· (MW 108.34)
(borylating reagent;3,4 preparation of substituted allyl boronates;5,6 preparation of enol borates10,11)
Physical Data: mp -87.5 °C; bp 74 °C; d 1.079 g cm-3.
Solubility: sol aprotic solvents (ether, THF, CH2Cl2, hydrocarbons); reacts with water and protic solvents.
Preparative Method: prepared from a 2:1 mole mixture of B(OMe)3 and BCl3.2
Handling, Storage, and Precautions: air and moisture sensitive; store and handle under an inert atmosphere.
Preparation of Organoboronates.
Chlorodimethoxyborane has been extensively used in organic synthesis for the preparation of boronic ester derivatives. Typically, ClB(OMe)2 is allowed to react with an organolithium reagent at low temperatures in THF or ether to afford the corresponding organoboronates. The boronates obtained are then usually elaborated without isolation. Alkyl and allyl sulfones have been converted into ketones and aldehydes via the corresponding a-sulfonylboronic esters. The a-sulfonylboronic esters were synthesized via lithiation of the sulfone and subsequent reaction with ClB(OMe)2 in THF (eq 1).3 Use of ClB(OMe)2 was critical for the borylation reaction, as both FB(OMe)2 and trimethoxyborane gave unsatisfactory results. The efficiency of the chlorodimethoxyborane
reagent has been attributed to the low solubility of LiCl in THF.3 Similarly, 2-aryl- and 2-alkylfurans have been converted into 2(3H)-butenolides via the oxidation of boronic ester derivatives (eq 2).4 The 5-furylboronate derivatives were prepared in a very efficient manner by reacting the corresponding lithiofurans with 1 equiv of ClB(OMe)2 in trimethoxyborane (prepared in situ by reacting BCl3 with an excess of B(OMe)3). Yields for the corresponding reactions were poor when trimethoxyborane or fluorodimesitylborane were used.
Preparation of Substituted Allylboronates.
The preparations of substituted allylboronic acid ester derivatives using halodialkoxyboranes,5,6 trialkoxyboranes,7 and halobis(dialkylamino)boranes8 have been extensively studied in recent years. For example, a variety of g-alkoxyallylboronates have been efficiently prepared via lithiation of allyl ethers and subsequent reaction with halodialkoxyboranes (eq 3).5 Most notably, the preparation of (E)- and (Z)-crotylboronates has been thoroughly investigated. Reaction of (E)- or (Z)-crotylpotassium (see also Schlosser's base) with either ClB(OMe)28b or F(BOMe)27a affords the corresponding crotyldimethoxyborane. The crude boronate can be hydrolyzed to the boronic acid, which upon esterification can then be converted
into a variety of crotylboronates, including the chiral diisopropyl tartrate (DIPT) modified crotylboronate reagents (eq 4).6,7 However, the borylation reaction (especially when carried out on a large scale) is accompanied by the formation of methyl dicrotylborinate and tricrotylborane, resulting in lower yield and erosion of the isomeric purity (92-95%) of the crotylboronate. Use of ClB(NMe2)28b gave the crotylboronate in high isomeric purity; however, the yield was low. These problems can be overcome by using Triisopropyl Borate, which gives the crotylboronate in high yield and >98% isomeric purity.7a Superior results were also obtained in the synthesis of alkyl boronic esters when B(O-i-Pr)3 was used in place of ClB(OMe)2.9 For example, reaction
of MeLi with ClB(OMe)2 gave methyldimethoxyborane in 43% yield, whereas the corresponding reaction with B(O-i-Pr)3 proceeded in 98% yield.9
Preparation of Enol Borates.
Reaction of ClB(OMe)2 with either lithium enolates10 or trimethylsilyl enol ethers11 affords the corresponding dimethyl enol borates. The enol borate (used without isolation) reacts with aldehydes to afford the dioxaborinane (1) (eq 5). The dioxaborinane (1) represents an internally protected aldol, which can be elaborated without the need for isolation and protection of the alcohol. Thus addition of an allyl metal such as allylmagnesium bromide affords the allylic diol (2) in good yield, albeit with low diastereoselectivity (eq 5).10 Alternatively, the dioxaborinane can be reduced with Sodium Borohydride to the corresponding diol.11
- 1. For a general discussion on the preparation and reactions of halodialkoxyboranes, see: Steinberg, H. Organoboron Chemistry; Interscience: New York, 1966; Vol. 1, pp 547-558.
- 2. Wiberg, E.; Smedsrud, H. Z. Anorg. Allg. Chem. 1935, 225, 204 (CA 1936, 30, 917).
- 3. (a) Baudin, J.-B.; Julia, M.; Rolando, C. TL 1985, 26, 2333. (b) For an alternative method of converting sulfones into carbonyl compounds using (TMSO)2, see: Hwu, J. R. JOC 1983, 48, 4432.
- 4. Pelter, A.; Rowlands, M. TL 1987, 28, 1203.
- 5. Preparation of (g-alkoxyallyl)boronates: Wuts, P. G. M.; Bigelow, S. S. JOC 1982, 47, 2498.
- 6. Preparation of crotylboronates: Roush, W. R.; Halterman, R. L. JACS 1986, 108, 294.
- 7. (a) Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz, A. D.; Halterman, R. L. JACS 1990, 112, 6339. (b) Roush, W. R.; Walts, A. E.; Hoong, L. K. JACS 1985, 107, 8186.
- 8. (a) Hoffman, R. W.; Kemper, B.; Metternich, R.; Lehmeier, T. LA 1985, 2246. (b) Hoffman, R. W.; Zeib, H.-J. JOC 1981, 46, 1309. (c) Hoffman, R. W.; Kemper, B. TL 1981, 22, 5263.
- 9. Brown, H. C.; Cole, T. E. OM 1983, 2, 1316.
- 10. Hoffman, R. W.; Froech, S. TL 1985, 26, 1643.
- 11. Hoffman, R. W.; Ditrich, K.; Froech, S. LA 1987, 977.
Michael R. Michaelides
Abbott Laboratories, Abbott Park, IL, USA
Copyright © 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.