Conjugate allylation of cyclic α,β-unsaturated esters

Article abstract of DOI:10.1055/s-2008-1077825

The conjugate allylation of a homologous series of α,β- unsaturated cyclic esters 8-10 by addition of diallylcuprate (method A), fluoride ion catalyzed addition of trimethylallylsilane (method B), and aluminium tris(2,6-diphenylphenoxide) (ATPH)-mediated addition of allyllithium (method C) was investigated. Method A was not selective in all cases. For methods B and C an influence of ester moiety and ring size on the regioselectivity was observed. Methyl cyclopentenoate 8c gave mainly the 1,2/1,2-product regardless the allylation method while tert-butyl and benzyl ester moieties favored the 1,4-products. For larger rings 9, 10 and the anellated system 19 methods B and C behave complementary depending on the ester function: Method B gave best results of 1,4-addition products for benzyl esters while method C worked better for tert-butyl esters. Thieme Stuttgart.

Full text of DOI:10.1055/s-2008-1077825

1618
LETTER
Conjugate Allylation of Cyclic a,b-Unsaturated Esters
Conjugate
Allylah
r
c
a
,
b
-
Un
i
saturate
s
dEsters tine Hofmann, Angelika Baro, Sabine Laschat*
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax +49(711)68564285; E-mail: sabine.laschat@oc.uni-stuttgart.de
Received 10 January 2008
an allylation reaction to an a,b-unsaturated bicy-
clo[3.3.0]octane precursor, because the conjugate addi-
tion of carbon nucleophiles to a,b-unsaturated carbonyl
compounds is one of the most valuable transformations in
Abstract: The conjugate allylation of a homologous series of a,b-
unsaturated cyclic esters 8–10 by addition of diallylcuprate (method
A), fluoride ion catalyzed addition of trimethylallylsilane (method
B), and aluminium tris(2,6-diphenylphenoxide) (ATPH)-mediated
addition of allyllithium (method C) was investigated. Method A organic synthesis and has been intensively investigated.4
was not selective in all cases. For methods B and C an influence of
ester moiety and ring size on the regioselectivity was observed.
Surprisingly, the conjugate allyl transfer to cyclic a,b-un-
saturated esters with exocyclic ester moiety has been rare-
Methyl cyclopentenoate 8c gave mainly the 1,2/1,2-product regard-
ly explored. For example, Majetich5 compared the
less the allylation method while tert-butyl and benzyl ester moieties
fluoride ion catalyzed addition of trimethylallylsilane
favored the 1,4-products. For larger rings 9, 10 and the anellated
system 19 methods B and C behave complementary depending on
(Sakurai conditions)6,7 to various Michael acceptors with
the addition of lithium diallylcuprate, which is well
known8 and successfully utilized for acyclic enoates.9 An
interesting method applied to acyclic chiral a,b-unsaturat-
ed esters was the stereo- and regioselective addition of al-
lyllithium in the presence of the bulky Lewis acid
aluminium tris(2,6-diphenylphenoxide) (ATPH).10,11
However, reliable allylation methods for cyclic deriva-
tives are missing. Therefore, we studied this issue in more
detail using five- to seven-membered cycloalkenoates as
model compounds in order to find an efficient procedure
for the preparation of target pentalene 4. The results are
reported below.
the ester function: Method B gave best results of 1,4-addition prod-
ucts for benzyl esters while method C worked better for tert-butyl
esters.
Key words: conjugate allylation, cycloalkenecarboxylates, regio-
selectivity, pentalene
The functionalized bicyclo[3.3.0]octane (pentalene) sys-
tem is a common structural motif in a large number of nat-
ural products and pharmaceuticals, for example,
carbacyclin (1), diquinanes, such as neorogiolane (2) or
the macrolactam cylindramide (3, Scheme 1).1,2
The required a,b-unsaturated cyclic esters 8–10
(Scheme 2) were prepared from the respective acids 5–7,
which were accessible according to literature proce-
dures.12–15 Esterification of 5–7 in CH2Cl2 with t-BuOH in
the presence of H2SO4 and anhydrous magnesium
sulfate16 yielded the esters 8a–10a, and reaction of acids
5–7 with benzylic alcohol in the presence of DCC and
DMAP17 gave the benzyl esters 8b–10b in good yield.
Methyl cyclopentenoate 8c is commercially available.
CO2H
O
H
H
HN
HO
HO
H
H
H
O
H
NH
HO
C5H11
H
O
1
3
OH
H
2
CO2t-Bu
CO2H
CO2Bn
H
CH2Cl2, r.t., 16 h
CH2Cl2, r.t., 16 h
O
BnOH, DMAP
DCC
t-BuOH, MgSO4
H2SO4
n
n
n
O
H
CO2Bn
4
8a 28%
9a 31%
10a 24%
5 n = 0
6 n = 1
7 n = 2
8b 98%
9b 84%
10b 87%
8
9
10
n = 0
1
2
Scheme 1
Scheme 2
Consequently, a variety of different strategies to substitut-
ed pentalenes has been reported.1b,3 During a modified
route to cylindramide (3) we were faced with the selective
preparation of pentalene derivative 4 with allylic side
chain as a key building block (Scheme 1). We envisaged
Next, we investigated the allylation of cyclopentenoates
8a–c via lithium diallylcuprate addition, Sakurai reaction,
and ATPH-assisted addition of allyllithium (methods A–
C, Scheme 3). The results of the comparative studies are
listed in Table 1.
As can be seen from Table 1, the addition of diallylcu-
prate formed in situ from the Grignard reagent and Cu-
Br·DMS (method A)9a to cyclopentenoates 8a–c either
SYNLETT 2008, No. 11, pp 1618–1622
Advanced online publication: 11.06.2008
DOI: 10.1055/s-2008-1077825; Art ID: G00708ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
8

LETTER
Conjugate Allylation of Cyclic a,b-Unsaturated Esters
1619
in the case of method C, where the allylation of 8a,b pro-
ceeded quantitatively, and the 1,4-addition adducts 11a
and 11b were obtained in 75 and 68% yield, respectively,
with similar diastereomeric ratios (entries 8, 9). The de-
crease of yield is due to tedious chromatographic separa-
tion of 2,6-diphenylphenol from 11. The results obtained
for benzyl ester 8b resemble those reported by Majetich.5
[M]
method A–C
+ 8
CO2R
CO2R
11a–c
+
(see Table 1)
OH
8a–c
12
A: CuBr·DMS, allylMgBr, THF
B: allylSiMe3/HMPA (1:1), TBAF
C: allylSnBu3, BuLi, ATPH
8, 11
R
a
b
c
t-Bu Bn Me
In order to determine the relative configuration, 1,4-ally-
lation product 11a with dr = 70:30 was submitted to ozo-
nolysis followed by reductive workup in MeOH, CH2Cl2,
and pyridine (4:4:1) giving alcohol 13,21 which was cy-
clized to the lactone 14 in 65% yield (Scheme 4). Com-
parison of its NMR spectra with literature data22 revealed
a trans/cis ratio of 73:27.
Scheme 3
yielded product mixtures in favor of the 1,2/1,2-product
1218 or, in the case of tert-butyl ester 8a, only unreacted
starting material was detected (entries 1–3). When the al-
lylations were performed under Sakurai conditions in the
presence of TBAF (method B)19 or under Yamamoto con-
ditions in the presence of ATPH (method C),20 the regio-
selectivity, that is, 1,4- versus bis-1,2-addition, was found
to be dependent on the ester moiety (entries 4–9). Where-
as methyl cyclopentenoate 8c gave preferably the 1,2/1,2-
addition product 12 by using method B (entry 4), the cor-
responding tert-butyl and benzyl esters 8a,b favored for-
mation of the desired 1,4-products 11a,b (entries 5, 6).
The effect of the ester moiety was even more pronounced
O
Ot-Bu
O
O
O3, NaBH4
MeOH–CH2Cl2–py
(4:4:1)
HO
TsOH
CH2Cl2
11a
dr = 70:30
–78 °C to r.t., 3 h
74%
reflux, 14 h
65%
H
13
14
trans/cis = 73:27
Scheme 4
Table 1 Allylation of cyclic a,b-unsaturated esters 8–10 under various conditions
Product ratio (%)a
Entry
1
Ester
8c
R =
Me
Bn
Method Temp (°C)
Time (h)
5
Ester
4
1,2/1,2-Product 1,4-Product
dra
Yield (%)
A
A
A
B
B
B
C
C
C
B
B
C
C
B
B
C
C
–78 to –10
–78 to –10
–78 to r.t.
0
85 (12)
11 (11c)
13 (11b)
–
–
2
8b
4
–
87 (12)
–
3
8a
t-Bu
Me
Bn
6
100
–
–
–
4
8c
0.5
86 (12)
14 (11c)
60 (11b)
37 (11a)
16 (11c)
100 (11b)
100 (11a)
97 (15b)
14 (15a)
3 (15b)
–
5
8b
0
10 min
20 min
0.5
–
40 (12)
94:6
79:21
–
47 (11b)
6
8a
t-Bu
Me
Bn
0
36
24
–
27 (12)
7
8c
–78
60 (12)
8
8b
–78
0.75
0.75
1, 16
1, 16
4
–
71:29
70:30
67:33
75:25
–
68 (11b)
75 (11a)b
67 (15b)
9
8a
t-Bu
Bn
–78
–
–
10
11
12
13
14
15
16
17
9b
0, r.t.
0, r.t.
–78
3
–
9a
t-Bu
Bn
86
62
–
–
9b
35 (17)
9a
t-Bu
Bn
–78
2.5
–
100 (15a)
78 (16b)
47 (16a)
21 (16b)
100 (16a)
80:20
84:16
80:20
80:20
79:21
78 (15a)b
59 (16b)c
30 (16a)
10b
10a
10b
10a
0 to r.t.
0, r.t.
–78 to r.t.
–78
36
22
53
46
–
–
t-Bu
Bn
2, 16
5
–
33 (18)
t-Bu
2
–
80 (16a)
a Product ratio and diastereomeric ratio were determined by GC.
b Tedious chromatographic separation of 2,6-diphenylphenol from products 11a and 15a, respectively, due to similar polarities caused a de-
crease of yields with regard to quantitative conversion.
c Due to similar polarities starting material 10b and product 16b were difficult to separate by chromatography, resulting in decreased yields
with regard to conversion.
Synlett 2008, No. 11, 1618–1622 © Thieme Stuttgart · New York

1620
C. Hofmann et al.
LETTER
Due to the poor results of allylcuprate addition, only the
conditions of method B and C were applied to the esters 9
and 10 with increased ring size (Scheme 5, Table 1).19,20
The results in Table 1 reveal that for six- and seven-mem-
bered esters 9, 10 methods B and C behave somewhat
complementary depending on the ester moiety. For exam-
ple, benzyl cyclohexenoate 9b was cleanly converted into
the 1,4-product 15b in 67% yield employing method B
(entry 10), whereas unreacted tert-butyl cyclohexenoate
9a was detected as the major product besides the 1,4-ad-
duct 15a (entry 11). In contrast, by using method C benzyl
ester 9b gave only trace amounts of the desired product
15b (entry 12), the tert-butyl ester 9a, however, produced
the 1,4-product 15a quantitatively (entry 13). A similar
behavior was observed for cycloheptenoates 10a,b (en-
tries 14–17).
H
H
H
H
O
O
method B
method C
+
19
OBn
O
OBn
O
O
O
O
O
19
+
4 54%, dr = 89:11
[M]
H
O
H
20 70%
Scheme 6
clopentenoates 8a,b yielded preferably the 1,4-products
11a,b. For cyclohexenoates 9, cycloheptenoates 10, and
pentalene ester 19 the fluoride-ion-catalyzed addition of
trimethylallylsilane gave mainly the desired 1,4-products
15, 16, and 4 if the benzyl esters were employed. In con-
trast, for the corresponding tert-butyl esters 9a and 10a
the ATPH-mediated allylation was required to obtain
good yields of the 1,4-addition adducts 15 and 16.
method B
SiMe3
CO2R
CO2R
+
9, 10
HMPA, TBAF
(see Table 1)
n
n
9a,b
10a,b
15a,b n = 1
16a,b n = 2
Acknowledgment
method C
, ATPH, BuLi
SnBu3
15, 16 R
This work was generously supported by the Deutsche Forschungs-
gemeinschaft, the Fonds der Chemischen Industrie, and the Mini-
sterium für Wissenschaft, Forschung und Kunst des Landes Baden-
Württemberg (Landesgraduierten fellowship for C.H.). We would
like to thank Fabian Sander for his contribution to the experimental
part, and the referees for valuable suggestions and comments.
a
b
t-Bu
Bn
OH
+
9, 10
15, 16
+
n
17 n = 1
18 n = 2
Scheme 5
References and Notes
(1) Reviews on polyquinanes: (a) Mehta, G.; Srikrishna, A.
Chem. Rev. 1997, 97, 671. (b) Fu, X.; Cook, J. M.
Aldrichimica Acta 1992, 25, 43. (c) Paquette, L. A. Top.
Curr. Chem. 1984, 119, 1. (d) Ramaiah, M. Synthesis 1984,
529. (e) Trost, B. M. Chem. Soc. Rev. 1982, 11, 141.
(f) Paquette, L. A. Top. Curr. Chem. 1979, 79, 41. (g) For
neorogiolane, see: Srikrishna, A.; Gowri, V. Tetrahedron:
Asymmetry 2007, 18, 1663. (h) For tetramic acid lactams,
see: Capon, R. J.; Skene, C.; Lacey, E.; Gill, J. H.;
Wadsworth, D.; Friedel, T. J. Nat. Prod. 1999, 62, 1256.
(2) For cylindramide, see: (a) Cramer, N.; Buchweitz, M.;
Laschat, S.; Frey, W.; Baro, A.; Mathieu, D.; Richter, C.;
Schwalbe, H. Chem. Eur. J. 2006, 12, 2488. (b)Cramer,N.;
Laschat, S.; Baro, A.; Schwalbe, H.; Richter, C. Angew.
Chem. Int. Ed. 2005, 44, 820; Angew. Chem. 2005, 117,
831. (c) Kanazawa, S.; Fusetani, N.; Matsunaga, S.
Tetrahedron Lett. 1993, 34, 1065.
(3) Some selected examples: (a) Harrington-Frost, N. M.;
Pattenden, G. Tetrahedron Lett. 2000, 41, 403. (b)Jasperse,
C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91, 1237.
(c) Seo, J.; Fain, H.; Blanc, J.-B.; Montgomery, J. J. Org.
Chem. 1999, 64, 6060. (d) Saitoh, F.; Mori, M.; Okamura,
K.; Date, T. Tetrahedron 1995, 51, 4439. (e) Piers, E.;
Orellana, A. Synthesis 2001, 2138. (f) Laschat, S.;
Becheanu, A.; Bell, T.; Baro, A. Synlett 2005, 2547.
(g) Anderl, T.; Emo, M.; Laschat, S.; Baro, A.; Frey, W.
Synthesis 2008, 1619.
Next, methods B and C were applied to the allylation of
the a,b-unsaturated pentalene precursor 19
(Scheme 6).23,24 Under the conditions of method B the
1,4-addition to compound 19 was predominant, providing
the desired pentalene 4 in 54% yield (referred to re-isolat-
ed 19) with a diastereomeric ratio of 89:11 in favor of the
trans isomer, as assigned by analogy (see Scheme 4). Be-
cause compound 19 was employed as enantiomerically
pure starting material no trace of the two other possible
diastereomers were found. Ester 19 was re-isolated in
43%. The ATPH-mediated allylation, however, did not af-
ford any 1,4-addition adduct 4, but the 1,2-product 20.
This result indicates that benzyl cyclohexene- (9b) and
cycloheptenecarboxylate (10b) provide much better mod-
els for the reactivity of the pentalene-derived benzyl ester
19 with regard to allylation than benzyl cyclopentenoate
8b.
In conclusion, the conjugate allylation of cyclic esters 8–
10 was influenced by the ester moiety and the ring size.
For cyclopentenecarboxylates 8 the regioselectivity of the
allylation was found to be dependent on the ester moiety.
Whereas methyl ester 8c gave the 1,2/1,2-product 12 re-
gardless the described method, tert-butyl and benzyl cy-
Synlett 2008, No. 11, 1618–1622 © Thieme Stuttgart · New York

LETTER
Conjugate Allylation of Cyclic a,b-Unsaturated Esters
1621
(4) Reviews: (a) Vicario, J. L.; Badia, D.; Carrillo, L. Synthesis
2007, 2065. (b) Christoffers, J.; Koripelly, G.; Rosiak, A.;
Rössle, M. Synthesis 2007, 1279. (c) Tsogoeva, S. B. Eur. J.
Org. Chem. 2007, 1701. (d) Lopez, F.; Feringa, B. L. In
Asymmetric Synthesis; Christmann, M.; Bräse, S., Eds.;
Wiley-VCH: Weinheim, 2007, 78–83. (e) Almaşi, D.;
Alonso, D. A.; Nájera, C. Tetrahedron: Asymmetry 2007, 18,
299. (f) Guo, H.-C.; Ma, J.-A. Angew. Chem. Int. Ed. 2006,
45, 354; Angew. Chem. 2006, 118, 362. (g) Alexakis, A. In
Transition Metals for Organic Synthesis, 2nd ed.; Beller, M.;
Bolm, C., Eds.; Wiley-VCH: Weinheim, 2004, 553–562.
(h) Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829.
(i) Dilman, A. D.; Ioffe, S. L. Chem. Rev. 2003, 103, 733.
(j) Alexakis, A.; Benhaim, C. Eur. J. Org. Chem. 2002,
3221. (k) Feringa, B. L.; Naasz, R.; Imbos, R.; Arnold, L. A.
In Modern Organocopper Chemistry; Krause, N., Ed.;
Wiley-VCH: Weinheim, 2002, 224–258. (l) Sibi, M. P.;
Manyem, S. Tetrahedron 2000, 56, 8033. (m)Feringa, B. L.
Acc. Chem. Res. 2000, 33, 346.
(19) General Procedures for the Allylation According
Method B
In a Schlenk flask 4 Å MS (2.00 g) and TBAF (1.31 g, 0.50
mmol) were dried under high vacuum for 30 min. Under N2
atmosphere DMF (15 mL) was added, the mixture stirred for
30 min, transferred via cannula in a Schlenk flask with 4 Å
MS (2.00 g), and stirred for a further 30 min. A solution of
the respective ester (1 mmol) in DMF (5 mL) was added
followed by HMPA (1.04 mL, 1.07 g, 6.00 mmol) and a
solution of trimethylallylsilane (0.95 mL, 685 mg, 6.00
mmol) in DMF (5 mL) at 0 °C. After stirring at 0 °C for 10
min, 1 N HCl in MeOH (5 mL) and H2O (40 mL) were
successively added, and the aqueous layer was extracted
with EtOAc (2 × 100 mL). The combined organic layers
were dried (MgSO4), concentrated under vacuum, and the
crude product was chromatographed on SiO2 with hexanes–
EtOAc.
Benzyl 2-Allylcyclohexanecarboxylate (15b)
Rf = 0.37 (hexanes–EtOAc, 10:1). 1H NMR (500 MHz,
CDCl3): d = 0.89–0.98 (m, 1.5 H, CH2), 1.14–2.03 (m, 13.5
H, Ha-1¢, Ha*-1¢, H-2, H*-2, H-3, H*-3, H-4, H*-4, H-5, H*-
5, H-6, H*-6), 2.06–2.16 (m, 2.5 H, Hb-1¢, Hb*-1¢, H-1), 2.65
(dt, J = 8.1, 4.1 Hz, 0.5 H, H*-1) 4.90–4.98 (m, 2 H, H-3¢),
5.06–5.15 (m, 3 H, ArCH2, ArCH2*), 5.65–5.76 (m, 1.5 H,
H-2¢, H*-2¢), 7.29–7.38 (m, 7.5 H, Ar, Ar*) ppm. 13C NMR
(125 MHz, CDCl3): d = 22.6*, 23.8*, 25.4, 25.4*, 25.6,
28.0*, 30.1, 30.8 (C-3, C-4, C-5, C-6), 37.2*, 38.7 (C-2),
34.9*, 39.3 (C-1¢), 44.8*, 49.4 (C-1), 65.8*, 65.9 (ArCH2),
115.9*, 116.3 (C-3¢), 128.09*, 128.1, 128.1*, 128.2, 128.5,
128.5* (Ar), 136.0, 136.1* (Ar), 136.3, 137.3* (C-2¢),
174.6*, 175.9 (CO) ppm. (* denotes minor diastereomer).
FT-IR (ATR): 2319 (s), 2856 (s), 2360 (s), 1732 (vs), 1259
(s), 1164 (s), 749 (vs) cm–1. MS (ESI): m/z (%) = 241 (15)
(5) Majetich, G.; Casares, A.; Chapman, D.; Behnke, M. J. Org.
Chem. 1986, 51, 1745.
(6) (a) Jacques, T.; Marko, I. E.; Pospisil, J. In Multicomponent
Reactions; Zhu, J.; Bienayme, H., Eds.; Wiley-VCH:
Weinheim, 2005, 398–452. (b) Hosomi, A.; Miura, K. Bull.
Chem. Soc. Jpn. 2004, 77, 835. (c) Bianchini, C.;
Glendenning, L. Chemtracts: Inorg. Chem. 1995, 7, 107.
(d) Schinzer, D. Synthesis 1988, 263. (e) Hosomi, A.;
Shirahata, A.; Sakurai, H. Tetrahedron Lett. 1978, 3043.
(f) Hosomi, A.; Sakurai, H. J. Am. Chem. Soc. 1977, 99,
1673. (g) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976,
1295.
(7) For cyclic enones and acyclic enoates, see also: Kuhnert, N.;
Peverley, J.; Robertson, J. Tetrahedron Lett. 1998, 39, 3215.
(8) Selected examples: (a) Rossiter, B. E.; Swingle, N. M.
Chem. Rev. 1992, 92, 771. (b) Hutchinson, D. K.; Fuchs, P.
L. Tetrahedron Lett. 1986, 27, 1429. (c) House, H. O.;
Fischer, W. F. J. Org. Chem. 1969, 34, 3615.
[M+ – O], 223 (36), 131 (28), 117 (20), 91 (71) [C7H7 ].
HRMS (ESI): m/z calcd for C17H22NaO2 [M + Na]:
281.1512; found: 281.1503.
+
Benzyl (3a¢R,4¢R,5¢R,6a¢S)-4¢-Allylhexahydro-2¢H-
spiro[1,3-dioxolane-2,1¢-pentalene]-5¢-carboxylate (4)
Rf = 0.58 (hexanes–EtOAc, 6:1); [a]D20 +23 (c 1.00,
CH2Cl2). 1H NMR (500 MHz, CDCl3): d = 1.45 (ddd,
J = 12.6, 7.3, 2.7 Hz, 1 H, Ha-2¢), 1.66–1.71 (m, 1 H, Ha-3¢),
1.74–1.87 (m, 2 H, Ha-6, Hb-2¢), 1.89–1.98 (m, 2 H, H-4¢, Hb-
3¢), 2.04 (ddd, J = 12.9, 8.6, 6.3 Hz, 1 H, Hb-6¢), 2.10–2.27
(m, 3 H, H-1¢¢, H-3a¢), 2.35–2.44 (m, 2 H, H-5¢, H-6a¢), 3.79–
3.98 (m, 4 H, OCH2CH2O), 5.09 (d, J = 5.3 Hz, 2 H, CH2Ph),
4.92 (ddt, J = 10.0, 2.1, 1.0 Hz, 1 H, Ha-3¢¢), 4.98 (ddt,
J = 17.1, 2.1, 1.4 Hz, 1 H, Hb-3¢¢), 5.73 (ddt, J = 17.1, 10.0,
7.2 Hz, 1 H, H-2¢¢), 7.28–7.38 (m, 5 H, Ph) ppm. 13C NMR
(125 MHz, CDCl3): d = 27.8 (C-2¢), 32.9, 33.1 (C-6¢, C-3¢),
37.8 (C-1¢¢), 46.7 (C-3a¢), 48.9, 51.1 (C-5¢, C-6a¢), 50.4 (C-
4¢), 63.8, 64.8 (OCH2CH2O), 66.1 (CH2Ph), 116.3 (C-3¢¢),
118.2 (C-1¢), 127.6, 128.1, 128.2 (Ph), 136.1 (CH2Ph), 136.4
(C-2¢¢), 174.6 (CO) ppm. FT-IR (ATR): 2946 (w), 2880 (w),
2362 (w), 2342 (w), 1455 (w), 1338 (w), 1152 (s), 1023 (s),
697 (s) cm–1. GC-MS (EI): m/z (%) = 342 (2) [M+], 301 (8)
[M+ – C3H5], 251 (6) [M+ – C7H7], 223 (6), 207 (14) [M+ –
CO2CH2C6H5], 107 (10) [C7H7O+], 99 (100), 91 (30)
(9) (a) Hon, Y.-S.; Chen, F.-L.; Huang, Y.-P.; Lu, T.-J.
Tetrahedron: Asymmetry 1991, 2, 879. (b) Scolastico, C.
Pure Appl. Chem. 1988, 60, 1689. (c) Bernardi, A.;
Cardani, S.; Pilati, T.; Poli, G.; Scolastico, C.; Villa, R. J.
Org. Chem. 1988, 53, 1600. (d) Bernardi, A.; Cardani, S.;
Poli, G.; Scolastico, C. J. Org. Chem. 1986, 51, 5041.
(10) Ito, H.; Nagahara, T.; Ishihara, K.; Saito, S.; Yamamoto, H.
Angew. Chem. Int. Ed. 2004, 43, 994; Angew. Chem. 2004,
116, 1012.
(11) (a) Ooi, T.; Kondo, Y.; Maruoka, K. Angew. Chem., Int. Ed.
Engl. 1997, 36, 1183; Angew. Chem. 1997, 109, 1231.
(b) Ooi, T.; Miura, T.; Kondo, Y.; Maruoka, K. Tetrahedron
Lett. 1997, 38, 3947. (c) Maruoka, K.; Imoto, H.; Saito, S.;
Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 4131.
(12) Brown, J. B.; Henbest, H. B.; Jones, E. R. H. J. Chem. Soc.
1950, 3634.
(13) Banwell, M. G.; Corbett, M.; Gulbis, J.; Mackay, M. F.;
Reum, M. E. J. Chem. Soc., Perkin Trans. 1 1993, 945.
(14) Naya, A.; Sagara, Y.; Ohwaki, K.; Saeki, T.; Ichikawa, D.;
Iwasawa, Y.; Noguchi, K.; Ohtake, N. J. Med. Chem. 2001,
44, 1429.
(15) Yang, F.; Newsome, J. J.; Curran, D. P. J. Am. Chem. Soc.
2006, 128, 14200.
+
[C7H7 ]. HRMS (ESI): m/z calcd for C21H26O4Na [M + Na]:
365.1723; found: 365.1722.
(20) General Procedures for the Allylation According
Method C
(16) Wright, S. W.; Hageman, D. L.; Wright, A. S.; McClure, L.
D. Tetrahedron Lett. 1997, 38, 7345.
(17) Collon, S.; Kouklovsky, C.; Langlois, Y. Eur. J. Org. Chem.
2002, 3566.
Trimethyl aluminium (1.10 mL, 1 M in hexane, 1.10 mmol)
was slowly added to a solution of 2,6-diphenylphenol (813
mg, 3.30 mmol) in toluene (6 mL) in a Schlenk flask, and the
mixture stirred at r.t. for 30 min. Then a solution of the
respective ester (1.00 mmol) in toluene (3 mL) was added.
After 5 min, the mixture was cooled to –78 °C and stirred for
(18) The initial 1,2-adduct, an enone, is capable of further 1,2-
addition, giving the tertiary alcohol.5
Synlett 2008, No. 11, 1618–1622 © Thieme Stuttgart · New York

1622
C. Hofmann et al.
LETTER
1 h. In a further flask n-BuLi (0.88 mL, 1.6 M in hexane,
1.40 mmol) was slowly added to a solution of allyltributyltin
(0.43 mL, 463 mg, 1.40 mmol) in THF (4 mL) at –78 °C, and
after stirring for 45 min, this allyllithium solution was
transferred via cannula to the solution of the ATPH complex,
and the reaction mixture stirred at –78 °C for a further 45
min. The reaction was quenched with MeOH (10 mL) and 1
N HCl (5 mL), and the aqueous layer extracted with Et2O (50
mL). The organic layer was separated, dried (MgSO4),
concentrated, and the crude product chromatographed on
SiO2 with hexanes–EtOAc (50:1).
J = 12.1, 10.7, 9.1, 6.5 Hz, 1 H, Hb-3¢), 2.59–2.68 (m, 2 H,
Ha-6¢, H-6a¢), 2.76 (dddd, J = 12.6, 2.9, 1.9, 1.9 Hz, 1 H, Hb-
6¢), 3.44 (dddd, J = 6.7, 2.2, 1.4, 1.4 Hz, 2 H, CH2CH=CH2),
3.44–3.51 (m, 1 H, H-3a¢), 3.85–3.95 (m, 4 H, OCH2CH2O),
5.09–5.20 (m, 2 H, CH2CH=CH2), 5.96 (ddt, J = 17.2, 10.3,
6.7 Hz, 1 H, CH2CH=CH2), 6.52 (dddd, J = 3.7, 1.9, 1.9, 0.9
Hz, 1 H, H-4¢) ppm. 13C NMR (125 MHz, CDCl3): d = 27.7
(C-3¢), 32.9 (C-6¢), 33.4 (C-2¢), 44.2 (CH2CH=CH2), 46.3
(C-6a¢), 49.6 (C-3a¢), 63.9, 64.9 (OCH2CH2O), 118.2
(CH2CH=CH2), 127.7 (C-1¢), 131.4 (CH=), 143.6 (C-5¢),
145.3 (C-4¢), 197.6 (CO) ppm. FT-IR (ATR): 2952 (s), 2875
(s), 1665 (vs), 1617 (s), 1202 (s), 1105 (vs), 1028 (vs), 993
(s), 914 (s), 735 (s) cm–1. MS (ESI): m/z (%) = 257 (100)
[M + Na], 235 (6) [M + H], 211 (8), 193 (16) [M+ – C3H5],
173 (8), 149 (76) [C11H17+], 131 (8), 121 (8) [C9H13+], 105
(16), 99 (8). HRMS (ESI): m/z calcd for C14H19O3 [M + H]:
235.1329; found: 235.1320.
tert-Butyl 2-Allylcyclopentanecarboxylate (11a)
Rf = 0.74 (hexanes–EtOAc, 10:1). 1H NMR (300 MHz,
CDCl3): d = 1.21–1.27 (m, 1 H, Ha-3), 1.44 [s, 9 H,
C(CH3)3], 1.45 [s, 4.5 H, C(CH3)3*], 1.49–1.54 (m, 1 H, Ha*-
4, Ha*-3), 1.58–1.69 (m, 2 H, H-4), 1.70–2.00 (m, 5.5 H, Hb-
3, H-5, Ha*-1¢, Hb*-3, Hb*-4, H*-5), 2.02–2.09 (m, 1 H, Ha-
1¢), 2.09–2.18 (m, 1.5 H, H-2, H*-2), 2.19–2.29 (m, 2.5 H,
H-1, Hb-1¢, Hb*-1¢), 2.78 (ddd, J = 7.8, 7.8, 5.6 Hz, 0.5 H,
H*-1), 4.95–5.05 (m, 3 H, H-3¢, H*-3¢), 5.75–5.86 (m, 1.5 H,
H-2¢, H*-2¢) ppm. 13C NMR (75 MHz, CDCl3): d = 23.5*,
24.6 (C-4), 28.1, 28.2* [C(CH3)3], 28.3*, 30.2 (C-5), 30.7*,
32.1 (C-3), 35.4*, 39.3 (C-1¢), 43.3*, 43.7 (C-2), 48.4*, 50.7
(C-1), 79.8, 80.0* [C(CH3)3], 115.3*, 115.6 (C-3¢), 137.3,
137.9* (C-2¢), 174.8*, 175.8 (CO) ppm. (* denotes minor
diastereomer). FT-IR (ATR): 1723 (s), 1365 (s), 1256 (s),
1144 (vs) cm–1. GC-MS (EI): m/z (%) = 210 (1) [M+], 154
(60) [M+ – C(CH3)], 137 (28) [M+ – OCMe3], 109 (56)
(21) tert-Butyl 2-(2-Hydroxyethyl)cyclopentane-
carboxylate (13)
Ozone was passed through a solution of 11a (70 mg, 0.33
mmol) in MeOH–CH2Cl2–pyridine (4:4:1) at –78 °C. Then
N2 was passed for 1 min, NaBH4 (33 mg, 0.84 mmol) was
added, and the reaction mixture warmed to 0 °C and stirred
for 3 h. After quenching with a sat. NH4Cl soln (5 mL), the
reaction mixture was extracted with EtOAc (20 mL). The
combined organic layers were washed with brine (10 mL),
dried (MgSO4), and concentrated under vacuum. The residue
was chromatographed on SiO2 with hexanes–EtOAc (3:1,
Rf = 0.34) to give 13 as a colorless oil (52 mg, 74%, dr
67:33). 1H NMR (500 MHz, CDCl3): d = 1.18–1.28 (m, 1 H,
Ha-3), 1.45 [s, 13.5 H, C(CH3)3, C(CH3)3*], 1.52–1.96 (m,
11 H, H-1¢, H*-1¢, Hb-3, H*-3, H-4, H*-4, H-5, H*-5), 2.11–
2.25 (m, 1.5 H, H-2, H-2*), 2.29 (dt, J = 8.8, 7.8 Hz, 1 H, H-
1), 2.76 (dt, J = 7.8, 4.6 Hz, 0.5 H, H*-1), 3.60–3.76 (m, 3 H,
H-2¢, H*-2¢) ppm. 13C NMR (125 MHz, CDCl3): d = 23.6*,
24.8 (C-4), 28.1, 28.2* [C(CH3)3], 28.5*, 30.6 (C-5), 31.2*,
33.3 (C-3), 34.1*, 38.4 (C-1¢), 40.2, 40.6* (C-2), 48.4, 50.9
(C-1), 61.6, 62.2 (C-2¢), 80.2*, 80.3 [C(CH3)3], 175.1*,
175.5 (CO) ppm. FT-IR (ATR): 2935 (s), 2871 (s), 1722
(vs), 1366 (s), 1145 (vs), 1051 (s), 847 (s) cm–1. GC-MS
(EI): m/z (%) = 184 (1), 158 (18) [M+ – C(CH3)], 141 (44)
[M+ – OCMe3], 129 (12), 112 (8) [M+ – CO2CMe3], 95 (50),
+
[M+ – CO2CMe3], 67 (32), 57 (100) [C4H9 ]. HRMS (ESI):
m/z calcd for C13H22NaO2 [M + Na]: 233.1512; found:
233.1510.
tert-Butyl 2-Allylcycloheptanecarboxylate (16a)
Rf = 0.68 (hexanes–EtOAc, 10:1). 1H NMR (500 MHz,
CDCl3): d = 1.25–1.34 (m, 1 H, Ha-3), 1.37–1.51 (m, 3 H,
Ha-4, CH2), 1.46 [s, 9 H, C(CH3)3], 1.53–1.75 (m, 6 H, Hb-3,
Hb-4, H-7, CH2), 1.89–1.99 (m, 2 H, Ha-1¢, H-2), 2.00–2.22
(m, 2 H, H-1, Hb-1¢), 4.96–5.04 (m, 2 H, H-3¢), 5.72–5.81
(m, 1 H, H-2¢) ppm. 13C NMR (125 MHz, CDCl3): d = 26.1,
26.2, 26.3*, 26.5* (C-5, C-6), 28.1, 28.2* [C(CH3)3], 28.3*,
29.3 (C-4), 28.6*, 30.3 (C-7), 30.7, 30.7* (C-3), 37.7*, 40.6
(C-1¢), 40.2*, 40.5 (C-2), 48.2*, 51.8 (C-1), 79.7, 79.8*
[C(CH3)3], 115.7*, 116.3 (C-3¢), 137.1, 138.0* (C-2¢),
175.1*, 176.4 (CO) ppm. FT-IR (ATR): 2923 (s), 1723 (vs),
1366 (s), 1142 (vs), 910 (s) cm–1. GC-MS (EI): m/z
(%) = 238 (4) [M+], 181 (100) [M+ – CMe3], 165 (24) [M+ –
OCMe3], 140 (14), 136 (16) [M+ – CO2CMe3], 122 (10), 109
+
+
67 (16), 57 (100) [C4H9 ], 41 (18) [C3H5 ]. HRMS (ESI):
m/z calcd for C12H22NaO3 [M + Na]: 237.1461; found:
237.1453.
(22) Tsunoi, S.; Ryu, I.; Okuda, T.; Tanaka, M.; Komatsu, M.;
Sonoda, N. J. Am. Chem. Soc. 1998, 120, 8692.
(23) Compound 19 was obtained from enantiomerically pure
pentalene-1,4-dione monoacetal1b via a-acylation, reduction
of the carbonyl group, and subsequent dehydration
following the method by Burgess.24
+
(20), 95 (56), 81 (24), 67 (12), 57 (90) [C4H9 ], 41 (24)
+
[C3H5 ], 29 (10). HRMS (ESI): m/z calcd for C15H27O2 [M +
H]: 239.2006; found: 239.2017.
1-{(3a¢R,6a¢S)-3¢,3a¢6¢,6a¢-tetrahydro-2¢H-spiro[1,3-
dioxolane-2,1¢-pentalen]-5¢-yl}but-3-en-1-one (20)
Rf = 0.38 (hexanes–EtOAc, 6:1). 1H NMR (500 MHz,
CDCl3): d = 1.54–1.72 (m, 3 H, Ha-3¢, H-2), 1.98 (dddd,
(24) Burgess, E. M.; Penton, H. R.; Taylor, E. A. J. Org. Chem.
1973, 38, 26.
Synlett 2008, No. 11, 1618–1622 © Thieme Stuttgart · New York