Chemistry Reference
In-Depth Information
O
Ph
Rh(COD)
2
OTf (5 mol %)
Ligand (5 mol %)
O
Ph
OEt
+
OEt
OH
H
2
(1 atm), 25°C
Dichloroethane (0.2M)
H
O
51a
52a
45a
PAr
2
PAr
2
RO
RO
PAr
2
PAr
2
(
R
)-BINAP: Ar= Ph
(
R
)
-
xylyl-BINAP: Ar= 3,5-Me
2
C
6
H
3
(
R
)-(3,5-
t
-Bu-4-MeO-C
6
H
2
)-MeO-BIPHEP: R = Me
Ar = (3,5-
t
-Bu-4-MeO-C
6
H
2
(
R
)
-
Cyclohexyl-SONIPHOS: R =
c-
C
6
H
11
CO, Ar = Ph
Yield
(%)
Catalyst
a
Entry
Chiral Ligand
Acid
% ee
1
Rh(COD)
2
OTf
(
R
)-BINAP
(
R
)-3,5-xylyl-BINAP
(
R
)-MeO-BIPHEP
(
R
)-Cl-MeO-BIPHEP
(
R
)-c-Hex-SONIPHOS
(
R
)-(3,5-
t
-Bu-4-MeOPh)-MeO BIPHEP
(
R
)-(3,5-
t
-Bu-4-MeOPh)-MeO BIPHEP
(
R
)-(3,5-
t
-Bu-4-MeOPh)-MeO BIPHEP
(
R
)-(3,5-
t
-Bu-4-MeOPh)-MeO BIPHEP
-
-
-
-
-
-
-
-
TPAA
84
63
2
Rh(COD)
2
OTf
69
69
3
Rh(COD)
2
OTf
71
75
4
Rh(COD)
2
OTf
70
81
5
Rh(COD)
2
OTf
76
71
6
Rh(COD)
2
OTf
65
91
7
Rh(COD)
2
BF
4
65
90
8
Rh(COD)
2
BARF
66
93
9
Rh(COD)
2
OTf
82
95
a
BARF = B(3,5-(CF
3
)
2
C
6
H
3
)
4
Scheme 8C.20.
The enantioselective 1,3-enyne-glyoxal reductive coupling reaction was applied to
the synthesis of the C-ring component of bryostatin
53
(Scheme 8C.22 ) [30] . Bryostatins
are a family of marine natural products isolated from bryozoan
Bugula neritina
[31] .
Bryostatins possess strong antineoplastic activity against a broad range of tumor types
as well as other pharmacological activities [32]. The retrosynthetic analysis of the bryo-
statin C-ring component led to dienone
55
, which can be constructed from
- ketoaldehyde
54
and 1,3 - enyne
51h
through Rh-catalyzed reductive coupling. Several commercially
available chiral diphosphine ligands were screened for this reaction, and (
R
) - tol - BINAP
was selected as the chiral ligand of choice. The reaction of
51h
with
54
was run with
5 mol % of Rh(COD)
2
OTf and (
R
) - tol - BINAP in the presence of TPAA (1.5 mol %) at
65°C to give the key intermediate dienone
55
with 91% ee in 70% yield (Scheme 8C.22)
[30] . The bryostatin C - ring component
53
was synthesized from
55
in four steps in 36%
overall yield.
Highly enantioselective vinylation of imines is still an elusive goal, to date. Neverthe-
less, it has been shown that Rh-catalyzed reductive coupling of acetylene (2 equiv) with
α
