobza P., Chem. Rev., 116, 5155–5187 (2016).
• 31) Tsuzuki S., Wakisaka A., Ono T., Sonoda T., Chem. Eur. J., 18, 951–960 (2012).