Cyclization and ring-expansion processes involving samarium diiodide promoted reductive formation and subsequent oxidative ring opening of cyclopropanol derivatives

Article abstract of DOI:10.1021/jo802749g

Samarium diiodide promoted reaction of various α-bromornethyl cycloalkanones, followed by subsequent treatment with trimethylsilyl chloride, leads to the production of cyclopropyl silyl ethers embedded in bicyclo[m.l.0]alkane frameworks. Treatment of the ethers with oxidative electron-transfer reagents, such as Fe(III), Ce(IV), and Mn(III) salts, generates ring-expanded ketones that convert to cyclic conjugated enones in moderate to good yields. In addition, the reduction-oxidation reaction sequences can be successfully performed in one pot. The regioselectivities of cyclopropane ring opening in the bicyclic substrates depend on the oxidizing agents used. For example, reactions promoted by FeCl₃ with pyridine lead to the expected ring-expansion process involving internal-bond cleavage of bicycloalkane and yielding cyclic enones as final products. In contrast, reactions with Ce(NH₄)I(NO₃)₆ or Mn(OAc) ₃ as oxidizing agents proceed by way of external-bond cleavage to give α-iodomethyl cycloalkanones.

Full text of DOI:10.1021/jo802749g

Cyclization and Ring-Expansion Processes Involving Samarium
Diiodide Promoted Reductive Formation and Subsequent Oxidative
Ring Opening of Cyclopropanol Derivatives
Hiroyuki Tsuchida, Mutsuko Tamura, and Eietsu Hasegawa*
Department of Chemistry, Faculty of Science, Niigata UniVersity, Ikarashi-2 8050,
Niigata 950-2181, Japan
ehase@chem.sc.niigata-u.ac.jp
ReceiVed December 17, 2008
Samarium diiodide promoted reaction of various R-bromomethyl cycloalkanones, followed by subsequent
treatment with trimethylsilyl chloride, leads to the production of cyclopropyl silyl ethers embedded in
bicyclo[m.1.0]alkane frameworks. Treatment of the ethers with oxidative electron-transfer reagents, such
as Fe(III), Ce(IV), and Mn(III) salts, generates ring-expanded ketones that convert to cyclic conjugated
enones in moderate to good yields. In addition, the reduction-oxidation reaction sequences can be
successfully performed in one pot. The regioselectivities of cyclopropane ring opening in the bicyclic
substrates depend on the oxidizing agents used. For example, reactions promoted by FeCl3 with pyridine
lead to the expected ring-expansion process involving internal-bond cleavage of bicycloalkane and yielding
cyclic enones as final products. In contrast, reactions with Ce(NH4)2(NO3)6 or Mn(OAc)3 as oxidizing
agents proceed by way of external-bond cleavage to give R-iodomethyl cycloalkanones.
Introduction
attracted both the mechanistic and synthetic interest of organic
chemists.4 Single electron transfers from cyclopropanol and enol
derivatives produce respective ꢀ-carbonyl alkyl and R-carbonyl
alkyl radicals (Scheme 1). The alkyl radical intermediates
Electron transfer (ET) is a fundamental reaction process,1 and
single electron transfer (SET) of neutral organic molecules
produces radical ions that often undergo fragmentation reactions
to generate free radical intermediates.2 If carbon radicals are
generated in this process, they often participate in synthetically
useful carbon-carbon bond-forming reactions.3 Cyclopropanols
and their derivatives are carbocyclic homologues of enols, and
as such, they undergo various transformations that are the similar
to enol derivatives. As a result, these strained compounds have
(2) (a) Schmittel, M.; Burghart, A. Angew. Chem., Int. Ed. Engl. 1997, 36,
2550–2589. (b) Berger, D. J.; Tanko, J. M. In The Chemistry of Double-Bonded
Functional Groups; Patai, S., Ed.; John Wiley & Sons: New York, 1997; pp
1281-1354. (c) Schmittel, M.; Ghorai, M. K. In Electron Transfer in Chemistry;
Balzani, V., Ed.; Wiley-VCH: Weinheim, 2001; Vol. 2, pp 5-54. (d) Hasegawa,
E. J. Photoscience 2003, 10, 61–69. (e) Roth, H. D. In ReactiVe Intermediate
Chemistry; Moss, R. A., Platz, M. S., Jones, M., Jr., Eds; John Wiley & Sons:
Hoboken, 2004; Chapter 6, pp 205-272. (f) Cossy, J.; Belloti, D. Tetrahedron
2006, 62, 6459–6470. (g) Griesbeck, A. G.; Hoffmann, N.; Warzecha, K. D.
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203. (i) Waske, P. A.; Tzvetkov, N. T.; Mattay, J. Synlett 2007, 669–685.
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10.1021/jo802749g CCC: $40.75
Published on Web 02/13/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 2467–2475 2467

Tsuchida et al.
SCHEME 1
SCHEME 2
SCHEME 3
CHART 1
generated in this manner serve as useful precursors of various
carbonyl compounds.3
Reactions of cyclopropanol derivatives promoted by various
oxidizing agents have been extensively investigated.5 Photoin-
duced electron transfer (PET) reactions of these compounds have
also been described.6 In both cases, the reactions that ensue are
initiated by cyclopropane ring cleavage. Interesting mechanistic
and synthetic issue associated with the regioselectivity of
cyclopropane ring opening (internal-bond cleavage vs external-
bond cleavage) arise in ET oxidation reactions of substances,
in which the cyclopropanol moiety is embedded within a
bicyclo[m.1.0]alkane framework (Scheme 2).5,6
We recently developed a novel cyclization-ring-expansion
reaction sequence that is promoted by initial reaction of a
substrate with samarium diiodide (SmI2)7,8 and followed by
oxidative ring opening of intermediate cyclopropanols.9,10 For
example, keto esters I are reductively converted to bicyclic-
cyclopropanols II when treated with SmI2. Metal oxidants
promote ring opening of these substances that generates seven-
membered ring ketones III (Scheme 3).9b Elimination reactions
(-HNu) of III produce substituted benzotropolones whose
structures are often found in naturally occurring theaflavins.11
The tandem cyclization-ring-expansion processes serve as
an effective protocol for the construction of various cyclic
compounds.12 In light of its potential synthetic significance, we
have probed the application of this methodology to other types
of substrates. Below, we describe the results of an investigation
that demonstrate that intramolecular SmI2-promoted Barbier
reactions8,13 of R-bromomethyl cycloalkanones can be used to
generate bicyclic cyclopropanols,14 which undergo oxidative
ring-opening reactions in an efficient manner. Also, the results
of an effort to incorporate these sequential reduction-oxidation
processes into a one-pot process are described.
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Kirihara, M.; Kakuda, H.; Ichinose, M.; Ochiai, Y.; Takizawa, S.; Mokuya, A.;
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2698. (c) Kagan, H. B. Tetrahedron 2003, 59, 10351–10372, and references
therein.
Results and Discussion
Preparation of Cyclopropanol Derivatives. The cyclopropyl
silyl ethers 2 (Chart 1) used in these studies were prepared by
using SmI2-promoted intramolecular Barbier reactions of the
corresponding R-bromomethyl cycloalkanones 1,10a followed
by trimethylsilylation of the resulting cyclopropanols. For
example, R-bromomethyl tetralone 1a was treated with SmI2,
and the crude mixture containing the corresponding cyclopro-
panol (not shown) was reacted with Me3SiCl in the presence of
Et3N to give cyclopropyl silyl ether 2a (Scheme 4).15 The related
cyclopropanol derivatives 2b (49%), 2c (79%), 2d (80%), and
2e (59%) were synthesized in a similar fashion. Also, the
benzopyrane containing fused cyclopropanol 4 (38%) and its
(8) Representative reviews: (a) Molander, G. A. Chem. ReV. 1992, 92, 29–
68. (b) Curran, D. P.; Fevig, T. L.; Jasperse, C. P.; Totleben, M. J. Synlett 1992,
943–961. (c) Molander, G. A.; Harris, C. R. Chem. ReV. 1996, 96, 307–338. (d)
Edmonds, D. J.; Johnston, D.; Procter, D. J. Chem. ReV. 2004, 104, 3371–3404.
(e) Flowers, R. A. Synlett 2008, 1427–1439.
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5067–5070. (b) Iwaya, K.; Tamura, M.; Nakamura, M.; Hasegawa, E. Tetrahe-
dron Lett. 2003, 44, 9317–9320.
(10) Some representative examples of SmI2-promoted cyclopropanol forma-
tion and rearrangements. Ring-expansion: (a) Hasegawa, E.; Kitazume, T.;
Suzuki, K.; Tosaka, E. Tetrahedron Lett. 1998, 39, 4059–4062. (b) Hamura, T.;
Suzuki, T.; Matsumoto, T.; Suzuki, K. Angew. Chem., Int. Ed. 2006, 45, 6294–
6296. Acyl migration: Inokuchi, T. J. Org. Chem. 2005, 70, 1497–1500.
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Pennington, M. Phytochemistry 1998, 49, 2511–2519.
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C. J. Tetrahedron 1993, 49, 10749–10784. (c) Rousseau, G. Tetrahedron 1995,
51, 2777–2849. (d) Yet, L. Tetrahedron 1999, 55, 9349–9403. (e) Yet, L. Chem.
ReV. 2000, 100, 2963–3007.
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(14) Preliminary communication: Hasegawa, E.; Tsuchida, H.; Tamura, M.
Chem. Lett. 2005, 34, 1688–1689.
(15) Direct addition of Me3SiCl to the reaction mixture of 1a and SmI2 was
not successful.
2468 J. Org. Chem. Vol. 74, No. 6, 2009

Formation and Ring-Opening of Cyclopropanol DeriVatiVes
SCHEME 4
SCHEME 6
SCHEME 5
TABLE 1. Reaction of 2a with Oxidizing Reagents (Ox)a
SCHEME 7
yields (%)
additive
conv of
entry
Ox
(equiv vs 2a) solvent 2a (%) 7a
9a
1b
2b
3
4
5
FeCl3
FeCl3
CANc
pyridine (1.0) DMF
100
74
100
100
100
72
33
53
18
19
0
0
0
27
33
Et2NH (1.0)
none
DMF
MeCN
AcOH
AcOH
Mn(OAc)3 ·2H2O none
PhI(OAc)2 none
On the basis of the observations described above, the FeCl3
and pyridine oxidation conditions were used in reactions of the
other cyclopropyl silyl ethers 2 (Scheme 6). Although reaction
of 2c under the conditions employed to react 2a was slow, 7c
was obtained in 76% yield based on the conversion of 2c.
Reaction of 2d with FeCl3 in the presence or absence of pyridine
generated 7d as the major product along with a small amount
of the spirocyclic product 10. In the case of 2e, 7e was obtained
in a moderate yield. Also, CAN could be used to promote the
transformation of 2e to 7e (52%). We also examined FeCl3/
pyridine-promoted reactions of silyl ether 5 and the unprotected
alcohol 4 (Scheme 7). Reactions of both 4 and 5 produced the
unexpected enone product 11 and the 2-methoxymethylketone
12, both of which are formed through external cyclopropane
bond cleavage.19
A plausible mechanism for ring-opening reactions of the
bicyclic cyclopropanol derivatives is represented in the pathway
proposed for reaction of 2a (Scheme 8). In the presence of SET
oxidizing agents, such as FeCl3, CAN, and Mn(OAc)3,2a,20 2a
is transformed to the corresponding radical cation, which then
transfers a Me3Si group to a nucleophile to generate the oxy
radical 13a.5b,d,e,g,i,j,m In the presence of the more basic amine
Et2NH versus pyridine (respective pKa values of their conjugate
acids in H2O are 10.98 and 5.2),21 the oxidizing ability of Fe(III)
would be lowered, leading to a deceleration of the rate of the
initial SET event. This is consistent with the observation that
the rates of reactions in the presence of pyridine are larger than
when Et2NH is used as a base (see entries 1 and 2, Table 1).
Selective internal-bond cleavage of oxy-radical 13a gives the
a Compound 2a (0.50 mmol), Ox (2.2 equiv for entries 1, 2, 3, 4; 1.1
equiv for entry 5), solvent (5.0-10.0 mL), at room temperature for 1 h.
b Crude product mixture was refluxed with NaOAc in MeOH for 2 h.
c Ce(NH4)2(NO3)6.
silyl ether 5 (28%) (Chart 1) were prepared from o-allyloxy
benzoyl chloride 3 by using previously described procedures.16
Oxidative Reactions of Cyclopropyl Silyl Ethers. Treatment
of cyclopropyl silyl ethers 2b with FeCl3 in the presence of
pyridine at room temperature led to formation of naphthol 6
(Scheme 5). When this process was carried out in the absence
of pyridine, the yield of 6 was significantly lowered (67%). In
contrast, reactions of 2b with Ce(NH4)2(NO3)6 (CAN),
Mn(OAc)3 ·2H2O, and PhI(OAc)2 gave complicated product
mixtures from which 6 could not be isolated. It is possible that
these stronger oxidizing reagents containing Ce(IV) and Mn(III)
could cause further oxidation of 6.17,18
The reactions of 2a with the above oxidizing reagents were
explored next (Table 1). Treatment of 2a with FeCl3 and
pyridine led to production of ꢀ-chloro benzosuberone 8a (crude
yield 96%). Upon stirring at reflux in a methanolic NaOAc
solution, the crude product mixture was converted to the
benzocycloheptadienone 7a (entry 1). When pyridine was
replaced by Et2NH in the FeCl3-promoted reaction, the reaction
became sluggish and rather complicated; 7a was the only
isolable product (entry 2). Also, reactions of 2a with CAN,
Mn(OAc)3 ·2H2O, and PhI(OAc)2 produced 7a (entries 3-5).
In reactions of 2a with the Mn(III) and I(III) oxidants, ꢀ-hydroxy
benzosuberone 9a was the major product (entries 4 and 5).
(19) In the preliminary communication of these results,14 incorrect structures
for the products derived from 4 and 5, ring-expanded enone and its ꢀ-methoxy
substituted analog, were reported. Later, it was also found that 11 gradually
polymerizes.
(16) Sasaki, M.; Collin, J.; Kagan, H. B. Tetrahedron Lett. 1988, 29, 6105–
6106.
(17) A similar observation was made when 1b was treated with tris(p-
bromophenyl)aminium hexachloroantimonate as a SET reagent, which could be
due to oxidative decomposition of 6.18
(20) In the case of PhI(OAc)2, an ionic mechanism could be operating instead
of a SET mechanism.5h
(18) Hasegawa, E.; Ogawa, Y.; Kakinuma, K.; Tsuchida, H.; Tosaka, E.;
Takizawa, S.; Muraoka, H.; Saikawa, T. Teterahedron 2008, 64, 7724–7728.
(21) (a) Hall, H. K., Jr. J. Am. Chem. Soc. 1957, 79, 5441–5444. (b) Bordwell,
F. G. Acc. Chem. Res. 1988, 21, 456–463.
J. Org. Chem. Vol. 74, No. 6, 2009 2469

Tsuchida et al.
SCHEME 8
bond cleavage of 13, might undergo a fast follow-up reaction
leading to formation of the external cyclopropane bond cleavage
product (i.e., Curtin-Hammet-type control).6f,25 However, a fast
oxidation of 14 by FeCl3 occurs to give the stable tertiary
carbocation intermediates 15 in other cases.
One-Pot Reaction. As described above, the samarium-
Barbier reaction of ꢀ-bromoketones serves as a useful method
for the preparation of cyclopropanol derivatives. In these
reactions, samarium cyclopropoxides are generated as interme-
diates and serve as precursors of the cyclopropanol or siloxy-
cyclopropane products. Owing to the fact that alkoxides are
known to be more easily oxidized than the corresponding
alcohols,26 ET oxidation reactions of samarium cyclopropoxides
formed in this manner should be possible. If so, it should be
possible to carry out the sequential reductive cyclization-oxidative
ring-opening reactions in one pot. As shown in Scheme 10, a
one-pot procedure would represent a more concise and eco-
nomical process, which is consistent with green and sustainable
chemistry,27 in contrast to the stepwise procedure described
above. Under the one-pot conditions, samarium cyclopropoxide
18 would need to be oxidized by the ET reagents that we have
used in the stepwise procedure. In addition, both the reductive
cyclization and oxidative ring-opening reactions would need to
take place in the same solvent. While SmI2 is normally prepared
in THF,7,8 THF has not been usually used for oxidative ET
reactions of cyclopropanol derivatives.5
SCHEME 9
To explore the one-pot technique, the conversion of 1a to 7a
was explored (Scheme 11). A THF solution of ꢀ-bromoketone
1a was first treated with SmI2 followed by the addition of FeCl3
and pyridine, with stirring at room temperature for 1 h and 85
°C for 2 h. As expected, the desired enone 7a was generated in
a 71% yield, which is better than the 65% yield that was
obtained by using the stepwise procedure.
A small amount of the R-iodomethyl tetralone 19a28 was also
formed (3%) in this one-pot reaction. NMR analysis of the crude
reaction mixture, generated by using the one-pot method at room
temperature, showed that 19a and ꢀ-iodo benzosuberone 20a29
were present in a 1:15 ratio. The effects of changes in amines
and oxidizing reagents (CAN and Mn(OAc)3) on the efficiencies
of the one-pot processes are summarized in Table 2.
alkyl radical 14a that is oxidized by another equivalent of the
oxidizing reagent to give carbocation 15a. Either nucleophilic
addition or deprotonation of 15a is expected to occur, depending
on the nature of a coexistent nucleophile/base, to produce the
observed products.
In bicyclic cyclopropoxy radicals, such as 13a, an alternative
external-bond cleavage mode is possible. In regard to this issue,
observations made in studies of the oxidation reaction of 2d
are notable. In this case, if the intermediate cyclopropoxy radical
13d undergoes external cyclopropane bond cleavage, the
intermediate radical 16d would be generated and would undergo
5-exo radical cyclization22 to produce 17 (Scheme 9).23 As
described above, the expected product of this reaction mode,
the compound 10, is indeed generated, although in low yield.
On the other hand, no products (e.g., R-methyl cycloalkanones)
arising from external-bond cleavage were obtained in reactions
of the other substrates 2. A plausible rationalization for these
observations invokes the possibility that a rapid equilibrium
exists between 14 and 16.24 If so, in some cases the thermo-
dynamically less stable radical 16, formed through external-
As described above, whereas FeCl3-promoted reaction of 1a
in the presence of pyridine gave 7a as the major product (entry
2), the ratio of 7a to 19a was reversed when this process was
conducted in the absence of pyridine (entry 1). Replacement of
pyridine by Et2NH led to a significant increase in the yield of
7a (entry 4).30 Increasing the equivalents of pyridine from 1 to
(25) Curtin-Hammett principle: IUPAC. Compendium of Chemical Terminol-
ogy, 2nd ed. (the “Gold Book”); compiled by McNaught, A. D.; Wilkinson, A.;
Blackwell Scientific Publications: Oxford, 1997. An example of Curtin-
Hammett-type control of ET-radical reaction: Yoon, U. C.; Kwon, H. C.; Hyung,
T. G.; Choi, K. H.; Oh, S. W.; Yang, S.; Zhao, Z.; Mariano, P. S. J. Am. Chem.
Soc. 2004, 126, 1110–1124.
(26) Mann, C. K.; Barnes, K. K. Electrochemical Reactions in Nonaqueous
Systems; Marcel Dekker: New York, 1970.
(27) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice;
Oxford University Press: Oxford, 1998.
(28) Compound 19a was identified by the direct comparison with the
compound synthesized by R-iodomethylation of R-methyltetralone.
(29) Isolation and full characterization of the unstable substane 20a has not
been successful. Therefore, the structure of 20a was tentatively assigned on the
basis of the similarity of 1H and 13C NMR with those of the corresponding
chloride 8a.
(30) Contrastive effect of Et2NH on the yield of 3a in entry 4 in Table 2
compared to that of entry 2 in Table 1 is interesting, although rationalization
seems difficult. As expected, samarium alkoxide 18a is more reactive than silyl
ether 2a, and therefore the reagent system of FeCl3 and Et2NH still has strong
enough oxidizing ability for 18a.
(22) (a) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317–323. (b)
Beckwith, A. L. J.; Schiesser, C. H. Tetrahedron 1985, 41, 3925–3941.
(23) Hasegawa, E.; Takizawa, S.; Iwaya, K.; Kurokawa, M.; Chiba, N.;
Yamamichi, K. J. Chem. Soc., Chem. Commun. 2002, 1966–1967.
(24) For a discussion of the reaction pathways for related radical rearrange-
ments involving cyclopropoxy radicals, see: (a) Ryu, I.; Fukushima, H.; Okuda,
T.; Matsu, K.; Kambe, N.; Sonoda, N.; Komatsu, M. Synlett 1997, 1265–1268.
(b) Chatgilialoglu, C.; Ferreiri, C.; Lucarini, M.; Venturini, A.; Zavitsas, A. Chem.
Eur. J. 1997, 3, 376–387.
2470 J. Org. Chem. Vol. 74, No. 6, 2009

Formation and Ring-Opening of Cyclopropanol DeriVatiVes
SCHEME 10
SCHEME 11
TABLE 2. One-Pot Technique for Sequential Reduction-oxidation-elimination reactions of 1aa
yieldsb (%)
entry
Ox
amine (equiv vs 1a)
conv of 1a (%)
7a
19a
1
2
3
4
5
6
7
8
9
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
CANc
CANc
none
100
100
97
100
100
83
100
100
100
25
71
67
94
47
tr
2
tr
2
38
3
8
pyridine (1.0)
pyridine (2.0)
Et2NH (1.0)
Et2NH (5.0)
none
pyridine (1.0)
none
pyridine (1.0)
4
18
88
87
90
84
Mn(OAc)3 ·2H2O
Mn(OAc)3 ·2H2O
a (i) Compound 1a (0.50 mmol), SmI2 (2.2 equiv), THF (12.0 mL), at room temperature for 30 min; (ii) Ox (2.2 equiv), THF (5.0 mL), at room
temperature for 1 h; (iii) heated at 85 °C for 2 h. b Based on the conversion of 1a. c Ce(NH4)2(NO3)6
2 equiv relative to 1a caused only a slight change in the ratio
and yields of 7a and 19a. Similarly, increasing the quantity of
Et2NH (up to 5 equiv) had an impact on the product ratio (entry
5).31 Notably, 19a was the exclusive product formed in reactions
in which CAN and Mn(OAc)3 were used as oxidants, regardless
of whether pyridine was present or absent (entries 6-9).
A characteristic color change to brown took place when CAN
or Mn(OAc)3 was added. This is likely associated with the
formation of iodine molecule (I2). This observation led to a
working hypothesis that iodide ion (I-) is oxidized by Ce(IV)
or Mn(III) to give I2 on the basis of their redox potentials (see
below).32 In order to determine if this hypothesis is correct,
experiments were performed to see if cyclopropanols react with
I2.33 When I2 was added to the mixture obtained from the
reaction of 1a with SmI2, 19a was produced exclusively (no 7a
was formed) (Scheme 12). Similarly, treatment of silyl ether
2a with I2 led to formation of 19a exclusively (Scheme 13).
We were interested in knowing if the oxidizing reagents used
in these processes would oxidize iodide ion. Then, we conducted
the reaction of 2a with FeCl3 and pyridine and with CAN in
J. Org. Chem. Vol. 74, No. 6, 2009 2471

Tsuchida et al.
SCHEME 12
ion gives 19a as an isolable product. Paths A and B both operate
in the reaction promoted by FeCl3 in the absence of an amine
(see entry 1 of Table 2).35
As described above, the combination of FeCl3 and amine is
effective for the one-pot transformation of 1a to 7a. Sequential
reductive cyclization-oxidative ring-opening reactions utilizing
these conditions were applied to reactions of other substrates.
The results are summarized in Scheme 15. In most of the cases,
the yields of desired 3-substituted-enones 7 were greater than
those arising from application of the stepwise procedure.
Importantly, the one-pot method was effective in transforming
the nonbenzocyclic substrates 22 to the enone 23. It should be
noted that when pyridine was replaced by Et2NH, the yield of
6 (61%) in the one-pot reaction of 1b did not significantly
change. However the one-pot reaction of 1d in the presence of
Et2NH was not efficient, resulting in the formation of 7d in
only a 39% yield. Thus, it appears that the method using pyridine
gives more consistent results than that using Et2NH. Finally,
the one-pot reaction of 3 did not form 11.
SCHEME 13
TABLE 3. Oxidation of 2a in the Presence of NaI
Summary. As shown by the results described above, ꢀ-bromo
ketones undergo cyclization and ring-expansion reactions that
involve sequential reductive formation and oxidative ring
opening of cyclopropanol intermediates. Characteristic features
of this unique two-step process are the operation of an
intramolecular samarium-Barbier reaction of R-bromomethyl
cycloalkanones and regioselective oxidative ring opening of the
resulting cyclopropanols embedded in bicyclo[m.1.0]alkane
frameworks. This reaction sequence leads to the production of
various 3-substituted cyclic-enones that serve as precursors for
yields (%)
NaI
conv of
entry
Ox
(equiv vs 2a) solvent 2a (%)
7a
19a
1b
2b
3
FeCl3/pyridine
FeCl3/pyridine
CANc
0.0
5.0
0.0
5.0
DMF
DMF
MeCN
MeCN
100
100
100
100
72
70
53
1
0
3
0
4
CANc
90
a Compound 2a (0.50 mmol), Ox (2.2 equiv), solvent (5.0-10.0 mL),
at room temperature for 1 h. b Pyridine (1.0 equiv), crude product
mixture was refluxed with NaOAc in MeOH for 2 h. c Ce(NH4)2(NO3)6
the formation of quarternary carbon-centered systems.36
A
further notable observation made in this effort is that this
sequence can be performed by using a one-pot procedure.37
Under the one-pot conditions, contrasting regioselectivities of
cyclopropane ring opening are observed depending upon the
nature of the oxidizing reagent used. The oxidizing reagent
dependency of these one-pot processes can be explained by
whether or not molecular iodine is produced. When the oxidizing
reagent is sufficiently strong to transform iodide ion into iodine,
the predominant pathway followed involves external-bond
cleavage of bicycloalkane framework.
the presence of NaI. The results are summarized in Table 3. In
the reaction of 2a with FeCl3 and pyridine, 7a was a major
product regardless of whether NaI was present or absent (entries
1 and 2). However, in the reaction with CAN, 19a became the
exclusive product in the presence of NaI (entries 3 and 4).34
This contrasting result is consistent with the hypothesis that
iodide ion is more efficiently oxidized by CAN than by FeCl3
with pyridine.
On the basis of above results, a plausible mechanism for the
one-pot reaction of the bromomethyl ketone 1a involves SET
oxidation of the cyclopropoxy-samarium intermediate 18a by
FeCl3 to produce the corresponding radical cation that then
undergoes samarium ion elimination and subsequent internal-
bond cleavage of cyclopropoxy radical 13a (Scheme 14, path
A). The formed alkyl radical 14a is oxidized by another
equivalent of FeCl3 to form the tertiary carobocation 15a that
is trapped by iodide ion to give 20a, which undergoes elimina-
tion to produce 7a. On the other hand, in the cases of oxidations
promoted by the relatively strong oxidants CAN and Mn(OAc)3,
iodide ion is transformed to I2 (Scheme 14, path B). A following
electrophilic attack of I2 on the cyclopropane ring of 18a results
in production of carbocation 21a, and elimination of samarium
Experimental Section
Preparations of Bromoalkyl-cycloalkanones: 2-Bromomethyl-
2-methyl-1-tetralone (1a). To the suspension of NaH (1.06 g, 26.4
mmol) in THF (13.0 mL) was added HMPA (4.6 mL, 26.4 mmol).
Subsequently, 2-methyl-1-tetralone (3.53 g, 22.0 mmol) in THF
(12.0 mL) was added, and the mixture was stirred under N2 at room
temperature. After 1 h, CH2Br2 (4.6 mL, 66 mmol) was added, and
the mixture was stirred at reflux (85 °C) for 22 h. Then, it was
(35) A question raised in this effort concerns why the weaker oxidizing
reagent FeCl3 promotes SET reaction of 18a but the stronger oxidizing reagents
CAN and Mn(OAc)3 do not. A clear explanation of this finding is not available
at the moment. It is possible to hypothesize that 18a more efficiently reacts
with iodine than with the metal reagents and that the latter SET steps between
18a and the reagents is reversible.
(36) Quaternary Stereocenters: Challenge and Solutions for Organic Syn-
thesis; Christoffers, J., Baro, A., Eds; Wiley-VCH: Weinheim, 2005.
(37) A reviewer suggested the applicability of the reductive regeneration of
samarium(II) from the produced samarium(III) to our reaction system, which
might be an interesting future subject to investigate since catalytic use of
samarium is also consistent with green and sustainable chemistry. Representative
examples of reductive regeneration of samarium(II): (a) Nomura, R.; Matsuno,
T.; Endo, T. J. Am. Chem. Soc. 1996, 118, 11666–11667. (b) Corey, E. J.; Zheng,
G. Z. Tetrahedron Lett. 1997, 38, 2045–2048. (c) Parrisha, J. D.; Little, R. D.
Tetrahedron Lett. 2001, 42, 7767–7770. (d) Shean, J. J.; Fang, J. M. J. Org.
Chem. 2001, 66, 3533–3537.
(31) At the moment, the origin of the amine effect causing the considerable
formation of 19a is unclear. It might be that the amine coordinates with the
samarium ion to weaken the Sm-O bond of cyclopropoxide, which then assists
the external bond cleavage of cyclopropoxy anion.
(32) Lange’s Handlectron Transfer in Chemistry, 13th ed.; Dean, J. A., Ed.;
McGraw-Hill: New York, 1985; Section 6.
(33) To the best of our knowledge, reactions of cyclopropanol derivatives
with iodine are unprecedented, whereas those with bromine have been reported.4
Also see: Murai, S.; Seki, Y.; Sonoda, N. J. Chem. Soc., Chem. Commun. 1974,
1032–1033.
(34) Our observation might be related to those made by Flowers5m in which
cyclopropanol ring-opening reactions are promoted by CAN in the presence of
certain nucleophiles.
2472 J. Org. Chem. Vol. 74, No. 6, 2009

Formation and Ring-Opening of Cyclopropanol DeriVatiVes
SCHEME 14
SCHEME 15
extracted with Et2O after addition of water. The extract was treated
with water, saturated aqueous Na2S2O3, saturated aqueous NaHCO3,
and brine and dried over anhydrous MgSO4. The residue obtained
after concentration was subjected to column chromatography on
silica gel (CH2Cl2/n-hexane ) 1/1) to give 2-bromomethyl-2-
methyl-1-tetralone 1a (2.71 g, 10.7 mmol, 49%). Compound 1b,
1c, 1d, and 1e were similarly prepared. Data for 1a: pale yellow
Hz, 1H), 3.62 (d, J ) 10.0 Hz, 1H), 7.09-7.40 (m, 4H); 13C NMR
(50 MHz) δ 22.2, 22.6, 32.8, 41.7, 49.7, 126.6, 127.6, 128.4, 131.1,
137.0, 140.7, 211.0; LRMS (EI) m/z (relative intensity) 266 (M+,
1), 268 (M+ + 2, 1), 91 (100). Data for 1e: yellow oil; IR (Neat)
1
1714 cm-1; H NMR (200 MHz) δ 1.50 (s, 3H), 2.62-2.86 (m,
2H), 2.98-3.18 (m, 2H), 3.57 (d, J ) 9.9 Hz, 1H), 4.09 (d, J )
9.9 Hz, 1H), 7.19-7.33 (m, 4H); 13C NMR (50 MHz) δ 27.0, 28.0,
37.9, 39.1, 52.6, 126.0, 127.1, 127.2, 128.3, 136.3, 139.6, 211.4;
LRMS (EI) m/z (relative intensity) 252 (M+, 16), 254 (M+ + 2,
15), 131 (100); HRMS (EI) calcd for C12H13O79Br 252.0149, found
252.0152 (M+), calcd for C12H13O81Br 254.0129, found 254.0125
(M+ + 2).
Preparation of 2-Bromomethyl-2-phenethylcyclohexanone
(22). 2-Phenethyl-2-mesyloxymethylcyclohexanone (915 mg, 2.95
mmol) and LiBr (852 mg, 9.81 mmol) were added to acetone (7.0
mL), and the mixture was refluxed at 65 °C for 42 h. Then, it was
extracted with Et2O after addition of water. The extract was treated
with water, saturated aqueous NaHCO3, and brine and dried over
anhydrous MgSO4. The residue obtained after concentration was
subjected to column chromatography on silica gel (EtOAc/n-hexane
) 1/10) and distilled under reduced pressure to give 2-bromom-
ethyl-2-phenethylcyclohexanone 22 (521.5 mg, 1.77 mmol, 60%).
Data for 22: pale yellow oil; IR (Neat) 2932, 1704 cm-1; 1H NMR
1
oil; IR (Neat) 1680 cm-1; H NMR (200 MHz) δ 1.30 (s, 3H),
1.96-2.09 (m, 1H), 2.30-2.44 (m, 1H), 2.91-3.05 (m, 1H), 3.50
(d, J ) 10.3 Hz, 1H), 3.81 (d, J ) 10.3 Hz, 1H), 7.22-7.35 (m,
2H), 7.44-7.52 (m, 1H), 8.04 (m, 1H); 13C NMR (50 MHz) δ 21.1,
25.1, 32.6, 40.6, 45.9, 126.8, 128.0, 128.7, 131.0, 133.6, 143.1,
199.0; LRMS (EI) m/z (relative intensity) 252 (M+, 30), 254 (M+
+ 2, 30), 173 (100); HRMS (EI) calcd for C12H13O79Br 252.0149,
found 252.0150 (M+), calcd for C12H13O81Br 254.0129, found
254.0122 (M+ + 2). Data for 1b: colorless oil; IR (KBr) 1702 cm-1
;
1H NMR (200 MHz) δ 1.34 (s, 3H), 2.95 (d, J ) 17.3 Hz, 1H),
3.39-3.66 (m, 3H), 7.35-7.79 (m, 4H); 13C NMR (50 MHz) δ
23.9, 39.3, 39.6, 50.0, 122.4, 126.6, 127.6, 135.2, 135.3, 152.2,
207.1; LRMS (EI) m/z (relative intensity) 238 (M+, 2), 240 (M+
+ 2, 2), 159 (100). Data for 1c: pale yellow oil; IR (Neat) 2924,
1668, 1442, 1250, 960, 738 cm-1; 1H NMR (200 MHz) δ 1.29 (s,
3H), 1.66-2.03 (m, 4H), 2.75-2.81 (m, 2H), 3.49 (d, J ) 10.0
J. Org. Chem. Vol. 74, No. 6, 2009 2473

Tsuchida et al.
(270 MHz) δ 1.63-2.62 (m, 12H), 3.55 (d, J ) 10.8 Hz, 1H),
3.81 (d, J ) 10.8 Hz, 1H), 7.14-7.32 (m, 5H); 13C NMR (68 MHz)
δ 20.7, 27.3, 29.9, 36.2, 36.9, 39.4, 39.6, 52.1, 126.0, 128.2, 128.4,
141.2, 212.2; LRMS (EI) m/z (relative intensity) 296 (M+, 2), 298
(M + 2, 2), 192 (100).
Hz, 1H), 6.80 (m, 1H), 6.98 (m, 1H), 7.09 (m, 1H), 7.52 (m, 1H);
13C NMR (68 MHz) d 1.4, 18.0, 26.3, 53.3, 62.1, 116.7, 121.4,
125.1, 126.6, 129.9, 150.6; LRMS (EI) m/z (relative intensity) 234
(M+, 93), 75 (100); HRMS (EI) calcd for C13H18O2Si 234.1076,
found 234.1079.
Reaction of Cyclopropyl Silyl Ether with FeCl3. To FeCl3 (1.10
mmol) and pyridine (0.50 mmol) in DMF (2.0 mL) was added 2
(0.50 mmol) in DMF (3.0 mL) under N2. The mixture was stirred
under N2 at room temperature for 1 h. Then, it was extracted with
Et2O after addition of water. The extract was treated with water,
saturated aqueous Na2S2O3, saturated aqueous NaHCO3, and brine.
The ether solution was dried over anhydrous MgSO4, and the filtrate
was concentrated. Then, NaOAc (2.5 mmol) and MeOH (5.0 mL)
were added to the residue, and the mixture was refluxed at 85 °C.
After 2 h, it was extracted with Et2O after addition of water. The
extract was treated with water, saturated aqueous Na2S2O3, saturated
aqueous NaHCO3, and brine and dried over anhydrous MgSO4. The
residue obtained after concentration was subjected to TLC (CH2Cl2/
n-hexane ) 1/1) and 7 was obtained. Same treatment of 4 and 5
with FeCl3 gave 1138 and 12. Data for 7e: yellow oil; IR (Neat)
1656 cm-1; 1H NMR (200 MHz) δ 2.34 (d, J ) 1.1 Hz, 3H), 2.67
(m, 2H), 2.97 (m, 2H), 6.28 (s, 1H), 7.29 (m, 3H), 7.48 (m, 1H);
13C NMR (50 MHz) δ 26.1, 29.9, 44.1, 126.9, 128.1, 128.7, 129.2,
129.6, 136.9, 141.0, 148.5, 202.5; LRMS (EI) m/z (relative intensity)
172 (M+, 51), 129 (100); HRMS (EI) calcd for C12H12O 172.0888,
found 172.0890. Data for 9a: white solid, mp 110.9-111.7 °C; IR
Preparation of Cyclopropyl Silyl Ethers: 6-Methyl-1-trim-
ethylsilyloxy-2,3-benzobicyclo[4.1.0]hepta-2-ene (2a). To a solu-
tion of SmI2 (0.1 M in THF, 11.0 mL, 1.10 mmol) was added 1a
(127 mg, 0.50 mmol) in THF (1.0 mL). The mixture was stirred
under N2 at room temperture for 30 min. Then, it was extracted
with Et2O after addition of 0.1 N aqueous HCl. The extract was
treated with water, saturated aqueous Na2S2O3, saturated aqueous
NaHCO3, and brine. The ether solution was dried over MgSO4,
and the filtrate was concentrated. Then, Et3N (0.21 mL, 1.50 mmol)
and Me3SiCl (0.15 mL, 1.20 mmol) were added to the residue in
CH2Cl2 (3.0 mL). The mixture was stirred at room temperture for
30 min. Then, it was extracted with Et2O after addition of water.
The extract was treated with water, saturated aqueous Na2S2O3,
saturated aqueous NaHCO3, brine, and dried over anhydrous
MgSO4. The residue obtained after concentration was subjected to
column chromatography on silica gel (EtOAc/n-hexane ) 1/5) to
give 6-methyl-1-trimethylsilyloxy-2,3-benzobicyclo[4.1.0]hepta-2-
ene 2a (111.0 mg, 0.44 mmol, 88%) as a colorless oil. 2b, 2c, 2d,
and 2e were similarly prepared. Data for 2e: colorless oil; IR (Neat)
1
2924, 1248, 836 cm-1; H NMR (270 MHz) δ 0.19 (s, 9H), 0.80
(d, J ) 5.7 Hz, 1H), 1.28 (d, J ) 5.7 Hz, 1H), 1.53 (s, 3H),
1.97-2.11 (m, 1H), 2.25 (m, 1H), 2.52-2.74 (m, 2H), 6.97-7.07
(m, 2H), 7.15 (m, 1H), 7.37 (m, 1H); 13C NMR (68 MHz) δ 1.4,
16.6, 22.9, 23.5, 27.6, 28.0, 64.6, 124.5, 125.5, 126.0, 128.1, 133.4,
141.6; LRMS (EI) m/z (relative intensity) 246 (M+, 5), 75 (100).
Preparation of 6a,7-Dihydrobenzo[b]cyclopropa[d]pyran-7a-
ol (4).16 To 2-allyloxybenzoic acid (172 mg, 0.96 mmol) in benzene
(5.0 mL) was added Et3N (0.51 mL, 3.6 mmol). The mixture was
cooled to 0 °C, and SOCl2 (0.18 mL, 2.4mmol) was added. The
mixture was stirred at 0 °C for 30 min and warmed to room
temperature. After 1.5 h, the filtrate was concentrated to obtain
2-allyloxybenzoyl chloride 3. Then, 3 in THF (2 mL) was added
to a solution of SmI2 (0.1 M in THF, 21.1 mL, 2.11 mmol). The
mixture was stirred at room temperature for 30 min. Then, it was
extracted with Et2O after addition of 0.1 N aqueous HCl. The extract
was treated with water, saturated aqueous Na2S2O3, saturated
aqueous NaHCO3, and brine and dried over anhydrous MgSO4. The
residue obtained after concentration was subjected to column
chromatography on silica gel (EtOAc/benzene ) 1/1) to give 6a,7-
dihydrobenzo[b]cyclopropa[d]pyran-7a-ol 4 (58.6 mg, 0.36 mmol,
38%). Data for 3: brown oil; 1H NMR (270 MHz) δ 4.46 (m, 2H),
5.32 (m, 1H), 5.51 (m, 1H), 5.97-6.13 (m, 1H), 6.93-7.12 (m,
2H), 7.56 (m, 1H), 8.08 (m, 1H). Data for 4: brown oil; IR (Neat)
1
(Nujol) 3408, 1662 cm-1; H NMR (270 MHz) δ 1.44 (s, 3H),
1.88-2.10 (m, 2H), 2.15 (broad s, 1H), 2.93 (dd, J ) 15.8, 10.1
Hz, 1H), 2.96 (d, J ) 11.1 Hz, 1H), 3.81 (d, J ) 10.3 Hz, 1H),
3.09 (d, J ) 11.6 Hz, 1H), 3.27 (dd, J ) 16.7, 8.4 Hz, 1H), 7.27
(m, 2H), 7.40 (m, 1H), 7.78 (m, 1H); 13C NMR (68 MHz) δ 29.9,
31.1, 42.3, 55.9, 71.7, 126.4, 128.6, 130.2, 131.7, 138.1, 144.0,
200.5; LRMS (EI) m/z (relative intensity) 190 (M+, 0.3), 129 (100).
Data for 11:38 pale yellow oil; IR (Neat) 2912, 1664, 1598, 1282
1
cm-1; H NMR (270 MHz) δ 5.00 (t, J ) 1.5 Hz, 2H), 5.58 (d, J
) 0.8 Hz, 1H), 6.31 (d, J ) 1.1 Hz, 1H), 6.95-7.10 (m, 2H), 7.48
(m, 1H), 7.99 (m, 1H); 13C NMR (68 MHz) δ 71.2, 118.0, 121.8,
122.4, 127.9, 136.0, 138.7, 160.5, 161.8, 181.8; LRMS (EI) m/z
(relative intensity) 160 (M+, 100); HRMS (EI) calcd for C10H8O2
160.0524, found 160.0523. Data for 12: brown oil; IR (Neat) 1690,
1606, 1478 cm-1; 1H NMR (200 MHz) δ 2.98-3.11 (m, 1H), 3.38
(s, 3H), 3.64-3.83 (m, 2H), 4.42 (dd, J ) 11.4, 9.9 Hz, 1H), 4.63
(dd, J ) 11.4, 4.9 Hz, 1H), 6.95-7.05 (m, 2H), 7.47 (m, 1H), 7.89
(m, 1H); 13C NMR (50 MHz) δ 46.4, 59.2, 68.2, 69.0, 117.8, 120.8,
121.3, 127.2, 135.9, 161.7, 192.0; LRMS (EI) m/z (relative intensity)
192 (M+, 36), 120 (100); HRMS (EI) calcd for C11H12O3 192.0786,
found 192.0784.
One-Pot Reduction-Oxidation Reaction of r-Bromomethyl
Cycloalkanone. To a solution of SmI2 (0.1 M in THF, 11.0 mL,
1.10 mmol) was added 1 or 22 (0.50 mmol) in THF (1.0 mL), and
the mixture was stirred under N2 at room temperature. After 30
min, FeCl3 (1.10 mmol) and pyridine (0.50 mmol) in THF (5.0
mL) was added, and the mixture was stirred. After 1 h, the mixture
was stirred at reflux (85 °C) for 2 h. Then, it was extracted with
Et2O after addition of water. The extract was treated with water,
saturated aqueous Na2S2O3, saturated aqueous NaHCO3, and brine
and dried over anhydrous MgSO4. The residue obtained after
concentration was subjected to TLC (CH2Cl2/n-hexane ) 1/1), and
7 or 2339 was obtained. The same treatment of 3 with FeCl3 gave
a complicated mixture. Data for 19a: orange oil; IR (Neat) 1674
cm-1; 1H NMR (270 MHz) δ 1.30 (s, 3H), 2.03 (m, 1H), 2.23 (m,
1H), 2.98 (m, 1H), 3.33 (d, J ) 10.0 Hz, 1H), 3.61 (d, J ) 9.7 Hz,
1H), 7.20-7.35 (m, 2H), 7.47 (m, 1H), 8.04 (m, 1H); 13C NMR
(68 MHz) δ 16.2, 22.7, 25.4, 34.9, 45.0, 126.8, 128.1, 128.7, 130.9,
133.5, 143.0, 197.9; LRMS (EI) m/z (relative intensity) 300 (M+,
1
3336, 1256, 1206 cm-1; H NMR (270 MHz) δ 1.17 (t, J ) 6.1
Hz, 1H), 1.34 (dd, J ) 9.7, 5.4 Hz, 1H), 1.84 (m, 1H), 3.23 (broad
s, 1H), 3.79 (d, J ) 10.8 Hz, 1H), 4.15 (dd, J ) 10.5, 1.1 Hz, 1H),
6.81 (m, 1H), 6.98 (m, 1H), 7.10 (m, 1H), 7.57 (m, 1H); 13C NMR
(68 MHz) δ 18.1, 27.3, 51.8, 62.3, 116.8, 121.6, 124.3, 126.9, 129.4,
150.7; LRMS (EI) m/z (relative intensity) 162 (M+, 51), 120 (100);
HRMS (EI) calcd for C10H10O2 162.0681, found 162.0677.
Preparation of 1,1a,2,7b-Tetrahydro-7b-trimethylsilyloxy-
benzo[b]cyclopropa[d]pyran (5). To 4 (145 mg, 0.89 mmol) in
CH2Cl2 (3.0 mL) were added Et3N (0.37 mL, 2.68 mmol) and
Me3SiCl (0.27 mL, 2.14 mmol). The mixture was stirred at room
temperture for 30 min. Then, it was extracted with Et2O after
addition of water. The extract was treated with water, saturated
aqueous NaHCO3, and brine and dried over anhydrous MgSO4. The
residue obtained after concentration was subjected to column
chromatography on silica gel (EtOAc/n-hexane ) 1/10) to give
1,1a,2,7b-Tetrahydro-7b-trimethylsilyloxy-benzo[b]cyclopropa[d]-
pyran 5 (151.5 mg, 0.65 mmol, 73%). Data for 5: pale yellow oil;
(38) Crich, D.; Chen, C.; Hwang, J.; Yuan, H.; Papadatos, A.; Walter, R. I.
J. Am. Chem. Soc. 1994, 116, 8937–8951.
(39) Moritani, Y.; Appella, D. H.; Jurkauskas, V.; Buchwald, S. L. J. Am.
Chem. Soc. 2000, 122, 6797–6798.
1
IR (Neat) 2952, 1250, 1210, 834 cm-1; H NMR (270 MHz) δ
0.17 (s, 9H), 1.16 (t, J ) 5.8 Hz, 1H), 1.35 (dd, J ) 9.7, 5.4 Hz,
1H), 1.90 (m, 1H), 3.90 (d, J ) 10.3 Hz, 1H), 4.21 (d, J ) 10.5
2474 J. Org. Chem. Vol. 74, No. 6, 2009

Formation and Ring-Opening of Cyclopropanol DeriVatiVes
16), 145 (100); HRMS (EI) calcd for C12H13OI 300.0011, found
(m, 1H); 13C NMR (68 MHz) δ 33.2, 37.5, 46.7, 49.4, 62.1, 126.5,
300.0015. Data for 23:39 pale yellow oil; IR (Neat) 2932, 1658
128.9, 130.4, 131.9, 137.8, 143.8, 197.1.
1
cm-1; H NMR (270 MHz) δ 1.78 (m, 4H), 2.14-2.60 (m, 6H),
2.80 (m, 1H), 5.93 (s, 1H), 7.16-7.33 (m, 5H); 13C NMR (68 MHz)
d 21.2, 25.1, 32.8, 34.1, 42.2, 42.7, 126.0, 128.1, 128.3, 129.3,
140.6, 160.7, 203.6; LRMS (EI) m/z (relative intensity) 214 (M+,
48), 91 (100); HRMS (EI) calcd for C15H18O 214.1358, found
Acknowledgment. We are grateful to Professor Yasushi Ono
(Niigata University) for providing the information on electro-
chemical data. We also thank Professor Patrick S. Mariano
(University of New Mexico) for his valuable comments and
editing. This work was partly supported by a grant from the
Uchida Energy Science Promotion Foundation.
214.1360. Data for 8a:6f white solid, mp 56.2-60.3 °C; H NMR
1
(200 MHz) δ 1.78 (s, 3H), 2.02 (ddd, J ) 15.4, 10.3, 1.2 Hz, 1H),
2.55 (ddt, J ) 15.4, 8.1, 1.2 Hz, 1H), 3.05 (dd, J ) 17.0, 7.9 Hz,
1H), 3.12 (dd, J ) 11.7, 1.4 Hz, 1H), 3.41 (dd, J ) 17.8, 10.8 Hz,
1H), 3.53 (d, J ) 11.7 Hz, 1H), 7.24-7.46 (m, 3H), 7.79 (m, 1H);
13C NMR (50 MHz) δ 31.4, 32.4, 44.9, 57.6, 69.3, 126.6, 129.0,
130.3, 132.0, 137.8, 143.8, 198.0. Data for 20a: yellow oil; 1H NMR
(270 MHz) δ 1.70 (dd, J ) 15.9, 10.0 Hz, 1H), 2.18 (s, 3H), 2.90
(dd, J ) 15.9, 7.8 Hz, 1H), 3.03-3.12 (m, 1H), 3.23-3.35 (m,
1H), 3.80 (d, J ) 11.9 Hz, 1H), 7.30 (m, 2H), 7.42 (m, 1H), 7.77
1
Supporting Information Available: H NMR, 13C NMR,
and IR charts of new compounds; additional procedures for the
preparation of some intermediate compounds and their 1H NMR
data and charts. This material is available free of charge via
the Internet at http://pubs.acs.org.
JO802749G
J. Org. Chem. Vol. 74, No. 6, 2009 2475