Communications
25.6 mmol) was slowly added. After the orange solution had been
stirred for 6 h, the reaction mixture was quenched with saturated
aqueous NH4Cl (70 mL), diluted with EtOAc (70 mL), and washed
with H2O (70 mL) and saturated aqueous NaCl (70 mL). The dried
extract (MgSO4) was concentrated in vacuo. The crude product 12
was dissolved in DMF (25.6 mL) and cooled to 08C. BnBr (17.5 g,
102 mmol, 11.8 mL) and NaH (1.02 g, 25.6 mmol, 60% in mineral oil)
were added to this solution. After 8 h, the mixture was quenched with
saturated aqueous NH4Cl (100 mL), diluted with EtOAc (100 mL),
and washed with H2O (100 mL) and saturated aqueous NaCl
(100 mL). The dried extract (MgSO4) was concentrated in vacuo
and purified by chromatography over silica gel eluting with EtOAc/
hexanes (50:50) to give 14 (2.26 g, 3.62 mmol, 70%) as a bright-yellow
crystalline solid. M.p.: 202–2038C; IR (neat): n˜ = 2930, 1597, 1524,
1302 cmꢀ1; 1H NMR (400 MHz, CDCl3): d = 8.09 (dd, J = 8.2, 1.2 Hz,
1H), 7.87 (dd, J = 8.0, 1.2 Hz, 1H), 7.33 (t, J = 8.6 Hz, 1H), 7.25–7.31
(m, 3H), 7.18–7.19 (m, 2H), 6.75 (d, J = 2.1 Hz, 1H), 6.51 (dd, J =
11.5, 2.2 Hz, 1H), 5.10 (s, 2H), 3.87 (s, 3H), 1.20–1.96 ppm (m, 22H);
13C NMR (100 MHz, CDCl3): d = 159.9 (d, JC,P = 16 Hz, 1C), 158.2 (d,
After screening a broad range of conditions for the con-
version of the phosphine oxide 37 into its corresponding
phosphine 38, we found that this process could be accom-
plished in a reasonable yield using [Ti(OiPr)4]/poly(methyl-
hydrosiloxane) (PMHS).[25] Reductive amination generated
the dimethylaminophosphine 39. Attempted removal of the
benzyl moiety under hydrogenation conditions (Pd/C or PtO2,
H2) gave problematic results. Fortunately, removal of the
benzyl ether from 37 could be cleanly accomplished using
BCl3.
In order to show the utility of the synthesized materials,
we chose to investigate palladium-mediated couplings using
amino phosphine 39 as a ligand (Scheme 7). The structure of
JC,P = 14 Hz, 1C), 150.7, 136.7, 136.5, 134.1 (d, JC,P = 1.9 Hz, 1C),
130.6, 129.8, 128.6, 128.4, 127.7, 127.6, 126.4, 125.8, 123.2, 107.6 (d,
JC,P = 12 Hz, 1C), 101.5 (d, JC,P = 1.7 Hz, 1C), 70.6, 55.5, 38.2, 37.6 (d,
JC,P = 3.9 Hz, 1C), 36.9, 26.8 (d, JC,P = 8.5 Hz, 1C), 26.7 (d, JC,P
=
8.9 Hz, 1C), 26.6 (d, JC,P = 2.0 Hz, 1C), 26.5 (d, JC,P = 3.3 Hz, 1C),
26.4 (d, JC,P = 3.3 Hz, 1C), 25.9 (d, JC,P = 1.4 Hz, 1C), 25.7 (d, JC,P
=
2.1 Hz, 1C), 25.0 (d, JC,P = 3.3 Hz, 1C), 24.7 (d, JC,P = 3.6 Hz, 1C);
HRMS (FAB + ) calcd for C32H38NO5PBr [M+H]: 626.1671; found:
626.1653.
Received: April 4, 2005
Revised: July 5, 2006
Published online: September 15, 2006
Scheme 7. Utility of the synthesized biaryl 39 in the Suzuki coupling.
Reagents and conditions: a) Pd(OAc)2 (5 mol%), 39 (10 mol%),
K3PO4, PhMe, 1008C, 20 h.
Keywords: biaryls · Diels–Alder reaction · Negishi coupling ·
.
palladium · phosphanes
this catalyst is based on the pioneering work of Buchwald and
co-workers.[26] Preliminary screening of 39 appears to indicate
that a highly active catalyst is generated for Suzuki couplings,
as demonstrated in the synthesis of the sterically challenging
tri-ortho-substituted biaryl 43. It is important to note that the
control experiment (in the absence of phosphine) with
boronic acid 41 and bromide 42 (Pd(OAc)2 (5 mol%),
K3PO4, PhMe, 1008C, 20 h) gave only a minor amount
(18%) of the desired coupled material 43. Use of PPh3 as
the ligand also gave inferior results. Further exploration in the
scope and utility of our Diels–Alder approach to biaryls for
the synthesis of novel ligand systems will be reported in due
course.
In summary, we have demonstrated a novel method for
the construction of highly substituted, orthogonally function-
alized biaryl compounds previously not accessible by tradi-
tional methods. Subsequent manipulation of the resultant
biaryls through palladium-coupling and/or reduction provides
access to a significant range of substitution patterns. Finally,
the potential utility of aminophosphine 39 as a ligand in
challenging cross-coupling reactions has been demonstrated.
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Experimental Section
14: Compound 8 (4.14 g, 20.4 mmol) was added to a pressure vessel
containing 7 (2.24 g, 5.11 mmol) and PhMe (10.2 mL) at room
temperature. The reaction mixture was heated at 808C. After 18 h,
the reaction mixture was cooled to 08C and Et3N (2.59 g, 3.58 mL,
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 6737 –6741