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One-Pot Synthesis of Cyanohydrin Derivatives from Alkyl Bromides Via Incorporation of Two One-Carbon Components by Consecutive Radical/Ionic Reactions

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One-Pot Synthesis of Cyanohydrin Derivatives from Alkyl Bromides Via Incorporation of Two One-Carbon Components by Consecutive Radical/Ionic Reactions One-pot synthesis of cyanohydrin derivatives from alkyl bromides via incorporation of two one-carbon components by consecutive radical/ionic reactions Shuhei Sumino, Akira Fusano, Hiroyuki Okai, Takahide Fukuyama and Ilhyong Ryu* Letter Open Access Address: Beilstein J. Org. Chem. 2014, 10, 150–154. Department of Chemistry, Graduate School of Science, Osaka doi:10.3762/bjoc.10.12 Prefecture University, Sakai, Osaka 599-8531, Japan Received: 30 September 2013 Email: Accepted: 10 December 2013 Ilhyong Ryu* - [email protected] Published: 14 January 2014 * Corresponding author This article is part of the Thematic Series "Multicomponent reactions II". Keywords: Guest Editor: T. J. J. Müller alkyl bromide; carbon monoxide; cyanohydrin; ethyl cyanoformate; multicomponent; radical reaction © 2014 Sumino et al; licensee Beilstein-Institut. License and terms: see end of document. Abstract The consecutive radical/ionic reaction consisting of radical formylation of alkyl bromides and nucleophilic addition of a cyanide ion was investigated, which gave moderate to good yields of cyanohydrin derivatives in one-pot. Introduction Radical carbonylation reactions have been recognized as a to the radical centre [14], thus we developed a hydroxymethyla- versatile tool for the synthesis of a wide variety of carbonyl tion method using Bu4NBH4 and a radical initiator [15-17]. compounds [1-4]. In 1990, we demonstrated that aldehydes can Recent work in collaboration with Dennis Curran has revealed be prepared from alkyl or aromatic halides and CO under that, with the use of NHC-borane [18], hydroxymethylation of typical radical chain reaction conditions using tributyltin aromatic iodides can be attained [19]. All these reactions consist hydride and AIBN [5,6]. Under the reaction conditions where a of the combination of radical formylation with CO and ionic catalytic amount of fluorous tin hydride and an excess amount hydride reduction by hydride reagents (Scheme 1, reaction 1). of sodium cyanoborohydride were used, initially formed alde- During the course of our study on borohydride-mediated radical hydes can be converted into hydroxymethylated compounds in hydroxymethylation of alkyl halides with CO, we found that one-pot [7-9], since borohydride acts not only as the reagent for cyanohydrin was obtained as a byproduct when Bu4NBH3CN the regeneration of tin hydride [10-13] but also as the reagent was used as a radical mediator [15], which led us to investigate for aldehyde reduction. Later on we found that borohydride the one-pot synthesis of cyanohydrins based on radical formyla- reagents can also serve as radical mediator delivering hydrogen tion. Thus, we thought that the two step radical/ionic reactions 150 Beilstein J. Org. Chem. 2014, 10, 150–154. Scheme 1: Sequential radical formylation and derivatization. can be extended to the consecutive C–C bond forming reac- cyanoformate (2a) was used together with Et3N [29], the cyano- tions. hydrin 3a was obtained in 62% yield. When we used higher CO pressure such as 120 atm, the yield of 3a increased to 79%. Cyanohydrins are important subunits frequently found in bio- logically active compounds and are also versatile building We examined various alkyl bromides 1 in the present radical/ blocks for further synthetic transformations [20,21]. The ionic three-component coupling reaction (Table 1). Primary common method to obtain cyanohydrins is the reaction of alde- alkyl bromides 1b–e containing a chlorine atom, an ester group, hydes with a cyanide sources such as TMSCN [22,23], ethyl a cyano group, or a phenyl group worked well to give the cyanoformate [24-26] or acyl cyanide [27,28]. We provide here corresponding cyanohydrin derivatives 3b–e in good yields an efficient one-pot method for the synthesis of cyanohydrin (Table 1, entries 2–5). The reaction of secondary and tertiary derivatives via consecutive radical/ionic C–C bond forming alkyl bromides 1f–i also proceeded well to give the corres- reaction of alkyl bromides, CO and ethyl cyanoformate ponding cyanohydrins 3f–i in good yields (Table 1, entries (Scheme 1, reaction 2). 6–9). The reaction using cyclopropylmethyl bromide (1j) afforded the lowest yield of cyanohydrin 3j, which possessed an Results and Discussion olefin structure arising from the ring-opening of a cyclopropyl- We examined AIBN-induced radical formylation of 1-bromo- carbinyl radical (Table 1, entry 10) [30,31]. octane (1a) with Bu3SnH under 80 atm of CO pressure in the presence of a cyanide source (Scheme 2). Under the employed Conclusion conditions, the reaction using TMSCN (2a') was slow, which In summary, we have demonstrated a three-component coupling gave 16% of 3a' and 51% of nonanal. The use of AcCN (2a'') reaction comprising alkyl bromides 1, CO and ethyl cyanofor- also gave 3a'' but only in 12% yield. However, when ethyl mate (2a) in the presence of Bu3SnH, AIBN, and Et3N, which Scheme 2: Examination of cyanide source. 151 Beilstein J. Org. Chem. 2014, 10, 150–154. Table 1: Three-component coupling reaction leading to cyanohydrin derivatives. entry alkyl bromide CO (atm) product yielda (%) 1b 120 79 1a 3a 2 80 60 1b 3b 3 80 83 1c 3c 4 120 76 1d 3d 5 120 61 1e 3e 6 120 61 1f 3f 7 120 74 1g 3g 8 120 73 1h 3h 152 Beilstein J. Org. Chem. 2014, 10, 150–154. Table 1: Three-component coupling reaction leading to cyanohydrin derivatives. (continued) 9 110 82 1i 3i 10 110 45 1j 3j a b Isolated yield after flash chromatography on SiO2. 0.03 M. gave moderate to good yields of cyanohydrin derivatives 3. This 5. Ryu, I.; Kusano, K.; Ogawa, A.; Kambe, N.; Sonoda, N. protocol represents a one-pot method [32,33] based on radical J. Am. Chem. Soc. 1990, 112, 1295. doi:10.1021/ja00159a088 6. Ryu, I.; Kusano, K.; Masumi, N.; Yamazaki, H.; Ogawa, A.; Sonoda, N. carbonylation and ionic cyanation. Tetrahedron Lett. 1990, 31, 6887. doi:10.1016/S0040-4039(00)97198-3 7. Gupta, V.; Kahne, D. Tetrahedron Lett. 1993, 34, 591. Experimental doi:10.1016/S0040-4039(00)61627-1 Typical procedure for radical/ionic three-component coupling 8. Ryu, I.; Niguma, T.; Minakata, S.; Komatsu, M.; Hadida, S.; reaction leading to cyanohydrin derivatives 1-cyanononyl ethyl Curran, D. P. Tetrahedron Lett. 1997, 38, 7883. carbonate (3a) [34] (Table 1, entry 1): A mixture of 1-bromo- doi:10.1016/S0040-4039(97)10076-4 9. Matsubara, H.; Yasuda, S.; Sugiyama, H.; Ryu, I.; Fujii, Y.; Kita, K. octane (1a, 96.6 mg, 0.5 mmol), ethyl cyanoformate (2a, Tetrahedron 2002, 58, 4071. doi:10.1016/S0040-4020(02)00256-9 79.3 mg, 0.8 mmol), tributyltin hydride (174.6 mg, 0.6 mmol), 10. Corey, E. J.; Suggs, W. J. Org. Chem. 1975, 40, 2554. triethylamine (13.2 mg, 0.13 mmol), and AIBN (24.6 mg, doi:10.1021/jo00905a039 11. Giese, B.; González-Gómez, J. A.; Witzel, T. 0.15 mmol) in C6H6 (17 mL) were placed in a 100 mL stainless steel autoclave. The reaction mixture was degassed 3 times with Angew. Chem., Int. Ed. Engl. 1984, 23, 69. doi:10.1002/anie.198400691 10 atm of CO and charged with 90 atm of CO at −40 °C 12. Stork, G.; Sher, P. M. J. Am. Chem. Soc. 1986, 108, 303. (MeCN–dry ice bath). Then the autoclave was allowed to warm doi:10.1021/ja00262a024 to room temperature, which caused the pressure gauge to indi- 13. Curran, D. P.; Hadida, S.; Kim, S.-Y.; Luo, Z. J. Am. Chem. Soc. 1999, cate 120 atm. Then the reaction was conducted at 80 °C for 3 h. 121, 6607. doi:10.1021/ja990069a After cooling to room temperature, the reaction mixture was 14. Ryu, I.; Uehara, S.; Hirao, H.; Fukuyama, T. Org. Lett. 2008, 10, 1005. concentrated and purified by silica gel flash chromatography doi:10.1021/ol7031043 15. Kobayashi, S.; Kawamoto, T.; Uehara, S.; Fukuyama, T.; Ryu, I. (hexane/EtOAc 97:3) to afford 3a (95.3 mg, 79%). 1H NMR Org. Lett. 2010, 12, 1548. doi:10.1021/ol1002847 (CDCl3, 500 MHz) δ 5.18 (t, J = 6.8 Hz, 1H), 4.4–4.2 (m, 2H), 16. Kobayashi, S.; Kinoshita, T.; Kawamoto, T.; Wada, M.; Kuroda, H.; 2.0–1.9 (m, 2H), 1.6–1.5 (m, 2H), 1.4–1.2 (m, 13H), 0.88 (t, J = Masuyama, A.; Ryu, I. J. Org. Chem. 2011, 76, 7096. 13 doi:10.1021/jo201064h 6.9 Hz, 3H); C NMR (CDCl3, 125 MHz) δ 153.56, 116.51, 65.27, 64.66, 32.31, 31.68, 29.12, 28.99, 28.71, 24.34, 22.53, 17. Kawamoto, T.; Ryu, I. Chimia 2012, 66, 372. 18. Curran, D. P.; Solovyev, A.; Makhlouf Brahmi, M.; Fensterbank, L.; 14.05, 13.93. Malacria, M.; Lacôte, E. Angew. Chem., Int. Ed. 2011, 50, 10294. doi:10.1002/anie.201102717 Acknowledgements See for a review on NHC-borane. We acknowledge a Grant-in-Aid for Scientific Research on 19. Kawamoto, T.; Okada, T.; Curran, D. P.; Ryu, I. Org. Lett. 2013, 15, Innovative Areas (No. 2105) from the Ministry of Education, 2144. doi:10.1021/ol4006294 Culture, Sports, and Technology (MEXT), Japan. 20. Gregory, R. J. H. Chem. Rev. 1999, 99, 3649. doi:10.1021/cr9902906 21. Brunel, J.-M.; Holmes, I. P. Angew. Chem., Int. Ed. 2004, 43, 2752. doi:10.1002/anie.200300604 References 22. Lidy, W.; Sundermeyer, W. Chem. Ber. 1973, 106, 587. 1. Ryu, I.; Sonoda, N. Angew. Chem., Int. Ed. Engl. 1996, 35, 1050. doi:10.1002/cber.19731060224 doi:10.1002/anie.199610501 23. Evans, D. A.; Truesdale, L. K.; Carroll, G. L. 2. Ryu, I.; Sonoda, N.; Curran, D. P. Chem.
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