Iodine/TBHP

Introduction

In recent times, several advancements were made in using catalytic amounts of iodine in combination with tert-butyl hydroperoxide (TBHP) as co-oxidant. The increased utility is mainly due to its inexpensive, environmentally benign nature, good efficiency and compatibility to work in place of rare or toxic heavy metal oxidants.[1] The I₂/TBHP catalytic system works efficiently for numerous C–C and C–X (X = heteroatom) bond-forming organic transformations under mild reaction conditions to offer the desired products in excellent yields.[2]

Table 1 Use of Iodine–TBHP

(A) Jiang et al. reported an I2/TBHP mediated domino oxidative cyclization for the one-pot synthesis of polysubstituted oxazoles from readily available styrenes and benzylamines under mild conditions.[3]
(B) Zhang et al. demonstrated the synthesis of 2-phenylquinazolines in good to excellent yields via tandem sp3 C–H functionalization of 2-amino benzophenones and benzylic amines.[4]
(C) Manjunath and Prabhu reported a metal-free catalytic route to 2-aminobenzoxazoles by amination of benzoxazoles via C–H bond activation of primary or secondary amines. Further the methodology was demonstrated to synthesize therapeutically active benzoxazoles.[5]
(D) An I2/TBHP catalyzed first efficient and direct synthesis of tertiary amides from alcohols and dimethylformamide has been developed. This transition-metal-free protocol provides a practical synthetic tool for the construction of N,N-dimethyl-substituted amides.[6]
(E) A metal-free oxidative coupling of methyl ketones and primary or secondary amines to α-keto amides was developed by Wan and his group. Four types of intermediates, α-iodo ketones, α-amino ketones, iminium intermediates and α-hydroxy amines were identified through a series of control experiments. The atom-economic methodology can be scaled-up, tolerates a variety of functional groups, and is operationally simple.[7]
(F) A novel I2/TBHP catalyzed selective 2-arylsulfonylation of indoles was demonstrated. Various substituted 2-arylsulfonyl indoles were obtained in good to excellent yields in one pot. The direct sulfonylation reaction occurred selectively at C-2 position of the indole ring and only a catalytic amount of iodine acted as an efficient promoter. This method is a novel alternative approach for the synthesis of biologically important hetero diaryl sulfones from sodium sulfinates.[8]
(G) Recently, we have developed an I2/TBHP mediated synthesis of isatin and iodoisatin from 2′-aminoacetophenone via intramoleular oxidative amidation of the sp3 C−H bond. The reaction proceeds through sequential iodination, Kornblum oxidation, and amidation in one pot. The stoichiometric amount of I2 plays a significant role in delivering iodoisatin exclusively in high yields.[9]
(H) Ji’s research group reported an I2/TBHP mediated oxidation of commercially available indoles to isatins in moderate to good yields.[10]

• References

• 1a Finkbeiner P, Nachtsheim BJ. Synthesis 2013; 979
• 1b Kirihara M, Asai Y, Ogawa S, Noguchi T, Hatano A, Hirai Y. Synthesis 2007; 3286
• 2a Hummel S, Kirsch SF. Beilstein J. Org. Chem. 2011; 7: 847
• 2b Zhao Q, Miao T, Zhang X, Zhou W, Wang L. Org. Biomol. Chem. 2013; 11: 1867
• 3 Jiang H, Huang H, Cao H, Qi C. Org. Lett. 2010; 12: 5561
• 4 Zhang J, Zhu D, Yu C, Wan C, Wang Z. Org. Lett. 2010; 12: 2841
• 5 Manjunath L, Prabhu KR. J. Org. Chem. 2011; 76: 7938
• 6 Xu K, Hu Y, Zhang S, Zha Z, Wang Z. Chem. Eur. J. 2012; 18: 9793
• 7 Wei W, Shao Y, Hu H, Zhang F, Zhang C, Xu Y, Wan X. J. Org. Chem. 2012; 77: 7157
• 8 Xiao F, Chen H, Xie H, Chen S, Yang L, Deng G.-J. Org. Lett. 2014; 16: 50
• 9 Ilangovan A, Satish G. J. Org. Chem. 2014; 79: 4984
• 10 Zi Y, Cai Z.-J, Wang S.-Y, Ji S.-J. Org. Lett. 2014; 16: 3094