An Improved Synthesis of β-Iodo Ethers and Iodohydrins from Alkenes

Abstract

1Abstract: The preparation of diverse β -iodo ethers and iodohydrins is efficiently achieved in mild conditions by reaction of alkenes with two equivalents of I 2 and alcohols (EtOH, i -PrOH, tBuOH) or water, respectively. β -Iodo ethers are useful intermediates for stereoselective radical reactions 1 and for the synthesis of E or Z alkenes with good to moderate diastereoselectivity. 2 Traditional methods for preparing these compounds are the reaction of alkenes with N -iodosuccinimide/alcohols 3 or I 2 /alcohols and a metal salt, such as Cu(II), 4 Ag(I) 1 and Ce(IV). 5 Although Rutledge and co-workers 6 reported a method of synthesis of iodohydrins ( β -iodo alcohols) by reaction of alkenes with 2.4 equivalents of iodine in a biphasic system (water, chloroform, and sulfolane) as well as a similar route to β -iodo ethers with alkenes, iodine, sulfolane and an alcohol, this system is somewhat complicated due to the possibility of the sulfone participating in the reaction, 6 prolonged reaction times (24-25 h), and more complex experimental procedures (such as anhydrous solvents).In previous work we studied an easy route for the preparation of iodohydrins from alkenes by reaction with iodine and water in the presence of diverse metal salts, and showed that the readily available and inexpensive Fe 2 (SO 4 ) 3 gave the best yields. 7a This methodology does not require special techniques and we decided to extend it to the reaction of alkenes with iodine/Fe 2 (SO 4 ) 3 in the presence of alcohols as a possible route to β -iodo ethers.Applying our methodology we obtained 1-ethoxy-2-iodo-1-phenylethane (1a) in 63% isolated yield by the reaction of styrene with I 2 , Fe 2 (SO 4 ) 3 and ethanol (solvent) at room temperature. Surprisingly, when a second equivalent of iodine was used in place of the ferric salt, we obtained the same product 1a in a shorter reaction time (2.5 h) and slight higher isolated yield (75%). This was unexpected, since according to the literature information the metal salt was supposed to be necessary in order to obtain good yields and avoid the formation of 1,2-diiodoalkanes as undesirable side products. 4a In our hands, no diiodo compound was detected by the analytical procedures employed [HRGC (high resolution GC), 1 H NMR and 13 C NMR] and although we have used ethanol without further purification, no iodohydrin arising from small amounts of water in the solvent was detected either.Based on the above results, we decided to investigate the preparation of diverse β -iodo ethers using alkenes, alcohols and 2 equivalents of I 2 and the results are shown for Dedicated to Prof. W. Bruce Kover on the occasion of his 60th birthday the formation of 1a-g in Table 1. In all the reactions the purity of the isolated products (>95%) was confirmed by 1 H NMR, 13 C NMR, FT-IR and HRGC and the yields of the β -iodo ethers were good to moderate even with secondary and tertiary alcohols. Only in the case of hex-1-ene did the reaction give predominantly the secondary ether mixed with some of its regioisomer (85:15 by...

Reaction of Alkenes with Hydrogen Peroxide and Sodium Iodide: A Nonenzymatic Biogenic‐Like Approach to Iodohydrins

“…2 c, [26] 2 f [27] were in complete accordance with literature values. General procedure for the preparation of iodohydrins 2 j and 2 k: A lower amount of H 2 O 2 (0.75 mL, 1.5 equiv, 7.5 mmol) was used to avoid competitive formation of hydroperoxides analogues.…”

“…Analytical data for compounds 2 g, [29] Procedure for the preparation of 2 d: HBF 4 (4.1 mL of 35 % aqueous solution, 4 equiv, 20 mmol) and H 2 O 2 (2 mL, 4 equiv, 20 mmol, 33 % aqueous solution) were used. Analytical data for compound 2 d [26] were in complete accordance with literature values.…”

Ultrasound promoted regioselective synthesis of β-iodoethers from olefin-I2-alcohol

“…In continuation of our work on sonochemically accelerated reactions [3][4][5][6][7], we became interested in the ultrasound promoted preparation of the b-iodoethers for two reasons (i) contradicting reports regarding the usage of metal salts as catalysts: Tl (I), Cu (II), Ce (IV) salts [8][9][10][11][12], whose presence is required to catalyse the reaction, while in another report by Mattos and coworker [13] excess of iodine is sufficient to obtain b-iodoethers in moderate to good yields (ii) to find the effect of ultrasound (35 kHz, in a sonic bath) for catalytic activity on the reaction and the use of metal salts as catalysts in presence of ultrasound.…”

Cohalogenation of limonene, carvomenthene and related unsaturated monoterpenic alcohols

“…of iodine in place of the metal salt 5 . Thus, using this simple methodology, iodohydrins 4,6 and β-iodoethers 5 were effectively prepared in good yields and high purity when the iodination of alkenes was performed in water or alcohols, respectively.…”

“…The role of the metal salt or of the second equivalent of iodine in the coiodination reactions is to decompose the π complex formed among alkene and iodine to the bridged iodonium ion 5,7 . In the case of Cu(OAc) 2 , cupric iodide is formed followed by disproportionation to cuprous iodide and iodine 7 (Scheme 2).…”