Handbook of Functionalized Organometallics Applications in S

HO
HO
Br
OH
O
X
N
N
O
N
3.2 Preparation and Reaction of Functionalized Aryl and Heteroaryl Boranes
NH
NH 2
B(OH) 2
R
B(OH) 2
Pd(OAc) 2 (2.5 mol %)
Na2CO3, H2O:CH3CN (2:1)
80 ºC, 2 h
NaO3S 60: TPPTS
(6.25 mol %)
P
R = H, CH2OH, OCH3, F, CO2Na 3
X = H: 77 - 95 %; X = OH: 85 - 99 %
NH 2
Br
O
OH
N
N
X
N
N
R
Pd(OAc) 2 (2.7 mol %)
Na2CO3, H2O:CH3CN (2:1)
80 ºC, 2 h
NaO3S 60: TPPTS
(6.75 mol %)
P
R
HO
O
OH
N
N
X
N
N
R=H,OCH3, F, CH2OH X = H: 77 - 90 %; X = OH: 85 - 99 %
3
Scheme 3.27 Suzuki±Miyaura cross-couplingof unprotected halonucleosides.
Firooznia has reported the synthesis of 4-substituted phenylalanine derivatives
via cross-coupling of protected (4-pinacolylboron)phenylalanine derivatives such
as 61 with aryl and alkenyl iodides, bromides and triflates [44]. They have further
shown that BOC derivatives of (4-pinacolylboron)phenylalanine ethyl ester 61 or
the corresponding boronic acids undergo Suzuki±Miyaura reactions with a number
of aryl chlorides in the presence of PdCl 2(PCy) 3 or NiCl 2(dppf), respectively
providing diverse sets of 4-substituted phenylalanine derivatives of type 62 [45].
This strategy has also been used for the synthesis of enantiomerically enriched
4-substituted phenylalanine derivatives (Scheme 3.28) [46].
ArCl
O
O
N
H
O
OEt
O
B
O
PdCl2(PCy3) 2
CsF, NMP, 100 ºC
12 - 18 h
61 62: 41-62%
Ar =4-CF 3C 6H 4,4-CO 2MeC 6H 4,2-CNC 6H 4, 3-MeOC 6H 4, 3-NO 2C 6H 4
Scheme 3.28 Synthesis of substituted phenylalanine derivatives
by Suzuki±Miyaura cross-coupling.
O
R
HO
O
N
H
OH
O
O
OEt
X
61
N
N
Ar
O
N
NH
NH 2
NH 2