Chemistry Reference
In-Depth Information
Interesting results in the area of solid-phase synthesis were reported by Bolton in 1996.
14
He developed a method for stereocontrolled construction of highly functionalized fused
bicyclic amino acid derivatives in which the key step involved an intramolecular PKR.
Cyclization precursors
49
and
50
were easily obtained via sulfonylation and
N
-alkylation
of either (
S
)-allyl or racemic propargyl glycine methyl esters
48a,b
, respectively. Treatment
of tosyl derivatives
49
and
50
with CO
2
(CO)
8
resulted in complete conversion to the cobalt
complex. Subsequent NMO oxidation provided cyclopentanone derivatives
51
as a single
enantiomer and diastereomer, respectively, in good yields (Scheme 4.13). As an extension of
this methodology, a solid-phase synthetic strategy using commercial Wang resin improved
the yield of
52
and simplified the purification steps.
CO
2
Me
i) TsCl, Et
3
N, CH
2
Cl
2
iii) Allyl bromide/
Cs
2
CO
3
,DMF
(78 %)
CO
2
Me
i)
TsCl, Et
3
N, CH
2
Cl
2
ii) Propargyl bromide/
Cs
2
CO
3
,DMF
(79 %)
R
CO
2
Me
NH
3
+
Cl
-
NTs
NTs
49
48a
(R = allyl)
48b
(R = propargyl)
50
(iv) Co
2
(CO)
8
/
NMO, CH
2
Cl
2
(iv) Co
2
(CO)
8
/
NMO, CH
2
Cl
2
(73 %)
(71 %)
CO
2
Me
H
CO
2
Me
O
NTs
O
NTs
H
(+/-)-52
(-)-51
Scheme 4.13
Stereocontrolled construction of highly functionalized fused bicyclic amino
acid derivatives.
In 2000, an interesting study on asymmetric PKR via optically pure alkyne-
Co
2
(CO)
5
PPh
3
complexes was reported by Kerr
et al
.
15
They investigated the use of amine
N
-oxides for the formation of monophosphine complexes
55a
and
55b
from corresponding
chiral hexacarbonyl compounds
54a
and
54b
, which were prepared from commercially
available phenylprop-2-yn-1-ols
53a
and
53b
(Scheme 4.14).
At low temperatures (
60
◦
C) no diastereoselectivity was observed for the formation of
complexes
55a
,
56a
and
55b
,
56b
from enantiomerically pure hexacarbonyl compounds
54a
and
54b
, respectively, with NMO. Surprisingly, chiral BNO gave a similar result for
complex
54b
; however, complex
54a
consistently afforded a 7:3 ratio of diastereomers
55a
:
56a
. The stereoselectivity of the reaction with
54a
is believed to originate from the
matching interaction of the chiral
N
-oxide with the propargylic stereocenter in combination
with Co
2
C
2
core of the complex. Stereopure complexes
55a
-
56b
, which were purified us-
ing a simple flash column, were converted into corresponding pure stereoisomers
57a
-
58b
using norbornene with anhydrous NMO at room temperature. By determining the ab-
solute stereochemistry of optically pure alkyne-Co
2
(CO)
5
PPh
3
complexes
55a
-
56b
and
cyclopentanones
57a
-
58b
, these studies explicitly demonstrated that decarbonylation and
alkene complexation occurs exclusively at the Co(CO)
3
vertex in monophosphinated alkyne
complexes in PK annulations.
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