Boron Reagent Activation in Suzuki–Miyaura Coupling - New Trends in Cross-Coupling: Theory and Applications - page 345

B(OR) 2 CuL

CuX

N N

N

X

L n Pd L n Pd

CuL n

Scheme 8.25 Copper-assisted transmetallation.

feature in SM couplings, means that conclusions regarding the mode of
transmetallation must be drawn with caution: water may effect a prior
hydrolysis of the boronic ester or facilitate the generation of the oxo-
palladium(II) intermediate.
Copper salts have been reported to increase the rate of transmetallation of
SM coupling reactions. 88,122 In these cases, it is proposed that the boronic
acid initially reacts with the copper salt, which then delivers an organo-
copper reagent to palladium more eciently than the boronic ester. The
addition of copper salts was shown to be an effective way to reduce proto-
deboronation in the esters 88 coupling of pinacolheteroarylboronic

(Scheme 8.25).

8.5.2 Trihydroxyborate Salts
Sodium aryl trihydroxyborate salts can be eciently prepared by dropwise
addition of a saturated aqueous sodium hydroxide solution to the parent
boronic acid in toluene; the product is isolated simply by filtration. These
trihydroxyborate salts have been reported to undergo clean SM coupling
under nominally base-free conditions (Scheme 8.26). 123 This may suggest
that the reaction proceeds by direct transmetallation, i.e. through the
boronate pathway. However, it should be noted that the solubility of the
trihydroxyborate salts in dry toluene is low. Indeed, this is a key aspect of
their preparation. Equilibrium between the trihydroxyborate salt and the
boronic acid and sodium hydroxide must also be considered and, moreover,
under nominally anhydrous conditions, dehydration of boronic acid to the
corresponding boroxine liberates water (one per boron), thus potentially
solubilizing the sodium hydroxide and facilitating the formation of the
oxo-palladium intermediate. In applications of trihydroxyborate salts to SM
couplings under aqueous conditions, 124 the liberation of an equivalent of
base plus the boronic acid is even more likely.

8.5.3 Triisopropylborate Salts
Lithium aryl triisopropylborate reagents have been successfully applied to
the SM coupling of unstable heteroaryl systems. The triisopropylborates are