Hypervalent Iodine-Based Activation of Triphenylphosphine for the Functionalization of Alcohols

Dedicated to Professor Victor Snieckus on the occasion of his 80^th birthday

Abstract

The use of hypervalent iodine reagents as a general tool for the activation of PPh₃ and its application to the functionalization of alcohols is reported. Combination of PPh₃ with PhICl₂ or TolIF₂ gives dihalophosphoranes that are characterized by ³¹P NMR, however, with PhIOAc₂, PhI(OTFA)₂, or the cyclic chloro(benzoyloxy)iodane, no phosphoranes were observed. Reaction of these iodanes with PPh₃ in the presence of primary, secondary, or tertiary alcohols results in either halogenation or acyl-transfer products in moderate to high yield.

Key words

Appel reaction - hypervalent iodine - halogenation - acylation - benzoylation

• References and Notes

• 1a Tian J. Gao WC. Zhou DM. Zhang C. Org. Lett. 2012; 14: 3020
• 1b Zhang C. Liu SS. Sun B. Tian J. Org. Lett. 2015; 17: 4106
• 2 Appel R. Angew. Chem., Int. Ed. Engl. 1975; 14: 801
• 3a Zhdankin VV. Stang PJ. Chem. Rev. 2002; 102: 2523
• 3b Wirth T. Hypervalent Iodine Chemistry: Modern Developments in Organic Synthesis. Springer; Berlin: 2003
• 3c Zhdankin VV. Stang PJ. Chem. Rev. 2008; 108: 5299
• 3d Yoshimura A. Zhdankin VV. Chem. Rev. 2016; 116: 3328
• 3e Zhdankin VV. Hypervalent Iodine Chemistry: Preparation Structure, and Synthetic Applications of Polyvalent Iodine Compounds. Wiley; Chichester: 2014
• 4a Tao J. Tran R. Murphy GK. J. Am. Chem. Soc. 2013; 135: 16312
• 4b Murphy GK. Abbas FZ. Poulton AV. Adv. Synth. Catal. 2014; 356: 2919
• 4c Coffey KE. Murphy GK. Synlett 2015; 26: 1003
• 5 Wright DW. Russell GA. Phenyliodine(III) Dichloride In e-EROS . Wiley; Hoboken, NJ: 2001
• 6a For syntheses of Ph₃PCl₂ with various reagents such as Cl₂, CCl₄, (COCl)₂, COCl₂, or C₂Cl₆, see: Michaelis A. Michaelis A. v. Soden H. Justus Liebigs Ann. Chem. 1885; 229: 295
• 6b Appel R. Angew. Chem., Int. Ed. Engl. 1975; 14: 801
• 6c Appel R. Geisler K. Scholer H. Chem. Ber. 1977; 110: 376

For NMR studies on the synthesis of 2 with C₂Cl₆, see:
• 6d Yin Q. Ye Y. Tang G. Zhao YF. Spectrochim. Acta, Part A 2006; 63: 192
• 6e Wiley GA. Stine WR. Tetrahedron Lett. 1967; 2321
• 6f Dillon KB. Lynch RJ. Reeve RN. Waddington TC. J. Chem. Soc. Dalton 1976; 1243
• 6g Appel R. Scholer H. Chem. Ber. 1977; 110: 2382
• 7a Kirk KL. Org. Process. Res. Dev. 2008; 12: 305
• 7b Bégué J.-P. Bonnet-Delpon D. Bioorganic and Medicinal Chemistry of Fluorine . John Wiley and Sons; Hoboken, NJ: 2008: 365
• 7c Ojima I. Fluorine in Medicinal Chemistry and Chemical Biology . Wiley-Blackwell; Chichester: 2009: 624

For syntheses of Ph₃PF₂ with various reagents such as XeF₂, SF₄, IF₅, DAST, COF₂, or HgF₂, see:
• 8a Kobayash Y. Akashi C. Chem. Pharm. Bull. 1968; 16: 1009
• 8b Frohn HJ. Maurer H. J. Fluorine Chem. 1986; 34: 73
• 8c Holmes RR. Chandrasekhar V. Day RO. Harland JJ. Payne JS. Holmes JM. Phosphorus Sulfur Relat. Elem. 1987; 30: 409
• 8d Gupta OD. Shreeve JM. J. Chem. Soc., Chem. Commun. 1984; 416
• 8e Doxsee KM. Hanawalt EM. Weakley TJ. R. Inorg. Chem. 1992; 31: 4420
• 9 Caputo CB. Winkelhaus D. Dobrovetsky R. Hounjet LJ. Stephan DW. Dalton Trans. 2015; 44: 12256
• 10 We believe its increased hydrolytic stability (relative Ph₃PCl₂) is due to the increased strength of P–F (490 kJ/mol) over P-Cl (326 kJ/mol) bonds.
• 11 Iranpoor N. Firouzabadi H. Davan EE. Tetrahedron Lett. 2013; 54: 1813
• 12 Gallos J. Varvoglis A. Chim. Chron., New Ser. 1987; 16: 87
• 13 Makowiec S. Rachon J. Heteroat. Chem. 2003; 14: 352
• 14 McNulty J. Capretta A. Laritchev V. Dyck J. Robertson AJ. Angew. Chem. Int. Ed. 2003; 42: 4051
• 15 Dormoy J.-R. Castro B. Triphenylphosphine Dichloride . In e-EROS . Wiley; Hoboken, NJ: 2001
• 16 Kobayashi Y. Akashi C. Chem. Pharm. Bull. 1968; 16: 1009
• 17a Mohandas TP. Mamman AS. Nair PM. Tetrahedron 1983; 39: 1187
• 17b Wicha J. Zarecki A. Kocór M. Tetrahedron Lett. 1973; 14: 3635
• 18 Taniguchi T. Hirose D. Ishibashi H. ACS Catal. 2011; 1: 1469
• 19 Carle MS. Shimokura GK. Murphy GK. Eur. J. Org. Chem. 2016; 3930
• 20 Reacting Ph₃PF₂ (4, 1.6 equiv) with 4-nitrophenethyl alcohol for 45 min at 160 °C using 10 mol% TiF₃ as an activating agent produced alkyl fluoride 5a in 66% yield.
• 21 The major competing reaction pathway in these experiments was alcohol dimerization, giving the ether. It is proposed that this arises from the alcohol outcompeting fluoride as the nucleophile. See ref. 16.
• 22 Zhang and co-workers reported phenethyl acetate to be the major byproduct of a reaction between 5, phenethyl alcohol, hexanoic acid, DMAP, and PPh₃. No indication of phenethyl trifluoroacetate was reported for the analogous reaction using iodane 7. See Table S1 in the supporting information of ref. 1a.
• 23 Only trace amounts of 15a or 15b were visible by ¹H NMR analysis of the crude reaction mixtures after 10 min. Prolonging the reaction times to 2–3 h did not significantly change the product ratios, suggesting that the reaction pathways are competing, as opposed to 14 reacting with the benzoate byproduct of the reaction to give 15. Concentrating the reaction mixtures before column chromatography appears to have increased the ratio of the benzoate products.
• 24 Zhdankin VV. Koposov AY. Litvinov DN. Ferguson MJ. McDonald R. Luu T. Tykwinski RR. J. Org. Chem. 2005; 70: 6484
• 25 Sample Experimental Procedure Into a conical flask was added the 4-phenyl-2-butanol (0.063 g, 0.42 mmol, 1 equiv) and CH₂Cl₂ (0.5 mL), and to this was added PPh₃ (1.1 equiv) and [bis(trifluoro-acetoxy)iodo]benzene (1.1 equiv). The reaction mixture was stirred at r.t. for 30 min, concentrated by rotary evaporation and subjected to column chromatography, where the stationary phase as acidified with 0.2% TFA in hexane. The crude reaction mixture was purified via column chromatography (10% EtOAc/hexane) to give 13c (0.066 g, 64% yield) as a colorless oil.¹⁹F NMR (282 MHz, CDCl₃): δ = –75.58. ¹H NMR (300 MHz, CDCl₃): δ = 7.34–7.16 (m, 5 H), 5.11 (m, 1 H), 2.74–2.60 (m, 2 H), 2.15–1.87 (m, 2 H), 1.39 (d, J = 6.3 Hz, 3 H);¹³C NMR (75 MHz, CDCl₃): δ = 157.1 (q, J = 41.5 Hz), 140.5, 128.6, 128.3, 126.3, 114.6 (q, J = 286.1 Hz), 75.8, 37.1, 31.4, 19.5.