Boron Reagent Activation in Suzuki–Miyaura Coupling - New Trends in Cross-Coupling: Theory and Applications - page 329

5 OH

5

Base

B -

B

[PdBrArL n ]

1

Slow

Ar

5

B - 5

HO

5
O

O

B as e

B [Pd(OH)ArL n ]

2

not observed

Scheme 8.6 Speciation and cross-coupling of borane 1 and borinic ester 2.

hydroxide with the alkyl borinic esters 2 was undetectable, owing to the
substantially lower Lewis acidity at boron arising from the availability of the
lone-pair on oxygen to populate partially the vacant p-orbital. By competing
1 and 2 for limiting aryl bromide, it could be shown that reagent 1 was
substantially more ecient than 2, the latter reagent also undergoing slower
rates of conversion when compared independently. Key to the overall
analysis was a measurement of the rate of hydrolysis of [PdBr(Ar)L] by OH to
give [Pd(OH)(Ar)L], which was found to be slow, thus leading to the conclusion
that the neutral borinic ester 2 transmetallates with [Pd(OH)ArL n ], whereas
the boronate complex derived from 1 transmetallates with [PdBrArL n ].

8.3.2 Boronic Acids
There are three general routes for the preparation of boronic acids
(Scheme 8.7). The most widely used proceeds via organometallic inter-
mediates such as organolithium 35 or organomagnesium reagents, 36,37 which
are trapped with a boric acid ester [e.g. B(Oi-Pr) 3 or B(OMe) 3 ], to provide a
boronic ester that rapidly hydrolyses to a boronic acid under acidic treat-
ment. The second method is through the hydrolysis of boronic esters, e.g.
pinacolboronic ester, which are readily prepared and purified by a variety of
methods. However, the liberated diol readily condenses with the boronic
acid product, which can cause issues with low conversions and purification.
This problem can be tackled either by intermediate formation of a distinct
species that can be purified from the diol, 38 or by consuming the diol in a
separate reaction that removes it from recombining with the boronic acid. 39
The third and most recently developed method is based on Pd- or Ni-cata-
lysed borylation of aryl halides that employs tetrahydroxydiboron. 40,41
In general, boronic acids dissolve more readily in organic solvents than in
neutral aqueous solutions. Under the former conditions, an equilibrium is
established with the trimeric anhydride (boroxine) species, an entropically
favoured transformation that liberates 3 equiv. of water (Scheme 8.8).
Boroxines are stabilized through their partial aromatic character, wherein
electron density is donated from oxygen to boron, formally generating a
triply zwitterionic cyclic compound. Although there are reports of boroxines