Boron Reagent Activation in Suzuki–Miyaura Coupling - New Trends in Cross-Coupling: Theory and Applications - page 342

OMe

OMe

1) [Pd(P t -Bu 3 ) 2 ]
2 equiv. CsF,
THF, 60 °C

OMe

B(OH) 2

B(DAN)

Br B(DAN)

2) HCl aq., THF, rt

OMe 59%

4

OMe

Scheme 8.22 Iterative cross-coupling to give a polyaromatic compound.

Bifunctional building blocks, composed of halide and DAN boronamide
functional groups, are used for iterative cross-coupling (ICC). The halide
motif undergoes the first coupling with a boronic acid; this can be con-
ducted in aqueous basic conditions as the DAN boronamide present is stable
towards these conditions. In contrast, the MIDA boronates require an-
hydrous coupling conditions to retain its functionality. 94 This step is then
followed by an acidic deprotection of the DAN protecting group, which re-
veals the boronic acid that can then undergo further coupling. This was
elegantly demonstrated through the synthesis of polyaromatic conjugated
systems from simple bifunctional benzene-based building blocks
(Scheme 8.22). 93 Up to four cycles of deprotection-cross-coupling were
demonstrated.

8.5 Boron Reagents for Which the Activation Mode Is
Yet To Be Established
Preformed tetrahedral borate salts and trigonal boronic esters are two
classes of SM coupling reagents that undergo cross-coupling under regular
SM coupling conditions, i.e. with no individual activating procedures, but for
which there has not been sucient mechanistic investigation to establish
their specific activation mechanisms. In essence, it is not yet clear whether
ligand substitution is required prior to transmetallation or whether the re-
agents can transmetallate directly.

8.5.1 Boronic Esters
Boronic esters tend to exhibit greater chemical stability than their corres-
ponding boronic acids due to the lower Lewis acidity and greater steric
shielding at boron. There are a number of methods to prepare boronic esters
(Scheme 8.23) and the products are generally amenable to column chro-
matography. Hydroboration of unsaturated carbon bonds by pinacolborane
(HBPin) or catecholborane (HBcat) is dicult, but with the addition of a
suitable metal catalyst they readily add to alkenes 95,96 and alkynes. 97 Systems
have been reported that employ non-precious metal catalysts 98-100 and even
metal-free catalysts. 101,102

The method can also be conducted