Boron Reagent Activation in Suzuki–Miyaura Coupling - New Trends in Cross-Coupling: Theory and Applications - page 346

NaOH (aq)
Toluene

PdCl 2 (dppf)
Toluene, reflux

B(OH) 2 B(OH) 3 Na Ar'

Z Z + Ar'-Br Z

13 examples
58% - 90% isolated yield

Scheme 8.26 SM coupling of aryl trihydroxyborate salts with aryl bromides.

i) B(O i- Pr) 3
Toluene/THF (4:1)

Br B(Oi-Pr) 3 Li

Z 73 - 99%

5 examples

Z

N N

ii) n -BuLi over 90 min

Scheme 8.27 Preparation of lithium triisopropylborate salts.

Base free = 75 - 98%, 4 examples

XPhos[Pd]
THF:water (1:2 )

B(Oi-Pr) 3 Li O

+

N N

98%

OMe

N Cl CO 2 Me N

With base = 71 - 98%, 11 examples

XPhos[Pd]
THF:water (1:2)
K 3 PO 4

B(Oi-Pr) 3 Li

N

+

81%

S

Br N S

Scheme 8.28 SM coupling of lithium heteroaryl triisopropylborate salts.

prepared from the borylation of organohalides, following lithium-halogen
exchange by treatment with BuLi. The product is isolated simply by evap-
orating the solvent and bromobutane co-product (Scheme 8.27).
Phosphine oxide ligands were originally employed 125 for the SM coupling of
the notoriously dicult 2-pyridyl systems, but the introduction of the XPhos
precatalyst (generation II) has substantially expanded the substrate scope and
afforded conditions that are general for the coupling of heteroarylborates
(Scheme 8.28). 126 A key observation is that under anhydrous conditions, no
coupling of the triisopropylborate reagent was observed, suggesting that
hydrolytic reagent activation is required for transmetallation. Although SM
coupling of triisopropylborate reagents does proceed without any added
base and was shown to be effective for base-sensitive organohalide coupling
partners, such as methyl esters or oxazoles, 126 the pH of these couplings
(THF-water, no added base) (Scheme 8.28) is between 12 and 13 and strongly
suggests liberation of 2-propanol and hydroxide. The addition of potassium
phosphate and CuCl in combination with ZnCl 2 led to improved yields,
although the origins of these effects have not been investigated. 127

8.5.4 Cyclic Triol Borate Salts
Cyclic triol borates are tetrahedral at boron as they are ligated by three
tethered alkoxides. 128 They are prepared by condensing the triol with the