T. Xie et al. / Tetrahedron Letters 56 (2015) 3982–3987
3983
Table 1
O
Bz
O
CH3
O-TBS
O
Optimization of reaction conditions for the SmI2-promoted synthesis of 1-methyl-2-
O
phenylcyclopropanola
N
Ns
OH
O
Me OH
Bt
O
O
SmI2,THF
HMPA, N2
H3C
H
Me
Vibralactone
Pactamycin
Figure 2. Natural products that bear cyclopent-3-enol scaffold.
1a
2a
Entry
The equiv of HMPA
Temperature (°C)
Time
10 h
Yieldb (%)
c
1
2
3
4
5
6
7
0
4
4
4
4
4
10
rt
rt
0
ꢀ30
ꢀ40
ꢀ78
rt
—
pancreatic lipase with an IC50 of 0.4 l
g/mL9a and the latter being
10 min
10 min
20 min
20 min
10 h
27
31
35
21
Trace
76
one of the well-known antibiotics (Fig. 2).9d Ring-closing of
diallyl carbinols via olefin metathesis catalyzed by ruthenium(II)
complexes afforded
a facile access to the cyclopent-3-enol
skeleton.10 Conjugated dienes react with highly reactive magne-
sium to form the 1,3-diene-magnesium reagents, which on treat-
ment with carboxylic acid esters at room temperature or reflux
followed by workup afforded cyclopent-3-enols in excellent
yields.11 Interestingly, the electroreduction of a solution of 1,3-di-
enes and an aliphatic carboxylic ester with a Mg electrode also
gives the enol in good yields.5 Recently, conjugated dienes by coor-
dination on Ti(II) complex when allowed to react with carboxylic
esters at room temperature would lead to cyclopentenol deriva-
tives in moderate yields.12 Although the methods reported above
are convenient and sometimes efficient, however, the stereochem-
istry of the cyclopent-3-enols was not involved.
10 min
a
Reaction conditions: substrate 1a (1.0 mmol), SmI2 (2.5 mmol) and HMPA in
dry THF (15 mL) under N2.
b
Isolated yield.
No reaction.
c
1). Considering that the addition of HMPA15 can enhance many
reactions promoted by SmI2, we then used it as an additive. In
the presence of HMPA (4 equiv), the purple color faded away
within several minutes and 1a was completely consumed (moni-
tored by TLC). Common work-up afforded the desired product 2a
in 27% yield (entry 2). Since the reaction was complicated and sev-
eral by-products were detected, decrease of the temperature was
applied. Slightly better results could be obtained at 0 °C (entry
3). However, further lowering the reaction temperature to ꢀ40 °C
did not improve the result remarkably and longer reaction time
was required (entries 4 and 5). Only trace amounts of 2a could
be obtained at ꢀ78 °C in 10 h (entry 6). The increase of the additive
loading was then attempted. To our delight, the yield improved
remarkably when 10 equiv of HMPA was added at ambient tem-
perature (entry 7, 76% yield).
The phenyl and methyl groups in cyclopropano1 2a were
assigned as cis- by 1H NOE data, which revealed no NOE between
the methyl substituent at C(1) and the benzylic H at C(2) on the
cyclopropanol ring, and also by comparison with the reported
spectra data for cis-1-methyl-2-phenylcycloprapanol.4b The
reaction is highly diastereoselective since no formation of the
other diastereomer could be detected by TLC analysis and crude
1H NMR.
Under the optimal conditions established, we then examined
the generality of the SmI2-mediated cyclization by using a variety
of b-benzotriazolyl ketones 1 (Table 2). Generally, the b-benzotria-
zolyl substrates reacted smoothly and gave the desired substituted
cyclopropanols 2 in moderate to good yields within 10 min. Both
electron-donating groups (Table 2, entries 2–4 and 10) and weak
electron-withdrawing groups (entries 5–8 and 15) on the phenyl
in R1 were well tolerated. However, the substrates bearing strong
electron-withdrawing groups such as –CF3 gave the desired
product only in poor yields (entries 9, 13 and 16). When R2 was
a phenyl (1k), the desired reaction failed (entry 11) and 1,3-
diphenylpropan-1-one resulting from the simple reductive deben-
zotriazolylation was obtained almost quantitatively. The presence
Herein we wish to report SmI2 mediated cleavage of
C–Bt(benzotriazolyl) bond in the readily available b-Bt ketones
for the diastereoselective synthesis of cis-1,2-disubstituted cyclo-
propanols and cyclopent-3-enols in good yields.
The properly located C–Bt bond could be readily cleaved by
SmI2. For example, the removal of a benzotriazolyl group from
the
a-benzotriazolyl ketones or N-acylbenzotriazoles was
achieved by SmI2 to afford the corresponding ketones13a or
a-diketones.13b The elimination of a benzotriazolyl group from
N-(
a
-amino)alkylbenzotriazoles,13c,d
N-(
a-benzotriazol-1-
ylalkyl)amides and N-(
a
-benzotriazol-1-ylalkyl)-sulfonamides13e
was readily realized with SmI2 as a reducing agent. The resulting
intermediates underwent either dimerization or cross-coupling
reaction with carbonyl compounds, thus affording the
corresponding dimers or
a-hydroxyalkylated amines or
sulfonamides. The benzotriazole adducts with an activated
double bond underwent the reductive debenzotriazolylation in
the presence of SmI2 to produce an
a-amino radical and
subsequent intramolecular radical addition to the double bond
afforded N-cycloalkylamines.13f
We envision the reductive cleavage of the C–Bt bond in
b-benzotriazolyl ketones
1 would lead to an intramolecular
cyclization and therefore provide a facile synthesis of substituted
cyclopropanols 2 (Scheme 1).
In our initial studies, b-benzotriazolyl ketone 1a, which could
be facilely prepared from the Michael addition between 4-phenyl-
but-3-en-2-one and benzotriazole (BtH),14 was added to the
SmI2/THF solution at room temperature. However, hardly any
desired product was detected under the condition (Table 1, entry
Bt
O
R2 OH
R3
of
a
-methyl (1l) led to a sharp decrease in yield (entry 12), indicat-
-steric hindrance might affect the intramolecular cycliza-
Sm(II)
R2
ing the
a
Ar
R3
1
tion process. However, when cyclized b-benzotriazolyl ketones 1n
and 1o were used as the substrates, the reactions proceeded
smoothly (entries 13 and 14). It is noteworthy that only one
diastereomer of 2 was obtained for all the substrates tested.
We then sought to extend the protocol to synthesize struc-
turally more versatile molecules. Interestingly, when 3a was used
Ar
2
N
N
N
Bt =
Scheme 1. Proposed SmI2-mediated synthesis of substituted cyclopropanols.