Chemistry Reference
In-Depth Information
Attempts to make larger ring systems or prepare lactones via Nicholas reactions with
carboxylic acid nucleophiles resulted in decomposition or dimerization of the starting ma-
terials. Nevertheless, the latter process enables the formation of 14-, 16-, and 18-membered
ring diolides. The use of chiral amine promoters in the Pauson-Khand step was also inves-
tigated but did not result in asymmetric induction.
In 2010, Tanyeli
et al.
developed a stereoselective synthesis of an optically ac-
tive cyclopenta[c]pyran and cyclopenta[c]furan ring system by intramolecular PKR.
34
2-Heteroaryl-substituted homoallyl
115
, homopropargyl
116
, and allyl alcohols
117
were efficiently resolved in high ee (91-99%) and with known stereochemistry through
enzymatic resolution. Each enantiomerically enriched enyne derived from the homoallyl
and homopropargyl alcohols afforded the conformationally most stable diastereomeric cy-
clopenta[c]pyran ring system as the sole product. In contrast, enantiomerically enriched
enynes derived from the allyl alcohols gave a diastereomeric cis:trans mixture of their
corresponding cyclopenta[c]furan ring system
123
and
126
(Scheme 4.31).
(iii) Co
2
(CO)
8
,NMO/
CH
2
Cl
2
(i) Propargyl bromide/
NaH, TBAI, THF
H
n
n
n
H
O
X
X
X
O
O
OH
(
S
)-
115a-b
a
: (X = S, n = 1)
b
: (X = N, n = 2)
(
S
)-(-)
121a-b
(cis 1,3)
(
S
)-(-)
118a-b
(iii) Co (CO) , NMO/
2
(ii) Allyl bromide/
NaH, TBAI, TH
F
8
n
CH
2
Cl
2
n
H
n
O
X
X
X
O
OH
O
H
(
S
)-
116a-b
a
: (X = S, n = 1)
b
: (X = N, n = 2)
(
S
)-(-)
119a-b
(
S
)-(-)
122a-b
(trans1,4)
O
O
(i) Propargyl bromide/
NaH, TBAI, THF
(iii)
Co
2
(CO)
8
,NMO/
CH
2
Cl
2
H
n
H
n
H
n
n
H
+
X
X
X
X
dr 3:1
O
OH
O
O
(
S
)(+)-
117a-b
a
: (X = O)
b
: (X = N)
(
S
)-(-)
120a-b
(
S
)-(-)
123a-b
(cis 1,2) (
S
)-(-)
124a-b
(trans 1,2)
Major isomer
Minor isomer
(iii)
Co
2
(CO)
8
,NMO/
CH
2
Cl
2
(
i
)
Propargyl bromide/
NaH, TBAI, THF
O
O
H
H
H
H
+
N
N
N
N
O
dr 1.5:3.5
OH
O
O
(
S
)-(+)-
117c
(
S
)-(+)-
120c
(
S
)-(+)-
125
(cis 1,2)
Minor isomer
(
S
)-(+)-
126
(trans 1,2)
Major isomer
Scheme 4.31
Stereoselective synthesis of optically active cyclopenta[c]pyrans and
cyclopenta[c]furans.
4.3
Intermolecular Diastereoselective Pauson-Khand Reaction
In contrast to the plethora of papers on intramolecular diastereoselective PKRs, only a
few studies on the intermolecular version of this transformation have been reported. The
first example of intermolecular PK cycloaddition was described by Hsung
et al.
in 2003.
35
In this study, chiral ynamides
127
and
128
were successfully used as starting materials
to obtain the corresponding adducts with excellent regioselectivity, albeit with modest
stereoselectivity. When norbornadiene and substituted ynamides were used, an unusual
endo addition occurred leading to cycloadducts
129-131
that were not observed in previous
studies using ynamines or ynamides (Scheme 4.32).
