9-Borabicyclononyl Trifluoromethanesulfonate

[62731-43-5]  · C9H14BF3O3S  · 9-Borabicyclononyl Trifluoromethanesulfonate  · (MW 270.08)

(Lewis acid for the preparation of vinyloxyboranes1-4 and boryl azaenolates;5-8 catalyst for coupling silyl enol ethers and acetals;9 catalyst for isomerization of epoxides to allylic alcohols10)

Alternate Name: 9-BBNOTf.

Physical Data: bp 81 °C/2.5 mmHg.

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

Form Supplied in: 0.5 M solution in hexane.

Preparative Method: equimolar amounts of 9-Borabicyclo[3.3.1]nonane and Trifluoromethanesulfonic Acid are mixed in hexane and stirred at 20 °C for 24 h after which time the product is isolated by vacuum distillation.1

Handling, Storage, and Precautions: use in a fume hood; 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.

Vinyloxyborane Enolates.

9-Borabicyclononyl vinyloxyboranes are conveniently prepared from active methylene carbonyl-containing compounds utilizing 9-BBNOTf in combination with a sterically hindered amine base. Typically the base, either Diisopropylethylamine or 2,6-Lutidine (2,6-lut), and 9-BBNOTf 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 nucleophiles for reaction with aldehydes in a crossed aldol reaction. Other boryl triflate reagents have been shown to have similar or complementary utility in this process (see Di-n-butylboryl Trifluoromethanesulfonate (Bu2BOTf) and Dicyclopentylboryl Trifluoromethanesulfonate ((c-C5H9)2BOTf)).

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

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 boron reagents and amines on the geometry of the resulting enolate. For example, when the vinyloxyboranes of ethyl cyclohexyl ketone are generated with (c-C5H9)2BOTf or 9-BBNOTf in the presence of i-Pr2NEt, and then treated with benzaldehyde, the ratio of crossed aldol products varies dramatically. As shown in eq 2, the enolate derived from (c-C5H9)2BOTf yields a preponderance of the 2,3-anti aldol product while that from 9-BBNOTf produces almost exclusively the 2,3-syn isomer.11 When the ethyl ketone contains a sterically demanding t-butyl group, generation of the enolate with 9-BBNOTf and Et3N produces predominately the E(O) vinyloxyborane. However, when the leaving group on the boron reagent is changed from triflate to iodide, the Z(O) vinyloxyborane predominates (eq 3).2

Several propionate synthons initially developed for the preparation of natural products containing polypropionate fragments have also been successfully utilized in combination with 9-BBNOTf to prepare vinyloxyboranes of Z(O) geometry. Generation of the enolate from S-phenyl propanethioate with 9-BBNOTf and i-Pr2NEt followed by condensation with various model aldehydes gave predominately the 2,3-syn aldol products (eq 4).3 These results are complementary to the cross aldol products obtained from S-t-butyl propanethioate. Treatment of the latter with (c-C5H9)2BOTf, i-Pr2NEt, and an aldehyde yields predominately the 2,3-anti aldol product (see Dicyclopentylboryl Trifluoromethanesulfonate).

Further extension of this methodology has led to the development of chiral masked propionate equivalents in which the boryl triflate generates chiral vinyloxyboranes of defined enolate geometry. Upon reaction with an aldehyde the chiral enolate is able to exert an influence on the absolute stereochemistry of the two newly formed chiral centers in the crossed aldol product. The a-hydroxy ethyl ketones derived from the enantiomers of hexahydromandelic acid are examples of such reagents. For additional examples see Di-n-butylboryl Trifluoromethanesulfonate. This reagent forms the Z(O) vinyloxyborane stereospecifically with 9-BBNOTf, Bu2BOTf, and (c-C5H9)2BOTf. Upon exposure to a sterically demanding aldehyde such as isobutyraldehyde, the reaction proceeds only with the enolates generated from 9-BBNOTf and Bu2BOTf. Excellent stereoselection is achieved in both cases (eq 5). The fact that the reaction does not proceed with the bulky cyclopentyl ligands on the vinyloxyborane has been attributed to steric congestion in the transition state.4

Boryl Azaenolates.

The azaenolate of a chiral 2-ethyloxazoline was prepared with 9-BBNOTf and i-Pr2NEt (eq 6). Subsequent condensation with aldehydes afforded predominately the 2,3-syn aldol products. The stereoselectivity of this reaction was rather low, ranging from 40 to 60% de.5

A number of methyl substituted nitrogen-containing heteroaromatics have been examined as azaenolate precursors in reactions with benzaldehyde. The azaenolates were generated with 9-BBNOTf and i-Pr2NEt in CH2Cl2 and, as shown in Table 1, many of the compounds are good substrates. 2-Methyl-4-phenyloxazole reacts selectively at the 2-position when the boron enolate is condensed with benzaldehyde. This contrasts to the lithium enolate in which condensation occurs exclusively at the 5-position (eq 7).6 Similar results were observed with 2-methylthiazole, as shown in eq 8. Thus the regioselective functionalization of these methyl substituted five-membered heteroaromatics is achieved by judicious choice of the reaction conditions utilized for azaenolate generation.

Reaction of 2,4-lutidine with benzaldehyde gave aldol-like products arising from condensation at both the 2- and 4-positions. The regioselectivity of the reaction could be controlled by the choice of boryl triflate and amine utilized. 9-BBNOTf and i-Pr2NEt produced an azaenolate which reacted with benzaldehyde exclusively at the 4-position while use of Bu2BOTf and Et3N generated an azaenolate which reacted solely at the 2-methyl group (eq 9).7

Nitrile derivatives also react with 9-BBNOTf and i-Pr2NEt to produce an azaenolate which was condensed with various substituted benzaldehydes to yield b-hydroxy nitrile products.8 The yields were low when aliphatic aldehydes were utilized as reactants, thus limiting the scope of this reaction.

Mukaiyama Reaction Catalyst.

b-Alkoxy ketones are produced when 9-BBNOTf is used to catalyze the coupling of enol silyl ethers with acetals (eq 10).9

Allylic Alcohols from Epoxides.

Epoxides are isomerized to allylic alcohols in the presence of 9-BBNOTf and 2,6-lut. The reaction proceeds most efficiently when the substrate is treated with equimolar equivalents of the triflate and amine reagents. When the possibility of producing regioisomeric alkenes exists, as in the example shown in eq 11, both are observed.10


1. Inoue, T.; Mukaiyama, T. BCJ 1980, 53, 174.
2. Brown, H. C.; Ganesan, K.; Dhar, R. K. JOC 1993, 58, 147.
3. Hirama, M.; Garvey, D. S.; Lu, L. D.-L.; Masamune, S. TL 1979, 20, 3937.
4. Masamune, S.; Choy, W.; Kerdesky, F. A. J.; Imperiali, B. JACS 1981, 103, 1566.
5. Meyers, A. I.; Yamamoto, Y. JACS 1981, 103, 4278.
6. Hamana, H.; Sugasawa, T. CL 1983, 333.
7. Hamana, H.; Sugasawa, T. CL 1984, 1591.
8. Hamana, H.; Sugasawa, T. CL 1982, 1401.
9. Ishihara, K.; Yamamoto, H.; Heathcock, C. H. TL 1989, 30, 1825.
10. Inoue, T.; Uchimaru, T.; Mukaiyama, T. CL 1977, 1215.
11. Van Horn, D. E.; Masamune, S. TL 1979, 20, 2229.

David S. Garvey

Abbott Laboratories, Abbott Park, IL, USA



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