Chemistry Reference
In-Depth Information
6.5.6
S-Chiral Bidentate (P,S) Ligands
The discovery that the phosphine-sulfoxide ligand
32
, which has a one atom tether sep-
aration, worked as P,S ligand with alkyne dicobalt-carbonyl complexes prompted Riera,
Verdaguer et al. to develop
N
-phosphinosulfinamide ligands (PNSO), which they designed
as more versatile ligands for the enantioselective PKR. Sulfinamides are among the most
accessible and useful chirogenic compounds. In fact, chiral
tert
-butylsulfinamide (
34a
)
and
p
-tolylsulfinamide (
34b
) have emerged as efficient chiral controllers in numerous
processes
41
(Scheme 6.24). Reductive amination of commercially available sulfinamides,
followed by phosphinylation at the nitrogen, and finally, protection with borane, yielded a
series of PNSO ligands in which the phosphorus is protected.
42
Whereas the
t
-Bu-PNSO
ligands remain stable upon deprotection (removal of borane with DABCO), the correspond-
ing deprotected
p
-Tol-PNSO analogs are prone to hydrolysis during purification on silica
gel. Interestingly, the PNSO ligand system is highly modular; the groups attached to the
phosphorous, the nitrogen and the sulfur can be varied independently.
O
O
1) BuLi, ClPPh
2
2) BH
3
.SMe
2
O
1) Ti(OEt)
4
,
Ph
S
RCHO
S
S
P
N
NH
2
Ph
NH
2) NaBH
4
3) DABCO
R
R
34a
t
-Bu-PNSO
35a
, R = Bn
35b
, R =
p
-MeO-Bn
35c
, R =
p
-F-Bn
O
BH
3
O
S
36a
, R = Bn; R' = Ph
36b
, R =
i
-Bu; R' = Ph
S
P
R'
NH
2
N
R'
36c
, R =
i
-Pr; R' = Ph
R
36d
, R =
i
-Bu; R' =
p
-MeO-Bn
34b
p
-Tol-PNSO
Scheme 6.24
Synthesis of PNSO ligands.
Ligand exchange of PNSO ligands with cobalt complexes derived from terminal alkynes
(
1i,c,h,n
) provided the corresponding bridged diastereomers
37
or
38
in excellent yield.
With the
t
-Bu-PNSO ligands
35
, the reaction gave good to excellent yields, affording the
bridged complexes
37
with selectivities between 7:1 and 12:1 (Table 6.5). Conveniently,
the major diastereomer can be isolated (usually, in 50% overall yield) by crystallization
of the crude product after filtration on silica. In contrast, the
p
-Tol-PNSO ligands
36
were not selective upon coordination to terminal alkyne complexes, often affording 1:1
diastereomeric mixtures (see Table 6.6). The discrepancy in reactivity between the
t
-Bu-
PNSO ligands
35
and the
p
-Tol-PNSO analogs
36
was attributed to the greater steric bias
and more hemilabile character of the former.
PK reaction of the diastereomerically pure tetracarbonyl complexes
37
with norbor-
nadiene was highly stereoselective, affording cyclopentenones in up to 99% ee (Table
6.7). The cycloaddition can be run using either thermal activation, or
N
-oxide activation
with
N
-methylmorpholine
N
-oxide (NMO) at room temperature. The parent
N
-benzyl
