Mono- and bicyclic cyclopentenes by rearrangement of 1-methylcyclobutylmethanols: synthesis of (±)-cuparene and formal syntheses of (±)-laurene and (±)-herbertene

Article abstract of DOI:10.1055/s-1998-2168

Addition of 1-methylcyclobutylmagnesium chloride (3) to acyclic (4d, e) and cyclic ketones (4a-c) yields 1-methylcyclobutylmethanols (5a-e), which may be rearranged to mono(11-14) and bicyclic cyclopentenes (6-10), respectively. Compounds 11, 12, and 13 are known precursors of (±)-laurene (15), (±)-cuparene (16), and (±)-herbertene (17), respectively. The cyclopentene 11 has been used in a two step synthesis of (±)cuparene (16).

Full text of DOI:10.1055/s-1998-2168

SYNTHESIS
October 1998
1523
Mono- and Bicyclic Cyclopentenes by Rearrangement of
1-Methylcyclobutylmethanols: Synthesis of (±)-Cuparene
and Formal Syntheses of (±)-Laurene and (±)-Herbertene1
Klaus Mandelt, Lutz Fitjer*
Institut für Organische Chemie der Universität Göttingen, Tammannstraße 2, D-37077 Göttingen, Germany
Fax: +49(551)395644; E-mail: lfitjer@gwdg.de
Received 17 December 1997; revised 11 March 1998
Abstract: Addition of 1-methylcyclobutylmagnesium chloride (3)
to acyclic (4d, e) and cyclic ketones (4a–c) yields 1-methylcy-
clobutylmethanols (5a–e), which may be rearranged to mono-
(11–14) and bicyclic cyclopentenes (6–10), respectively. Com-
pounds 11, 12, and 13 are known precursors of (±)-laurene (15),
(±)-cuparene (16), and (±)-herbertene (17), respectively. The
cyclopentene 11 has been used in a two step synthesis of (±)-
cuparene (16).
Key words: 1-methylcyclobutylmethanols, cascade rearrange-
ments, mono- and bicyclic cyclopentenes
The cyclobutylmethyl to cyclopentyl rearrangement is an
important method for the construction of cyclopentanes.2
Scheme 2
New reagents for the synthesis of suitable precursors
should therefore be welcome. It was in this context that
we generated the hitherto unknown 1-methylcyclobutyl-
magnesium chloride (3), studied its addition to acyclic
(4d,e) and cyclic ketones (4a–c), and rearranged the 1-
methylcyclobutylmethanols (5a–e) formed. In all cases,
high yields of mono- (11–14) and bicyclic cyclopentenes
(6–10), respectively, were obtained. Of these, 11,3 124 and
135 are known precursors of (±)-laurene (15),6 (±)-cupa-
rene (16)7 and (±)-herbertene (17),8 respectively. Howev-
er, as will be shown later, 11 may be used in a short syn-
thesis of (±)-cuparene (16) as well.
product formation involved a cyclobutylmethyl to cyclo-
pentyl rearrangement (10,11,13), eventually followed by
a second cyclobutylmethyl to cyclopentyl rearangement
(6,7), a cyclopentylmethyl to cyclohexyl rearrangement
(8,9), or a 1,2-methyl shift (12,12 14). With thionyl chlo-
ride in pyridine (Method B), the formation of 7 could be
avoided, and with hydrochloric acid in methanol (Method
C), the 1,2-methyl shifts leading to 12 and 14 could be
suppressed.13
Of the products formed, 11 has formerly been used by
McMurry3 in a five step synthesis of (±)-laurene (15), 12
by de Mayo4 in a four step synthesis of (±)-cuparene (16),
and 13 by Turner5 in a two step synthesis of (±)-her-
bertene (17). We adopted the protocol of Turner5 and ap-
plied it to 11. Towards this end, 11 was cyclopropanated
with diiodomethane/zinc-silver,14 and the two stereoiso-
meric cyclopropanes formed were hydrogenated over pla-
tinium dioxide in acetic acid. As was to be expected, both
cyclopropanes collapsed to a single product, i.e. (±)-
cuparene (16) (Scheme 4). After a single chromatography,
the product was pure.
For the generation of 1-methylcyclobutylmagnesium
chloride (3), the readily available methylenecyclobutane
(1)9 was first hydrochlorinated to 1-chloro-1-methyl-cy-
clobutane (2)10 and then reacted with magnesium in di-
ethyl ether (Scheme 1). For the following reactions, the
ketones 4a–e were first complexed with cerium(III) chlo-
ride (2.0 equiv) in tetrahydrofuran before the addition of
the Grignard reagent 3 (1.6 equiv).11 The reactions were
complete after 15 min at –78°C and 2 hours at room tem-
perature (Scheme 2). In the absence of cerium(III) chlo-
ride the yields of the products decreased sharply.
In summary, 1-methylcyclobutylmagnesium chloride (3)
adds to acyclic and cyclic ketones with formation of 1-
methylcyclobutylmethanols, which may be rearranged to
mono- und bicyclic cyclopentenes of great structural di-
versity. The addition products to acyclic ketones yield
monocyclic cyclopentenes (11–14), and the addition
products to cyclic ketones bicyclooctenes (6, 7), bicy-
Scheme 1
Quantitative rearrangements were observed when 5a–e clononenes (8, 9) or spiro[4.5]decenes (10), depending on
were heated with equimolar amounts of a 0.074 M solu- the ring size of the ketone used. The monocyclic cyclo-
tion of anhydrous p-toluenesulfonic acid in benzene for pentene 11 was used in a two step synthesis of (±)-cupare-
3 h to 70°C (Method A). With the exception of 7, only ne (16). It is obvious, that with other cyclobutane-based
hydrocarbons were formed (Scheme 3). In all cases, the Grignard reagents and/or other ketones than those em-

SYNTHESIS
Papers
1524
ployed here, other substitution patterns and/or frame-
works should be accessible.
1H and 13C NMR spectra were measured on a Bruker AMX 300 spec-
trometer using CDCl3 as solvent, and CHCl3 (δH = 7.24) and CDCl3
(δC = 77.00), respectively, as internal standards. Analytical GC was
carried out on a Carlo-Erba GC 6000 Vega Series 2 instrument em-
ploying a split/splitless injector, a FID 40 detector, and hydrogen as
the carrier gas, or on a Carlo-Erba GC 6000 Vega Series 2 instrument
employing a thermal conducticity detector, and H2 as the carrier gas.
The latter instrument was used for preparative GC as well. Product
ratios were not corrected for relative response. Rf values are quoted
for Macherey & Nagel Polygram SIL G/UV254 plates. Colourless sub-
stances were detected with 3.5% alcoholic 12-molybdophosphoric
acid (Merck) and subsequent warming. Impregnated TLC plates were
prepared by dipping the plates for 10 sec into a solution of 10% (w/w)
AgNO3 in MeOH/H2O (2:1, v/v) and drying for 1 h at 110°C. The
silica gel impregnated with 10% (w/w) AgNO3 for column chroma-
tography was prepared by adding the theoretical amount of silica gel
to a solution of AgNO3 in MeCN, evaporation of the solvent on a
rotary evaporator, and drying the residue for 48 h at 80°C/0.5 mbar
prior to use. 1-Chloro-1-methylcyclobutane (2)10 (purity 97%, GC)
was prepared by hydrochlorination of methylenecyclobutane (1).9
The 13C NMR data were in accord with literature data.15 Of the sol-
vents used, Et2O (Na), THF (LiAlH4) and pyridine (KOH) were dried
as indicated and distilled. The benzene used was of analytical grade.
All preparations were carried out under argon. All new compounds
gave satisfactory elemental analyses (5a–e, 6, 10: C ± 0.29, H ± 0.21)
or correct high resolution mass spectral data (7–9, 14).
1-Methylcyclobutylmagnesium Chloride (3):
Mg turnings (1.94 g, 80 mmol) and a few crystals of I2 were covered
with Et2O (50 mL), and a small portion of the full amount of 2 (8.37 g,
80 mmol) was added under argon with stirring. The reaction was start-
ed by heating briefly until the rest of 2 was added at such a rate as to
maintain a gentle reflux. After the addition was complete, the mixture
was heated for 2.5 h at reflux. The solution (50 mL) was transferred
to a stock vessel and two aliquots titurated in a four weeks interval. In
both cases the solution was 1.28 M (81%).
Method A: p-TsOH/benzene; Method B: SOCl2/pyridine; Method C:
HCl/MeOH
Scheme 3
1-Methylcyclobutylmethanols 5a–e; General Procedure:
•
Finely powdered CeCl3 7H2O (8.94 g, 24 mmol) was dehydrated for
6 h at 140°C/0.6 mbar. The dry material was suspended in THF
(85 mL) and stirred under Ar overnight. After the appropriate ketone
4 (12 mmol) had been added, stirring was continued for 2 h until the
mixture was cooled to –78°C and a 1.28 M solution of 3 in Et2O
(15.0 mL, 19.2 mmol) was added dropwise. After 15 min at –78°C
and 2 h at r.t. the mixture was hydrolyzed with 2 N HCl (50 mL). The
aqueous phase was extracted with Et2O (4 × 40 mL), and the com-
bined organic phases were washed with aq sat NaHCO3 solution (60
mL), brine (60 mL) and dried (MgSO4). The solvents were evaporat-
ed and the crude products were either chromatographed directly (5a–
c), or to achieve a better separation from unchanged starting material,
were treated with NaBH4 (400 mg, 11 mmol) in EtOH (70 mL) for 4
h at r.t. (5d,e). In this case, the reaction mixture was diluted with H2O
(75 mL) and extracted with Et2O (6 × 75 mL), and the combined ex-
tracts were washed with brine (2 × 50 mL), dried (MgSO4) and con-
centrated. In all cases, a final chromatography on silica gel (0.05–
0.20 mm) in pentane/Et2O [5a,c,d,e (5:1); Rf 0.19 (5a), 0.36 (5c),
0.35 (5d), 0.21 (5e); 5b (9:1); Rf 0.14 (5b)] yielded the pure products.
With the exception of 5c (mp 28–30°C), all products were colourless
liquids.
1-(1-Methylcyclobutyl)cyclobutanol (5a):
1H NMR: δ = 1.11 (s, 3 H, CH3), 1.42–1.60 (m, 4 H), 1.62–1.78 (m,
1 H), 1.80–2.12 (m, 6 H), 2.21–2.30 (m, 2 H).
13C NMR: δ = 12.4, 14.1 (t), 20.9 (q), 28.0, 31.2 (t), 43.0, 80.2 (s).
Scheme 4

SYNTHESIS
October 1998
1525
1-(1-Methylcyclobutyl) cyclopentanol (5b):
1H NMR: δ = 1.16 (s, 3 H, CH3), 1.42–1.82 (m, 13 H), 1.82–2.07 (m,
2 H).
13C NMR: δ = 22.8 (q), 22.9, 26.4, 27.8, 29.2, 41.1, 41.8 (t), 45.7 (s),
119.1 (d), 149.7 (s).
13C NMR: δ = 13.8 (t), 23.8 (q), 24.6, 29.3, 35.3 (t), 44.0, 86.7 (s).
3a-Methyl-2,3,3a,4,5,6-hexahydro-1H-indene (9):
1H NMR: δ = 0.95 (s, 3 H, CH3), 1.10–1.29 (m, 2 H), 1.50–1.80 (m,
6 H), 1.92–2.03 (m, 2 H), 2.07–2.22 (m, 1 H), 2.32–2.48 (m, 1 H),
5.26 (mc, 1 H, H-7).
1-(1-Methylcyclobutyl) cyclohexanol (5c):
1H NMR: δ = 0.96–1.12 (m, 1 H), 1.15 (s, 3 H, CH3), 1.20–1.46 (m,
7 H), 1.46–1.58 (m, 4 H), 1.58–1.72 (m, 2 H), 1.80–1.98 (m, 1 H),
2.12–2.26 (m, 2 H).
13C NMR: δ = 19.1 (q), 20.5, 24.2, 25.2, 29.2, 36.3 (t), 40.2 (s), 41.5
(t), 116.4 (d), 147.9 (s).
13C NMR: δ = 14.2, 21.6 (t), 23.2 (q), 25.8, 27.5, 30.1 (t), 45.9, 73.7 (s).
1-Methylspiro[4.5]dec-1-ene (10):
1-(1-Methylcyclobutyl)-1-(p-tolyl)ethanol (5d):
1H NMR: δ = 1.00–1.45 (m, 8 H), 1.50–1.70 (m, 2 H), 1.58 (mc, 3H,
CH3), 1.73 (t, J = 6.5 Hz, 2 H, H-4), 2.14 (mc, 2 H, H-3), 5.24 (mc, 1
H, H-2).
1H NMR: δ = 0.92 (s, 3 H, CH3), 1.11–1.23 (m, 1 H), 1.38–1.50 (m,
1 H), 1.41 (s, 3 H, CH3), 1.52–1.66 (m, 1 H), 1.62 (s, 1 H, OH), 1.70–
1.88 (m, 1 H), 2.24 (s, 3 H, CH3), 2.34 (ddd, J = 10, 10, 10 Hz, 1H),
2.49 (ddd, J = 10, 10, 10 Hz, 1 H), 7.02 (AA'-part of an AA'BB'-
system, 2 H), 7.21 (BB'-part of an AA'BB'-system, 2 H).
13C NMR: δ = 13.8 (t), 20.9, 23.4, 23.6 (q), 27.6, 28.7 (t), 46.3, 76.6
(s), 125.9, 128.2 (d), 135.9, 142.8 (s).
13C NMR: δ = 12.4 (q), 23.4, 26.1, 29.1, 34.2 (coincidence of two
lines) (t), 49.9 (s), 122.7 (d), 147.8 (s).
1-(1,2-Dimethylcyclopent-2-enyl)-4-methylbenzene (11):
13C NMR: δ = 13.1, 20.9, 24.1 (q), 29.9, 43.3 (t), 53.3 (s), 125.1,
126.1, 128.8 (d), 134.9, 145.4, 146.7 (s).
1-(1-Methylcyclobutyl)-1-(m-tolyl)ethanol (5e):
1H NMR: δ = 0.92 (s, 3 H, CH3), 1.11–1.23 (m, 1 H), 1.38–1.50 (m,
1 H), 1.41 (s, 3 H, CH3), 1.52–1.66 (m, 1 H, OH), 1.65 (s, 1 H), 1.70–
1.88 (m, 1 H), 2.26 (s, 3 H, CH3), 2.34 (ddd, J = 10, 10, 10 Hz, 1 H),
2.49 (ddd, J = 10, 10, 10 Hz, 1 H), 6.92–7.00 (m, 1 H), 7.08–7.11 (m,
2 H), 7.12–7.15 (m, 1 H).
1-(5,5-Dimethylcyclopent-1-enyl)-4-methylbenzene (12):
13C NMR: δ = 21.1, 27.4 (q), 29.3, 42.4 (t), 46.5 (s), 126.8, 127.3,
128.6 (d), 135.0, 136.1, 151.9 (s).
1-(1,2-Dimethylcyclopent-2-enyl)-3-methylbenzene (13):
13C NMR: δ = 13.1, 21.7, 24.0 (q), 29.9, 43.3 (t), 53.5 (s), 123.3,
125.2, 126.2, 126.9, 127.9 (d), 137.4, 146.7, 148.4 (s).
13C NMR: δ = 13.8 (t), 21.7, 23.3, 23.7 (q), 27.6, 28.7 (t), 46.3, 76.7
(s), 123.1, 126.7, 127.1, 127.4 (d), 137.0, 145.8 (s).
1-(5,5-Dimethylcyclopent-1-enyl)-3-methylbenzene (14):
1H NMR: δ = 1.20 (s, 6 H, 2 CH3), 1.85 (t, J = 6 Hz, 2 H, H-4'), 2.34
(s, 3 H, CH3), 2.36 (dt, J = 2.5, 6 Hz, 2 H, H-3'), 5.70 (t, J = 2.5 Hz, 1
H, H-1´), 7.02–7.24 (m, 4 H).
Rearrangement of 5a–e to Mono- and Bicyclic Cyclopentenes 6, 8,
10–14; General and Typical Procedures:
Method A: To a solution of anhyd p-TsOH in benzene (0.074 M,
13.5 mL, 1.00 mmol) was added the appropriate substituted methanol
5 (1.00 mmol) and the mixture was heated to 70°C. After 3 h, the
mixture was diluted with pentane (5 mL), washed with aq sat
NaHCO3 solution (3 × 5 mL), dried (molecular sieves 3 Å) and con-
centrated. The residue was subjected to preparative GC on column A
(3.5 m × 1/4" all glass system, 15% OV 101 on Chromosorb W AW/
DMCS 60/80 mesh) or column B (3.5 m × 1/4" all glass system, 15%
FFAP on Chromosorb W AW/DMCS 60/80 mesh), or chromato-
graphed on a silica gel column coated with 10% (w/w) AgNO3 in pen-
tane. 6,7: column A, 120°C, retention times (min): 3.67 (6), 7.46 (7),
7.77 (5a); 8,9: column B, 8.5 min at 95°C, 20°C/min to 190°C, reten-
tion times (min) 7.75 (8), 9.53 (9); 10: column A, 140°C, retention
time (min): 7.09 (10); 11,12: column A, 185°C, retention time (min):
5.60 (11,12); 13,14: chromatography on silica gel coated with 10%
(w/w) AgNO3 in pentane, Rf 0.09 (13), 0.07 (14). The 1H NMR data
of 11,3 124 and 135 were identical with literature data. The 13C NMR
have not yet been reported and are given below. With the exception
of 7 (mp 39–41°C), all products were colourless liquids.
13C NMR: δ = 21.5, 27.4 (q), 29.4, 42.4 (t), 46.6, 124.5, 127.2, 127.3,
127.7, 128.3 (d), 137.3, 138.0, 152.1 (s).
Method B: To a solution of 5a (140 mg, 1.00 mmol) in pyridine
(3.0 mL) was added at 0°C with stirring a solution of SOCl2 (236 mg,
2.00 mmol) in the same solvent (1.0 mL). After 3 h at 0°C, GC anal-
ysis [3.5 m × 1/4" all glass system, 15% OV 101 on Chromosorb W
AW/DMCS 60/80 mesh, 100°C, rel. retention times: 1.00 (6), 2.12
(5a)] indicated complete rearrangement to 6. The mixture was diluted
with H2O (5 mL) and extracted with pentane (3 × 5 mL), and the com-
bined extracts were washed with aq sat NH4Cl (4 × 5 mL) and dried
(molecular sieves 3 Å). Preparative GC yielded a sample identical (1H
NMR) with authentic 6.
Method C: To a solution of the appropriate alcohol 5d,e (836 mg,
4.20 mmol) in MeOH (10.0 mL) was added concd HCl (1.0 mL) and
the mixture was heated to reflux. After 2 h, the solution was neutral-
ized with 10% aq NaOH, diluted with H2O (6 mL), and extracted with
pentane (3 × 10 mL). The combined organic phases were washed with
brine (10 mL) and dried (MgSO4). The solvent was evaporated, and
the remaining material (741 mg (95%) from 5d, 726 mg (93%) from
5e) was subjected to capillary GC [30 m–0.32 mm (i.d.) deactivated
fused-silica capillary column coated with 0.25 µm DB FFAP; 10 min
100°C, 10°C/min to 220°C; 0.6 bar H2; retention times (min): 9.34
(11), 9.51 (12), 7.46 (13), 7.95 (14)] indicating a product ratio of 96:4
for 11 and 12, and of 97:3 for 13 and 14.
3a-Methyl-1,2,3,3a,4,5-hexahydropentalene (6):
1H NMR: δ = 1.00 (s, 3 H, CH3), 1.25–1.37 (m, 1 H), 1.51–1.70 (m,
2 H), 1.73–1.81 (m, 1 H), 1.83–2.08 (m, 2 H), 2.09–2.19 (m, 2 H),
2.33–2.45 (m, 1 H), 2.60–2.75 (m, 1 H), 5.11 (mc, 1 H, H-6).
13C NMR: δ = 22.5 (q), 22.5, 26.4, 35.8, 38.6, 40.3 (t), 55.5 (s), 116.0
(d), 158.2 (s).
6a-Methyloctahydropentalen-3a-ol (7):
(±)-Cuparene (16):
1H NMR: δ = 0.98 (s, 3 H, CH3), 1.35 (br s, 1 H, OH), 1.42–1.73 (m,
10 H), 1.74–1.85 (m, 2 H).
To a stirred suspension of freshly prepared zinc-silver couple14
(3.93 g) in anhyd Et2O (8.0 mL) under N2 was added a 96:4 mixture
of 11 and 12 (560 mg, 3.00 mmol) followed by CH2I2 (8.04 g,
30.0 mmol). After the vigorous reaction had subsided, the mixture
was heated for 2 h to reflux. After dilution with pentane (20 mL) the
solution was decanted, the residue was washed with pentane (10 mL),
and the combined organic phases were successively treated with sat
aq NH4Cl solution (30 mL), washed with H2O (2 × 15 mL), and dried
13C NMR: δ = 22.4 (t), 23.1 (q), 41.1, 41.8 (t), 50.2, 89.6 (s).
7a-Methyl-2,4,5,6,7,7a-hexahydro-1H-indene (8):
1H NMR: δ = 1.00 (s, 3 H, CH3), 1.10–1.29 (m, 2 H), 1.50–1.64 (m,
3 H), 1.67–1.81 (m, 3 H), 1.90–2.07 (m, 1 H), 2.09–2.35 (m, 3 H),
5.14 (mc, 1 H, H-3).

SYNTHESIS
Papers
1526
(MgSO4). The solvent was evaporated and the residue chromato-
graphed on silica gel (0.05–0.20 mm) in pentane (column 60 × 1.5
cm; Rf 0.44, 0.50) yielding 570 mg (95%) of a 70:30 mixture of two
stereoisomeric cyclopropanes according to capillary GC [30 m ×
0.32 mm (i.d.) deactivated fused-silica capillary column coated with
0.25 µm DB FFAP; 10 min 100°C, 10°C/min to 220°C; 0.6 bar H2;
retention times (min): 12.40 (70%), 13.56 (30%)]. A fraction of this
material (100 mg, 0.50 mmol) was dissolved in glacial AcOH (20
mL) and hydrogenated over PtO2 (1.0 g) and 1.1 atm hydrogen pres-
sure at r.t. in a shaking gear until capillary GC [retention times (min):
11.90 (16), 12.40, 13.56] indicated that the reaction was complete (4.5
h). After dilution with pentane (30 mL) the mixture was filtrated, and
the filtrate was washed with H2O (3 × 30 mL), satd aq NaHCO3 solu-
tion (30 mL) and dried (MgSO4). The solvent was evaporated and the
residue chromatographed on silica gel (0.05–0.20 mm) in pentane
(column 60 × 1.5 cm; Rf 0.52) yielding 55 mg (55%) of pure 16. The
1H and 13C NMR data were in accord with literature data.16
(3) McMurry, J. E.; von Beroldingen, L. A. Tetrahedron 1974, 30,
2027.
(4) de Mayo, P.; Suau, R. J. Chem. Soc., Perkin Trans. 1 1974,
2559.
(5) Turner, J. V.; Chandrasekaran, S. Tetrahedron Lett. 1982, 23,
3799.
(6) Irie, T.; Suzuki, Y.; Yasunari, Y.; Kurosawa, E.; Masamune, T.
Tetrahedron 1969, 25, 459.
(7) Enzell, C.; Erdtman, H. Tetrahedron 1958, 4, 361.
(8) Matsuo, A.; Yuki, S.; Nakayama, M. J. Chem. Soc., Chem.
Commun. 1981, 864.
(9) Fitjer, L.; Quabeck, U. Synthesis 1987, 299.
(10) Shand, W., Jr.; Schomaker, V.; Fischer, J. R. J. Am. Chem. Soc.
1944, 66, 636.
(11) Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima, T.; Kami-
ya, Y. J. Am. Chem. Soc. 1989, 111, 4392.
(12) For a related rearrangement leading to slightly different propor-
tions of 11 and 12, see: Salaün, J.; Fadel, A. Tetrahedron 1985,
41, 413.
(13) It has been shown by McMurry3 that olefin 11, as generated by
direct dehydration of the corresponding tertiary alcohol with
HCl in MeOH does not rearrange further.
This work was supported by the Fonds der Chemischen Industrie.
Technical assistance of U. Kaiser and R. Gerke is gratefully
acknowledged.
(14) Denis, J. M.; Conia, J. M. Synthesis 1972, 549.
(15) Krapivin, A. M.; Finkel´shtein, E. S.; Vdovin, V. M. Izv. Akad.
Nauk SSSR, Ser. Khim. 1986, 2697; Bull. Acad. Sci. USSR, Div.
Chem. Sci. (Engl. Transl.) 1986, 2472; Chem. Abstr. 1987, 107,
175 379.
(1) Cascade Rearrangements, part 21. For part 20 see: Fitjer, L.;
Majewski, M.; Monzó-Oltra, H. Tetrahedron 1995, 51, 8835.
(2) Wong, H. N. C. In Methods of Organic Chemistry (Houben–
Weyl); de Meijere, A., Ed., Georg Thieme Verlag: Stuttgart
1997; Vol. E 17e, p 495.
(16) Abad, A.; Agulló, C.; Arnó, M.; Cuñat, A. C.; Garcia, M. T.; Za-
ragozá, R. J. J. Org. Chem. 1996, 61, 5916.