Dicyclopentylboryl Trifluoromethanesulfonate

[72251-50-4]  · C11H18BF3O3S  · Dicyclopentylboryl Trifluoromethanesulfonate  · (MW 298.13)

(Lewis acid for the preparation of vinyloxyboranes1-4)

Alternate Name: dicyclopentylboryl triflate.

Physical Data: colorless liquid, bp 70-72 °C/1.0 mmHg.

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

Form Supplied in: 0.5 M solution in CH2Cl2.

Preparative Method: Trifluoromethanesulfonic Acid is added dropwise to an equimolar amount of tricyclopentylborane, with intermittent cooling to maintain the reaction temperature at approximately rt. Upon completion of the addition the reaction is stirred at rt for an additional 30 min followed by isolation of the product by vacuum distillation.2b

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.

Vinyloxyborane Enolates.

Dicyclopentyl vinyloxyboranes are conveniently prepared from active methylene carbonyl compounds utilizing (c-C5H9)2BOTf in combination with a sterically hindered amine base. Typically the base, Diisopropylethylamine or 2,6-Lutidine (2,6-lut), and reagent are premixed in Et2O or CH2Cl2 at -78 °C to 0 °C and then the carbonyl component is added. Enolate generation is allowed to occur over the next 15-30 min, 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 9-Borabicyclononyl Trifluoromethanesulfonate (9-BBNOTf) and Di-n-butylboryl Trifluoromethanesulfonate (Bu2BOTf)).

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. Consequently, 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, the more sterically hindered boryl triflates increase the selectivity for the formation of the E(O) 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, reaction of the resulting enolates with benzaldehyde results in a ratio of crossed aldol products which varies dramatically. As shown in eq 1, 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.1

The propionate synthon S-t-butyl propanethioate upon reaction with (c-C5H9)2BOTf and i-Pr2NEt yields selectively the E(O) vinyloxyborane. Condensation of this enolate with various aldehydes affords the crossed aldol products, with the 2,3-anti diastereomer predominating (eq 2).2 This combination of enolate substrate and reactants complements the results obtained from S-phenyl propanethioate, 9-BBNOTf, and i-Pr2NEt in which the 2,3-syn aldol product predominates (see 9-Borabicyclononyl Trifluoromethanesulfonate). Other functionality is also well tolerated on the thioester enolates. For example, the E(O) enolate derived from t-butyl a-bromothioacetate has been utilized in a Darzens-like condensation that selectively yields the trans-substituted epoxides (eq 3).3 This procedure complements the synthesis of cis-substituted epoxide derivatives which are produced via aldol reactions of the Z(O) vinyloxyborane derived from a bromoacetyl oxazolidinone (see Di-n-butylboryl Trifluoromethanesulfonate).

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 are such reagents and have been shown to form the Z(O) vinyloxyborane stereospecfically with 9-BBNOTf, Bu2BOTf, and (c-C5H9)2BOTf. However, the size of the ligands attached to boron does have a measurable effect upon the extent of the enantioselectivity achieved in the aldol process, as exemplified in (eq 4).4

1. Van Horn, D. E.; Masamune, S. TL 1979, 20, 2229.
2. (a) Hirama, M.; Masamune, S. TL 1979, 20, 2225. (b) Evans, D. A.; Nelson, J. V.; Vogel, E.; Taber, T. R. JACS 1981, 103, 3099.
3. Polniaszek, R. P.; Belmont, S. E. SC 1989, 19, 221.
4. (a) Masamune, S.; Choy, W.; Kerdesky, F. A. J.; Imperiali, B. JACS 1981, 103, 1566. (b) Choy, W.; Ma, P.; Masamune, S. TL 1981, 22, 3555.

David S. Garvey

Abbott Laboratories, Abbott Park, IL, USA

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