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BULLETIN OF THE
KOREAN CHEMICAL SOCIETY
7
Table 1. Stereoselective 1,2-reduction of ketone 9
3 in 78% yield. Finally, TBS protection of hydroxyl group in
(97%), deprotection of the ketal moiety (70%), 1,2-addition
3
of methyl Grignard reagent to ketone, and spontaneous dehy-
dration produced the [4.3.1]propellane model compound 2 in
65% two-step yield.
In order to confirm the relative stereochemistry of 3,
alcohol 3 was converted into the corresponding 4-
nitrobenzoate 12. The single crystal X-ray crystallography
of 12 proved all cis arrangement of C -methyl group, C -
a
1
7
Entry Reagents
Condition
10a:10b:10c
hydroxyl group, and cyclopropane ring clearly (Figure 2).
b
ꢀ
ꢀ
ꢀ
1
2
3
4
5
6
7
DIBAL
LiEt BH
9-BBN
Et O, −78 C, 2 h
1.3:1:1
NR
1:1.3:2
0:0:1
2
3
THF, −78 C, 24 h
THF, −78 C, 5 h
c
c
ꢀ
NaBH /CeCl3 MeOH, −78 C, 1 h
4
ꢀ
ꢀ
ꢀ
LiAlH(Ot-Bu)
K-selectride
L-selectride
Red-Al
3
THF, −78 C to rt., 24 h NR
THF, −78 C, 3 h
THF, −78 C, 20 min
c,d
c,d
e
1:0:1.6
33:0:1
ꢀ
8
a
b
c
CH
2
Cl
2
, −78 C, 30 min 4.8:1:0
1
The ratio was determined by H 400Hz NMR analysis.
The 50% isolated yield as a mixture (10a and 10b).
The ratio of crude product.
d
Purification was not possible due to the decomposition of the crude
product.
e
Figure 2. Single crystal X-ray crystallography of the ester 12.
The 41% isolated yield for 10a only.
In summary, stereoselective synthesis of [4.3.1]propel-
lane model compound 2, a common structural motif in
phainanoids A–F (1a-1f), was achieved in 13 steps from
In order to construct the syn-C /C relationship, various
kinetic reduction conditions were investigated (Table 1). Reduc-
1
7
2
,5-dimethoxycinnamic acid (6). The key steps are regiose-
tion by LiEt BH or LiAlH(Ot-Bu) did not proceed at all. Use
3
3
lective demethylation of C -methoxy group, PIFA-mediated
of DIBAL-H, 9-BBN, NaBH /CeCl , or K-selectride provided
7
4
3
6
oxidation of phenol moiety, syn-selective 1,2-reduction of
dienone functional group, and hydroxyl group-directed
cyclopropanation reaction.
Acknowledgments. This research w assisted financially by
National Research Foundation of Korea (NRF-2016R1
A2B2007840).
1
0a and 10b along with unexpected rearomatized phenol 10c.
Although L-selectride afforded the desired alcohol 10a with
excellent selectivity in the crude mixture, rearomatization of
0a into 10c occurred significantly during work-up procedure.
1
Red-Al reagent proved to be the best choice so far in terms of
both yield and selectivity.
ꢀ
Supporting Information. Additional supporting informa-
tion is available in the online version of this article.
Stereoselective reduction of ketone 9 with Red-Al at −78 C
was followed by selective hydrogenation of the sterically less
ꢀ
hindered alkene at −15 C to afford the allylic alcohol 11 in
46% two-step yield (Scheme 3). The hydroxyl group-directed
References
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Scheme 3. Synthesis of [4.3.1]propellane model compound 2.
ꢀ
(
a) Red-Al, CH
2
Cl
2
, −78 C, 30 min; (b) 10% Pd/C, H
2
, EtOAc,
, CH Cl
, −78 C to rt., 3 h,
O = 1:1, 0 C to rt., 3 h, 70%; (f)
, 0 C, 30 min; (ii) MgSO , CH Cl , rt., 3 h,
5%; (g) 4-nitrobenzoyl chloride, TEA, DMAP, CH Cl
6 h, 89%.
ꢀ
−
0
15 C, 6 h (46% overall in two steps); (c) Et
2
Zn, CH
2
I
2
2
2
,
ꢀ
ꢀ
2 2
C, 2 h, 78%; (d) TBSOTf, 2,6-lutidine, CH Cl
6
9, 3282.
ꢀ
97%; (e) TsOH, acetone:H
2
. W. G. Dauben, G. H. Berezin, J. Am. Chem. Soc. 1963, 85, 468.
ꢀ
(i) MeMgBr, CH
2
Cl
2
4
2
2
ꢀ
6
2
2
, 0 C to rt.,
1
Bull. Korean Chem. Soc. 2018
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