Catalyzed asymmetric Diels - Alder reactions of benzoquinone. Total synthesis of (-)-ibogamine

Article abstract of DOI:10.1002/hlca.200290014

The Diels - Alder reaction of 1,4-benzoquinone with 1,3-dienes catalyzed by Mikami's [Ti{(S)-binol(2 -)}Cl₂] complex (binol = [1,1′-binaphthalene]-2,2′-diol) gives cycloadducts in good yield and in high enantiomer excess. A model is proposed to

Full text of DOI:10.1002/hlca.200290014

4306
Helvetica Chimica Acta Vol. 85 (2002)
Catalyzed Asymmetric DielsÀAlder Reactions of Benzoquinone.
Total Synthesis of (À)-Ibogamine
by James D. White* and Younggi Choi
Department of Chemistry, Oregon State University, Corvallis, Oregon, USA
(phone: 541-737-2173; fax: 541-737-2660; e-mail: james.white@orst.edu)
Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday and in recognition of his numerous
contributions to asymmetric synthesis.
The DielsÀAlder reaction of 1,4-benzoquinone with 1,3-dienes catalyzed by Mikami×s [Ti{(S)-
binol(2À)}Cl2] complex (binol ˆ [1,1'-binaphthalene]-2,2'-diol) gives cycloadducts in good yield and in high
enantiomer excess. A model is proposed to explain the observed absolute configuration of cycloadducts, and the
reaction is used as the key step in an asymmetric synthesis leading to the alkaloid (À)-ibogamine.
1. Introduction. The asymmetric DielsÀAlder reaction has become one of the
most widely used constructs for the assembly of enantiomerically enriched chiral
carbocycles [1]. In its catalyzed version, the reaction offers an especially powerful
synthetic method, which can lead to adducts from achiral materials in good yield and
high enantiomer excess (ee) at or below room temperature [2]. Most catalyzed
cycloadditions have relied on two-point ligation of an achiral dienophile with the chiral
catalyst to form a relatively rigid, highly asymmetric, activated complex [3]. Typical
dienophiles in this class are b-dicarbonyl compounds, where chelation with a metal such
as titanium bound to a chiral ligand creates a complex in which only one face of the
dienophile is exposed for reaction with its diene partner. As a result, asymmetric
DielsÀAlder additions in this mode can be very efficient. The asymmetric DielsÀAlder
reaction with a dienophile such as a simple a,b-unsaturated ketone or a 1,4-quinone
raises the question of whether stereocontrol can be exercised effectively by single-point
ligation of a chiral catalyst with the lone pair of electrons of only one carbonyl group.
This question was first answered in the affirmative by Mikami and co-workers who
showed that the reaction of 1,4-naphthoquinone with 1-methoxybuta-1,3-diene in the
presence of a [TiIV{binol(2À)}] catalyst (binol ˆ [1,1'-naphthalene]-2,2'-diol) led to
diketone 1 in high ee (Scheme 1) [4]. Subsequently, we found that benzoquinone in the
presence of the Mikami catalyst underwent DielsÀAlder cycloaddition with a 1,3-diene
derivative in similarly high ee [5]. Other examples from the laboratories of Corey [6]
and Nicolaou [7] illustrate the participation of substituted benzoquinones in
asymmetric DielsÀAlder reactions catalyzed by Mikami×s [Ti{binol(2À)}Cl2] system,
although the argument for single-point ligation in these cases is less clear. Recently, it
was shown that a,b-unsaturated ketones, for which single-point ligation is obligatory,
undergo DielsÀAlder addition to cyclopentadiene in the presence of a chiral
imidazolidinone to give cycloadducts in moderate to high ee; however, the generality

Helvetica Chimica Acta Vol. 85 (2002)
4307
of this process remains to be established [8]. Thus, while precedent exists to suggest
that 1,4-benzoquinone may serve as a chiral dienophile in the presence of an
asymmetric catalyst, the proposition that this strategy offers a practical and general
entry to DielsÀAlder adducts of consistently high enantiomer purity remained to be
demonstrated.
Scheme 1
2. Results and Discussion. In principle, any asymmetric catalyst attached to one of
the carbonyl groups of 1,4-benzoquinone breaks the D2d symmetry of this dienophile
and should, therefore, be capable of producing an asymmetric DielsÀAlder adduct if i)
the 1,3-diene component is not symmetrical, and ii) the rate of the catalyzed reaction
substantially exceeds that of the uncatalyzed process. Our first experiments with 1,4-
benzoquinone, various dienes, and the [Ti{taddol(2À)}Cl2] catalyst [9] (taddol ˆ 2,2-
dimethyl-a,a,a',a'-tetraphenyl-1,3-dioxolane-1,4-dimethanol) at room temperature
were not encouraging, the ee of DielsÀAlder adducts generally being below 60%; it
became clear that this catalyst system was not sufficiently active to accelerate
cycloaddition at lower temperatures where improved stereoselectivity might be
observed. Therefore, we turned to Mikami×s [Ti{binol(2À)}Cl2] catalyst, an established
commodity in the context of asymmetric DielsÀAlder addition to naphthoquinone [4],
and were pleased to find that DielsÀAlder adducts of 1,4-benzoquinone could be
obtained in good yield and high ee with this catalyst. Thus, addition of 2-methylpenta-
1,3-diene to benzoquinone in the presence of 10 mol-% of [Ti{(S)-binol(2À)}Cl2] gave
2 in 80% ee (Scheme 2). The dione 2 was unstable to chromatography and was
immediately subjected to reduction according to Gemal and Luche [10] with NaBH4
and cerium(III) chloride heptahydrate to afford a mixture of diol 3 and hydroxy ketone
4. The latter was converted to its (S)-Mosher ester 5 [11], which permitted the
determination of ee by analysis of its 19F-NMR spectrum; 4 was also esterified with (R)-
and (S)-O-methylmandelic acids to produce O-methylmandelates 6 and 7. Shielding of
Ha by the phenyl ring of (R)-O-methylmandelate 6 relative to its (S)-diastereoisomer 7
and applying the model of Trost and co-workers [12] enabled the absolute
configuration of these esters and hence 2 to be determined as shown.
We next examined the cycloaddition of (silyloxy)dienes 8 and 9 with 1,4-
benzoquinone in the presence of [Ti{(S)-binol(2À)}Cl2] and, again, found that the
reaction was greatly accelerated relative to the uncatalyzed process (Scheme 3). Luche
reduction of cycloadducts 10 and 11 to 12 and 13, respectively, with subsequent
ketalization by 2,2-dimethoxypropane and oxidation of the protected allylic alcohols 15
and 16 led to a,b-unsaturated ketones 17 and 18. These ketones allowed us to
determine that the DielsÀAlder reactions with 8 and 9 had taken place with an ee of 83

4308
Helvetica Chimica Acta Vol. 85 (2002)
Scheme 2
DCC ˆ dicyclohexylcarbodiimide, DMAP ˆ N,N-dimethylpyridin-4-amine
and 79%, respectively, as measured by HPLC (chiral OD column). Diol 13 was
conveniently crystalline, and its absolute configuration was determined by X-ray
crystallographic analysis (Fig. 1). Although none of the substances in the series
originating from diene 8 could be crystallized, the (R)- and (S)-O-methylmandelates 19
and 20, respectively, prepared from 15 established that 10 possessed the absolute
configuration shown [12]. Thus, all three cycloadducts 2, 10, and 11 obtained with the
[Ti{(S)-binol(2À)}Cl2] complex are found to have the same absolute configuration;
furthermore, they are in the same enantiomeric series that Mikami and co-workers
obtained with 1,4-naphthaquinone using the same catalyst. A transition state that

Helvetica Chimica Acta Vol. 85 (2002)
4309
Scheme 3
TMS ˆ Me3Si, TBS ˆ tBuMe2Si, DCC ˆ dicyclohexylcarbodiimide, DMAP ˆ N,N-dimethylpyridin-4-amine
rationalizes these results is presented in Fig. 2, although it must be remembered that
the precise structure of the Mikami catalyst is unknown.
Unfortunately, an attempt to extend the [Ti{binol(2À)}Cl2]-catalyzed DielsÀAlder
reaction of quinones to methyl 1,4-benzoquinone-2-carboxylate was less successful
(Scheme 4). The latter, prepared by oxidation of methyl 2,5-dihydroxybenzoate as
reported by Kraus and Taschner [13] and used in situ, was reacted with diene 9 to give
cycloadduct 21 in only 36% ee whose absolute configuration was not determined. The
racemic version of 21 has provided a convenient platform from which to launch
syntheses of polyhydroxylated sesquiterpenoids of the agarofuran family, including

4310
Helvetica Chimica Acta Vol. 85 (2002)
Fig. 1. ORTEP Plot of 13 with displacement ellipsoids at the 30% probability level. Configuration shown is
absolute.
Fig. 2. Proposed [Ti{(S)-binol(2À)}Cl2]Àbenzoquinone complex in which the top face of the more remote
double bond of the quinone is exposed for endo cycloaddition with 24, leadingto 27
(Æ)-euonyminol [14], but an efficient asymmetric entry to the highly functionalized
decalin core of this group remains elusive at this point. On the other hand, our effort to
exploit the catalyzed asymmetric DielsÀAlder reaction of 1,4-benzoquinone in a
synthesis of the indole alkaloid (À)-ibogamine (22) was more successful.
(À)-Ibogamine (22) and its congener (À)-ibogaine (23) are found in the west-
African shrub Tabernanthe iboga [15]; these alkaloids have attracted attention due to
anecdotal evidence that they reduce addiction to heroin and cocaine [16]. The

Helvetica Chimica Acta Vol. 85 (2002)
4311
Scheme 4
structures of 22 and 23 were determined by Taylor and co-workers in 1957who
employed both chemical degradation and X-ray crystallographic analysis [17], and the
¬
absolute configuration of 22 was established by Blaha and co-workers [18]. Following
the first synthesis of (Æ)-ibogamine by the B¸chi group in 1965 [19], numerous routes
to the racemic alkaloid have been published [20], including one by Sallay [21], which
began with a DielsÀAlder cycloaddition to 1,4-benzoquinone. Only one asymmetric
pathway to ibogamine has been reported, and this concluded at a 80 :20 mixture
favoring the (‡)-enantiomer [22].
Our plan for the synthesis of (À)-ibogamine (22) built upon the earlier work of
Sallay [21], but foresaw the possibility of turning Sallay×s route into one of greater
economy by employing a more highly functionalized diene in the initial DielsÀAlder
reaction. Thus, our first focal point became the preparation of a 1,3-disubstituted
butadiene, which carried appendages appropriate for constructing the non-indolic
portion of 22 without the need to forge additional CÀC bonds beyond the DielsÀAlder
step. This led us to the hexa-1,3-diene derivative 24, which was obtained by a Suzuki
coupling of (E)-boronate 25, prepared by the reaction of but-1-yne with catecholbor-
ane (ˆ1,3,2-benzodioxaborole) [23], with the 2-bromoallyl silyl ether 26 (Scheme 5).
The latter was acquired from 2-bromoallyl bromide by the method of Beswick and
Widdowson [24].
The DielsÀAlder addition of 1,4-benzoquinone to 24 in the presence of Mikami×s
[Ti{(S)-binol(2À)}Cl2] complex proceeded to completion in less than 30 min at room
temperature and gave a single endo adduct assigned structure 27 (Scheme 6). The
adduct was unstable towards chromatographic purification on silica gel, which resulted
in its conversion to the oxidized product 28, and it was not possible to determine either
the enantiomer purity or the absolute configuration of 27. For this reason, the crude

4312
Helvetica Chimica Acta Vol. 85 (2002)
Scheme 5
DielsÀAlder adduct was subjected immediately to Luche reduction with NaBH4 and
cerium(III) chloride, and the stable endo hydroxy ketone 29 resulting from reduction of
the less hindered carbonyl group was purified for further assay. A small amount (7%)
of the dihydronaphthalenediol 30 was also isolated from this reaction, presumably a
consequence of tautomerization of the diketone 27. HPLC Analysis of 29, employing a
chiral OD column and a hexane/iPrOH mixture as eluent, established that the ee of this
substance, and hence 27, was 81%. An increase in the catalyst concentration from 10 to
30 mol-% improved the ee of 27 to 87%, but no further enhancement occurred with
increasing quantities of the catalyst (see Table). For comparison, the same DielsÀAlder
reaction between 1,4-benzoquinone and 24 was run in the presence of [Ti{tad-
dol(2À)}Cl2] catalysts 31 and 32. In these cases, the reaction was much slower than that
with the Mikami catalyst and gave only a modest yield of adduct in low ee. The ee
improved with catalyst 31 as the reaction temperature was decreased from room
temperature to 08 and then to À158, but this was at the expense of chemical yield. It is
clear from the results in the Table that binol is a much superior chiral ligand to taddol in
catalyzing the addition of 1,4-benzoquinone to 24; however, it is important to note that
only the protocol specified by Mikami [4] in which the catalyst is prepared in situ from
binol and diisopropoxytitanium dichloride was effective. An alternative catalyst

Helvetica Chimica Acta Vol. 85 (2002)
4313
Scheme 6
TBS ˆ tBuMe2Si, DCC ˆ dicyclohexylcarbodiimide DMAP ˆ N,N-dimethyl-pyridin-4-amine
preparation in which binol, titanium tetraisopropoxide, and silicon tetrachloride were
used [25] resulted in both a lower yield and diminished ee of 27.
As with 4 and 15, it was possible to ascertain the absolute configuration of 27
indirectly by employing the (R)- and (S)-O-methylmandelates 33 and 34, respectively,
derived from hydroxy ketone 29. The upfield shift of Ha (cf. Formulae 6 and 7) in 33
relative to 34 (Dd 0.2 ppm) conforms to the model of Trost and co-workers [12] for this
diastereoisomer 33 and gave assurance that we could proceed towards an asymmetric
synthesis of (À)-ibogamine from its precursor. Subsequently, we developed a
conclusive means for verifying that 27 was in the correct enantiomeric series when
exhaustive Luche reduction of cycloadduct 27 was found to give cis-diol 35 (Scheme 7).
The latter, when treated with N-bromosuccinimide, afforded a mixture of inseparable
bromoepoxy alcohols 36 and 37, which upon oxidation with pyridinium dichromate

4314
Helvetica Chimica Acta Vol. 85 (2002)
Table. Catalyzed Asymmetric DielsÀAlder Reaction of 1,4-Benzoquinone with 24
Catalyst ([mol-%])
Reaction time [h]
Reaction temp. [8]
Product yield [%]
ee [%]
[Ti{(S)-binol}Cl2] (10)
[Ti{(S)-binol}Cl2] (20)
[Ti{(S)-binol}Cl2] (30)
31 (30)
31 (30)
31 (30)
0.5
0.5
0.5
24
24
24
r.t.
r.t.
r.t.
r.t.
0
65
62
65
41
29
25
23
81
82
87
26
55
58
10
À 15
32 (30)
24
r.t.
yielded bromoepoxy ketones 38 and 39. These compounds were separated with relative
ease by chromatography, and 38, which was highly crystalline, was subjected to X-ray
analysis by the anomalous dispersion technique. Fig. 3 displays the absolute config-
uration of 38, which by extension confirms the absolute configuration of cycloadduct
27. Importantly, the absolute configuration of 27 is consistent with that of 1, 2, 10, and
Scheme 7
TBS ˆ tBuMe2Si, NBS ˆ N-bromosuccinimide, PDC ˆ pyridinium dichromate

Helvetica Chimica Acta Vol. 85 (2002)
4315
11 obtained with the (S)-binol catalyst, lending confidence to future stereochemical
predictions that may be made with this system. In contrast to 35, hydroxy ketone 29 did
not produce a bromoepoxy compound upon exposure to N-bromosuccinimide but
instead gave bromohydrin 40 resulting from external solvolytic attack at the
intermediate bromonium ion 41 (Scheme 8).
Fig. 3. ORTEP Plot of 38 with displacement ellipsoids at the 30% probability level. Configuration shown is
absolute.
Scheme 8
TBS ˆ tBuMe2Si, NBS ˆ N-bromosuccinimide
With diol 35 of known absolute configuration in hand, it was now necessary to
modify the left-hand ring of this structure in a way that would lead to the tricyclic
framework of the non-indolic portion of 22. The first requirement toward this end was
reduction of both olefinic bonds of 35, a transformation that was accomplished in a
single step by hydrogenation over rhodium on alumina (Scheme 9). The selection of
this catalyst ensured that no hydrogenolysis of the three allylic O-functions would occur
during saturation of 35, but equally important was delivery of hydrogen to the
trisubstituted olefin exclusively from the exo face, thereby positioning the alkoxy-
methyl substituent on the concave interior of the cis-decalin structure 42 for a
subsequent cyclization that would create the azatricyclic core of 22.
Oxidation of diol 42 to diketone 43 with pyridinium dichromate was straightfor-
ward, but it now became necessary to distinguish between the two keto groups of 43 to
proceed with chemistry on the ring that contained them. Our first attempt to
discriminate between the keto groups of 43 involved cleavage of the silyl ether to give
44, which we had hoped could be closed to the six-membered hemiketal 45. This would
have provided a means for blocking one ketone while synthetic operations were
conducted on the other. Although the endo configuration of the hydroxymethyl
substituent in 44 appeared to favor formation of 45, no means could be found for

4316
Helvetica Chimica Acta Vol. 85 (2002)
Scheme 9
TBS ˆ tBuMe2Si, TIPS ˆ iPr3Si, PDC ˆ pyridinium dichromate, PPTS ˆ pyridinium p-toluenesulfonate
effecting this conversion. A possible rationale for this failure is that the cis-decalin 44
cannot attain a conformation in which both the hydroxymethyl and ethyl substituents
occupy the axial orientation necessary for internal hemiketalization. In any case, this
result forced us to consider other means for differentiating the keto groups of 43, and it
was quickly discovered that only the less hindered ketone formed a dimethyl ketal 46.
The process of ketalization led to simultaneous cleavage of the (tert-butyl)dimethylsilyl
ether of 43, a result that conveyed the message that more robust protection of the
primary alcohol would be needed for the next transformation. Ketal 46 was, therefore,
converted to its more durable triisopropylsilyl ether 47.
The pivotal Beckmann rearrangement envisioned for enlargement of the ketone
ring of 47 to an e-lactam required the preparation of (E)-oxime 48, and this was
accomplished in high yield with hydroxylamine hydrochloride and AcONa in MeOH at
reflux (Scheme 10). Although ketoximes are known to undergo Beckmann rearrange-
ment under a wide variety of conditions [26]1), previous experience had taught us that
1
)
For a contemporary view of the Beckmann rearrangement, see [26b].

Helvetica Chimica Acta Vol. 85 (2002)
4317
Scheme 10
TIPS ˆ iPr3Si, DMAP ˆ N,N-dimethylpyridin-4-amine
oxime tosylates are particularly good substrates for this transformation [27]. In the
event, exposure of 48 to TsCl and Et3N containing a small quantity of DMAP led to its
smooth conversion to lactam 49. None of the isomeric lactam resulting from migration
of the less substituted C-atom was detected in the reaction mixture.
Our attention next turned to conversion of 49 into the azatricyclic core of
ibogamine for which connection of the N-atom to the C-atom bearing the iPr3SiO group
was the key. A displacement across the endo face of the bicycle to forge this NÀC bond
required an active N-nucleophile, and it was initially supposed that the secondary
amine derived from reduction of lactam 49 would be best suited to this purpose. Lactam
49 was therefore reduced with sodium bis(2-methoxyethoxy)aluminum hydride (Red-
Al), and the resulting amine 50 was then treated with Bu4NF to give amino alcohol 51.
Surprisingly, all attempts to effect transannular cyclization of 51, for example via a
Mitsunobu reaction [28], were unsuccessful. Subsequent examination of the transition

4318
Helvetica Chimica Acta Vol. 85 (2002)
state for this displacement not only provided an explanation for its failure but also
suggested a remedy. Specifically, as the N-atom of 51 is brought towards the CH2OH
group for backside attack, a steric interaction develops between the endo H-atom of the
CH2 adjacent to the N-atom and the endo MeO substituent in the azepine ring. This
steric confrontation is evidently sufficient to block cyclization. On the other hand, 49
with a sp2 rather than a sp3 C-atom adjacent to the N-atom would suffer no such steric
impediment, and closure of the lactam to the tricyclic core of 22 should, therefore, be
more facile. On the basis of this hypothesis, 49 was advanced to alcohol 52 and then to
its tosylate 53. That our conjecture was indeed correct was confirmed by the fact that
exposure of 53 to NaH in THF produced the tricyclic lactam 54 cleanly and in good
yield. The displacement of tosylate 53 by the lactam N-atom must be energetically quite
favorable since the amide resonance of 53 is clearly lost in the course of its conversion
to 54.
The remaining transformation of 54 into (À)-ibogamine (22) first required release
of the keto function masked as its dimethyl ketal, a process that was most efficiently
accomplished by transketalization with acetone in the presence of an acidic catalyst
[29] (Scheme 11). The resulting keto lactam 55 was next subjected to a Fischer indole
synthesis [30] with phenylhydrazine in AcOH, the initially formed hydrazone requiring
extended treatment with hot BF3 ¥ Et2O to complete the reaction. Only one indole can
be formed from 55 since the keto group is situated next to a bridgehead C-atom, and 56
was indeed produced in good yield by this process. The final stage, reduction of lactam
56, proved to be more difficult than expected, conventional reagents such as LiAlH4
being completely ineffective. Fortunately, a protocol due to Sundberg and co-workers
[31] using diborane generated in situ from NaBH4 and BF3 ¥ Et2O was successful and
furnished crystalline (À)-ibogamine (22), identical with a sample of the natural
alkaloid kindly provided by Professor Huffman of Clemson University.
Scheme 11

Helvetica Chimica Acta Vol. 85 (2002)
4319
3. Conclusions. The preparation of (À)-ibogamine (23) in 14 steps from 1,4-
benzoquinone and 10% overall yield is a powerful illustration of the value of the
asymmetric DielsÀAlder reaction as a starting point in a multistep synthesis.
Furthermore, the knowledge that catalyzed asymmetric DielsÀAlder reactions can
now be applied with efficiency to 1,4-benzoquinone, at least with Mikami×s
[Ti{binol(2À)}Cl2] system, opens the way to more structurally varied chiral products
than were attainable previously. It can be expected that much use will be made of this
new paradigm of synthesis in the future.
We are grateful to Professor Alexandre F. T. Yokochi for the X-ray crystal structures of 13 and 38. Financial
support was provided by the National Science Foundation (CHE-0076103) and the National Institutes of Health
(GM-58889).
Experimental Part
General. CC ˆ Column chromatography. HPLC: tR in min. IR Spectra: nÄ in cmÀ1. NMR Spectra: d in ppm
rel. to SiMe4, J in Hz. MS: in m/z.
(1S,4R,4aS,5S,8aR)-1,4,4a,5,8,8a-Hexahydro-5,7-dimethylnaphthalene-1,4-diol (3) and (4S,4aR,8S,8aS)-
4a,5,8,8a-Tetrahydro-4-hydroxy-6,8-dimethylnaphthalen-1(4H)-one (4). To a soln. of 1m [Ti{(S)-binal(2À)}Cl2]
in CH2Cl2 (0.1 ml) and 1,4-benzoquinone (108 mg, 1 mmol) in CH2Cl2 (5 ml) at r.t. was added a soln. of (3E)-2-
methylpenta-1,3-diene (121 mg, 1.47mmol) in toluene (2 ml), and the mixture was stirred for 30 min at r.t. The
resultant soln. was diluted with MeOH (5 ml) and cooled to 08, and NaBH4 (38 mg, 1 mmol) and CeCl3 ¥ 7 H2O
(373 mg, 1 mmol) were added. The mixture was stirred for 1 h at 08 and then diluted with Et2O (30 ml). The
soln. was washed with H2O and sat. aq. NaCl soln., dried (MgSO4), and evaporated, and the residue separated
by column chromatography (silica gel; AcOEt/hexanes 1:3): 138 mg (71% from benzoquinone) of 3/4 as a
colorless oil.
Data of 3: Rf (AcOEt/hexanes 1 :3) 0.05. [a]2D3 ˆ À164.5 (c ˆ 1.0, CHCl3). IR (neat): 3405, 2960, 2875, 1437,
1
1378, 1061, 998, 774. H-NMR (300 MHz, CDCl3): 1.23 (d, J ˆ 7.5, 3 H); 1.69 (m, 3 H); 1.77 (br. s, 1 H); 1.82
1.89 (m, 1 H); 2.00 2.07( m, 2 H); 2.26 2.40 (m, 2 H); 2.51 2.64 (m, 1 H); 4.15 4.22 (m, 1 H); 4.39 4.47
(m, 1 H); 5.43 5.58 (m, 1 H); 5.63 5.69 (m, 1 H); 5.82 (ddd, J ˆ 2.3, 4.4, 10.2, 1 H). 13C-NMR (75 MHz,
‡
CDCl3): 17.4; 24.0; 27.7; 34.1; 37.6; 39.0; 64.9; 70.7; 128.9; 129.3; 130.7; 135.4. CI-MS: 193 (M[ ‡ H] ), 176, 159,
‡
147, 143, 131, 119, 109, 98, 86. HR-CI-MS: 194.1306 (C H18O2 ; calc. 194.1307).
12
Data of 4: Rf (AcOEt/hexanes 1 :3) 0.05. 1H-NMR (300 MHz, CDCl3): 1.35 (d, J ˆ 7.6, 3 H); 1.58 1.62
(m, 3 H); 1.93 2.06 (m, 3 H); 2.25 2.62 (m, 2 H); 2.67 2.78 ( m, 1 H); 4.84 4.89 (m, 1 H); 5.27 5.31
(m, 1 H); 5.77 5.85 (m, 1 H); 6.56 (dt, J ˆ 2.1, 10.3, 1 H). 13C-NMR (75 MHz, CDCl3): 19.2; 23.7; 26.9; 34.4;
44.5; 50.3; 70.9; 127.0; 130.1; 131.3; 147.9; 200.8.
(R)-O-Methylmandelate 6: 1H-NMR (400 MHz, CDCl3): 6.24 (Ha).
(S)-O-Methylmandelate 7: 1H-NMR (400 MHz, CDCl3): 6.42 (Ha).
(1S,4R,4aR,5S,8aR)-1,4,4a,5,8,8a-Hexahydronaphthalene-1,4,5-triol (12). To
a soln. of 1m [Ti{(S)-
binol(2À)}Cl2] in CH2Cl2 (0.2 ml) and 1,4-benzoquinone (216 mg, 2 mmol) in CH2Cl2 (5 ml) at r.t. was added
a soln. of 8 (426 mg, 3 mmol) in toluene (2 ml), and the mixture was stirred for 30 min at r.t. The soln. was
diluted with MeOH (5 ml) and cooled to 08, and NaBH4 (114 mg, 3 mmol) and CeCl3 ¥ 7 H2O (1.12 g, 3 mmol)
were added. The mixture was stirred for 1 h at 08 and diluted with Et2O (50 ml). The soln. was washed with H2O
and sat. aq. NaCl soln., dried (MgSO4), and evaporated to give a crude diol. To a stirred soln. of this diol
(325 mg, 1.3 mmol) in MeOH (5 ml) at 08 was added TsOH (2 mg), and the mixture was stirred for 1 h at 08. The
mixture was evaporated and the residue chromatographed (silica gel; AcOEt/hexanes 1:3, then MeOH/CH2Cl2
1:15): 237mg (65% from benzoquinone) of 12. Colorless oil. Rf (AcOEt/hexanes 1:3) 0.05. IR (neat): 3345,
3025, 2886, 1406, 1248, 1088, 1039, 1002. 1H-NMR (300 MHz, CDCl3): 2.13 2.23 (m, 2 H); 2.29 2.34 (m, 1 H);
2.34 2.41 (m, 1 H); 3.93 (s, 3 H); 3.96 3.99 (m, 1 H); 4.43 (t, J ˆ 4.4, 1 H); 4.50 (d, J ˆ 7.6, 1 H); 5.76 5.84
(m, 3 H); 5.91 (dt, J ˆ 3.6, 10, 1 H). 13C-NMR (75 MHz, CDCl3): 28.1; 32.9; 39.3; 63.5; 67.3; 67.9; 127.9; 130.4;
‡
‡
130.8; 133.3. CI-MS: 183 ([M ‡ H] ), 165, 147, 130, 129, 119, 105, 91, 86. HR-CI-MS: 183.1021 (C H15O3 ; calc.
10
183.1021).
(1S,4R,4aR,5S,8R,8aR)-5-{[(tert-Butyl)dimethylsilyl]oxy}-1,4,4a,5,8,8a-hexahydro-8-methylnaphthalene-
1,4-diol (13). To a soln. of 1m [Ti{(S)-binol(2À)}Cl2] in CH2Cl2 (0.1 ml) and 1,4-benzoquinone (107mg,

4320
Helvetica Chimica Acta Vol. 85 (2002)
1.0 mmol) in CH2Cl2 (5 ml) at r.t. was added a soln. of 9 (754 mg, 3.81 mmol) in toluene (2 ml), and the mixture
was stirred for 30 min at r.t. The mixture was diluted with MeOH (5 ml) and cooled to 08, and NaBH4 (68 mg,
1.79 mmol) and CeCl3 ¥ 7 H2O (671 mg, 180 mmol) were added. The mixture was stirred for 1 h at 08 and diluted
with Et2O (50 ml). The soln. was washed with H2O and sat. aq. NaCl soln., dried (MgSO4), and evaporated, and
the residue was chromatographed (silica gel; AcOEt/hexanes 1:5): 203 mg (73%, benzoquinone) of 13. White
solid. Rf (AcOEt/hexanes 1:5) 0.16. M.p. 148 1498. [a]2D3 ˆ ‡246.4 (c ˆ 1.26, CHCl3). IR (KBr): 3412, 3325,
2957, 2929, 2854, 1469, 1248, 1086, 1025. 1H-NMR (400 MHz, CDCl3): 0.18 (s, 3 H); 0.19 (s, 3 H); 0.91 (s, 9 H);
1.27( d, J ˆ 7.5, 3 H); 1.95 2.00 (m, 1 H); 2.07 2.17 ( m, 1 H); 2.38 (dt, J ˆ 4.2, 7.5, 1 H); 2.46 2.53 (m, 1 H);
3.89 3.97( m, 1 H); 3.98 4.06 (m, 1 H); 4.44 4.54 (m, 2 H); 5.66 (ddd, J ˆ 2.9, 4.8, 10.1, 1 H); 5.71 5.80
(m, 2 H); 5.84 (ddd, J ˆ 2.4, 4.7, 10.1, 1 H).13C-NMR (75 MHz, CDCl3): À4.4; À3.1; 16.6; 18.3; 26.2; 34.0; 37.9;
t
‡
41.6; 63.4; 64.6; 69.4; 125.6; 130.4; 133.1; 138.2. CI-MS: 253 ([M À Bu] ), 235, 217, 199, 179, 161, 143, 128, 105,
‡
86. HR-CI-MS: 311.2049 (C17H31O3Si ; calc. 311.2043).
(1S,4R,4aR,5S,8R,8aR)-1,4,4a,5,8,8a-Hexahydro-8-methylnaphthalene-1,4,5-triol (14). To a stirred soln. of
13 (105 mg, 0.34 mmol) in MeOH (5 ml) at r.t. was added TsOH (1 mg), and the mixture was stirred for 1 h at
508. The mixture was evaporated and the residue chromatographed (silica gel; AcOEt/hexanes 1:3, then
MeOH/CH2Cl2 1:15): 56 mg (85%) of 14. Colorless oil. Rf (AcOEt/hexanes 1:3) 0.05. 1H-NMR (300 MHz,
CDCl3): 1.23 (d, J ˆ 7.6, 3 H); 1.97 (dt, J ˆ 4.2, 6.4, 1 H); 2.44 (dt, J ˆ 4.6, 7.9, 1 H); 2.48 2.57 (m, 1 H); 3.03
(d, J ˆ 8.7, 1 H); 3.23 (d, J ˆ 7, 1 H); 3.69 (d, J ˆ 7.4, 1 H); 4.18 (dt, J ˆ 4, 6.6, 1 H); 4.37 4.44 ( m, 1 H); 4.55
(t, J ˆ 7.6, 1 H); 5.71 5.76 (m, 1 H); 5.80 (ddd, J ˆ 2.7, 4.4, 10.1, 1 H); 5.84 5.92 (m, 2 H). 13C-NMR (75 MHz,
CDCl3): 17.1; 33.6; 37.7; 40.8; 63.2; 63.4; 68.8; 127.6; 129.9; 134.5; 136.8.
(3aR,6S,6aR,9aS,9bR)-3a,6,6a,7,9a,9b-Hexahydro-2,2-dimethylnaphtho[1,8-de][1,3]dioxin-6-ol (15). To a
stirred soln. of 12 (132 mg, 0.73 mmol) in DMF (2 ml) at r.t. was added 2,2-dimethoxypropane (0.2 ml,
1.64 mmol) and TsOH (2 mg), and the mixture was stirred for 16 h. The mixture was diluted with sat. aq.
NaHCO3 soln. (1 ml) and extracted with Et2O (25 ml). The extract was washed with sat. aq. NaCl soln., dried
(MgSO4), and evaporated and the residue chromatographed (silica gel; AcOEt/hexanes 1:3): 140 mg (87%) of
15. Colorless oil. Rf (AcOEt/hexanes 1:3) 0.13. [a]2D3 ˆ ‡17.7 (c ˆ 1.39, CHCl3). IR (neat): 3423, 3024, 2985,
2903, 1378, 1223, 1104, 1062. 1H-NMR (300 MHz, CDCl3): 1.38 (s, 3 H); 1.48 (s, 3 H); 2.13 2.22 (m, 3 H); 2.30
2.39 (m, 1 H); 2.52 2.60 (m, 1 H); 4.06 4.14 (m, 1 H); 4.41 4.48 (m, 1 H); 4.48 4.55 (m, 1 H); 5.72 5.80
(m, 1 H); 5.84 (ddd, J ˆ 0.7, 3.5, 10.2, 1 H); 5.94 (ddd, J ˆ 1.6, 3.2, 10.2, 1 H); 6.00 6.08 (m, 1 H). 13C-NMR
‡
(75 MHz, CDCl3): 24.4; 25.7; 29.7; 35.2; 64.3; 65.5; 102.2; 127.5; 129.6; 131.6; 133.0. CI-MS: 223 ([ M ‡ H] ), 207,
‡
165, 147, 129, 117, 91. HR-CI-MS: 223.1342 (C H19O3 ; calc. 223.1334).
13
(3aR,6S,6aR,7R,9aS,9bR)-3a,6,6a,7,9a,9b-Hexahydro-2,2,7-trimethylnaphtho[1,8-de][1,3]dioxin-6-ol (16).
As described for 15, with 14 (24 mg, 0.12 mmol), DMF (1 ml), 2,2-dimethoxypropane (0.1 ml, 0.82 mmol), and
TsOH (1 mg), extraction with Et2O (15 ml). CC (silica gel; AcOEt/hexanes 1:5) gave 26 mg (91%) of 16.
Colorless oil. Rf (AcOEt/hexanes 1:5) 0.23. [a]D23 ˆ ‡150.7( c ˆ 1.9, CHCl3). IR (neat): 3474, 2984, 2936, 2903,
2878, 1373, 1221, 1068, 1031, 978. 1H-NMR (300 MHz, CDCl3): 1.23 (d, J ˆ 7.5, 3 H); 1.40 (s, 3 H); 1.50 (s, 3 H);
1.95 (ddd, J ˆ 3.8, 6.1, 9.7, 1 H); 2.34 2.46 (m, 1 H); 2.69 (ddd, J ˆ 6, 10.6, 11.9, 1 H); 2.89 (d, J ˆ 12.3, 1 H); 4.08
(ddd, J ˆ 3.6, 6, 12.2, 1 H); 4.32 4.39 (m, 1 H); 4.72 (ddt, J ˆ 1.2, 3.5, 10.4, 1 H); 5.62 (ddd, J ˆ 3.1, 4.1, 10, 1 H);
5.87 5.92 ( m, 2 H); 6.11 (ddd, J ˆ 1.6, 6, 10, 1 H). 13C-NMR (75 MHz, CDCl3): 17.5; 26.3; 29.2; 32.5; 36.6; 38.2;
‡
61.2; 62.9; 68.7; 103.0; 123.2; 132.3; 139.5. CI-MS: 237 ([M ‡ H] ), 221, 179, 161, 144, 143, 123, 117, 106, 91, 86.
‡
HR-CI-MS: 237.1491 (C H21O3 ; calc. 237.1491).
14
(3aR,6aR,9aS,9bR)-6a,7,9a,9b-Tetrahydro-2,2-dimethylnaphtho[1,8-de][1,3]dioxin-6(3aH)-one (17). To a
stirred suspension of DessÀMartin periodinane (80 mg, 0.19 mmol) in CH2Cl2 (5 ml) at r.t. was added a soln. of
15 (28 mg, 0.13 mmol) in CH2Cl2 (1 ml), and the mixture was stirred for 30 min at r.t. The reaction was quenched
by the simultaneous addition of sat. aq. NaHCO3 soln. (3 ml) and 10% aq. Na2S2O3 soln. (3 ml). This mixture
was stirred for 30 min. Then the org. layer was washed with sat. aq. NaCl soln., dried (MgSO4), and evaporated,
and the residue was chromatographed (silica gel; AcOEt/hexanes 1:3): 24 mg (88%) of 17. White solid. Rf
(AcOEt/hexanes 1:3) 0.3. M.p. 80 818. The ee was measured by HPLC (Diacel Chiralpak OD, hexanes/iPrOH
99 :1, flow rate 1.05 ml/min): tminor 21.8, tmajor 24.8. [a]2D3 ˆ ‡110.2 (c ˆ 0.64, CHCl3). IR (neat) 3033, 2987, 2891,
1681, 1379, 1226, 1084. 1H-NMR (300 MHz, CDCl3): 1.42 (s, 3 H); 1.46 (s, 3 H); 1.87( dddd, J ˆ 2.6, 5.2, 5.2, 16.8,
1 H); 2.70 (ddd, J ˆ 3.4, 5.1, 6.8, 1 H); 2.85 (dddt, J ˆ 0.9, 3.3, 6, 16.8, 1 H); 3.16 (ddd, J ˆ 7.6, 7.6, 7.6, 1 H); 4.36
4.43 (m, 1 H); 4.86 (dt, J ˆ 2.7, 8, 1 H); 5.67 (m, 1 H); 5.99 6.05 (m, 1 H); 6.06 (dd, J ˆ 2.3, 10.4, 1 H); 6.94
(ddd, J ˆ 0.8, 3.1, 10.4, 1 H). 13C-NMR (75 MHz, CDCl3): 24.1; 25.1; 30.5; 40.3; 42.0; 62.1; 67.3; 102.4; 126.6;
‡
129.8; 130.5; 150.0; 198.8. CI-MS: 221 ([M ‡ H] ), 205, 162, 149, 134, 133, 117, 105, 85. HR-CI-MS: 221.1179
(C13H17O3; calc. 221.1178).

Helvetica Chimica Acta Vol. 85 (2002)
4321
(3aR,6aR,7R,9aS,9bR)-6a,7,9a,9b-Tetrahydro-2,2,7-trimethylnaphtho[1,8-de][1,3]dioxin-6(3aH)-one (18).
To a stirred suspension of DessÀMartin periodinane (46 mg, 0.11 mmol) in CH2Cl2 (5 ml) at r.t. was added a
soln. of 16 (17mg, 0.07mmol) in CH 2Cl2 (1 ml), and the mixture was stirred for 1 h at r.t. The reaction was
quenched by the simultaneous addition of sat. aq. NaHCO3 soln. (2 ml) and 10% aq. Na2S2O3 soln. (2 ml), and
the mixture was stirred for 1 h. The org. layer was washed with sat. aq. NaCl soln., dried (MgSO4), and
evaporated, and the residue was chromatographed (silica gel; AcOEt/hexanes 1:5): 15 mg (89%) of 18. White
solid. Rf (AcOEt/hexanes 1:5) 0.14. M.p. 73 748. The ee was measured by HPLC (Diacel Chiralpak OD,
hexanes/iPrOH 97:3, flow rate 0.9 ml/min): tminor 13.3, tmajor 14.8. [a]D23 ˆ ‡52.6 (c ˆ 0.94, CHCl3). IR (neat):
1
2988, 2936, 2876, 1686, 1375, 1225, 1087. H-NMR (300 MHz, CDCl3): 1.43 (d, J ˆ 6.8, 3 H); 1.44 (s, 3 H); 1.48
(s, 3 H); 2.22 2.30 (m, 1 H); 2.72 (ddd, J ˆ 0.8, 4, 6.5, 1 H); 3.11 (ddd, J ˆ 7.5, 7.5, 7.5, 1 H); 4.43 (ddd, J ˆ 2.6,
5.3, 7.8, 1 H); 4.88 (dt, J ˆ 2.7, 8, 1 H); 5.63 (dt, J ˆ 2.9, 10.1, 1 H); 5.95 (ddt, J ˆ 0.9, 2.5, 10.1, 1 H); 6.03 (dd, J ˆ
2.3, 10.3, 1 H); 6.86 (ddd, J ˆ 0.8, 3.2, 10.3, 1 H). 13C-NMR (75 MHz, CDCl3): 18.7; 25.1; 30.4; 32.9; 42.9; 47.5;
‡
62.4; 67.6; 102.3; 125.7; 131.7; 136.7; 148.3; 199.8. CI-MS: 235 ([ M ‡ H] ), 219, 177, 159, 148, 131, 121, 105, 94, 91.
‡
HR-CI-MS: 235.1333 (C14H19O3 ; calc. 235.1334).
(R)-O-Methylmandelate 19: 1H-NMR (400 MHz, CDCl3): 1.39 (s, 3 H); 1.48 (s, 3 H); 1.88 (dt, J ˆ 5.5, 17.1,
1 H); 2.13 (dddd, J ˆ 3.1, 4.9, 11.2, 17.1, 1 H); 2.42 (ddt, J ˆ 1.3, 5, 16.5, 1 H); 2.49 2.56 (m, 1 H); 3.47( s, 3 H);
4.22 4.27( m, 1 H); 4.63 4.68 (m, 1 H); 4.84 (s, 1 H); 5.32 5.36 (m, 1 H); 5.51 (ddd, J ˆ 1.6, 1.9, 10.3, 1 H);
5.82 (ddd, J ˆ 2.5, 3.4, 10.3, 1 H); 5.84 (dt, J ˆ 2.9, 10.3, 1 H). 13C-NMR (100 MHz, CDCl3): 21.7; 25.3; 30.0; 33.7;
34.8; 57.8; 60.9; 68.7; 73.1; 83.0; 101.7; 127.4; 128.7; 128.9; 129.1; 129.2; 129.7; 130.6; 136.5; 170.6.
(S)-O-Methylmandelate 20: 1H-NMR (400 MHz, CDCl3): 1.24 (dt, J ˆ 5.2, 17.2, 1 H); 1.38 (s, 3 H); 1.46
(s, 3 H); 1.83 1.99 (m, 1 H); 2.13 2.29 (m, 1 H); 2.35 2.45 (m, 1 H); 3.46 (s, 3 H); 4.17 4.23 ( m, 1 H); 4.53
4.59 (m, 1 H); 4.80 (s, 1 H); 5.33 5.37( m, 1 H); 5.63 5.73 (m, 3 H). 13C-NMR (75 MHz, CDCl3): 21.1; 25.3;
29.9; 33.5; 34.7; 57.7; 60.9; 68.7; 72.9; 82.9; 101.6; 127.7; 128.8; 129.1; 129.3; 129.7; 130.3; 136.6; 170.5.
Methyl (1R,4S,4aS,8aR)-4-{[(tert-Butyl)dimethylsilyl]oxy}-4,5,8,8a-tetrahydro-1-methyl-5,8-dioxonaphtha-
lene-4a(1H)-carboxylate (21). To a stirred soln. of methyl gentisate (ˆ methyl 3,6-dioxocyclohexa-1,4-diene-1-
carboxylate; 168 mg, 1 mmol) at 08 was added silver(I) oxide (464 mg, 2 mmol) in one portion. The mixture was
warmed to r.t. and stirred for 4 h. To 0.1m [Ti{(S)-binol(2À)}Cl2] in CH2Cl2 (1 ml, 0.1 mmol) in CH2Cl2 (5 ml)
was added the soln. obtained above, and the mixture was stirred for 5 min at r.t. A soln. of 9 (713 mg, 3.6 mmol)
in toluene (1 ml) was added, and the mixture was stirred for 30 min at r.t. The mixture was evaporated, and the
residue was chromatographed (silica gel; AcOEt/hexanes 1:10): 186 mg (51%) of 21. Colorless oil. Rf (AcOEt/
hexanes 1:10) 0.13. The ee was measured by HPLC (Diacel Chiralpak OD, hexanes/iPrOH 98 :2, flow rate 1 ml/
min): tmajor 7.4, tminor 19.0. [a]2D3 ˆ À67.7 (c ˆ 1.18, CHCl3). IR (neat): 1749, 1710, 1686, 1253, 1227, 1089, 1058,
1037, 842. 1H-NMR (300 MHz, CDCl3): À0.09 (s, 3 H); 0.01 (s, 3 H); 0.76 (s, 9 H); 1.42 (d, J ˆ 7.6, 3 H); 2.13
2.22 (m, 1 H); 3.66 (d, J ˆ 4.8, 1 H); 3.80 (s, 3 H); 4.77 4.79 (m, 1 H); 5.67 5.70 ( m, 2 H); 6.58 (d, J ˆ 10.3,
1 H); 6.77 (d, J ˆ 10.3, 1 H). 13C-NMR (75 MHz, CDCl3): À4.9; À4.8; 17.5; 18.2; 26.0; 30.1; 50.8; 53.4; 66.6; 67.5;
‡
126.3; 133.1; 133.8; 144.7; 169.5; 196.4. CI-MS: 365 ([M ‡ H] ), 349, 307, 275, 267, 247, 225, 201, 195, 173, 141, 91.
‡
HR-CI-MS: 365.1782 (C19H29O5Si ; calc. 365.1784).
2-{{[(tert-Butyl)dimethylsilyl]oxy}methyl}hexa-1,3-diene (24). Into a flame-dried pressure bottle cooled to
À788 was condensed but-1-yne (3.25 g, 60.1 mmol) under Ar. Then 1m catecholborane in THF (60 ml, 60 mmol)
was injected into the stirred mixture, and the soln. was heated at 708 for 24 h. After the soln. had cooled to r.t., it
was distilled under reduced pressure: 8.57g (82%) of 2-[(1E)-but-1-enyl]-1,3,2-benzodioxoborole (25).
Colorless oil. B.p. 77 788/2.5 Torr. IR (neat): 3199, 2959, 1643, 1246, 742. 1H-NMR (300 MHz, CDCl3): 1.11
(t, J ˆ 7.4, Me); 2.33 (ddq, J ˆ 1.7, 7.5, 7.5, 2 H); 5.83 (dt, J ˆ 1.7, 18.0, 1 H); 7.01 7.28 (m, 5 H). 13C-NMR
‡
(75 MHz, CDCl3): 12.2; 28.8; 106.1; 112.2; 122.5; 148.2; 159.2. CI-MS: 174 (M ), 159, 146, 134, 120, 115, 101, 93,
‡
69. HR-CI-MS: 174.0852 (C10H1111BO2 ; calc. 174.0852).
To a soln. of 1.04 g (3 mol%) of [Pd(PPh3)4] in THF (80 ml) was added a soln. of 26 (7.53 g, 30.0 mmol) in
THF (10 ml), and the mixture was stirred for 1 h at r.t. To this mixture was added a soln. of 25 (5.80 g,
33.3 mmol) in THF (10 ml) followed by 66.6 mmol (2 equiv.) of EtONa, and the resultant mixture was heated
under reflux for 7h. The mixture was allowed to cool to r.t. during 1 h and was treated with 3 m aq. NaOH (1 ml)
and H2O2 (30%, 1 ml) for 1 h at r.t. The mixture was extracted with hexane (3 Â 30 ml), the extract washed with
sat. aq. NaCl soln., dried (MgSO4), and evaporated, and the residue was chromatographed (silica gel; Et2O/
pentane 1:30): 4.96 g (73%) of 24. Colorless oil. Rf (hexanes) 0.4. IR (neat): 2957, 2883, 2359, 2337, 1253, 1110.
1H-NMR (300 MHz, CDCl3): 0.09 (s, 6 H); 0.92 (s, 9 H); 1.02 (t, J ˆ 7.4, Me); 2.11 (m, 2 H); 4.32 (m, 2 H); 4.98
(s, 1 H); 5.19 (m, 1 H); 5.70 (dt, J ˆ 6.5, 16.1, 1 H); 6.06 (d, J ˆ 16.1, 1 H). 13C-NMR (75 MHz, CDCl3): À5.4
‡
(2 C); 13.5; 18.3; 25.9 (3 C); 26.1; 63.0; 112.1; 128.7; 131.4; 144.8. CI-MS: 227 ([M ‡ H] ), 211, 195, 193, 169,
‡
139, 137, 95, 83, 75. HR-CI-MS: 227.1815 (C H27OSi ; calc. 227.1831).
13

4322
Helvetica Chimica Acta Vol. 85 (2002)
(4aS,5S,8aR)-7-{{[(tert-Butyl)dimethylsilyl]oxy}methyl}-5-ethyl-4a,5,8,8a-tetrahydronaphthalene-1,4-dione
(27). To 1m [Ti{(S)-binol(2À)}Cl2] in CH2Cl2 (1.7ml) and 1,4-benzoquinone (603 mg, 5.58 mmol) in CH 2Cl2
(3 ml) at r.t. was added a soln. of 24 (1.47g, 6.49 mmol) in toluene (2 ml), and the mixture was stirred for 30 min
at r.t. The mixture was evaporated, and the crude 27 was used immediately for the next reaction because of its
facile oxidation to 28.
Data of 28: IR (neat) 2951, 2926, 2847, 1664, 838.1H-NMR (300 MHz, CDCl3): 0.04 (s, 6 H); 0.80 (t, J ˆ 7.5,
3 H); 0.93 (s, 9 H); 1.51 1.72 (m, 2 H); 2.85 (dd, J ˆ 2.4, 6.3, 23.6, 1 H); 3.13 (dd, J ˆ 4.7, 23.6, 1 H); 3.47 3.53
(m, 1 H); 4.22 (br. s, 1 H); 5.77 (m, 1 H); 6.71 (d, J ˆ 1.6, 2 H). 13C-NMR (75 MHz, CDCl3): À5.4 (2 C); 9.9;
18.4; 25.0; 25.9 (3 C); 28.2; 35.5; 66.1; 121.8; 134.9; 136.1; 136.6; 140.4; 143.2; 186.6; 186.9.
(4S,4aR,8S,8aS)-6-{{[(tert-Butyl)dimethylsilyl]oxy}methyl}-8-ethyl-4a,5,8,8a-tetrahydro-4-hydroxynaph-
thalen-1(4H)-one (29) and (5S)-7-{{[(tert-Butyl)dimethylsilyl]oxy}methyl}-5-ethyl-5,8-dihydronaphthalene-1,4-
diol (30). To a soln. of 27 obtained above in MeOH (5 ml) at 08 was added NaBH4 (211 mg, 5.58 mmol) and
CeCl3 ¥ 7 H2O (2.08 g, 5.58 mmol), and the mixture was stirred for 1 h at 08. The mixture was diluted with Et2O
(30 ml), the soln. was washed with H2O and sat. aq. NaCl soln., dried (MgSO4), and evaporated, and the residue
was chromatographed (silica gel; AcOEt/hexanes 1:3): 29 (1.23 g, 65% from benzoquinone) and 30 (130 mg,
7%).
Data of 29: Rf (AcOEt/hexanes 1:3) 0.34. [a]D23 ˆ À35.3 (c ˆ 1.45, CHCl3). IR (neat): 3370, 2953, 2926,
2853, 1685, 1673, 1254, 1073, 836, 777). 1H-NMR (300 MHz, CDCl3): 0.93 (t, J ˆ 7.4, 3 H); 1.80 2.27 (m, 5 H);
2.73 (m, 2 H); 3.98 (m, 2 H); 4.92 (m, 1 H); 5.62 (s, 1 H); 5.83 (dd, J ˆ 2, 7, 10.3, 1 H); 6.57 (ddd, J ˆ 2, 3.5, 10.3,
1 H). 13C-NMR (75 MHz, CDCl3): À5.3; À5.2; 12.5; 18.4; 22.2; 25.6; 25.9 (3 C); 41.3; 43.7; 48.2; 67.0; 70.7;
‡
125.7; 129.6; 134.1; 147.4; 199.7. CI-MS: 335 ([ M À H] ), 321, 279, 261, 205, 187, 159, 75. HR-CI-MS: 335.2047
‡
(C19H31O3Si ; calc. 335.2043).
Data of 30. IR (neat): 3363, 2930, 2958, 2858, 1487, 1463, 1256, 1071, 836, 779. 1H-NMR (300 MHz, CDCl3):
0.09 (s, 6 H); 0.79 (t, J ˆ 7.4, 3 H); 0.95 (s, 9 H); 1.62 1.75 (m, 2 H); 3.04 (dt, J ˆ 3.1, 21, 1 H); 3.28 (dd, J ˆ 2.7,
21, 1 H); 3.55 3.64 (m, 1 H); 4.21 4.24 (m, 2 H); 4.74 4.86 (m, 2 H); 5.87 5.92 ( m, 1 H); 6.50 6.51
(m, 2 H). 13C-NMR (75 MHz, CDCl3): À4.8; 10.5; 18.9; 25.6; 26.4; 29.0; 36.2; 67.3; 112.8; 113.4; 123.7; 123.8;
‡
127.5; 135.1; 147.0. CI-MS: 334 (M ), 319, 305, 277, 259, 247, 231, 189, 173, 145, 131, 115, 86. HR-CI-MS: 334.1968
‡
(C19H30O3Si ; calc. 334.1964).
(1S,4aS,5S,8aR)-7-{{[(tert-Butyl)dimethylsilyl]oxy}methyl}-5-ethyl-1,4,4a,5,8,8a-hexahydro-4-oxonaphtha-
len-1-yl (R)-O-Methylmandelate (33). To a soln. of 29 (45 mg, 0.13 mmol), (R)-O-methylmandelic acid (24 mg,
0.15 mmol), and DCC (30 mg, 0.15 mmol) in CH2Cl2 (4 ml) at r.t. was added DMAP (8 mg, 0.07mmol). After
30 min, the mixture was passed through a plug of cotton, which was rinsed with hexanes. The eluant was diluted
with sat. aq. NaHCO3 soln. (1 ml), the org. phase, washed with sat. aq. NaCl soln., dried (MgSO4), and
evaporated, and the residue was chromatographed (silica gel; AcOEt/hexanes 1:7): 53 mg (82%) of 33. Colorless
oil. Rf (AcOEt/hexanes 1:7) 0.25. [a]2D3 ˆ À67.1 (c ˆ 1.2, CHCl3). IR (neat): 2950, 2920, 2852, 1751, 1689, 1252,
1168. 1H-NMR (300 MHz, CDCl3) (integrations for the crude product in two regions, labeled a and b): 0.05
(s, 6 H); 0.91 (s, 9 H); 0.92 (t, J ˆ 7.4, 3 H); 1.72 2.09 (m, 4 H); 2.15 (m, 1 H); 2.79 (t, J ˆ 3.9, 1 H); 2.89
(m, 1 H); 3.42 (s, 3 H); 3.88 4.01a (m, 2 H); 4.81 (s, 1 H); 5.58 (m, 1 H); 5.83 (dd, J ˆ 2.5, 10.4, 1 H); 5.93
(dt, J ˆ 2.4, 5.3, 1 H); 6.24b (ddd, J ˆ 2.1, 4.0, 10.4, 1 H); 7.31 7.52 (m, 5 H). 13C-NMR (75 MHz, CDCl3): À5.3;
À5.2; 12.4; 18.4; 22.8; 25.5; 25.9 (3 C); 40.9; 41.0; 47.9; 57.4; 66.9; 73.3; 82.4; 125.5; 127.0 (2 C); 128.9; 131.0;
‡
133.9; 135.8; 142.4; 170.0; 198.7. CI-MS: 483 ([M À H] ), 469, 427, 353, 319, 261, 187, 121. CI-MS: 483 ([M À
‡
‡
H] ), 469, 427, 353, 319, 261, 187, 121. HR-CI-MS: 483.2567 (C H39O5Si ; calc. 483.2559).
28
(1S,4aS,5S,8aR)-7-{{[(tert-Butyl)dimethylsilyl]oxy}methyl}-5-ethyl-1,4,4a,5,8,8a-hexahydro-4-oxonaphtha-
len-1-yl (S)-O-Methylmandelate (34). As described for 33, with 29 (14 mg, 0.04 mmol), (S)-O-methylmandelic
acid (11 mg, 0.06 mmol), DCC (13 mg, 0.06 mmol), CH2Cl2 (3 ml), and DMAP (3 mg, 0.02 mmol). CC (silica
gel; AcOEt/hexanes 1:5) gave 17mg (82%) of 34. Colorless oil. Rf (AcOEt/hexanes 1:5) 0.22. [a]2D3 ˆ À29.0
(c ˆ 1.53, CHCl3). 1H-NMR (300 MHz, CDCl3): 0.02 (s, 6 H); 0.89 (s, 9 H); 0.91 (t, J ˆ 7.7, 3 H); 1.36 (m, 1 H);
1.71 1.97 (m, 3 H); 2.09 (m, 1 H); 2.64 2.78 (m, 2 H); 3.42 (s, 3 H); 3.70 (d, J ˆ 12.9, 1 H); 3.78 (d, J ˆ 12.9,
1 H); 4.81 (s, 1 H); 5.52 (m, 1 H); 5.87( dd, J ˆ 2.7, 10.3, 1 H); 5.94 (dt, J ˆ 2.5, 5.1, 1 H); 6.45 (ddd, J ˆ 1.7, 3.8,
10.3, 1 H); 7.31 7.49 (m, 5 H). 13C-NMR (75 MHz, CDCl3): À5.3 (2 C); 12.4; 18.3; 22.4; 25.5; 25.9 (3 C); 40.7;
40.9; 47.9; 57.3; 66.4; 73.2; 82.3; 124.5; 127.2 (2 C); 128.8 (2 C); 129.0; 131.1; 133.7; 136.0; 142.5; 169.9; 198.6.
(1S,4R,4aS,5S,8aR)-7-{{[(tert-Butyl)dimethylsilyl]oxy}methyl}-5-ethyl-1,4,4a,5,8,8a-hexahydronaphtha-
lene-1,4-diol (35). To a soln. of 27, obtained from 24 as described above, in MeOH (15 ml) at r.t. was added
NaBH4 (633 mg, 16.7mmol) and CeCl 3 ¥ 7 H2O (6.24 g, 16.7mmol), and the mixture was stirred for 8 h at r.t.
Workup as for 29 gave 35 (1.18 g, 62% from benzoquinone). White solid. Rf (AcOEt/hexanes 1:3) 0.33. M.p.
105 1068. [a]2D3 ˆ À129.7( c ˆ 1.95, CHCl3). IR (neat) 3387, 2956, 2928, 2881, 2858, 1254, 1005, 834, 776.

Helvetica Chimica Acta Vol. 85 (2002)
4323
1H-NMR (300 MHz, CDCl3): 0.02 (s, 6 H); 0.91 (s, 9 H); 1.04 (t, J ˆ 7.4, 3 H); 1.69 (m, 2 H); 1.89 2.11
(m, 4 H); 2.14 (d, J ˆ 6, 1 H); 2.23 2.35 (m, 2 H); 4.01 (m, 2 H); 4.15 (m, 1 H); 4.44 (m, 1 H); 5.65 (d, J ˆ 10.2,
1 H); 5.76 5.83 (m, 2 H). 13C-NMR (75 MHz, CDCl3): À5.3 (2 C) 12.4; 18.3; 23.1; 24.2; 25.9 (3 C); 37.0; 37.3;
‡
40.9; 64.4; 66.7; 70.3; 127.2; 128.4; 130.3; 137.5. CI-MS: 337 ([ M À H] ), 321, 303, 262, 205, 189, 171, 161. HR-CI-
‡
MS: 337.2202 (C H33O3Si ; calc. 337.2199).
19
(1R,2S,4R,8R,9S,10R)-2-Bromo-2-{{[(tert-butyl)dimethylsilyl]oxy}methyl}-10-ethyl-11-oxatricyclo[6.2.1.04,9]-
undec-6-en-5-one (38) and (1R,3R,7R,8R,9R,10S)-10-Bromo-1-{{[(tert-butyl)dimethylsilyl]oxy}methyl}-9-eth-
yl-11-oxatricyclo[5.3.1.03,8]undec-5-en-4-one (39). To a soln. of 35 (28 mg, 0.08 mmol) in THF (4 ml) was added
NBS (16 mg, 0.09 mmol), and the mixture was stirred for 1 h at r.t. The mixture was passed through a short pad
of silica gel, with AcOEt/hexanes 1 :5, the eluent was evaporated, and the residue was purified by CC (AcOEt/
hexanes 1 :5): 31 mg (91%) of 36/37 as colorless oil. The mixture was dissolved in CH2Cl2 (2 ml), and the soln.
was added dropwise to a suspension of PDC (68 mg, 0.18 mmol) and AcONa (15 mg, 0.18 mmol) in CH2Cl2
(4 ml). The resulting mixture was stirred for 2 h at r.t. and then filtered through Florisil, and the filtrate was
evaporated. CC (AcOEt/hexanes 1 :20 ! 1:10) of the residue afforded 22 mg (73%) of 38/39.
Data of 38: A pure sample of 38 was obtained as a white solid by repeated chromatography. Rf (AcOEt/
hexanes 1:5) 0.24. M.p. 106 1078. [a]2D3 ˆ À29.2 (c ˆ 0.36, CHCl3). IR (neat): 1689. 1H-NMR (300 MHz,
CDCl3): 0.05 (s, 6 H); 0.91 (s, 9 H); 1.01 (t, J ˆ 7.4, 3 H); 1.33 1.62 (m, 2 H); 1.99 (dd, J ˆ 10.3, 16.1, 1 H); 2.25
(dd, J ˆ 8.1, 16.1, 1 H); 2.50 (t, J ˆ 3.8, 1 H); 2.72 (t, J ˆ 7.5, 1 H); 2.85 (ddd, J ˆ 3.8, 8.1, 11.0, 1 H); 3.64 (d, J ˆ
10.7, 1 H); 3.75 (d, J ˆ 10.7, 1 H); 4.23 (s, 1 H); 4.47( t, J ˆ 4.4, 1 H); 5.96 (d, J ˆ 9.9, 1 H); 6.84 (dd, J ˆ 5.0, 9.9,
1 H). 13C-NMR (75 MHz, CDCl3): À5.4; 11.4; 18.3; 22.6; 25.8; 35.6; 43.1; 44.5; 46.5; 69.9; 70.8; 71.6; 82.9; 128.8;
‡
‡
141.5; 201.6. CI-MS: 415 (M ), 359, 335, 277, 259, 203, 175, 161, 105. HR-CI-MS: 413.1142 (C19H30BrO3Si , calc.
413.1148).
Data of 39: determined from the mixture with 38. Rf (AcOEt/hexanes 1:5) 0.22. 1H-NMR (300 MHz,
CDCl3): 1.08 (t, J ˆ 7.4, 3 H); 1.61 (m, 1 H); 1.7 0 (m, 1 H); 1.7 6 (m, 1 H); 2.13 2.21 (m, 2 H); 2.37( dd, J ˆ 12.1,
14.5, 1 H); 2.68 (m, 1 H); 3.59 (s, 2 H); 3.93 (m, 1 H); 4.38 (m, 1 H); 5.96 (d, J ˆ 9.9, 1 H); 7.01 (dd, J ˆ 5.7, 9.9,
1 H). 13C-NMR (75 MHz, CDCl3): À5.3 (2 C); 11.7; 23.7; 25.9 (3 C); 36.1; 42.1; 49.5; 51.4; 63.5; 66.9; 106.0;
127.2; 147.0; 201.6.
(4S,4aR,6S,7R,8R,8aR)-6-Bromo-6-{{[(tert-butyl)dimethylsilyl]oxy}methyl}-8-ethyl-4a,5,6,7,8,8a-hexahy-
dro-4,7-dihydroxynaphthalen-1(4H)-one (40). To a soln. of 29 (28 mg, 0.08 mmol) in CH2Cl2 (3 ml) at r.t. was
added NBS (16 mg, 0.09 mmol), and the mixture was stirred for 1 h. The mixture was passed through a short pad
of silica gel with AcOEt/hexanes 1:3, the eluent was evaporated, and the residue was purified by CC (silica gel;
AcOEt/hexanes 1:3): 25 mg of 40 (71%). Colorless oil. Rf (AcOEt/hexanes 1:3) 0.16. IR (neat). 3445, 2953,
2853, 1663, 1248. 1H-NMR (300 MHz, CDCl3): 1.01 (t, J ˆ 7.4, 3 H); 1.79 2.13 (m, 4 H); 2.31 (m, 1 H); 2.64
(dt, J ˆ 1.0, 4.4, 1 H); 3.00 (m, 1 H); 3.48 (d, J ˆ 3.3, 1 H); 3.97( d, J ˆ 10.9, 1 H); 4.01 (d, J ˆ 10.9, 1 H); 4.07
(br. s, 1 H); 4.91 (m, 1 H); 5.94 (dd, J ˆ 2.6, 10.3, 1 H); 6.70 (ddd, J ˆ 1.8, 3.2, 10.3, 1 H). 13C-NMR (75 MHz,
CDCl3): À5.4 (2 C); 12.3; 18.3; 23.3; 25.8 (3 C); 26.7; 42.4; 42.8; 46.5; 69.2; 70.7; 74.4; 75.2; 129.7; 149.4; 202.1.
‡
HR-CI-MS: 435.1391 (C19H34BrO4Si ; calc. 435.1389).
(1S,4R,4aS,5S,7R,8aR)-7-{{[(tert-Butyl)dimethylsilyl]oxy}methyl}-5-ethyldecahydronaphthalene-1,4-diol
(42). To a soln. of 35 (913 mg, 2.70 mmol) in AcOEt (10 ml) was added 5% Rh on Al2O3 (1.40 g), and the
mixture was placed under a balloon filled with H2. After 24 h, the mixture was filtered through a pad of Celite
with AcOEt (10 ml), and the filtrate was evaporated. CC (silica gel; AcOEt/hexanes 1:3) of the residue gave 42
(871 mg, 94%). Colorless oil. Rf (AcOEt/hexanes 1:3) 0.22. M.p. 123 1248. [a]2D3 ˆ À3.4 (c ˆ 2.3, CHCl3). IR
(neat): 3439, 2952, 2928, 2856, 1500, 1462, 1254, 1104, 1079, 836. 1H-NMR (300 MHz, CDCl3): 0.04 (s, 6 H); 0.89
(s, 9 H); 0.93 (t, J ˆ 7.1, 3 H); 1.06 (br.s, 1 H); 1.23 1.91 (m, 15 H); 3.44 (dd, J ˆ 6.4, 9.9, 1 H); 3.49 (dd, J ˆ 4.5,
9.9, 1 H); 3.74 (ddd, J ˆ 4.5, 9.4, 11.5, 1 H); 4.09 (br. s, 1 H). 13C-NMR (75 MHz, CDCl3): À5.3 (2 C); 12.3; 18.4;
‡
24.3; 24.7; 26.0 (3 C); 26.5; 32.9; 33.3; 39.9; 41.3; 41.9; 43.1; 66.7; 69.0; 73.2. CI-MS: 343 ([ M ‡ H] ), 325, 283,
‡
267, 209, 193, 175. HR-CI-MS: 343.2674 (C H39O3Si ; calc. 343.2669).
19
(4aS,5S,7R,8aR)-7-{{[(tert-Butyl)dimethylsilyl]oxy}methyl}-5-ethyloctahydronaphthalene-1,4-dione (43).
To a soln. of pyridinium dichromate (1.20 g, 3.20 mmol) in CH2Cl2 (10 ml) was added a soln. of 42 (730 mg,
2.13 mmol) in CH2Cl2 (3 ml), and the mixture was stirred for 4 h at r.t. The mixture was diluted with Et2O
(30 ml), and the soln. was filtered through a Celite pad. The filtrate was evaporated, and the residue was
chromatographed (silica gel; AcOEt/hexanes 1:3): 635 mg (88%) of 43. Colorless oil. Rf (AcOEt/hexanes 1:5)
1
0.16. [a]2D3 ˆ ‡88.5 (c ˆ 1.42, CHCl3). IR (neat): 2959, 2925, 2852, 1713, 1250, 1098, 837. H-NMR (300 MHz,
CDCl3): 0.02 (s, 6 H); 0.86 (s, 9 H); 0.87(overlapping m, 1 H); 0.88 (t, J ˆ 7.4, 3 H); 1.21 1.35 (m, 2 H); 1.53
1.76 (m, 4 H); 2.00 (m, 1 H); 2.35 2.49 (m, 1 H); 2.59 (dt, J ˆ 4.5, 13.6, 1 H); 2.65 2.74 (m, 2 H); 2.83
(m, 1 H); 3.09 (m, 1 H); 3.34 (dd, J ˆ 6.4, 9.9, 1 H); 3.43 (dd, J ˆ 5.4, 9.9, 1 H). 13C-NMR (75 MHz, CDCl3):

4324
Helvetica Chimica Acta Vol. 85 (2002)
À5.5 (2 C); 12.3; 18.2; 25.8 (3 C); 26.2; 29.6; 30.6; 37.0 (2 C); 40.4; 40.6; 49.3; 51.8; 67.7 ; 208.9; 210.9. CI-MS: 339
‡
‡
([M ‡ H] ), 323, 281, 263, 207, 189, 147, 75. HR-CI-MS: 339.2352 (C H35O3Si ; calc. 339.2356).
19
(4aR,6R,8S,8aS)-8-Ethyl-3,4,4a,5,6,7,8,8a-octahydro-6-(hydroxymethyl)naphthalen-1(2H)-one (46).
A
soln. of 43 (570 mg, 1.68 mmol) and PPTS (43 mg, 0.17 mmol) in MeOH (10 ml) was heated at 558 for 3 h,
after which the mixture was allowed to cool to r.t. The soln. was diluted with sat. aq. NaHCO3 soln. (3 ml) and
extracted with Et2O (20 ml). The extract was washed with sat. aq. NaCl soln., dried (MgSO4), and evaporated,
and the residue was chromatographed (silica gel; AcOEt/hexanes 1:2): 404 mg (89%) of 46. Colorless oil. Rf
(AcOEt/hexanes 1:2) 0.16. [a]2D3 ˆ ‡15.7( c ˆ 0.21, CHCl3). IR (neat): 3419, 2923, 2867, 2831, 1712, 1461, 1123,
1097. 1H-NMR (300 MHz, CDCl3): 0.66 (ddd, J ˆ 12.7, 12.7, 12.7, 1 H); 0.84 (t, J ˆ 7.5, 3 H); 1.18 (m, 1 H); 1.31
(ddd, J ˆ 12.3, 12.3, 12.3, 1 H); 1.49 1.67( m, 4 H); 1.7 6 (m, 1 H); 1.7 9 (dt, J ˆ 5.0, 14.3, 1 H); 1.89 (br. s, OH);
2.08 (ddd, J ˆ 2.1, 5.0, 14.3, 1 H); 2.13 (ddt, J ˆ 2.5, 9, 14.3, 1 H); 2.22 (ddt, J ˆ 2.6, 4.6, 13.1, 1 H); 2.41 (dt, J ˆ
6.8, 14.3, 1 H); 2.91 (m, 1 H); 3.19 (s, 3 H); 3.29 (s, 3 H); 3.44 (dd, J ˆ 6.0, 10.6, 1 H); 3.46 (dd, J ˆ 6.4, 10.6,
1 H). 13C-NMR (75 MHz, CDCl3): 12.4; 26.3; 28.1; 28.2; 30.1; 38.6; 40.5; 41.7; 45.7; 47.2; 47.9; 48.2; 68.1; 100.5;
‡
‡
211.6. CI-MS: 270 (M ), 253, 239, 221, 207, 189, 125, 101, 84. HR-CI-MS: 270.1830 (C H26O4 ; calc. 270.1831).
15
(4aR,6R,8S,8aS)-8-Ethyl-3,4,4a,5,6,7,8,8a-octahydro-4,4-dimethoxy-6-{[(triisopropylsilyl)oxy]methyl}-
naphthalen-1(2H)-one (47). To a soln. of iPr3SiCl (332 mg, 1.72 mmol) and 1H-imidazole (117mg, 1.72 mmol) in
DMF (5 ml) at r.t. was added a soln. of 46 (310 mg, 1.15 mmol) in DMF (1 ml, 1.15 mmol), and the mixture was
stirred for 2 h at r.t. The mixture was diluted with pentane (20 ml), the soln. was washed with H2O (3 Â 10 ml)
and sat. NaCl soln., dried (MgSO4), and evaporated, and the residue was chromatographed (silica gel; AcOEt/
hexanes 1:5): 456 mg (93%) of 47. Colorless oil. Rf (AcOEt/hexanes 1 :10) 0.23. [a]2D3 ˆ ‡6.6 (c ˆ 1.16, CHCl3).
IR (neat): 2956, 2942, 2864, 2361, 1719, 1116, 1097, 1055. 1H-NMR (300 MHz, CDCl3): 0.64 (ddd, J ˆ 13.1, 13.1,
13.1, 1 H); 0.85 (t, J ˆ 7.5, 3 H); 1.03 1.07 (m, 21 H); 1.19 (m, 1 H); 1.28 (ddd, J ˆ 12.0, 12.0, 12.0, 1 H); 1.49
1.69 (m, 4 H); 1.73 1.87 (m, 2 H); 2.08 (ddd, J ˆ 2.1, 4.8, 11.3, 1 H); 2.21 (ddt, J ˆ 2.8, 5.3, 13.1, 1 H); 2.40
(dt, J ˆ 6.1, 13.5, 1 H); 2.92 (m, 1 H); 3.19 (s, 3 H); 3.30 (s, 3 H); 3.45 (dd, J ˆ 6.8, 9.5, 1 H); 3.53 (dd, J ˆ 5.8, 9.5,
1 H). 13C-NMR (75 MHz, CDCl3): 11.9; 12.4; 17.9; 26.3; 28.0; 28.4; 30.3; 38.6; 41.0; 41.8; 45.9; 47.7; 47.8; 48.4;
‡
‡
68.5; 100.6; 211.5. CI-MS: 426 (M ), 409, 383, 351, 221, 184, 171, 147, 101. HR-CI-MS: 426.3162 (C24H46O4Si ;
calc. 426.3165).
(4aR,6R,8S,8aS)-8-Ethyl-3,4,4a,5,6,7,8,8a-octahydro-4,4-dimethoxy-6-{[(triisopropylsilyloxy]methyl}naph-
thalen-1(2H)-one Oxime (48). A suspension of 47 (312 mg, 0.73 mmol), hydroxylamine hydrochloride (508 mg,
2.31 mmol), and AcONa (600 mg, 7.31 mmol) in MeOH (3 ml) was heated gently under reflux for 3 h. After
cooling to r.t., the mixture was evaporated, and the residue was chromatographed (silica gel; MeOH/CH2Cl2
1:60): 261 mg (81%) of 48. Colorless oil. Rf (AcOEt/hexanes 1:5) 0.21. [a]2D3 ˆ ‡20.1 (c ˆ 1.05, CHCl3). IR
1
(neat): 3404, 2956, 2941, 2864, 1462, 1120, 1099, 1056, 881. H-NMR (300 MHz, CDCl3): 0.87( t, J ˆ 7.5, 3 H);
0.88 (m, 1 H); 1.07( m, 21 H); 1.3 1.7 (m, 9 H); 1.93 (m, 1 H); 2.02 (m, 1 H); 2.77 (t, J ˆ 3.4, 1 H); 3.18 (s, 3 H);
3.23 (s, 3 H); 3.33 (m, 1 H); 3.46 3.57( m, 2 H); 7.06 (br.s, 1 H).13C-NMR (75 MHz, CDCl3): 11.9; 12.5; 17.9;
20.1; 26.6; 26.7; 26.8; 30.2; 41.4; 41.7; 43.1; 45.5; 47.3; 47.5; 68.7; 101.2; 158.2.
(5aR,7R,9S,9aS)-9-Ethyldecahydro-5,5-dimethoxy-7-{[(triisopropylsilyl)oxy]methyl}-2H-benz[b]azepin-2-
one (49). To a mixture of TsCl (203 mg, 1.07mmol), Et 3N (0.15 ml, 1.07mmol), and a cat. amount of DMAP in
CH2Cl2 (3 ml) was added a soln. of 48 (186 mg, 0.43 mmol) in CH2Cl2 (5 ml), and the mixture was stirred for 3 h
at r.t. The mixture was diluted with CH2Cl2 (10 ml), the soln. was washed with H2O and sat. aq. NaCl soln., dried
(MgSO4), and evaporated, and the residue was chromatographed (silica gel; AcOEt/hexanes 1:3, then MeOH/
CH2Cl2 1:15): 138 mg (74%) of 49. Colorless oil. Rf (AcOEt/hexanes 1:3) 0.12. [a]2D3 ˆ À8.4 (c ˆ 2.38, CHCl3).
IR (neat): 2956, 2941, 2864, 1663, 1461, 1106, 1055, 882. 1H-NMR (300 MHz, CDCl3): 0.83 (ddd, J ˆ 12.8, 12.8,
12.8, 1 H); 0.92 (t, J ˆ 7.4, 3 H); 0.96 1.13 (m, 22 H); 1.31 (dq, J ˆ 7.4, 7.4, 1 H); 1.49 1.83 (m, 6 H); 1.91
(ddt, J ˆ 1.7, 7.5, 13.6, 1 H); 2.19 2.28 (m, 1 H); 2.47( dt, J ˆ 1.2, 13.1, 1 H); 3.15 (s, 3 H); 3.18 (s, 3 H); 3.50
(br. d, J ˆ 6.0, 2 H); 3.79 (br. s, 1 H). 13C-NMR (75 MHz, CDCl3): 11.4; 11.8; 17.9; 23.3; 25.3; 25.8; 29.65; 29.70;
‡
40.6; 42.8; 46.8; 47.2; 47.3; 49.6; 68.2; 102.0; 176.5. CI-MS: 442 ([M ‡ H] ), 410, 398, 378, 366. HR-CI-MS:
‡
442.3353 (C24H48NO4Si ; calc. 442.3353).
(5aR,7R,9S,9aS)-9-Ethyldecahydro-5,5-dimethoxy-7-{[(triisopropylsilyl)oxy]methyl}-2H-benz[b]azepine
(50). To a soln. of 49 (43 mg, 0.1 mmol) in benzene (3 ml) at r.t. was added 3.4m Red-Al in toluene (0.3 ml), and
the mixture was refluxed at 808 for 1 h. After the soln. had cooled to r.t., AcOEt (5 ml) was added. The mixture
was evaporated, and the residue was chromatographed (silica gel; MeOH/CH2Cl2 1 :30 ! 1:15): 39 mg (92%) of
50. Colorless oil. Rf (MeOH/CH2Cl2 1:15) 0.16. IR (neat): 3441, 2941, 2892, 2863, 2827, 1469, 1462, 1455, 1260,
1108, 1065. 1H-NMR (300 MHz, CDCl3): 0.83 0.91 (m, 1 H); 0.90 (t, J ˆ 7.2, 3 H); 1.04 1.10 (m, 21 H); 1.23
1.41 (m, 4 H); 1.54 1.68 (m, 6 H); 1.75 1.82 (m, 3 H); 2.81 2.93 (m, 2 H); 3.01 (dt, J ˆ 7.2, 12.8, 1 H); 3.13

Helvetica Chimica Acta Vol. 85 (2002)
4325
(s, 3 H); 3.21 (s, 3 H); 3.52 (br. d, J ˆ 5.6, 2 H). 13C-NMR (75 MHz, CDCl3): 11.8; 11.9; 18.0; 21.9; 24.7; 26.1;
‡
27.5; 30.1; 40.6; 43.7 ; 46.8; 47.3; 47.7 ; 47.9; 55.5; 68.7; 104.1. HR-CI-MS: 427.3482 (CH49NO3Si ; calc. 427.3482).
24
(5aR,7R,9S,9aS)-9-Ethyldecahydro-7-(hydroxymethyl)-5,5-dimethoxy-2H-benz[b]azepin-2-one (52). To a
soln. of 49 (125 mg, 0.28 mmol) in THF (3 ml) at r.t. under Ar was added 1m Bu4NF in THF (0.4 ml, 0.4 mmol),
and the mixture was stirred for 1 h at r.t. The mixture was diluted with CH2Cl2 (10 ml), the soln. was washed
with sat. aq. NaCl soln., dried (MgSO4), and evaporated, and the residue was chromatographed (silica gel;
MeOH/CH2Cl2 1 :15): 79 mg (99%) of 52. Colorless oil. Rf (MeOH/CH2Cl2, 1:15) 0.1. [a]2D3 ˆ À31.7( c ˆ 1.1,
CHCl3). IR (neat): 3385, 2956, 2929, 2872, 1655, 1452, 1104, 1054. 1H-NMR (300 MHz, CDCl3): 0.93 (ddd, J ˆ
12.3, 12.3, 12.3, 1 H); 0.94 (t, J ˆ 7.3, 3 H); 1.09 (ddd, J ˆ 12.4, 12.4, 12.4, 1 H); 1.33 (dq, J ˆ 7.2, 7.2, 2 H); 1.51
1.87( m, 7H); 1.93 ( ddt, J ˆ 2.3, 7.6, 15.2, 1 H); 2.26 (m, 1 H); 2.48 (dt, J ˆ 1.4, 13.7, 1 H); 3.16 (s, 3 H); 3.18
(s, 3 H); 3.49 (m, 2 H); 3.79 (m, 1 H); 5.25 (br. s, 1 H). 13C-NMR (75 MHz, CDCl3): 11.4; 23.2; 25.3; 25.7; 29.4;
‡
29.7 ; 40.0; 42.8; 46.6; 47.3; 47.4; 49.6; 67.7 ; 101.9; 176.8. CI-MS: 286M( ), 268, 254, 222, 204, 146, 114, 101. HR-
‡
CI-MS: 286.2013 (C15H28NO4 ; calc. 286.2019).
(5aR,7R,9S,9aS)-9-Ethyldecahydro-5,5-dimethoxy-7-{{[(4-methylphenyl)sulfonyl]oxy}methyl}-2H-benz[b]-
azepin-2-one (53). To a mixture of TsCl (21 mg, 0.11 mmol), Et3N (31 ml, 0.23 mmol), and a cat. amount of
DMAP in CH2Cl2 (3 ml) was added 52 (21 mg, 0.08 mmol), and the mixture was stirred for 3 h at r.t. The
mixture was diluted with CH2Cl2 (10 ml), the soln. was washed with H2O and sat. aq. NaCl soln., dried (MgSO4),
and evaporated, and the residue was chromatographed (silica gel; MeOH/CH2Cl2 1:15): 33 mg (100%) of 53.
Colorless oil. Rf (MeOH/CH2Cl2 1:15) 0.29. [a]D23 ˆ À27.2 (c ˆ 1.2, CHCl3). IR (neat): 2956, 1660, 1456, 1357,
1
1188, 1176, 1104, 1052. H-NMR (300 MHz, CDCl3): 0.74 (ddd, J ˆ 12.8, 12.8, 12.8, 1 H); 0.94 (t, J ˆ 7.3, 3 H);
0.96 (ddd, J ˆ 12.7, 12.7, 12.7, 1 H); 1.31 (dq, J ˆ 7.3, 7.3, 2 H); 1.41 1.58 (m, 3 H); 1.68 (dt, J ˆ 3.5, 13.6, 1 H);
1.71 1.95 (m, 3 H); 2.15 2.27( m, 1 H); 2.37 2.49 ( m, 1 H); 2.47( s, 3 H); 3.11 (s, 3 H); 3.15 (s, 3 H); 3.72
3.80 (m, 2 H); 3.82 (dd, J ˆ 6.6, 9.6, 1 H); 4.97(br. s, 1 H); 7.36 (d, J ˆ 8.2, 2 H); 7.76 (d, J ˆ 8.2, 2 H).13C-NMR
(75 MHz, CDCl3): 11.4; 21.6; 22.9; 25.3; 25.6; 29.0; 29.7 ; 37.0; 42.5; 46.3; 47.36; 47.44; 49.1; 74.2; 101.7; 127.9;
‡
‡
129.9; 132.7; 144.9; 176.6. CI-MS: 408 ([M À MeO] ), 376, 285, 204, 173. HR-CI-MS: 439.2029 (C22H33NO6S ;
calc. 439.2028).
(5aR,7R,9S,9aS)-9-Ethyl-4,5,5a,6,7,8,9,9a-octahydro-5,5-dimethoxy-1,7-methano-1H-benz[b]azepin-2(3H)-
one (54). To a soln. of NaH (3 mg, 0.11 mmol) in THF (3 ml) at 08 under Ar was added a soln. of 53 (16 mg,
0.04 mmol) in THF (1 ml), and the mixture was stirred for 30 min at r.t. and then refluxed for 1 h. The mixture
was diluted with sat. aq. NH4Cl soln. (0.5 ml), the soln. extracted with CH2Cl2, the extract was washed with sat.
aq. NaCl soln., dried (MgSO4), and evaporated, and the residue was chromatographed (silica gel; MeOH/
CH2Cl2 1:15): 6.6 mg (71%) of 54. Colorless oil. Rf (MeOH/CH2Cl2 1:15) 0.1. [a]2D3 ˆ À21.2 (c ˆ 1.1, CHCl3).
IR (neat): 2930, 2358, 1658, 1634, 1454, 1404, 1102, 1064, 1051. 1H-NMR (300 MHz, CDCl3): 0.91 (t, J ˆ 7.3,
3 H); 1.12 (ddt, J ˆ 2.4, 9.2, 13.6, 1 H); 1.30 1.81 (m, 7H); 1.92 2.13 ( m, 3 H); 2.27( ddd, J ˆ 1.0, 7.4, 13.2, 1 H);
2.72 (dt, J ˆ 0.9, 13.3, 1 H); 3.09 (m, 1 H); 3.17( s, 3 H); 3.19 (s, 3 H); 3.60 (br. d, J ˆ 2.8, 1 H); 3.75 (ddd, J ˆ 2.6,
4.3, 11.6, 1 H). 13C-NMR (75 MHz, CDCl3): 12.2; 25.8; 27.2; 27.4; 28.3; 30.0; 31.4; 40.5; 42.8; 47.7 (2 C); 50.1;
‡
‡
50.7; 103.1; 179.2. CI-MS: (M ), 267, 252, 236, 220, 204, 138, 101. HR-CI-MS: 267.1835 (C H25NO3 ; calc.
15
267.1834).
(5aR,7R,9S,9aS)-9-Ethyl-3,4,5a,6,7,8,9,9a-octahydro-1,7-methano-1H-benz[b]azepine-2,5-dione (55). To a
soln. of TsOH ¥ H2O (11 mg, 0.06 mmol) in acetone (3 ml) at 08 under Ar was added a soln. of 54 (15 mg,
0.06 mmol) in acetone (1 ml), and the mixture was stirred for 12 h at r.t. The mixture was diluted with sat. aq.
NaHCO3 soln. (0.5 ml) and extracted with CHCl3. The extract was washed with sat. aq. NaCl soln., dried
(MgSO4), and evaporated: 11 mg of 55 (86%). Colorless oil. 1H-NMR (300 MHz, CDCl3): 0.97( t, J ˆ 7.3, Me);
1.33 1.60 (m, 4 H); 1.69 1.87( m, 2 H); 1.89 2.06 (m, 2 H); 2.54 (ddd, J ˆ 4.9, 9.7, 13.8, 1 H); 2.62 2.74
(m, 3 H); 3.02 (ddd, J ˆ 7.4, 10.1, 13.6, 1 H); 3.17 (d, J ˆ 11.8, 1 H); 3.84 3.97( m, 2 H). 13C-NMR (75 MHz,
CDCl3): 12.0; 26.0; 27.1; 28.6; 30.2; 31.5; 37.1; 38.4; 49.6; 49.9; 52.1; 175.8; 210.5.
(‡)-Ibogamine-7-one (56). To a soln. of 55 (7mg, 0.03 mmol) in AcOH (1 ml) at r.t. was added a soln. of
phenylhydrazine (5 mg, 0.05 mmol) in AcOH (1 ml), and the mixture was stirred for 1 h at 508. The mixture was
allowed to cool to r.t. during 1 h, after which BF3 ¥ Et2O (9 mg, 0.06 mmol) was added. The resulting yellow soln.
was stirred for 12 h at 808. After the mixture had cooled to r.t., it was diluted with CH2Cl2, the soln. was washed
with H2O and sat. aq. NaCl soln., dried (MgSO4), and evaporated, and the residue was chromatographed (silica
gel; MeOH/CH2Cl2 1:30): 7 mg (77%) of 56. Pale yellow solid. Rf (MeOH/CH2Cl2 1:30) 0.23. M.p. 230 2328.
1
[a]2D3 ˆ ‡27.9 (c ˆ 0.7, CHCl ). IR (neat): 3429, 1631. H-NMR (300 MHz, CDCl3): 0.98 (t, J ˆ 7.4, 3 H); 1.48
3
2.19 (m, 8 H); 3.03 (m, 1 H); 3.18 (d, J ˆ 11.8, 1 H); 3.74 (d, J ˆ 15.7, 1 H); 3.81 (m, 1 H); 3.97( dd, J ˆ 1.7, 15.7,
1 H); 4.15 (s, 1 H); 7.06 7.18 (m, 2 H); 7.25 (m, 1 H); 7.50 (m, 1 H); 7.89 (br.s, 1 H). 13C-NMR (75 MHz,

4326
Helvetica Chimica Acta Vol. 85 (2002)
CDCl3): 12.1; 27.5; 28.6; 30.7; 32.1; 32.8; 35.9; 38.9; 49.3; 51.5; 102.6; 110.3; 118.2; 119.7 ; 121.7; 127.8; 135.0;
‡
‡
138.8; 175.8. CI-MS ([M ‡ H] ): 295, 279, 135, 122, 91, 73. HR-CI-MS: 294.1731 (C19H22N2O ; calc. 294.1732).
(À)-Ibogamine (22). To a soln. of 56 (4.2 mg, 0.014 mmol) in dry THF (3 ml) was added NaBH4 (28 mg,
0.74 mmol) in one portion. The mixture was cooled to 08, and BF3 ¥ Et2O (160 mg, 1.13 mmol) was syringed into
the mixture dropwise. The resulting yellow suspension was stirred at r.t. for 3 h under Ar. The solvent was
evaporated, and MeOH (2 ml), H2O (0.4 ml), and 10% HCl soln. (0.2 ml) were added. This soln. was stirred at
r.t. for 4 h, after which the MeOH was evaporated, and the residue was taken up in CH2Cl2 (10 ml). The mixture
was neutralized with sat. aq. NaHCO3 soln., and the aq. layer was extracted with CH2Cl2. The org. extract was
dried (MgSO4) and evaporated and the residual yellow solid was chromatographed (silica gel; MeOH/CH2Cl2
1.30): 3.1 mg (78%) of 22 (78%). Pale yellow crystalline solid. Rf (MeOH/CH2Cl2 1:15) 0.23. M.p. 156 1578.
[a]2D3 ˆ À45.8 (c ˆ 0.2, EtOH). IR (neat): 3400. 1H-NMR (400 MHz, CDCl3): 0.91 (t, J ˆ 7.1, 3 H); 1.24 (m, 1 H);
1.43 1.62 (m, 3 H); 1.66 (ddd, J ˆ 3.4, 6.4, 13.2, 3 H); 1.77 1.90 (m, 2 H); 2.06 (m, 1 H); 2.72 (m, 1 H); 2.91
(s, 1 H); 2.96 (ddd, J ˆ 1.6, 3.8, 11.7, 1 H); 3.02 3.11 (m, 2 H); 3.17( m, 1 H); 3.33 (ddd, J ˆ 4.4, 12.3, 16.6, 1 H);
3.42 (m, 1 H); 7.06 7.31 (m, 3 H); 7.48 (d, J ˆ 7.1, 1 H); 7.67 (br.s, 1 H). 13C-NMR (75 MHz, CDCl3): 11.9; 20.5;
26.3; 27.7; 31.9; 34.0; 41.1; 41.9; 49.9; 54.3; 57.7; 109.1; 110.1; 117.9; 119.2; 121.1; 129.6; 134.7; 141.5. CI-MS: 281
‡
‡
([M ‡ H] ), 195, 149, 136, 97, 69. HR-CI-MS: 280.1938 (C H24N2 ; calc. 280.1940).
19
REFERENCES
[1] W. Carruthers, in −Cycloaddition Reactions in Organic Synthesis×, Pergamon, Oxford, 1990.
[2] H. B. Kagan, O. Riant, Chem. Rev. 1992, 92, 1007; L. C. Diaz, J. Braz. Chem. Soc. 1997, 8, 289; D. A. Evans,
J. S. Johnson, in −Comprehensive Asymmetric Catalysis×, Eds. E. N. Jacobsen, A. Pfaltz, and H. Yamamoto,
Springer, New York, 1999, Vol. 3, p. 1177; E. J. Corey, Angew. Chem., Int. Ed. 2002, 41, 1650; K. C.
Nicolaou, S. A. Snyder, T. Montagnon, G. Vassilikogiannakis, Angew. Chem., Int. Ed. 2002, 41, 1668.
[3] J. M. Hawkins, S. Loren, J. Am. Chem. Soc. 1991, 113, 7794.
[4] K. Mikami, M. Terada, Y. Motoyama, T. Nakai, Tetrahedron: Asymmetry 1991, 2, 643; K. Mikami, Y.
Motoyama, M. Terada, J. Am. Chem. Soc. 1994, 116, 2812.
[5] J. D. White, Y. Choi, Org. Lett. 2000, 2, 2373.
[6] M. Breuning, E. J. Corey, Org. Lett. 2001, 3, 1559.
[7] K. C. Nicolaou, G. Vassilikogiannakis, W. M‰gerlein, R. Kranich, Angew. Chem. 2001, 113, 2543; Angew.
Chem., Int. Ed. 2001, 40, 2482; K. C. Nicolaou, G. Vassilikogiannakis, W. Magerlein, R. Kranich, Chem.
Eur. J. 2001, 7, 5359.
[8] A. B. Northrup, D. W. C. MacMillan, J. Am. Chem. Soc. 2002, 124, 2458.
[9] K. Narasaka, N. Iwasawa, M. Inoue, T. Yamada, M. Nakashima, J. Sugimori, J. Am. Chem. Soc. 1989, 111,
5340; T. A. Engler, M. A. Letavic, F. Takusagawa, Tetrahedron Lett. 1992, 33, 6731; T. A. Engler, M. A.
Letavic, K. O. Lynch Jr., F. Takusagawa, J. Org. Chem. 1994, 59, 1179; D. Seebach, R. Dahinden, R. E.
Marti, A. K. Beck, D. A. Plattner, F. N. M. K¸hnle, J. Org. Chem. 1995, 60, 1788; C. Haase, C. R. Sarko, M.
Dimare, J. Org. Chem. 1995, 60, 1777.
[10] A. L. Gemal, J. L. Luche, J. Am. Chem. Soc. 1981, 103, 5454.
[11] J. A. Dale, H. S. Mosher, J. Am. Chem. Soc. 1973, 95, 512.
[12] B. M. Trost, J. L. Belletire, S. Godleski, P. G. McDougal, J. M. Balkovec, J. J. Baldwin, M. E. Christy, G. S.
Ponticello, S. L. Varga, J. P. Springer, J. Org. Chem. 1986, 51, 2370.
[13] G. A. Kraus, M. J. Taschner, J. Org. Chem. 1980, 45, 1175.
[14] J. D. White, N. S. Cutshall, T. S. Kim, H. Shin, J. Am. Chem. Soc. 1995, 117, 9780; J. D. White, H. Shin, T. S.
Kim, N. S. Cutshall, J. Am. Chem. Soc. 1997, 119, 2404.
[15] T. A. Henry, −The Plant Alkaloids×, J. A. Churchill Ltd., London, 1949.
[16] P. Popik, P. Skolnick, in −The Alkaloids: Chemistry and Biology×, Ed. G. A. Cordell, Academic Press, San
Diego, 1998, Vol. 52, p. 197.
[17] W. I. Taylor, J. Am. Chem. Soc. 1957, 79, 3298; D. F. Dickel, C. L. Holden, R. C. Maxfield, L. E. Paszek,
W. I. Taylor, J. Am. Chem. Soc. 1958, 80, 123; M. F. Bartlett, D. F. Dickel, W. I. Taylor, J. Am. Chem. Soc.
1958, 80, 126.
¬
¬
[18] K. Blaha, Z. Koblicova, J. Trojanek, Collect. Czech. Chem. Commun. 1974, 39, 2258.
[19] G. B¸chi, D. L. Coffen, K. Kocsis, P. E. Sonnet, F. E. Ziegler, J. Am. Chem. Soc. 1965, 87, 2073; G. B¸chi,
D. L. Coffen, K. Kocsis, P. E. Sonnet, F. E. Ziegler, J. Am. Chem. Soc. 1966, 88, 3099.

Helvetica Chimica Acta Vol. 85 (2002)
4327
[20] W. Nagata, S. Hirai, T. Okumura, K. Kawata, J. Am. Chem. Soc. 1968, 90, 1650; M. Ikezaki, T. Wakamatsu,
Y. Ban, J. Chem. Soc., Chem. Commun. 1969, 88; P. Rosenmund, W. H. Haase, J. Bauer, R. Frische, Chem.
Ber. 1975, 108, 1871; Atta-ur-Rahman, J. A. Beisler, J. Harley-Mason, Tetrahedron 1980, 36, 1063; T.
Imanishi, N. Yagi, M. Hanaoka, Chem. Pharm. Bull. 1985, 33, 4202; J. W. Huffman, G. Shanmugasundaram,
R. Sawdaye, P. C. Raveendranath, R. C. Desai, J. Org. Chem. 1985, 50, 1460; M. E. Kuehne, P. J. Reider, J.
Org. Chem. 1985, 50, 1464; C. Herdeis, C. Hartke-Karger, Liebigs Ann. Chem. 1991, 99; K. J. Henry Jr.,
P. A. Grieco, W. J. Dubay, Tetrahedron Lett. 1996, 37, 8289.
[21] S. I. Sallay, J. Am. Chem. Soc. 1967, 89, 6762.
√
[22] B. M. Trost, S. A. Godleski, J. P. Genet, J. Am. Chem. Soc. 1978, 100, 3930.
[23] H. C. Brown, S. K. Gupta, J. Am. Chem. Soc. 1972, 94, 4370; F. Bjˆrkling, T. Norin, C. R. Unelius, J. Org.
Chem. 1987, 52, 292.
[24] P. J. Beswick, D. A. Widdowson, Synthesis 1985, 492.
[25] E. J. Corey, Y. Matsumura, Tetrahedron Lett. 1991, 32, 6289.
[26] a) R. E. Gawley, Org. React. 1998, 35, 1; b) M. T. Nguyen, G. Raspoet, L. G. Vanquickenborne, J. Am.
Chem. Soc. 1997, 119, 2552.
[27] J. D. White, P. Hrnciar, F. Stappenbeck, J. Org. Chem. 1999, 64, 7 87 1.
[28] C. Simon, S. Hosztafi, S. Makleit, J. Heterocycl. Chem. 1997, 34, 349.
[29] S. Atarashi, J. K. Choi, D. C. Ha, D. J. Hart, D. Kuzmich, C. S. Lee, S. Ramesh, S. C. Wu, J. Am. Chem. Soc.
1997, 119, 6226.
[30] B. Robinson, −The Fischer Indole Synthesis×, Wiley & Sons, New York, 1982.
[31] R. J. Sundberg, J. Hong, S. Q. Smith, M. Sabat, Tetrahedron 1998, 54, 6259.
Received June 20, 2002