Enantioselective Synthesis of a Polyfunctionalized Tetracycle Related to Pentacyclic Triterpenes by Using an Anionic Cycloaddition Reaction

Article abstract of DOI:10.1002/hlca.200390315

Herein we report a convergent enantioselective synthesis of a polyfunctionalized ABCD tetracycle by using an anionic cycloaddition reaction between a chiral bicyclic CD Nazarov intermediate (see 6), derived from the (-)-Weiland-Mischer ketone, and an achi

Full text of DOI:10.1002/hlca.200390315

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Helvetica Chimica Acta Vol. 86 (2003)
Enantioselective Synthesis of a Polyfunctionalized Tetracycle Related to
Pentacyclic Triterpenes by Using an Anionic Cycloaddition Reaction
by Alain Rouillard, Marc-Andre¬ Bonin, and Pierre Deslongchamps*
¡
¬
Laboratoire de synthese organique, Departement de Chimie, Institut de Pharmacologie de Sherbrooke,
e
¬
¬
Universite de Sherbrooke, 3001, 12 Avenue Nord, Sherbrooke (Quebec), J1 H5N4 Canada
(phone: ‡‡ 1819-564-5300; fax: 819-820-6823; e-mail: Pierre.Deslongchamps@usherbrooke.ca)
Dedicated to Professor Duilio Arigoni on the occasion of his 75th birthday
Herein we report a convergent enantioselective synthesis of a polyfunctionalized ABCD tetracycle by using
an anionic cycloaddition reaction between a chiral bicyclic CD Nazarov intermediate (see 6), derived from the
(À)-Weiland Mischer ketone, and an achiral cyclohexenone (see 5) adequately functionalized to furnish the
ring A of pentacyclic triterpenes (Scheme 5). The chiral bicyclic CD Nazarov intermediate forms ring B upon
cycloaddition with the achiral cyclohexenone to yield an ABCD tetracycle with a cis-anti-trans-anti-trans
configuration (see 4). Further transformations on this adduct allowed reduction of the angular aldehyde
function at C(10) to a Me group ( ! 17) and introduction of an unsaturation at C(5)ÀC(6) by using the ketone
function at C(7) ( ! 3; Scheme 6).
Introduction. Pentacyclic triterpenes such as betulinic acid (1), an anti-HIV and
anti-cancer agent [1], and 3,21-dioxoolean-18-enoic acid (2), the first naturally
occurring nonprotein inhibitor of Tie-2 kinase [2], have been derivatized [1][3] for
studies on their bioactive functions and to enhance their potencies.
To fulfill the need for new analogs of these pentacyclic triterpenes, and to
accomplish their total syntheses with a versatile strategy, we turned our attention to the
novel anionic cycloaddition between the a,b-unsaturated b-keto ester 6 (Nazarov
intermediate) derived from the (À)-Wieland Mischer ketone (ˆ(8aR)-3,4,8,8a-
tetrahydro-8a-methylnaphthalene-1,6(2H,7H)-dione) and the adequately functional-
ized cyclohexenone 5 (Scheme 1). Anionic cycloaddition between an a,b-unsaturated
b-keto ester, derived from the Hajos-Parrish ketone, and a cyclohexenone, leading to
steroid-like compounds, have recently been successfully studied in our laboratory [4].
Retrosynthethic analysis of the ABCD ring of these pentacyclic triterpenes, which are

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3731
Scheme 1
basically the same for most pentacyclic triterpenes, led us to imagine that they might be
derived from the tetracyclic enone 3. This tetracycle 3 can be derived from tetracyclic
aldehyde 4, which can be formed via an enantioselective anionic cycloaddition between
the bicyclic Nazarov reagent 6 and cyclohexenone 5.
Results and Discussion.
b-Keto ester 6 was derived from the (À)-Weiland
Mischer ketone [5] by two approaches. The first one started with the formation of
enol triflate 8 (Scheme 2) from the known (À)-ketone 7 [6], which was submitted to Pd-
catalyzed carboxylation to yield ester 9 [7]. This ester was reduced to the alcohol, with
Dibal-H, which was oxidized with Dess Martin periodinane (ˆ1,1,1-tris(acetyloxy)-
1,1-dihydro-1,2-benziodoxol-3(1H)-one) to give aldehyde 10. This aldehyde 10 was
submitted to a Reformatsky addition of tert-butyl acetate. The resulting secondary
alcohol was oxidized with Dess Martin periodinane to give b-keto ester 11, which was
transesterified with allyl alcohol to yield b-keto ester 6 in 38% overall yield in seven
steps starting from 7.
Alternatively b-keto ester 6 can be synthesized from the known alcohol 12 [6]
(Scheme 3). Removal of the ketal protecting group of 12 followed by sodium acetylide
addition and Rupe rearrangement [8] yielded the enone 13 in good yield. The OH
group of 13 was then protected as a benzyl ether with benzyl trichloroethanimidate [9].
The resulting enone 14 was then kinetically deprotonated with LiHMDS and added on
allyl carbonocyanidate [10] to afford b-keto ester 6 in 24% overall yield in five steps
starting from 12.
We found that aldehyde 5 (Scheme 4) was the best candidate to produce ring A of
pentacyclic triterpenes via the anionic cycloaddition strategy [11]. The known enone 15
[12] was formylated followed by DDQ oxidation, or phenylseleno addition and
oxidative elimination, to afford aldehyde 5 in good yield.
We attempted the anionic cycloaddition between b-keto ester 6 and cyclohexenone
5 under the standard conditions (Cs2CO3, CH2Cl2, room temperature) without any
success. We then investigated other solvents and found that the use of AcOEt afforded

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 2
¹
a) Tf2O, Proton Sponge , CH2Cl2; 90%. b) K2CO3, LiCl, MeOH, NMP (1-methylpyrrolidin-2-one),
[PdCl2(PPh3)2], 200 psi CO, 1308; 83%. c) Dibal-H (diisobutylaluminium hydride), CH2Cl2, À788; 86%. d)
Dess Martin periodinane, CH2Cl2, 08; 89%. e) tBuO2CCH2ZnBr, Et2O, 08 to r.t.; 87%. f) Dess Martin
periodinane, CH2Cl2, 08; 92%. g) DMAP (N,N-dimethylpyridin-4-amine), toluene, AllOH, 82%.
Scheme 3
a) 50% aq. H2SO4 soln., Et2O; 88%. b) Na, NH3 (l), acetylene, Et2O; 83%. c) 1. HCO2H, H2SO4, r.t., then 908;
2. K2CO3, MeOH; 47%. d) CCl3C(ˆNH)OCH2Ph, CF3SO3H, CH2Cl2; 77%. e) LiHMDS (lithium salt of
1,1,1,3,3,3-hexamethyldisilazane), NCCO2All, THF; 53% (90% corrected).

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3733
Scheme 4
a) MeONa, benzene, HCO2Et, THF; 94%. b) 1. PhSeCl, pyridine, CH2Cl2; 2. 30% H2O2 soln., CH2Cl2 or DDQ
(4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile), dioxane; 99%.
the desired cycloaddition product after 96 h (Scheme 5). Those conditions afforded
aldehyde 4 as a single enantiomer after decarboxylation with [Pd(PPh3)4]. NaBH4
Reduction of this aldehyde 4 yielded tetracyclic (hydroxymethyl)dione 16. This
tetracyclic hydroxy compound 16 was then converted to tetracycle 17 via formation of
the corresponding phenyl carbonothioate followed by radical reduction [13]. The
configurations of tetracycles 4, 16, and 17 were confirmed by spectral analysis.
Scheme 5
a) Cs2CO3, AcOEt, r.t., 96 h; 70%. b) [Pd(PPh3)4], morpholine, THF; 85%. c) NaBH4, EtOH, THF, À788,
99%. d) PhOC(ˆS)Cl, pyridine, CH2Cl2; 80%. e) Bu3SnH, AIBN (2,2'-azobis[2-methylpropanenitrile]),
toluene, reflux; 99%.

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1
By using C6D6 as the solvent for the H-NMR analysis of 17, we were able to assign the d at d 1.75 (J ˆ
12.2 Hz) to HÀC(8) and the dt at d 2.41 (J ˆ 3.8 and 12.2 Hz) to HÀC(9). COSY Experiments confirmed that
these two protons were coupled with each other. We were then able to irradiate each of the four angular Me
groups in a NOE difference experiment. We found that the s at d 1.30 and 1.09 showed a NOE with the dt at d
2.41 and had no effect on the d at 1.75 (Fig. 1). We also found that the s at d 1.01 showed a NOE with the d at d
1.75 and had no effect on the dt at d 2.41. We were then able to assign the s at d 1.01 to the angular Me group at
C(10).
Fig. 1. Conformation and NOEs of 17. Triterpene
numbering.
Analysis of the anionic cycloaddition transition state showed that the a-approach of
the cyclohexenone 5 to the (À)-keto ester 6 has a strong steric interaction between the
angular Me group of b-keto ester 6 and the aldehyde function of cyclohexenone 5
(Fig. 2). This supports the proposal that the transition state with the lower energy
barrier is the one where cyclohexenone 5 approaches from the b face of the b-keto ester
6 yielding tetracyclic aldehyde 4 after decarboxylation with [Pd(PPh3)4].
Fig. 2. Cyclohexenone approach to b-keto ester 6 (enol
form) leading to the transition state of the anionic cyclo-
addition
Tetracycle 17 was then converted to tetracyclic enone 3 in a good yield by forming
the lithium enolate of the C(7) ketone under kinetic control and trapping with PhSeCl
followed by oxidative elimination on treatment with hydrogen peroxide (Scheme 6).
The synthesis of the polyfunctionalyzed tetracycle enone 3 tends to confirm that the
anionic cycloaddition strategy will allow the synthesis of a variety of natural and

Helvetica Chimica Acta Vol. 86 (2003)
3735
unnatural pentacyclic triterpenes. To reach this goal, one will have to introduce the
angular Me group at C(8). Research in this direction is presently underway.
Scheme 6
a) 1. LiHMDS, CH2Cl2, 08, 2. PhSeCl, 3 30% aq. H 2O2 soln., 99%.
A research chair from BioChem Pharma Inc. is gratefully acknowledged as well as financial support from
¬
NSERC Canada and FCAR Quebec.
Experimental Part
General. All reactions were performed under N2 with oven- or flame-dried glassware. Solvents were
distilled and dried according to standard procedures. Anal. TLC: precoated glass plates (0.25 mm) with silica gel
Merck 60 F 250. Flash chromatography (FC): Merck 230 400 mesh silica gel 60. [a]D: Perkin-Elmer 141
polarimeter, set at 589 nm; 10.0-cm cell. IR Spectra: Perkin-Elmer 1600-FT-IR spectrometer; in cmÀ1. 1H- and
13C-NMR Spectra: Bruker AC-300 spectrometer; referenced with respect to the residual signals of the solvent; d
in ppm, J in Hz. MS: ZAB-1F micromass spectrometer.
(4aR,6R,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-8a-methyl-6-(phenylmethoxy)naphthalen-1-ol Trifluoromethane-
sulfonate (8). Trifluoromethanesulfonic acid anhydride (2.4 ml, 14.1 mmol) was added at 08 to a soln. of ketone
¹
7 (2.26 g, 8.3mmol) and Proton Sponge (2.31 g, 10.8 mmol) in CH2Cl2 (100 ml). The mixture was warmed to r.t.
and stirred for 16 h. The reaction was then quenched with sat. aq. NaHCO3 soln. and extracted 4 times with
CH2Cl2. The combined org. phase was dried (MgSO4) and evaporated and the crude product purified twice by
FC (AcOEt/hexanes 1:4, Rf 0.66): 8 (3.02 g, 90%). Yellow oil. IR (film): 3030, 2940, 2866, 1674, 1411, 1247,
1209, 1142, 997, 877. 1H-NMR (300 MHz, CDCl3): 7.40 7.18 (m, 5 arom. H); 5.59 (t, J ˆ 4.3, ˆCH); 4.57 (s,
PhCH2O); 3.47 3.38 (m, CH2OCH); 2.29 2.16 (m, CH2CHˆ); 2.09 2.01 (m, (CH2)2CHC); 1.90 1.81 (m,
CH2); 1.62 1.26 (m, 6 H, CH2); 1.13( s, Me). 13C-NMR (75 MHz, CDCl3): 118.47 (q, J ˆ 319); 156.4; 138.7;
‡
128.4; 127.9; 127.6; 115.5; 77.1; 70.1; 41.8; 38.0; 33.4; 32.1; 27.3; 24.2; 24.1; 17.1. CI-MS: 422 ([M ‡ NH4] ), 313
‡
‡
([M À C7H7] ). HR-MS: 422.1603(C 19H27F3NO4S ; calc. 422.1613).
(4aR,6R,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-8a-methyl-6-(phenylmethoxy)naphthalene-1-carboxylic Acid
Methyl Ester (9). K2CO3 (2.07 g, 15 mmol), LiCl (490 mg, 11.3mmol), and MeOH (6.1 ml, 150 mmol) were
added to a soln. of 8 in NMP (80 ml). This mixture was purged with CO, and then dichlorobis(triphenylphos-
phine)palladium (100 mg, 0.15 mmol) was added. The mixture was then placed under a 200-psi atmosphere of
CO at 1308 for 24 h in a Parr bomb. The bomb was then cooled down to r.t. and the pressure released. After
addition of aq. sat. NH4Cl soln. (200 ml) and brine (200 ml), the mixture was extracted with Et2O/hexanes 1:1.
The org. phase was dried (MgSO4) and evaporated and the crude product purified by FC (AcOEt/hexanes 1 :4;
Rf 0.6): 9 (975 mg, 83%). Colorless oil. IR (film): 3028, 2933, 2861, 1711, 1248, 1218, 1106, 1073. 1H-NMR
(300 MHz, CDCl3): 7.37 7.24 (m, 5 arom. H); 6.69 (t, J ˆ 3.7, ˆ CH); 4.56 (s, PhCH2O); 3.69 (s, MeO); 3.42
3.33 (m, CH2OCH); 2.36 (dt, J ˆ 13.2, 3.7, (CH2)2CHC); 2.25 2.20 (m, CH2CHˆ); 2.00 2.93( m, 1 H, CH2
ax.); 1.87 1.80 (m, 1 H, CH2 ax.); 1.63 1.32 ( m, 5 H, CH2); 1.19 (s, Me); 1.09 (td, J ˆ 13.6, 3.9, 1 H,
PhCH2OCHCH2 eq.). 13C-NMR (75 MHz, CDCl3): 167.7; 140.3; 139.0; 138.5; 128.4; 127.6; 127.4; 77.6; 69.9; 51.2;
‡
‡
‡
41.5; 36.0; 34.2; 33.4; 28.0; 26.3; 24.6; 17.9. EI-MS: 315 ([M ‡ H] ), 314 (M ), 283([ M À OMe] ), 223([ M À
‡
‡
C7H7] ). HR-MS: 314.1889 (C20H26O3 ; calc. 314.1882).
(4aR,6R,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-8a-methyl-6-(phenylmethoxy)naphthalene-1-carboxaldehyde
(10). At À788, 1m Dibal-H in CH2Cl2 (6.8 ml, 6.8 mmol) was added dropwise to 9 in CH2Cl2 (50 ml). The
reaction was monitored by TLC until completion. Then MeOH (15 ml) was added, the mixture warmed to r.t, 1m

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Helvetica Chimica Acta Vol. 86 (2003)
HCl added, and the mixture extracted with CH2Cl2. The combined org. phase was dried (MgSO4) and
evaporated and the crude product purified by FC (AcOEt/hexanes 1:4; Rf 0.20): corresponding naphthalene-1-
methanol (778 mg, 86%). Colorless oil. IR (film): 3403, 3029, 2930, 2861, 1453, 1358, 1090, 1072, 1016, 735, 698.
1H-NMR (300 MHz, CDCl3): 7.38 7.22 (m, 5 arom. H); 5.56 (t, J ˆ 3.4, ˆCH); 4.57 (s, PhCH2O); 4.10 (q,
CH2OH); 3.44 3.34 (m, CH2OCH); 2.13 2.09 ( m, CH2CHˆ); 2.05 1.95 (m, (CH2)2CHC); 1.86 1.79 (m,
CH2); 1.62 1.35 (m, 6 H, OH, CH2); 1.28 (dt, J ˆ 13.3, 3.9, 1 H, PhCH2OCHCH2 eq.); 1.04 (s, Me). 13C-NMR
(75 MHz, CDCl3): 145.9; 139.0; 128.4; 127.6; 127.4; 122.6; 77.7; 69.9; 63.5; 41.1; 36.1; 34.4; 33.8; 28.0; 25.5; 25.2;
‡
‡
‡
‡
18.9. EI-MS: 286 (M ), 268 ([M À H2O] ), 195 ([M À C7H7] ). HR-MS 286.1938 (C19H26O2 ; calc. 286.1933).
Dess Martin periodinane (1.49 g, 3.51 mmol) was added at 08 to a soln. of the naphthalene-1-methanol
(see above; 670 mg, 2.34 mmol) in CH2Cl2 (100 ml). The mixture was then warmed to r.t. and stirred for 45 min.
The mixture was diluted with hexanes (100 ml) and filtered through a silica-gel pad, which was eluted with
AcOEt/hexanes 3:7. The soln. was evaporated and the residue purified by FC (AcOEt/hexanes 1 :4; Rf 0.50): 10
(665 mg, 89%). Colorless oil. IR (film): 3030, 2972, 2933, 2863, 1686, 1455, 1358, 1191, 1105, 1073, 736, 698.
1H-NMR (300 MHz, CDCl3): 9.33 (s, CHO); 7.37 7.25 (m, 5 arom. H); 6.62 (t, J ˆ 3.7, ˆCH); 4.57 (s,
PhCH2O); 3.44 3.34 (m, CH2OCH); 2.69 (dt, J ˆ 13.5, 6.3, (CH2)2CHC); 2.43 2.37 ( m, CH2CHˆ); 2.03 1.96
(m, 1 H, CH2 ax.); 1.89 1.82 (m, 1 H, CH2 ax.); 1.65 1.31 (m, 5 H, CH2); 1.13 1.07 ( m, 4 H, Me, OCHCH2
ax.). 13C-NMR (75 MHz, CDCl3): 194.2; 152.8; 149.9; 139.0; 128.4; 127.5; 127.4; 77.4; 69.9; 41.4; 35.7; 33.9; 32.6;
‡
‡
‡
‡
27.8; 27.5; 24.4; 17.1. CI-MS: 302 ([M ‡ NH4] ], 290 ([272 ‡ NH4] ), 285 ([M ‡ H] ), 273([272 ‡ H] ), 193
‡
‡
‡
‡
([M À C7H7] ), 181 ([272 À C7H7] ). HR-MS 285.1848 (C19H25O2 ([M ‡ H] ) calc. 285.1854).
(4aR,6R,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-8a-methyl-b-oxo-6-(phenylmethoxy)naphthalene-1-propanoic
Acid 1,1-Dimethylethyl Ester (11). The Reformatsky reagent was prepared as follows: tert-butyl bromoacetate
(2.6 ml, 17.6 mmol) was added to a suspension of Zn pieces (1.35 g, 20.6 mmol) in Et2O (60 ml). A crystal of I2
was added, and the mixture was heated to reflux. When the reaction turned milky, the reflux was continued for
further 2 h and then cooled to r.t. The concentration of the organozinc in Et2O was ca. 0.25m. This zinc enolate of
tert-butyl acetate soln. (25 ml, 6.22 mmol) was added at 08 to a soln. of 10 (510 mg, 1.8 mmol) in Et2O (25 ml).
The mixture was then warmed to r.t. and stirred for 3h. The mixture was quenched with sat. aq. NH 4Cl soln. and
extracted with Et2O (3 Â 50 ml). The combined org. phase was dried (MgSO4) and evaporated and the crude
product purified by FC (AcOEt/hexanes 1:4; Rf 0.33): corresponding b-hydroxy ester (718 mg, 87%). Colorless
oil. IR (film): 3436, 3062, 2975, 2932, 2863, 1727, 1454, 1366, 1150, 1073, 737, 698. 1H-NMR (300 MHz, CDCl3):
7.36 7.24 (m, 5 arom. H); 5.70 (t, J ˆ 3.9, ˆCH); 4.58 4.52 (m, PhCH2O, CHOH); 3.42 3.35 (m, CH2OCH);
2.87 (s, OH); 2.63 2.40 ( m, CH2COOtBu); 2.16 1.79 (m, 5 H, CH, CH2); 1.56 1.40 (m, 15 H, tBu, CH2); 0.97
(s, Me). 13C-NMR (75 MHz, CDCl3): 172.2; 147.1; 139.0; 128.3; 127.5; 127.4; 123.1; 81.0; 77.6; 69.9; 65.8; 43.3;
‡
‡
41.3; 36.6; 34.7; 33.8; 28.1; 28.0; 25.6; 25.2; 18.8. EI-MS: 344 ([M À C4H9] ). HR-MS 344.1992 (C21H28O4 ; [M À
‡
C4H9] ; calc. 344.1987).
Dess Martin periodinane (1.49 g, 3.51 mmol) was added to a 08 soln. of the b-hydroxy ester (see above;
530 mg, 1.33) in CH2Cl2 (50 ml). The mixture was warmed to r.t. and stirred for 45 min. The resulting soln. was
diluted with hexanes (50 ml) and filtered through silica gel, which was eluted with AcOEt/hexanes 3:7. The soln.
was evaporated and the residue purified by FC (AcOEt/hexanes 1:4; Rf 0.47): 11 (486 mg, 92%). Colorless oil.
IR (film): 3029, 2976, 2932, 2863, 1731, 1672, 1455, 1366, 1310, 1252, 1154, 1073, 737, 698. 1H-NMR (300 MHz,
CDCl3): 7.36 7.24 (m, 5 arom. H); 6.62 (t, J ˆ 3.9, ˆ CH); 4.56 (s, PhCH2O); 3.57 (d, J ˆ 15.3, 1 H,
COCH2CO); 3.47 (d, J ˆ 15.3, 1 H, COCH2CO); 3.42 3.32 (m, CH2OCH); 2.47 (dt, J ˆ 13.4, 3.7, (CH2)2CHC)
2.33 2.27 (m, CH2CHˆ); 1.99 1.92 (m, 1 H, CH2 ax.); 1.85 1.79 (m, 1 H, CH2 ax.); 1.65 1.29 (m, 14 H, tBu,
CH2); 1.17 (s, Me); 1.02 (td, J ˆ 3.8, 13.7, 1 H, PhCH2OCHCH2 eq.). 13C-NMR (75 MHz, CDCl3): 194.2; 167.4;
148.6; 140.8; 139.0; 128.3; 127.5; 127.4; 81.5; 77.5; 69.9; 48.4; 41.5; 36.6; 34.2; 32.9; 28.0; 27.9; 26.7; 24.3; 17.8. EI-
‡
‡
‡
‡
MS: 398 (M ), 342 ([M À C4H8] ), 251 ([M À C4H8 À C7H7] ). HR-MS 398.2451 (C25H34O4 ; calc. 398.2457).
(4aR,6R,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-8a-methoxy-b-oxo-6-(phenylmethoxy)naphthalene-1-propanoic
Acid Prop-2-enyl Ester (ˆ Nazarov Intermediate; 6). DMAP (6 mg, 0.05 mmol) was added to a soln. of 11
(78 mg, 0.20 mmol) in toluene (4 ml) and allyl alcohol (1 ml). The mixture was refluxed for 16 h and then
filtered through silica gel, which was eluted with AcOEt/hexanes 3:7. The soln. was evaporated and the residue
purified by FC (AcOEt/hexanes 1:4; Rf 0.36): 6 (61 mg, 82%): Colorless oil. IR (film): 3085, 3029, 2930, 2859,
1742, 1673, 1455, 1358, 1073, 737, 698. 1H-NMR (300 MHz, CDCl3): 12.30 (s, OH (enol)); 7.36 7.24 (m, 5 arom.
H); 6.62 (t, J ˆ 3.8, ˆCH); 5.97 5.84 (m, CH2CHˆCH2); 5.36 5.21 (m, CH2CHˆCH2); 5.09 (s, CHˆ(enol));
4.62 (dt, J ˆ 5.8, 1.4, ˆCHCH2O); 4.56 (s, PhCH2O); 3.66 (d, J ˆ 2.5, COCH2CO); 3.40 3.32 (m, CH2OCH);
2.44 (dt, J ˆ 13.3, 3.7, (CH2)2CHC) 2.34 2.28 (m, CH2CHˆ); 1.99 1.94 (m, 1 H, CH2 ax.); 1.85 1.79 (m, 1 H,
CH2 ax.); 1.61 1.20 (m, 6 H, CH2); 1.17 (s, Me); 1.05 (td, J ˆ 4.0, 13.6, 1 H, PhCH2OCHCH2 eq.). 13C-NMR
(75 MHz, CDCl3): 193.6; 167.7; 148.7; 141.2; 139.0; 131.7; 128.3; 127.6; 127.4; 118.7; 69.9; 65.8; 46.7; 41.5; 36.7;

Helvetica Chimica Acta Vol. 86 (2003)
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‡
‡
‡
34.2; 32.9; 29.7; 27.9; 26.7; 24.3; 17.8. EI-MS: 382 (M ), 291 ([M À C7H7] ). HR-MS: 382.2150 (C24H30O4 ; calc.
382.2144).
1-[(4aR,6R,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-6-hydroxy-8a-methylnaphthalen-1-yl]ethanone (13). A 50%
aq. H2SO4 soln. (15 ml) was added to a soln. of alcohol 12 (2.6 g, 11.5 mmol) in Et2O (100 ml). The mixture was
stirred for 30 min and decanted. The Et2O phase was dried (MgSO4) and evaporated and the crude product
purified by FC (hexanes/AcOEt 6 :4; Rf 0.13): corresponding alkoxy ketone (1.84 g, 88%). IR (film): 3391,
2933, 2862, 1705, 1469, 1451, 1364, 1342, 1308, 1273, 1144, 1107, 1052, 1026. 1H-NMR (300 MHz, CDCl3): 3.60
3.50 (m, CHOH); 2.68 2.56 (m, 1 H); 2.22 2.16 (m, 1 H); 2.06 1.97 (m, 2 H); 1.89 1.84 (m, 1 H); 1.79 1.36
(m, 9 H); 1.10 (s, Me). 13C-NMR (75 MHz, CDCl3): 215.9; 70.3; 47.6; 43.7; 37.4; 36.7; 30.8; 30.7; 27.4; 26.2; 15.7.
‡
‡
‡
EI-MS: 182 (M ). HR-MS: 182.1312 (C11H18O2 , M ; calc. 182.1307).
Sodium (2 g, 88.4 mmol) was dissolved in NH3 (l) (200 ml) at À708. Acetylene was then bubbled through
the soln. until the blue color disappeared. The soln. of the alkoxy ketone (see above; 1.61 g, 8.85 mmol) in Et2O
(20 ml) was added slowly to this sodium acetylide soln. Then the NH3 (l) was evaporated. The resulting soln. was
quenched with sat. aq. NH4Cl soln. and extracted with Et2O and the extract dried (MgSO4) and evaporated: diol
mixture (1.52 g, 83%) that was used without further purification. The diol mixture (1.52 g, 7.35 mmol) was
dissolved in formic acid (26 ml), and 2 drops of conc. H2SO4 soln. were added. This soln. was stirred at r.t. for 2 h,
heated to 908 for 10 min, then cooled to 08, and quenched with H2O. The pH was adjusted to 12 with KOH, the
soln. extracted with CH2Cl2, the extract dried (MgSO4) and evaporated, and the crude product dissolved in
MeOH (40 ml). H2O (2.6 ml) and K2CO3 were added, and this soln. was stirred for 1 h. After completion of
formate hydrolysis, this soln. was evaporated, the residue dissolved in CH2Cl2, the CH2Cl2 soln. washed with
H2O, dried (MgSO4), and evaporated, and the crude product purified by FC (hexanes/AcOEt 6 :4; Rf 0.15): 13
(714 mg, 47%). IR (film): 3368, 2930, 2861, 1665, 1618, 1457, 1422, 1370, 1243, 1064, 1031, 944. 1H-NMR
(300 MHz, CDCl3): 6.63( t, J ˆ 3.9, CHˆCCˆO); 3.63 3.59 (m, CHOH); 2.47 (dt, J ˆ 9.6, 3.7, 1 H); 2.32 2.24
(m, 1 H); 2.23( s, MeCˆO); 1.84 1.81 (m, 1 H); 1.80 1.66 (m, 2 H); 1.56 1.35 (m, 5 H); 1.14 (s, MeC(C)3);
0.99 (td, J ˆ 17.4, 3.9, 1 H). 13C-NMR (75 MHz, CDCl3): 200.1; 149.3; 139.8; 71.0; 41.5; 37.3; 36.2; 33.1; 31.3; 27.9;
‡
‡
‡
‡
‡
26.6; 24.3; 17.8. EI-MS: 208 (M ), 193([ M À CH3] ), 190 ([M À H2O] ). HR-MS: 208.1457 (C13H20O2 , M ;
calc. 208.1463).
1-[(4aR,6R,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-8a-methyl-6-(phenylmethoxy)naphthalen-1-yl]ethanone (14).
Benzyl trichloroethanimidate (1.28 ml, 6.83mmol) and then trifluoromethanesulfonic acid (152 ml, 1.72 mmol)
were added at 08 to a soln. of 13 (714 mg, 3.43 mmol) in CH2Cl2 (100 ml). The soln. was stirred for 1 h, then
quenched with sat. NaHCO3 soln. and extracted with CH2Cl2. The extract was dried (MgSO4) and evaporated,
and the crude product purified by FC (hexanes/AcOEt 9 :1; Rf 0.4): 14 (782 mg, 77%). [a]2D0 ˆ À79.3( c ˆ 1.11,
toluene). IR (film): 2931, 2860, 1668, 1455, 1366, 1355, 1243, 1220, 1108, 1090, 1073, 1226. 1H-NMR (300 MHz,
CDCl3): 7.35 7.28 (m, 5 arom. H); 6.63( t, J ˆ 4.0, CH2CHˆCCOMe); 4.56 (s, PhCH2O); 3.38 3.31 (m,
CHOCH2Ph); 2.48 (dt, J ˆ 13.4, 3.7, CH2CHCH2CHOH); 2.32 2.26 (m, 2 H); 2.24 (s, MeCO); 2.00 1.91 (m,
1 H); 1.85 1.78 (m, 1 H); 1.62 1.23( m, 10 H); 1.16 (s, MeC(C)3); 0.95 (td, J ˆ 17.4, 3.9, 1 H). 13C-NMR
(75 MHz, CDCl3): 200.0; 149.3; 139.8; 139.0; 128.3; 127.5; 127.3; 77.5; 69.8; 41.7; 36.5; 34.2; 33.2; 28.0; 27.9; 26.6;
‡
‡
‡
24.5; 17.8. EI-MS: 298 (M ). HR-MS: 298.1937 (C20H26O2 , M ; calc. 298.1933).
Nazarov Intermediate 6. At À788, 1m LiHMDS in THF (8.34 ml) was added to a soln. of 14 (2.48 g,
8.34 mmol) in THF (100 ml). The soln. was stirred at À788 for 2 h. Then, a soln. of allyl carbonocyanidate
(924 mg, 8.34 mmol) in THF (10 ml) was added. The resulting soln. was stirred for 15 min, neutralized with sat.
NH4Cl soln., warmed to r.t., and extracted with Et2O. The extract was washed with brine, dried (MgSO4), and
evaporated and the crude product purified by FC (hexanes/AcOEt 95 :5): 6 (1.68 g, 53%) and starting 14
(918 mg, 37%). 6: [a]D20 ˆ À19.0 (c ˆ 1.00, CDCl3). IR (film): 2933, 2863, 1742, 1672, 1620, 1495, 1454, 1420,
1358, 1304, 1273, 1197, 1144, 1073, 992, 936. 1H-NMR (300 MHz, CDCl3): 12.13( s, 0.07 H, OH (enol)); 7.36 7.24
(m, 5 arom. H); 6.62 (t, J ˆ 3.8, HCˆCCˆO); 5.97 5.84 (m, CH2CHˆCH2); 5.36 5.21 (m, CH2CHˆCH2);
4.62 (dt, J ˆ 5.8, 1.4, OCH2CHˆCH2); 4.56 (s, PhCH2O); 3.66 (d, J ˆ 2.5, OˆCCH2CˆO); 3.40 3.32 (m,
CHOCH2Ph); 2.44 (dt, J ˆ 13.3, 3.7, CCH(CH2)2); 2.34 0.86 (m, 11 H); 1.17 (s, Me). 13C-NMR (75 MHz,
CDCl3): 193.6; 167.7; 148.7; 141.2; 139.0; 131.7; 128.3; 127.6; 127.4; 118.7; 69.9; 65.8; 46.7; 41.5; 36.7; 34.1; 32.9;
‡
‡
‡
29.7; 27.9; 26.7; 24.3; 17.8. EI-MS: 382 ( M ). HR-MS: 382.2134 (C24H30O4 , M ; calc. 382.2144).
4-Methoxy-3,3-dimethyl-6-oxocyclohexa-1,4-diene-1-carboxaldehyde (5). MeOH (818 ml, 20.2 mmol) was
added to a suspension of NaH (60% in oil; 826 mg, 20.2 mmol) in benzene (100 ml). This NaOMe soln. was
cooled to 08, then a soln. of 15 (2.83g, 18.4 mmol) in THF (50 ml) was added slowly. The soln. was stirred for
10 min, and ethyl formate (10.4 ml, 128.8 mmol) was added slowly. The mixture was warmed to r.t. and stirred
for 12 h. H2O (100 ml) was then added, and the org. phase was extracted once with an aq. 1m NaOH. The aq.
phase was acidified to pH 6 at 08 and extracted with AcOEt, the extract dried (MgSO4) and evaporated, and the

3738
Helvetica Chimica Acta Vol. 86 (2003)
crude product purified by FC (hexanes/AcOEt 2 :8): corresponding aldehyde (3.15 g, 94%). IR (film): 2967,
2931, 2894, 2844, 1723, 1642, 1598, 1567, 1471, 1436, 1418, 1388, 1364, 1237, 1199, 1176, 1152, 1131, 1019, 993, 971,
956, 868, 838, 825, 679, 584, 559. 1H-NMR (300 MHz, CDCl3): 13.86 (s, OH); 7.17 (s, CHOH); 5.22 (s,
OˆCCHˆC); 3.70 (s, MeO); 2.26 (s, CH2); 1.11 (s, 6 H, 2 Me). 13C-NMR (75 MHz, CDCl3): 192.4; 183. 1; 161.4;
‡
‡
‡
106.0; 99.0; 56.2; 38.5; 36.9; 25.4 (2C). EI-MS: 182 (M ). HR-MS 182.0947 (C10H14O3 , M ; calc. 182.0943).
At 08, pyridine (1.67 ml, 20.2 mmol) was added to a soln. of PhSeCl (3.68 g, 19.3 mmol) in CH2Cl2 (100 ml)
and the resulting soln. was stirred for 10 min. A soln. of the aldehyde (see above; 3.35 g, 18.4 mmol) in CH2Cl2
(100 ml) was added dropwise to the PhSeCl soln. The mixture was then warmed to r.t., stirred for 2 h, quenched
with 1m aq. HCl, and extracted with CH2Cl2. The extract was dried (MgSO4) and evaporated and the crude
product was dissolved in CH2Cl2 (50 ml). To the CH2Cl2 soln., 30% H2O2 soln. (10 ml) was added, and the
mixture was stirred for 15 min at r.t. H2O (50 ml) was then added, the resulting soln. extracted with CH2Cl2, the
extract washed with brine, dried (Na2SO4), decanted, and evaporated and the residue triturated in Et2O/
hexanes 1:1 5 (3.24 g, 99%).
Alternatively, DDQ (4.69 g, 21 mmol) was added to a soln. of the aldehyde (see above; 3.76 g, 21 mmol) in
dioxane (70 ml), and the mixture was stirred for 5 min. Then pentane (210 ml) was added and the solid filtered
and dried under vacuum. The crude product was then triturated in Et2O/hexanes 1:1: 5 (3.76 g, 99%). IR (film):
3020, 2931, 2879, 1702, 1648, 1620, 1584, 1464, 1410, 1386, 1360, 1221, 1174, 1102, 986, 934, 844, 727, 683, 629, 509.
1H-NMR (300 MHz, CDCl3): 10.21 (s, CHˆO); 7.31 (s, CHˆCCˆO); 5.56 (s, CHˆCOMe); 3.77 (s, MeO); 1.34
(s, 6 H, 2 Me). 13C-NMR (75 MHz, CDCl3): 190.3; 186.9; 180.0; 157.4; 130.5; 101.0; 56.1; 40.2; 25.1 (2C). EI-MS:
‡
‡
‡
‡
‡
180 (M ), 181 ([M ‡ H] ), 165 ([M À CH3] ). HR-MS: 180.0782 (C10H12O3 , M ; calc. 180.0786, 165.0554
‡
‡
(C9H9O3 , [M À Me] ; calc. 165.0552).
(4aR,4bS,6aR,8R,10aR,10bR,12aR)-1,4,4a,4b,5,6,7,8,9,10,10a,10b,11,12,12a-Hexadecahydro-2-methoxy-
1,1,10a-trimethyl-4,11-dioxo-8-(phenylmethoxy)chrysene-4a-carboxaldehyde (4). A soln. of 5 (75 mg, 416 mmol)
in AcOEt (5 ml) was added to a soln. of 6 (159 mg, 416 mmol) and Cs2CO3 (136 mg, 416 mmol) in AcOEt (5 ml).
The mixture was then stirred at r.t. for 96 h. The resulting soln. was filtered through silica gel, which was washed
with AcOEt. The soln. was evaporated and the crude product dissolved in THF (30 ml). Morpholine (110 ml,
1.246 mmol) and a catalytic amount of [Pd(PPh3)4] were added. The mixture was stirred at r.t. for 1 h and then
filtered through silica gel, which was washed with AcOEt. The soln. was evaporated and the crude product
purified by FC (toluene/AcOEt 9 :1): 4 (139 mg, 70%). IR (film): 2934, 2862, 1709, 1642, 1606, 1455, 1354, 1222,
1203, 1135, 1094, 1027, 989, 912, 847, 733, 699. 1H-NMR (300 MHz, CDCl3): 9.86 (d, J ˆ 1.6, CHˆO); 7.35 7.24
(m,
5
arom. H); 5.3 4 s(, MeOCˆCH); 4.54 (s, PhCH2O); 3.73 (s, MeOCˆC); 3.38 3.28 (m,
(CH2)2CHOCH2Ph); 2.71 2.64 (m, 2 H); 2.57 2.34 (m, 4 H); 1.93 0.85 ( m, 10 H); 1.23( s, Me); 1.18 (s,
Me); 0.94 (s, Me). 13C-NMR (75 MHz, CDCl3): 209.4; 201.3; 197.1; 181.7; 139.1; 128.3; 127.6; 127.4; 99.5; 77.2;
69.8; 61.6; 58.7; 56.3; 44.2; 41.7; 40.9; 39.6; 36.7; 36.5; 34.4; 29.7; 28.7; 28.0; 27.9; 23.9; 11.2; 11.1. EI-MS: 478
‡
‡
‡
‡
‡
(M ). HR-MS: 180.0782 (C10H12O3 , M ; calc. 180.0786), 478.2708 (C30H38O5 , [M À Me] ; calc. 478.2719).
(4aR,4bS,6aR,8R,10aR,10bR,12aR)-4b,5,6,6a,7,8,9,10,10a,10b,12,12a-Dodecahydro-4a-(hydroxymethyl)-
2-methoxy-1,1,10a-trimethyl-8-(phenylmethoxy)chrysene-4,11(1H,4aH)-dione (16).
A soln. of 4 (23mg,
48 mmol) in THF (3ml) was added at 0 8 to a soln. of NaBH4 (1.8 mg, 48 mmol) in MeOH (1.5 ml). The
mixture was stirred at 08 for 1 h, then concentrated, diluted with AcOEt, washed with H2O, dried (MgSO4), and
evaporated. The crude product was then purified by FC (hexanes/AcOEt 3:7): 16 (23mg, 99%). [ a]2D0 ˆ À29.8
(c ˆ 0.91, toluene). IR (film): 3414, 2931, 2852, 1704, 1640, 1614, 1454, 1360, 1218, 1069, 733. 1H-NMR
(300 MHz, CDCl3): 7.39 7.23 (m, 5 arom. H); 5.33 (s, MeOCˆCHCˆO); 4.60 (d, J ˆ 11.5, 1 H, CH2OH); 4.53
(s, PhCH2O); 3.73 (d, J ˆ 11.5, 1 H, CH2OH); 3.71 (s, MeO); 3.36 3.26 (m, CHOCH2Ph); 2.80 0.71 (m, 17 H);
1.22 (s, Me); 1.20 (s, Me); 0.96 (s, Me). 13C-NMR (75 MHz, CDCl3): 209.9; 201.4; 181.1; 139.0; 128.3; 127.5; 127.4;
99.9; 69.8; 60.4; 59.3; 56.0; 53.4; 44.8; 41.9; 40.8; 39.6; 39.2; 36.9; 36.6; 34.4; 30.0; 28.7; 28.3; 28.1; 27.9; 24.4; 11.3.
‡
‡
‡
EI-MS: 480 (M ). HR-MS: 480.2886 (C30H40O5 , M ; calc. 480.2876).
(4aR,4bS,6aR,8R,10aR,10bR,12aR)-4b,5,6,6a,7,8,9,10,10a,10b,12,12a-Dodecahydro-2-methoxy-1,1,4a,10a -
tetramethyl-8-(phenylmethoxy)chrysene-4-11(1H,4aH)-dione (17). A soln. of 16 (250 mg, 548 mmol), pyridine
(177 ml, 2.19 mmol), phenyl carbonochloridothioate (303 ml, 2.19 mmol), and a catalytic amount of DMAP in
CH2Cl2 (25 ml) was stirred for 16 h. The mixture was then evaporated and the crude product purified by FC
1
(hexanes/AcOEt 8 :2): corresponding carbonothioate (268 mg, 80%). H-NMR (300 MHz, CDCl3): 7.41 7.07
(m, 10 arom. H); 5.41 (d, J ˆ 10.7, 1 H, CH2OC(ˆS)OPh); 5.37 (s, MeOCˆCH); 4.80 (d, J ˆ 10.7, 1 H,
CH2OC(ˆS)OPh); 4.54 (s, PhCH2O); 3.72 (s, MeOCˆCH); 3.36 3.29 (m, CHOCH2Ph); 2.80 0.76 (m, 16 H);
1.22 (s, Me); 1.20 (s, Me); 0.97 (s, Me). 13C-NMR (75 MHz, CDCl3): 209.1; 196.6; 194.6; 180.3; 160.1; 153.2;
138.9; 129.5; 128.3; 127.6; 127.4; 126.6; 121.8; 99.7; 71.6; 69.8; 59.6; 56.1; 51.1; 44.7; 42.6; 40.8; 39.8; 39.4; 37.1;

Helvetica Chimica Acta Vol. 86 (2003)
3739
‡
‡
‡
36.5; 34.3; 29.7; 28.4; 28.1; 27.9; 24.4; 11.3. EI-MS: 617 ([M ‡ H] ). HR-MS: 617.2939 (C37H44O6S , [M ‡ H] ;
calc. 617.2937).
A catalytic amount of AIBN and freshly distilled Bu3SnH (98 ml, 368 mmol) were added to a soln. of the
carbonothioate (see above; 151 mg, 245 mmol) in toluene (10 ml). The mixture was degassed and then refluxed
for 2 h. The mixture was evaporated and the crude product purified by FC (hexanes/AcOEt 8 :2): 17 (114 mg,
99%). [a]2D0 ˆ À32.5 (c ˆ 1.00, toluene). IR (film): 2925, 2849, 1704, 1643, 1616, 1455, 1355, 1220, 1196, 1132,
1091, 1067, 1026, 985, 850. 1H-NMR (300 MHz, CDCl3): 7.33 7.22 (m, 5 arom. H); 5.29 (s, MeOCˆCHCˆO);
4.54 (s, PhCH2O); 3.69 (s, MeO); 3.37 3.27 (m, CHOCH2Ph); 2.77 (dt, J ˆ 13.5, 3.5, CCH(CH2)2); 2.67 2.52
(m, 2 H); 2.29 (td, J ˆ 11.7, 3.6, 1 H); 2.11 (dd, J ˆ 6.3, 2.7, 1 H); 1.93 0.76 (m, 11 H); 1.3 8 (s, Me); 1.17 (s, Me);
1.16 (s, Me); 0.97 (s, Me). 1H-NMR (300 MHz, C6D6; triterpene numbering): 7.65 7.14 (m, 5 arom. H); 5.36 (s,
MeOCˆCHCˆO); 4.55 (s, PhCH2O); 3.35 3.24 (m, CHOCH2Ph); 3.19 (dt, J ˆ 13.4, 3.7, CCH(CH2)2); 2.96 (s,
MeO); 2.49 (d, J ˆ 15.6, 1 H, CH2(6)CˆO); 2.41 (td, J ˆ 12.2, 3.8, CH2CH(9)CHCˆO); 2.25 (dd, J ˆ 15.6, 7.1,
1 H, CH2(6)CˆO); 2.06 0.70 (m, 11 H); 1.75 (d, J ˆ 12.2, CHCH(8)CˆO); 1.42 0.98 (m, 3 H); 1.30 (s, Me);
1.09 (s, Me); 1.01 (s, MeÀC(10)). 13C-NMR (75 MHz, CDCl3): 210.3; 201.2; 179.7; 139.0; 128.4; 127.5; 127.4;
127.3; 99.2; 69.7; 59.2; 55.9; 50.6; 48.3; 44.8; 41.1; 39.9; 39.7; 36.6; 34.4; 28.7; 28.6; 27.9; 26.8; 17.5; 13.6; 11.5. EI-
‡
‡
‡
MS: 464 (M ). HR-MS: 464.2916 (C30H40O4 , M ; calc. 464.2926).
(4aR,4bS,6aR,8R,10aR,10bR)-4b,5,6,6a,7,8,9,10,10a,10b-Decahydro-2-methoxy-1,1,4a,10a-tetramethyl-8-
(phenylmethoxy)chrysene-4,11(1H,4aH)-dione (3). At 08, 1m LiHMDS (1.51 ml) was added to a soln. of 17
(140 mg, 302 mmol) in CH2Cl2 (10 ml). The soln. was stirred at 08 for 5 min, then PhSeCl (290 mg, 1.51 mmol)
was added. After 30 min, the mixture was quenched with sat. aq. NH4Cl soln., warmed to r.t., and extracted with
CH2Cl2. The extract was dried (Na2SO4) and decanted. A 30% aq. H2O2 soln. (500 ml) was then added to the org.
soln., and the mixture was stirred for 10 min and washed with H2O. The org. phase was dried (Na2SO4),
decanted, and evaporated and the crude product purified by FC (hexanes/AcOEt 8 :2): 3 (139 mg, 99%). IR
1
(film): 2982, 2929, 2861, 1664, 1612, 1452, 1350, 1201, 1148, 1084, 990, 754. H-NMR (300 MHz, CDCl3): 7.35
7.21 (m, 5 arom. H); 5.99 (s, (C)3CˆCHCˆO); 5.30 (s, MeOCˆCHCˆO); 4.55 (s, PhCH2O); 3.73 (s, MeO);
3.40 3.31 (m, CHOCH2Ph); 2.89 (dt, J ˆ 3.6,3.5, CCH(CH2)2); 2.43 0.96 ( m, 11 H); 1.42 (s, Me); 1.3 8 (s, 2
Me); 0.88 (s, Me). 1H-NMR (300 MHz, C6D6; triterpene numbering): 7.65 7.15 (m, 5 arom. H); 6.15 (s,
C(5)ˆCHCˆO); 5.23( s, MeOCˆCHCˆO); 4.56 (s, PhCH2O); 3.49 (dt, J ˆ 13.6, 3.8, CCH(CH2)2); 3.42 3.89
(m, CHOCH2Ph); 2.92 (s, MeO); 2.74 2.56 (m, 3H); 2.20 0.82 ( m, 8 H); 1.95 (d, J ˆ 12.6, 1 H); 1.35 (s, Me);
1.21 (s, Me); 1.15 (s, Me); 1.03( s, Me). 13C-NMR (75 MHz, CDCl3): 200.7, 199.3, 176.7, 167.0, 139.1, 128.4, 128.3,
127.5, 127.3, 126.3, 99.2, 69.7, 56.3, 55.9, 50.0, 45.3, 41.9, 40.9, 37.9, 37.5, 34.7, 30.0, 28.8, 28.4, 28.1, 25.7, 21.1, 12.3.
‡
‡
‡
EI-MS: 462 (M ). HR-MS: 462.2779 (C30H38O4 , M ; calc. 462.2770).
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Chem. 2003, 68, 2183.
[5] P. Buchschacher, A. F¸rst, Org. Synth. 1985, 63, 3 7;1990, Coll. Vol. VII, 368.
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Medcalfe, M. W. Moon, P. M. Tomkins, J. Chem. Soc.(C) 1971, 1292.
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[8] C. D. Dzierba, K. S. Zandi, T. Mˆllers, K. J. Shea, J. Am. Chem. Soc. 1996, 118, 4711.
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[10] D. M. Donnelly, J.-P. Finet, B. A. Rattigan, J. Chem. Soc., Perkin Trans. 1 1993, 1729.
¬
[11] A. Rouillard, Ph.D. Thesis, Universite de Sherbrooke, unpublished results.
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Received August 20, 2003