Di-n-butylboryl Trifluoromethanesulfonate


[60669-60-4]  · C9H18BF3O3S  · Di-n-butylboryl Trifluoromethanesulfonate  · (MW 274.11)

(Lewis acid for the preparation of vinyloxyboranes,1-6 boryl azaenolates;7,8 catalyst for macrolactonization9)

Physical Data: bp 60 °C/2.0 mmHg.

Solubility: sol common inert organic solvents such as Et2O, CH2Cl2, and hexane.

Form Supplied in: 1.0 M solution in CH2Cl2 and Et2O.

Preparative Method: Trifluoromethanesulfonic Acid is added slowly to an equimolar amount of Tri-n-butylborane with gentle warming (50 °C) until butane evolution commences. The remaining acid is added at such a rate to maintain a reaction temperature of less than 50 °C. After the addition is complete, the mixture is stirred for an additional 30 min at 25 °C and then the product is isolated by vacuum distillation.1c

Handling, Storage, and Precautions: the neat liquid as well as solutions are moisture and air sensitive. Therefore the material should be stored and transferred under a dry inert atmosphere. Use in a fume hood.

Vinyloxyboranes (Boron Enolates).

Dibutyl vinyloxyboranes are conveniently prepared from active methylene carbonyl containing compounds utilizing Bu2BOTf in combination with a sterically hindered amine base. Typically the base, Diisopropylethylamine or 2,6-Lutidine (2,6-lut), and Bu2BOTf are premixed in Et2O or CH2Cl2 at -78 °C and then the carbonyl component is added. Enolate generation is allowed to occur over the next 15-30 min at temperatures ranging from -78 °C to 0 °C, resulting in the formation of vinyloxyboranes which are suitable for reaction with aldehydes in a crossed aldol reaction. Other boryl triflate reagents have similar or complimentary utility in this process (see 9-Borabicyclononyl Trifluoromethanesulfonate (9-BBNOTf) and Dicyclopentylboryl Trifluoromethanesulfonate ((c-C5H9)2BOTf)).

With unsymmetrical methyl ketones, use of Bu2BOTf and i-Pr2NEt results in the regioselective formation of the vinyloxyborane at the least hindered carbon. However, if 9-BBNOTf and 2,6-lut are used, the regioselectivity of vinyloxyborane formation is reversed (eq 1).10

The relative stereochemistry of the two new chiral centers formed in the aldol product is a direct consequence of the vinyloxyborane enolate geometry with Z(O) enolates affording the 2,3-syn aldol products and the E(O) vinyloxyboranes leading to the 2,3-anti isomers. As a result, a number of studies have examined the effects of various boryl triflates and amines on the ratio of kinetic enolates formed. In general, it has been found that with a given base, more sterically hindered boryl triflates lead to increased amounts of the E(O) enolate. For example, when 3-pentanone is treated with Bu2BOTf or (c-C5H9)2BOTf in the presence of i-Pr2NEt, the ratio of Z(O):E(O) enolates drops from 32:1 to 4:1 (eq 2).1c

With ketones in which no combination of boryl triflate and amine produces a vinyloxyborane of predominately one geometry, Bu2BOTf has been utilized to catalyze the exchange with a trimethylsilyl enol ether of defined stereochemistry (eq 3). In order to maintain high stereoselectivity in the subsequent aldol reaction, it is necessary to remove the TMSOTf byproduct prior to the addition of the aldehyde (eq 3).11

Probably the greatest utility of this reagent has been in the stereoselective formation of chiral vinyloxyboranes with defined enolate geometries from which the absolute stereochemistry of the new chiral centers formed in the aldol process are controlled. A number of chiral masked propionate equivalents useful for the synthesis of polypropionate-like natural products have been developed for this purpose. Chiral a-hydroxy ethyl ketones derived from both enantiomers of hexahydromandelic acid have been shown to form the Z(O) vinyloxyborane stereospecifically with 9-BBNOTf, Bu2BOTf, and (c-C5H9)2BOTf. However, the size of the ligands attached to boron has a measurable effect upon the extent of the enantioselectivity achieved in the aldol process, as exemplified in eq 4.1b

The other major class of chiral boron enolate reagents developed for this purpose employs a propionate unit attached to a chiral auxiliary. These are typified by the chiral oxazolidinones derived from a-amino alcohols initially developed by Evans (eq 5),2a with subsequent variants involving thiazolidinethiones, oxazolidinethiones,3 sultams,4 and camphor-derived oxazolidinones2b being reported more recently.

Other functional groups which can be utilized for further synthetic manipulation are well tolerated on the chiral vinyloxyborane. These have included thioethers,12a selenoethers,12b carboxylic esters,2a and halogens. For example, the bromoacetyl oxazolidinone in eq 6 has been utilized in a Darzens-like condensation for the enantioselective synthesis of cis-substituted epoxides.12c This procedure is complemented by the synthesis of trans-substituted epoxide derivatives from the E(O) vinyloxyborane derived from a-bromo-t-butylthioacetate.

Vinyloxyboranes also react with electrophiles other than aldehydes. For example, the chiral vinyloxyborane generated from an N-propionyloxazolidinone, Bu2BOTf, and i-Pr2NEt reacts with N-Bromosuccinimide to produce the chiral bromide shown in eq 7 as the principal adduct.13 High enantioselectivity has also been achieved in sulfenylation and selenation reactions with chiral boron enolates, an example of which is shown in eq 8.14

The boron enolate of t-butyl thioacetate has been employed in the condensation with a variety of Schiff bases to produce b-amino acid derivatives. Reported yields range from 40-80% and the conditions are sufficiently mild to allow for the preparation of a highly functionalized intermediate used in the synthesis of bleomycin (eq 9).5 The boron component of various vinyloxyboranes is also capable of activating Bis(dimethylamino)methane, resulting in a convenient one-pot procedure for the preparation of b-dimethylamino carbonyl compounds (eq 10).15

Simple carboxylic esters are not active enough to form enolates in the reaction with a boryl triflate and an amine; however, glycolate and thioglycolate esters are readily transformed into vinyloxyboranes which upon further reaction with aldehydes yield predominately the 2,3-syn aldol products (eq 11).6

Boryl Azaenolates.

Nitrile derivatives react with Bu2BOTf and i-Pr2NEt to produce enolates which condense with various substituted benzaldehydes to yield b-hydroxy nitrile products. Poor yields result when aliphatic aldehydes are utilized as reactants, thus limiting the scope of this reaction.7 2-Ethylpyridine yields predominately the 2,3-syn aldol product when the enolate is generated with Bu2BOTf in the presence of Triethylamine (eq 12). No reaction occurs when i-Pr2NEt is used.8


Trimethylsilyl o-trimethylsilyloxycarboxylates cyclize to the corresponding macrolides in the presence of 1 equiv of a dialkylboryl triflate. Pr2BOTf gives higher yields of product than either Et2BOTf or Bu2BOTf (eq 13).9

1. (a) Mukaiyama, T.; Inoue, T. CL 1976, 559. (b) Masamune, S.; Choy, W.; Kerdesky, F. A. J.; Imperiali, B. JACS 1981, 103, 1566. (c) Evans, D. A.; Nelson, J. V.; Vogel, E.; Taber, T. R. JACS 1981, 103, 3099.
2. (a) Evans, D. A.; Bartroli, J.; Shih, T. L. JACS 1981, 103, 2127. (b) Yan, T.-H.; Tan, C.-W.; Lee, H.-C.; Lo, H.-C. Huang, T.-Y. JACS 1993, 115, 2613.
3. Hsiao, C.-H.; Liu, L.; Miller, M. J. JOC 1987, 52, 2201.
4. Oppolzer, W.; Blagg, J.; Rodriguez, I.; Walther, E. JACS 1990, 112, 2767.
5. Otsuka, M.; Yoshida, M.; Kobayashi, S.; Ohno, M. TL 1981, 22, 2109.
6. (a) Sugano, Y.; Naruto, S. CPB 1988, 36, 4619. (b) Sugano, Y.; Naruto, S. CPB 1989, 37, 840.
7. Hamana, H.; Sugasawa, T. CL 1982, 1401.
8. Hamana, H.; Sugasawa, T. CL 1984, 1591.
9. Taniguchi, N.; Kinoshita, H.; Inomata, K.; Kotake, H. CL 1984, 1347.
10. Inoue, T.; Mukaiyama, T. BCJ 1980, 53, 174.
11. Kuwajima, I.; Kato, M.; Mori, A. TL 1980, 21, 4291.
12. (a) Woo, P. W. K. TL 1985, 26, 2973. (b) Masamune, S.; Kaiho, T.; Garvey, D. S. JACS 1982, 104, 5521. (c) Abdel-Magid, A.; Lantos, I.; Pridgen, L. N. TL 1984, 25, 3273.
13. Evans, D. A.; Ellman, J. A.; Dorow, R. L. TL 1987, 28, 1123.
14. Paterson, I.; Osborne, S. SL 1991, 145.
15. Nolen, E. G.; Aliocco, A.; Vitarius, J.; McSorley, K. CC 1990, 1532.

David S. Garvey

Abbott Laboratories, Abbott Park, IL, USA

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