Dehydroxymethyl Bromination of Alkoxybenzyl Alcohols by Using a Hypervalent Iodine Reagent and Lithium Bromide

Abstract

We describe the dehydroxymethylbromination of alkoxybenzyl alcohol by using a hypervalent iodine reagent and lithium bromide in F₃CCH₂OH at room temperature. Selective monobromination or dibromination was possible by adjusting the molar ratios of hypervalent iodine reagent and lithium bromide.

Key words

hypervalent iodine reagent - bromination - bromoarenes - benzylic alcohol - regioselectivity

• References and Notes

• 1a Hunsdiecker H. Hunsdiecker C. Ber. Dtsch. Chem. Ges. B 1942; 75: 291
• 1b Johnson RG. Ingham RK. Chem. Rev. 1956; 56: 219
• 1c Wilson CV. Org. React. (N.Y.) 1957; 9: 332
• 1d Sheldon RA. Kochi JK. Org. React. (N.Y.) 1972; 19: 279
• 1e Crich D. In Comprehensive Organic Synthesis . Vol. 7. Trost BM. Fleming I. Pergamon; Oxford: 1991: 717
• 1f Wang Z. Zhu L. Yin F. Su Z. Li Z. Li C. J. Am. Chem. Soc. 2012; 134: 4258
• 2a Hamamoto H. Umemoto H. Umemoto M. Ohta C. Doshita M. Miki Y. Synlett 2010; 21: 2593
• 2b Hamamoto H. Hattori S. Takemaru K. Miki Y. Synlett 2011; 22: 1563
• 3 Miki Y. Umemoto H. Doshita M. Hamamoto H. Tetrahedron Lett. 2012; 53: 1924

For recent reviews, see:
• 4a Stang PJ. Zhdankin VV. Chem. Rev. 1996; 96: 1123
• 4b Zhdankin VV. Stang PJ. Chem. Rev. 2002; 102: 2523
• 4c Hypervalent Iodine Chemistry: Modern Developments in Organic Synthesis. Wirth T. Springer; Berlin: 2003
• 4d Tohma H. Kita Y. Adv. Synth. Catal. 2004; 346: 111
• 4e Moriarty RM. J. Org. Chem. 2005; 70: 2893
• 4f Wirth T. Angew. Chem. Int. Ed. 2005; 44: 3656
• 4g Zhdankin VV. Stang PJ. Chem. Rev. 2008; 108: 5299
• 4h Ochiai M. Miyamoto K. Eur. J. Org. Chem. 2008; 4229
• 4i Ochiai M. Synlett 2009; 159
• 4j Dohi T. Kita Y. Chem. Commun. 2009; 2073
• 4k Duschek A. Kirsch SF. Angew. Chem. Int. Ed. 2011; 50: 1524
• 4l Merritt EA. Olofsson B. Synthesis 2011; 517
• 4m Silva LF. Jr. Olofsson B. Nat. Prod. Rep. 2011; 28: 1722
• 4n Yoshimura A. Zhdankin VV. Chem. Rev. 2016; 116: 3328
• 4o Li YF. Hari DP. Vita MV. Waser J. Angew. Chem. Int. Ed. 2016; 55: 4436
• 4p Hypervalent Iodine Chemistry . Wirth T. Springer; Berlin: 2016
• 5a Nair V. Panicker SB. Augustine A. George TG. Thomas S. Vairamani M. Tetrahedron 2001; 57: 7417
• 5b Roy SC. Guin C. Rana KK. Maiti G. Tetrahedron Lett. 2001; 42: 6941
• 5c Mo S. Zhu Y. Shen Z. Org. Biomol. Chem. 2013; 11: 2756
• 5d Zhang P. Hong L. Li G. Wang R. Adv. Synth. Catal. 2015; 357: 345
• 5e Xu J. Zhu X. Zhou G. Ying B. Ye P. Su L. Shen C. Zhang P. Org. Biomol. Chem. 2016; 14: 3016
• 6a Dieter RK. Nice LE. Velu SE. Tetrahedron Lett. 1996; 37: 2377
• 6b Subbarayappa A. Ghosh S. Patoliya PU. Ramanshandraiah G. Agrawal M. Gandhi MR. Upadhyay SC. Ghosh PK. Ranu BC. Green Chem. 2008; 10: 232
• 6c Wang G.-W. Gao J. Green Chem. 2012; 14: 1125
• 7a Rousseau G. Robin S. Tetrahedron Lett. 2000; 41: 8881
• 7b Koo B.-S. Lee CK. Lee K.-J. Synth. Commun. 2002; 32: 2115
• 7c Lee CK. Koo B.-S. Lee YS. Cho HK. Lee K.-J. Bull. Korean Chem. Soc. 2002; 23: 1667
• 7d Adimurthy S. Patoliya PU. Synth. Commun. 2007; 37: 1571
• 8 Tohma H. Maegawa T. Takizawa S. Kita Y. Adv. Synth. Catal. 2002; 344: 328
• 9 1-Bromo-2-methoxybenzene (2a) (see Ref. 10); Typical Procedure LiBr·H₂O (0.2 mmol) and PhI(OAc)₂ (0.2 mmol) were added to a solution of 4-methoxybenzyl alcohol (1a; 0.2 mmol) in F₃CCH₂OH (1 mL) at r.t. When the reaction was complete (TLC), sat. aq Na₂SO₃ was added and the mixture was extracted with CH₂Cl₂. The combined organic layers were washed with brine, dried (Na₂SO₄), and concentrated in vacuo. The residue was purified by column chromatography (silica gel) to give a yellow oil; yield: 34.1 mg (91%); ¹H NMR (CDCl₃): δ = 3.79 (s, 3 H), 6.79 (dd, J = 2.0, 8.6 Hz, 2 H), 7.38 (dd, J = 2.0, 8.6 Hz, 2 H).
• 10 Braddock DC. Cansell G. Hermitage SA. Synlett 2004; 461