Dichlorination of α-Diazo-β-dicarbonyls Using (Dichloroiodo)benzene

Abstract

α-Diazo-β-dicarbonyl compounds were chlorinated using (dichloro)iodobenzene and an activating catalyst. A broad range of reaction rates was observed, which paralleled the relative stability/nucleo­philicity of the diazo compounds. Acyclic diazocarbonyls reacted faster than cyclics, and β-diketones were much faster to react than β-keto esters or β-diesters. Lewis acid activation was used for the first time, allowing us to overcome instances of poor chemoselectivity. Though the yields ranged from low to good, this chlorination reaction has again proven a mild and effective halogenation strategy.

Key words

diazo compounds - hypervalent iodine - halogenation - catalysis - ylides

• References and Notes

• 1 Willgerodt O. J. Prakt. Chem. 1886; 33: 6
• 2a Stang PJ, Zhdankin VV. Chem. Rev. 1996; 96: 1123
• 2b Zhdankin VV, Stang PJ. Chem. Rev. 2002; 102: 2523
• 2c Zhdankin VV, Stang PJ. Chem. Rev. 2008; 108: 5299
• 2d Zhdankin VV. ARKIVOC 2009; (i): 1
• 2e Zhdankin VV. Hypervalent Iodine Chemistry: Preparation, Structure, and Synthetic Applications of Polyvalent Iodine Compounds. Wiley; Chichester: 2013: 468
• 3 Moriarty RM, Kosmeder JW, Zhdankin VV, Courillon C, Lacôte E, Malacria M, Darses B, Dauban P. Iodosylbenzene. In e-EROS Encyclopedia of Reagents for Organic Synthesis [Online]. Wiley; New York: 2012. DOI: 10.1002/047084289X.ri039.pub4
• 4 Koser GF, Ollevier T, Desyroy V. [Hydroxy(tosyloxy)iodo]-benzene. In e-EROS Encyclopedia of Reagents for Organic Synthesis [Online]. Wiley; New York: 2004. DOI: 10.1002/047084289X.rh070.pub2
• 5a Eisenberger P, Gischig S, Togni A. Chem. Eur. J. 2006; 12: 2579
• 5b Kieltsch I, Eisenberger P, Togni A. Angew. Chem. Int. Ed. 2007; 46: 754
• 6 Moriarty RM, Chany CJ, Kosmeder JW. (Diacetoxyiodo)benzene. In e-EROS Encyclopedia of Reagents for Organic Synthesis [Online]. Wiley; New York: 2005. DOI: 10.1002/047084289X.rd005m.pub2
• 7a Merritt EA, Olofsson B. Synthesis 2011; 517
• 7b Dong DQ, Hao SH, Wang ZL, Chen C. Org. Biomol. Chem. 2014; 12: 4278
• 8a Moriarty RM, Prakash I, Prakash O, Freeman WA. J. Am. Chem. Soc. 1984; 106: 6082
• 8b Huang ZZ, Yu XC, Huang X. Tetrahedron Lett. 2002; 43: 6823
• 8c Matveeva ED, Podrugina TA, Grishin YK, Tkachev VV, Zhdankin VV, Aldoshin SM, Zefirov NS. Russ. J. Org. Chem. 2003; 39: 536
• 8d Zhdankin VV, Maydanovych O, Herschbach J, Bruno J, Matveeva ED, Zefirov NS. J. Org. Chem. 2003; 68: 1018
• 9 Roedig A, Aman H, Fahr E. Liebigs Ann. Chem. 1964; 675: 47
• 10 Tao J, Tran R, Murphy GK. J. Am. Chem. Soc. 2013; 135: 16312
• 11a Murphy GK, Abbas FZ, Poulton AV. Adv. Synth. Catal. 2014; 356: 2919
• 11b Coffey KE, Moreira R, Abbas FZ, Murphy GK. Org. Biomol. Chem. 2015; 13: 682
• 12 Zanka A, Takeuchi H, Kubota A. Org. Process Res. Dev. 1998; 2: 270
• 13a Kim JJ, Kweon DH, Cho SD, Kim HK, Lee SG, Yoon YJ. Synlett 2006; 194
• 13b Mei Y, Bentley PA, Du J. Tetrahedron Lett. 2008; 49: 3802
• 13c Wang J, Li H, Zhang D, Huang P, Wang Z, Zhang R, Liang Y, Dong D. Eur. J. Org. Chem. 2013; 5376

For an example using PhICl₂, see:
• 13d Duan X, Zhou H, Tian X, Liu J, Ma J. Synthesis 2015; 47: 777
• 14 Patrick TB, Scheibel JJ, Cantrell GL. J. Org. Chem. 1981; 46: 3917
• 15 Lee KI, Youn JI, Shim YK, Kim WJ. Bull. Korean Chem. Soc. 1992; 13: 226
• 16 Olah GA, Welch J. Synthesis 1974; 896
• 17 Yusubov MS, Zhdankin VV. Curr. Org. Synth. 2012; 9: 247
• 18a Sket B, Zupan M, Zupet P. Tetrahedron 1984; 40: 1603
• 18b Chen JM, Zeng XM, Middleton K, Zhdankin VV. Tetrahedron Lett. 2011; 52: 1952
• 19 Yusubov MS, Drygunova LA, Zhdankin VV. Synthesis 2004; 2289
• 20 Thorat PB, Bhong BY, Karade NN. Synlett 2013; 24: 2061
• 21 Podgorsek A, Jurisch M, Stavber S, Zupan M, Iskra J, Gladysz JA. J. Org. Chem. 2009; 74: 3133
• 22 Kitamura T, Tazawa Y, Morshed MH, Kobayashi S. Synthesis 2012; 44: 1159
• 23a Richardson RD, Wirth T. Angew. Chem. Int. Ed. 2006; 45: 4402
• 23b Ochiai M, Miyamoto K. Eur. J. Org. Chem. 2008; 4229
• 23c Dohi T, Kita Y. Chem. Commun. 2009; 2073
• 24 Caution: Diazo compounds are reported to be toxic and potentially explosive. Appropriate safety measures should be observed when working with them.
• 25a Regitz M, Maas G. Diazo Compounds: Properties and Synthesis . Academic Press; Orlando: 1986. xi
• 25b Doyle MP, Mckervey MA, Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds : From Cyclopropanes to Ylides. Wiley; New York: 1998: 652
• 26 Bug T, Hartnagel M, Schlierf C, Mayr H. Chem. Eur. J. 2003; 9: 4068
• 27 Abel EW, Stone FG. A, Wilkinson G. Comprehensive Organometallic Chemistry II: A Review of the Literature 1982–1994 . Pergamon Press; Oxford: 1995. 1st ed.

In carbenoid reactions, elevated temperatures are required for diazo Meldrum’s acid to react. See:
• 28a Somai Magar KB, Lee YR, Kim SH. Tetrahedron 2013; 69: 9294
• 28b Shi J, Yan Y, Li Q, Xu HE, Yi W. Chem. Commun. 2014; 50: 6483
• 29 For example, chlorination of 23d using 5 mol% DMAP or 2,6-lutidine, or either 1 mol% or 10 mol% pyridine gave mixtures of 24d/25d. The best improvement came from using 5 mol% pyridine in DCE, which gave 24d in 51% yield. However, chlorinating 23a in DCE gave 24a in only 43% yield, so this effect was not pursued.
• 30 Using DCE in the AlCl₃-catalyzed reactions gave lower yields than CH₂Cl₂: 24b, 8%; 24d, 49%.
• 31 Another dramatic Lewis acid effect was found when chlorinating 10-diazoanthrone. In contrast to pyridine, which gave anthroquinone as the product, using AlCl₃ gave 10,10-dichloroanthrone as the sole product.
• 32 Zhao XF, Zhang C. Synthesis 2007; 551