Asymmetric phase-transfer catalysis by quaternary ammonium ions derived from Cinchona-alkaloid analogs containing 1,1'-binaphthalene moieties

Article abstract of DOI:10.1002/(SICI)1522-2675(19990707)82:7<981::AID-HLCA981>3.0.CO;2-V

The synthesis and catalytic properties of a new type of enantioselective phase-transfer catalysts, incorporating both the quinuclidinemethanol fragment of Cinchona alkaloids and a 1,1'-binaphthalene moiety, are described. Catalyst (+)-(aS,3R,4S,8R,9S)-4 with the quinuclidine fragment attached to C(7') in the major groove of the 1,1'-binaphthalene residue was predicted by computer modeling to be an efficient enantioselective catalyst for the unsymmetric alkylation of 6,7-dichloro-5-methoxy-2-phenylindanone (1; Scheme 1, Fig. 1). Its synthesis involved the selective oxidative cross- coupling of two differently substituted naphthalen-2-ols to afford the asymmetrically substituted 1,1'-binaphthalene derivative (±)-17 in high yield (Scheme 3). Chromatographic optical resolution via formation of diastereoisomeric camphorsulfonyl esters and functional-group manipulation gave access to the 7-bromo-1,1'-binaphthalene derivative (-)-(aS)-11 (Scheme 4). Nucleophilic addition of lithiated (-)-(aS)-11 to the quinuclidine Weinreb amide (+)-(3R,4S,8R)-8 afforded the two ketones (aS,3R,4S,8R)-27 and (aS,3R,4S,8S)-28 as an inseparable mixture of diastereoisomers (Scheme 6). Stereoselective reduction of this mixture with DIBAL-H (diisobutylaluminum hydride; preferred formation of the C(8)-C(9) erythro-pair of diastereoisomers with 18% de) or with NaBH₄ (preferred formation of the threo-pair of diastereoisomers with 50% de) afforded the four separable diastereoisomers (+)-(aS,3R,4S,8S,9S)-29, (+)-(aS,3R,4S,8R,9R)-30, (-)- (aS,3R,4S,8S,9R)-31, and (+)-(aS,3R,4S,8R,9S)-32 (Scheme 6). A detailed conformational analysis, combining ¹H-NMR spectroscopy and molecular- mechanics computations, revealed that the four diastereoisomers displayed distinctly different conformational preferences (Figs. 2 and 3). These novel Cinchona-alkaloid analogs were quaternized to give (+)-(aS,3R,4S,8R,9S)-4, (+)-(aS,3R,4S,8S,9S)-5, (+)-(aS,3R,4S,8R,9R)-6, and (-)-(aS,3R,4S,8S,9R)-7 (Scheme 7) which were tested as phase-transfer agents in the asymmetric allylation of phenylindanone 1. Without any optimization work, (+)- (aS,3R,4S,8R,9S)-4 was found to catalyze the allylation of 1 yielding the predicted enantiomer (+)-(S)-3b in 32% ee. The three diastereoisomeric catalysts (+)-5, (+)-6, and (-)-7 gave access to lower enantioselectivities (6 to 22% ee's), which could be rationalized by computer modeling (Fig. 4).

Full text of DOI:10.1002/(SICI)1522-2675(19990707)82:7<981::AID-HLCA981>3.0.CO;2-V

Helvetica Chimica Acta ± Vol. 82 (1999)
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Asymmetric Phase-Transfer Catalysis by
Quaternary Ammonium Ions Derived from Cinchona-Alkaloid
Analogs Containing 1,1'-Binaphthalene Moieties
by Laurent Ducry and François Diederich*
Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH-Zentrum,
Universitätstrasse 16, CH-8092 Zürich
The synthesis and catalytic properties of a new type of enantioselective phase-transfer catalysts,
incorporating both the quinuclidinemethanol fragment of Cinchona alkaloids and a 1,1'-binaphthalene moiety,
are described. Catalyst (‡)-(aS,3R,4S,8R,9S)-4 with the quinuclidine fragment attached to C(7') in the major
groove of the 1,1'-binaphthalene residue was predicted by computer modeling to be an efficient enantioselective
catalyst for the unsymmetric alkylation of 6,7-dichloro-5-methoxy-2-phenylindanone (1; Scheme 1, Fig. 1). Its
synthesis involved the selective oxidative cross-coupling of two differently substituted naphthalen-2-ols to
afford the asymmetrically substituted 1,1'-binaphthalene derivative ( Æ )-17 in high yield (Scheme 3).
Chromatographic optical resolution via formation of diastereoisomeric camphorsulfonyl esters and func-
tional-group manipulation gave access to the 7-bromo-1,1'-binaphthalene derivative ( )-(aS)-11 (Scheme 4).
Nucleophilic addition of lithiated ( )-(aS)-11 to the quinuclidine Weinreb amide (‡)-(3R,4S,8R)-8 afforded the
two ketones (aS,3R,4S,8R)-27 and (aS,3R,4S,8S)-28 as an inseparable mixture of diastereoisomers (Scheme 6).
Stereoselective reduction of this mixture with DIBAL-H (diisobutylaluminum hydride; preferred formation of
the C(8) C(9) erythro-pair of diastereoisomers with 18% de) or with NaBH4 (preferred formation of the threo-
pair of diastereoisomers with 50% de) afforded the four separable diastereoisomers (‡)-(aS,3R,4S,8S,9S)-29,
(‡)-(aS,3R,4S,8R,9R)-30,
(
)-(aS,3R,4S,8S,9R)-31, and (‡)-(aS,3R,4S,8R,9S)-32 (Scheme 6).
A detailed
conformational analysis, combining 1H-NMR spectroscopy and molecular-mechanics computations, revealed
that the four diastereoisomers displayed distinctly different conformational preferences (Figs. 2 and 3). These
novel Cinchona-alkaloid analogs were quaternized to give (‡)-(aS,3R,4S,8R,9S)-4, (‡)-(aS,3R,4S,8S,9S)-5, (‡)-
(aS,3R,4S,8R,9R)-6, and ( )-(aS,3R,4S,8S,9R)-7 (Scheme 7) which were tested as phase-transfer agents in the
asymmetric allylation of phenylindanone 1. Without any optimization work, (‡)-(aS,3R,4S,8R,9S)-4 was found
to catalyze the allylation of
1
yielding the predicted enantiomer (‡)-(S)-3b in 32% ee. The three
diastereoisomeric catalysts (‡)-5, (‡)-6, and ( )-7 gave access to lower enantioselectivities (6 to 22% eeꢀs),
which could be rationalized by computer modeling (Fig. 4).
1. Introduction. ± Chiral catalysts for asymmetric synthesis are in increasing demand
[1 ± 4]. In asymmetric phase-transfer catalysis (PTC), the most commonly used
catalysts are either chiral quaternary ammonium salts (quats) derived from Cinchona
and Ephedra alkaloids, or chiral crown ethers [5 ± 9]. A particularly successful example
for the use of quats derived from Cinchona alkaloids in asymmetric PTC was described
by Dolling and co-workers [10]. The methylation of phenylindanone 1 with MeCl,
catalyzed by the cinchonine-derived quaternary benzyl ammonium salt (‡)-
(3R,4S,8R,9S)-2, was reported to provide methylated indanone (‡)-(S)-3a with an
ee (enantiomeric excess) up to 92% (Scheme 1). Based on molecular-model examina-
tions and an X-ray crystal structure of the quat, the authors proposed a tight ion-pair
model for the interaction between the cationic catalyst and the enolate form of substrate
1 in the transition state of the alkylation step. In this model, the enolate binds to the

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catalyst by a combination of ion-pairing, H-bonding, and p-p stacking interactions. The
alkylating agent subsequently approaches the less hindered face of the enolate,
opposite to the catalyst, which accounts for the observed asymmetric induction.
Scheme 1. Phase-Transfer-Catalyzed Alkylation of Phenylindanone 1 [10].
Other examples of asymmetric PTC by quats derived from Cinchona alkaloids and
modified derivatives are the stereoselective syntheses of a-amino acids by alkylation of
Schiff-base derivatives of glycine esters [11 ± 13]. In addition to enantioselective
alkylation reactions, Cinchona alkaloid quats have been used in asymmetric aldol
reactions [14], Michael additions [15], epoxidations [16], a-hydroxylations [17], and
reductions [18].
Recently, we became interested in substituting the quinoline part in Cinchona
alkaloids by chiral cleft-type aromatic moieties such as 2,2'-disubstituted 9,9'-
spirobi[9H-fluorenes] [19] or 2,2'-disubstituted 1,1'-binaphthalenes, hoping to generate
hybrid materials with enhanced molecular-recognition and catalytic properties. Here,
we present the computer-assisted design, synthesis, and catalytic properties of the first
such hybrid systems composed of the quinuclidine moiety of Cinchona alkaloids and a
1,1'-binaphthalene derivative. In addition to their application as ligands in asymmetric
catalysis [16d][20], Cinchona alkaloids are the most widely used components in chiral
auxiliaries for enantiomer separations [21][22]. Similarly, substituted 1,1'-binaphtha-
lenes are popular chiral ligands in asymmetric transition-metal catalysis [23], and
represent versatile chiral scaffolds in molecular recognition [24 ± 26].
The hybrid system (‡)-(aS,3R,4S,8R,9S)-41)2) was designed with the aid of
computer modeling as a new phase-transfer catalyst for the enantioselective allylation
of phenylindanone 1. The stereoselective formation of quaternary C-atom stereo-
centers as in the alkylation of 1 (Scheme 1) remains a challenging task in synthetic
organic chemistry [28]. Three diastereoisomeric catalysts, (‡)-(aS,3R,4S,8S,9S)-5, (‡)-
(aS,3R,4S,8R,9R)-6, and ( )-(aS,3R,4S,8S,9R)-7 were also obtained and tested as
1
)
The descriptors (aR) and (aS) are used for assignments of the sense of axial chirality; for recent examples,
see [27].
2
)
The arbitrary numbering corresponds to that in use for the natural Cinchona alkaloids quinine and
quinidine.

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phase-transfer catalysts. The observed trends in enantioselectivities could be, in all
cases, rationalized by the molecular modeling, and the preferentially formed
enantiomers predicted.
2. Results and Discussion. ± 2.1. Computer-Assisted Design of Phase-Transfer
Catalyst (‡)-(aS,3R,4S,8R,9S)-4. It is notable that only 1,1'-binaphthalenes bearing
ligating functionalities at the 2,2'-positions in the minor groove have so far been
successfully used in catalysis. A 1,1'-binaphthalene ligand with phosphine substituents
at the 7,7'-positions in the major groove has been described [29]; however, no
application in asymmetric catalysis has been reported to date. Molecular-recognition
studies had previously demonstrated a high potential of the major groove, with its large
polarizable aromatic surfaces, for selective substrate recognition [22][26], and,
therefore, it seemed worthwhile to explore the attachment of the quinuclidinemethanol
moiety to C(7') of the 1,1'-binaphthalene fragment. This attachment was also suggested
by a computer-assisted screening of potential catalyst geometries.
A series of binaphthalene derivatives with the quaternized quinuclidinemethanol
moiety attached to either the minor or the major groove and having various
configurations at C(8) and C(9) of the Chinchona-alkaloid fragment (for the
numbering, see Formulae 4 ± 7), as well as opposite axial chirality ((aS) or (aR)) with
respect to the binaphthalene moiety were, therefore, examined as potential phase-
transfer catalysts. Pseudo-Monte-Carlo Multiple Minimum (MCMM) conformational
searches (5000 steps) in CHCl3, with the MM2* force field3) and the GB/SA solvation
model [31] implemented in MacroModel V. 6.0 [32], were performed to estimate the
most stable ion-pairing complex with one clear conformational preference formed
between the various potential catalysts and the enolate of phenylindanone 1. These
modeling studies predicted that compound (‡)-(aS,3R,4S,8R,9S)-4, with the quinucli-
dine moiety attached to the major groove, would have the highest stereoelectronic
complementarity for the enolate substrate (Fig. 1). The two MeO groups in the minor
groove of the binaphthalene moiety in (‡)-4 would result from the synthesis of the
chiral cleft (vide infra) whereas the MeOCH2 substituent at C(3'') would be introduced
as a site for potential further functionalization targeting the immobilization of the
catalyst in aerogel materials [33][34].
3
)
MM2* is a modification of the MM2 force field [30].

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Fig. 1. Schematic (a) and computer-calculated (b) representations of the complex between the designed catalyst
(‡)-(aS,3R,4S,8R,9S)-4 and the enolate of phenylindanone 1
The calculated most favorable conformation of the ion-pairing complex between
(‡)-4 and the enolate of 1 (Fig. 1) resembles the one postulated by Dolling and co-
workers for the corresponding complex of (‡)-2 [10]. The absolute configurations at
C(8) and C(9) in both catalysts are the same. The enolate O-atom forms a strong H-
bond to the OH group at C(9) (H ´´´ O distance: 1.62 Š) and is located at a distance of
4.95 Š from the quaternary N-atom in (‡)-4. The Ph ring of 1 undergoes p-p stacking
interactions with the electron-deficient 4-(trifluoromethyl)benzyl residue. The inda-
none moiety in 1 is buried within the major groove of the binaphthalene, resulting in
multiple hydrophobic contacts. On one hand, it undergoes p-p stacking interactions
with one naphthalene ring, similar to those observed between the indanone fragment
and the quinoline ring in the complex of (‡)-2. On the other hand, the complex formed
by (‡)-4 features additional edge-to-face (C H ´´´ p) interactions between the

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indanone fragment and the second naphthalene ring of the chiral cleft. As a result, the
computed ion-pairing complex of (‡)-4 features a total of 54 van der Waals contacts
under 4 Š, whereas only 30 such contacts are calculated for the complex of (‡)-2. Thus,
the enolate should be tightly oriented in the complex formed by (‡)-4, leading to a
strong preference for attack by the alkylation agent from the side not shielded by the
catalyst.
2.2. Synthesis of the New Phase-Transfer Catalyst. Among the various protocols for
the synthesis of Cinchona alkaloids published by Uskokovic and co-workers [35], the
reaction of a quinuclidine-8-carboxylic acid with a metallated arene to give the
corresponding ketone, and subsequent diastereoselective reduction [35f] appeared to
be the most convenient preparation of (‡)-4 [35j]. This method had already been
applied to the synthesis of analogs of Cinchona alkaloids incorporating a 9,9'-
spirobifluorene moiety [19].
As the activated quinuclidine-8-carboxylic-acid derivative, we chose the Weinreb
amide (‡)-(3R,4S,8R)-8 (Scheme 2) [36]. Oxidation of the commercially available
5-vinylquinuclidine-2-methanol ((‡)-(3R,4S,8R)-9) to the corresponding carboxylic
acid, followed by in situ formation of the acyl chloride and subsequent reaction with
N,O-dimethylhydroxylamine hydrochloride under basic conditions afforded (‡)-
(3R,4S,8R)-10 in 44% yield. Subsequent hydrogenation gave the desired Weinreb
amide (‡)-(3R,4S,8R)-8 in quantitative yield.
Scheme 2. Synthesis of Weinreb Amide (‡)-(3R,4S,8R)-8
a) CrO3, H2SO4, acetone, 08 to r.t., 5 h. b) PCl5, CH2Cl2, reflux 4 h. c) MeHNOMe ´ HCl, Et3N, 08 to r.t., 3 h;
44% (starting from (‡)-9). d) H2, Pd/C, EtOH, 2 bar, 3 h, quant.
The preparation of the 7'-bromo-1,1'-binaphthalene building block ( )-(aS)-11 on
the way to (‡)-4 proved quite challenging owing to its unsymmetrical structure.
Whereas protocols for the synthesis of symmetric 1,1'-binaphthalene derivatives by
oxidative homo-coupling of naphthalene-2-ols are well-established [37], cross-coupling
methods leading to unsymmetrical 1,1'-binaphthalene-2,2'-diols remain relatively

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unexplored [37 ± 39]. Hovorka et al. reported that the efficiency of CuII-mediated cross-
coupling reactions between two differently substituted naphthalene-2-ols depends on
the nature of the substituents in both partners [37] [38]. A synthetically useful degree
of cross-coupling was obtained only when the difference in electron density in the
naphthalene rings of both reacting partners was large, a finding which became the
subject of further mechanistic studies [40] and ab initio calculations [41]. Therefore, we
prepared two naphthalene-2-ols with different electron densities in the aromatic rings,
in order to favor cross-coupling over undesirable homo-coupling. Methyl 3-hydroxy-
naphthalene-2-carboxylate (13) was synthesized from the corresponding carboxylic
acid 12 (Scheme 3). Monobromination of diol 14 by the method published for the
preparation of 2-bromonaphthalene from naphthalen-2-ol [42] afforded 7-bromo-
naphthalen-2-ol (15). As expected from the work by Hovorka et al., the subsequent
CuII-mediated cross-coupling between 13 and 15 indeed provided the desired unsym-
metrical 1,1'-binaphthalene (‡)-17 in very good yield (79%) and with high selectivity
(85 mol-%) over the two homo-coupled products (‡)-16 (7 mol-%) and (‡)-18
(8 mol-%).
Scheme 3. Synthesis of 1,1'-Binaphthalene ( Æ )-17 by CuII-Mediated Cross-Coupling
a) HCl (g), MeOH, r.t., 12 h; quant. b) Br2, PPh3, MeCN, 2508, 1 h; 64%. c) CuCl2, t-BuNH2, MeOH, 508,
2 h; 79%.
The optical resolution of ( Æ )-17 was achieved by a procedure recently published
[43] for the resolution of substituted 1,1'-binaphthalene-2,2'-diols. Diol ( Æ )-17 was
reacted with (‡)-(1S)-camphor-10-sulfonyl chloride, and the resulting two diaste-
reoisomers (‡)-(aS)-19 (40%) and ( )-(aR)-20 (40%) were separated by column
chromatography (SiO2; CH2Cl2/AcOEt 99 : 1; Scheme 4). Analytical HPLC analysis
(SiO2; CH2Cl2/AcOEt 100 : 0 ! 80 : 20) showed that the purity of each diastereoisomer
was above 99%.

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Scheme 4. Optical Resolution of Diol ( Æ )-17 and Synthesis of ( )-(aS)-11, the Precursor to the New Cinchona-
Alkaloid Analogs
a) (‡)-(1S)-Camphor-10-sulfonyl chloride, Et3N, CH2Cl2, 08 to r.t., 5 h. b) BuLi, THF, 788, 2 h, then 1m HCl,
MeOH. c) NaOH, H2O, MeOH, reflux, 12 h. d) HCl (g), MeOH, r.t., 12 h; 60% (starting from (‡)-19). e)
NaOH, MeOH, H2O, reflux, 20 h. f) (MeO)2SO2, KOH, reflux, 3 h; 97% (starting from (‡)-19). g) DIBAL-H,
CH2Cl2, 788 to r.t., 2.5 h; 72%. h) (MeO)2SO2, NaH, acetone, r.t., 1 h; 97%.
The absolute configuration of (‡)-(aS)-19 was determined through derivatization
to a product of known configuration. The Br substituent was reductively removed by
treatment of (‡)-(aS)-19 with BuLi, followed by quenching with MeOH and 1m HCl
(Scheme 4). Subsequent cleavage of the camphorsulfonyl auxiliaries and reesterifica-
tion of the resulting carboxylic acid afforded ( )-21 (60%), which had been reported to
have the (aS)-configuration [39c]. In a separate study, the (aR)-configuration was
assigned to (‡)-21 by comparing its circular-dichroism (CD) spectrum to that of (‡)-
(aR)-dimethyl 2,2'-dihydroxy-1,1'-binaphthalene-3,3'-dicarboxylate [38b].
After chromatographic separation of the diastereoisomers, the camphorsulfonyl
auxiliary in (‡)-(aS)-19 was removed by hydrolysis (Scheme 4). Subsequent methyl-
ation of the two resulting OH groups and the carboxylic acid yielded ( )-(aS)-22

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(97%), reduction with DIBAL-H afforded alcohol (‡)-(aS)-23 (72%), and methyl-
ation with (MeO)2SO2 eventually provided ( )-(aS)-11 (97%).
The coupling to Weinreb amide (‡)-8 was first investigated with racemic 1,1'-
binaphthalene ( Æ )-11. However, sequential addition of BuLi and (‡)-8 to bromide
( Æ )-11 under various conditions repeatedly failed to furnish the desired ketone. A
more detailed investigation of the lithiation step unexpectedly showed that the starting
material was completely recovered when one equivalent of BuLi or t-BuLi was added
(with or without TMEDA (N,N,N',N'-tetramethylethylenediamine) as co-solvent). The
first equivalent of base is presumably complexed by the three MeO groups, thereby
preventing the halogen-lithium exchange. Lithiation was achieved with an excess of
BuLi (2 or more equiv.). However, the lithiated intermediate proved to be very labile
in Et2O and THF. This was shown by deuteration experiments in which the mixture was
quenched with CD3OD directly after the addition of BuLi. Bromide ( Æ )-11 was
completely reduced to ( Æ )-24, demonstrating complete lithiation, but a proton and not
a deuterium was present at C(7') as indicated by the 1H- and 2D-NMR spectra
(Scheme 5). The same experiment carried out in (D8)THF afforded the deuterated
product ( Æ )-25, which established that the proton or deuterium comes from the
solvent. A very different result was obtained when bromide ( Æ )-11 was first converted
to the corresponding tin derivative ( Æ )-26 by treatment with Bu3SnLi [44]. In that
case, the lithiated derivative obtained by transmetallation of ( Æ )-26 with BuLi was
found to be stable at 788 for prolonged periods of time and could be trapped by
CD3OD to afford ( Æ )-25. Apparently, the other products of the two lithiation
reactions, starting from either ( Æ )-11 or ( Æ )-26, differentially affect the reactivity of
the aggregates of the lithiated 1,1'-binaphthalene in THF [45].
Scheme 5. Deuteration Experiments
a) BuLi, THF, 788, then CD3OD. b) Bu3SnLi, THF, 08, 30 min; 51%.

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Based on these results, the addition of the lithiated 1,1'-binaphthalene to the
Weinreb amide was re-investigated (Scheme 6). In a first approach, BuLi was added to
a pre-formed mixture of ( )-(aS)-11 and (‡)-(3R,4S,8R)-8, giving, in 46% yield,
(aS,3R,4S,8R)-27 and (aS,3R,4S,8S)-28 as an inseparable mixture of diastereoisomers
(ca. 1:1), owing to rapid epimerization at C(8). A second approach was to first
transmetallate stannane ( Æ )-26 with BuLi and then add a solution of (‡)-(3R,4S,8R)-8
in THF, which afforded the same product mixture in 42% yield. Epimerization at C(8)
could again not be prevented, even by using less than 1 equiv. of BuLi; therefore, the
direct route via lithiation of ( )-(aS)-11 was preferred.
Scheme 6. Synthesis of the Cinchona-Alkaloid Analogs (‡)-29, (‡)-30, ( )-31, and (‡)-32
a) BuLi, THF,
788, 15 min; 46%. b) DIBAL-H, benzene, 08, 4 h. c) NaBH4, EtOH, 08, 15 min. The
diastereoisomeric ratios were determined by analytical HPLC in the case of the DIBAL-H reduction and by
1
integration of the H-NMR signals in case of the reduction with NaBH4.
In the subsequent reduction of the diastereoisomer mixture with DIBAL-H in
benzene, we hoped to selectively obtain the C(8) C(9) erythro-diastereoisomers as
was observed in the reduction of quininone and quinidinone to give quinine and
quinidine, respectively [35f], or in the reduction of a related ketone in which the
quinoline moiety was replaced by a 9,9'-spirobifluorene moiety [19]. The diastereo-
selectivity of the reduction step is presumably a result of initial chelation of the Lewis-
acidic Al-atom of the reducing agent to the quinuclidine N-atom, followed by
intramolecular delivery of hydride to the ketone. The reduction of the mixture of
(aS,3R,4S,8R)-27 and (aS,3R,4S,8S)-28 under the reported conditions [35f] afforded
the diastereoisomeric alcohols (‡)-(aS,3R,4S,8S,9S)-29, (‡)-(aS,3R,4S,8R,9R)-30, ( )-
(aS,3R,4S,8S,9R)-31, and (‡)-(aS,3R,4S,8R,9S)-32, which were separated and config-
urationally assigned (see below). Thus, the selectivity of the reduction was incomplete
and the expected diastereoisomers with the erythro-configuration at C(8) C(9) ( )-

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(aS,3R,4S,8S,9R)-31 and (‡)-(aS,3R,4S,8R,9S)-32 were obtained with only 18% de
(diastereoisomeric excess). Steric hindrance might account for this reduced selectivity
since the 1,1'-binaphthalene moiety is much larger than the quinoline ring present in the
naturally occurring Cinchona alkaloids. NaBH4 reduction of quininone and quinidi-
none in EtOH has also been reported to proceed stereoselectively, affording the
C(8) C(9) threo-pair of diastereoisomers presumably by attack from the less hindered
face of the CˆO group [35f]. Again, with the diastereoisomer mixture of binaph-
thalene-substituted ketones, reduced stereocontrol was observed and the C(8) C(9)
threo-pair of diastereoisomers, (‡)-(aS,3R,4S,8S,9S)-29 and (‡)-(aS,3R,4S,8R,9R)-30
was obtained with 50% de (Scheme 6). Nevertheless, the stereoselectivity of the
reductions with DIBAL-H and NaBH4 is similar to that reported by Gutzwiller and
Uskokovic [35f], and the relative configurations at C(8) and C(9) can hence be
attributed on this basis.
Separation of the four enantiomerically pure Cinchona-alkaloid analogs was
achieved by column chromatography on SiO2 with CH2Cl2/MeOH/conc. aq. NH4OH
90 :9 :1 as the eluent, and the elucidation of their absolute configurations was
subsequently addressed by 1H-NMR methods. In each case, all H-atoms of the
binaphthalene moiety could be assigned on the basis of their chemical shifts and
coupling patterns. The protons in the quinuclidine ring were assigned on the basis
of {1H,1H}-COSY experiments, and 1H{1H}-NOE (nuclear Overhauser effect) measure-
ments were then performed to determine the absolute configuration of the
diastereoisomers. The (8S)-configuration was assigned to compounds (‡)-
(aS,3R,4S,8S,9S)-29 and ( )-(aS,3R,4S,8S,9R)-31 on the basis of a strong NOE between
HA C(2) and H C(8) (Fig. 2). For diastereoisomer (‡)-(aS,3R,4S,8R,9R)-30, irradi-
ation of H C(9) yielded a strong NOE of the resonance around d ˆ 2.40 ppm which
corresponds to HA C(2). Correspondingly, irradiation of HA C(2) gave an NOE of
the resonance at d ˆ 4.15 ± 4.30 ppm corresponding to H C(9). Consequently, proton
H
C(8) must be in an axial position, and the (8R)-configuration was attributed to (‡)-
(aS,3R,4S,8R,9R)-30. In the case of (‡)-(aS,3R,4S,8R,9S)-32, no NOE was detected
between HA C(2) and H C(8), but signal overlap interfered with the assignment of
the absolute configuration. Having established the C(8) configuration for the three
other diastereoisomers, however, the configuration of the last diastereoisomer could be
unambiguously deduced. Owing to the rotational freedom around the C(8) C(9) and
C(9) C(7') bonds, the absolute configuration at C(9) could, unfortunately, not be
directly established by the NOE experiments. The absolute configuration at C(9) could
nonetheless be deduced on the assumption that the reduction steps described above
proceeded with stereoselectivity similar to that of the reported examples.
The CD spectra of the four diastereoisomeric Cinchona-alkaloid analogs are very
similar, since they are dominated by the chiroptical contributions from the 1,1'-
binaphthalene chromophore. Thus, they were not very useful in providing further
support for the configurational assignments made.
The synthesis of the target phase-transfer catalysts was completed by quaterniza-
tion of the four diastereoisomeric Cinchona-alkaloid analogs (‡)-29, (‡)-30, ( )-31,
and (‡)-32 with 4-(trifluoromethyl)benzyl bromide (Scheme 7). Three of the resulting
diastereoisomeric quats, (‡)-(aS,3R,4S,8R,9S)-4, (‡)-(aS,3R,4S,8S,9S)-5, and ( )-
(aS,3R,4S,8S,9R)-7, were obtained in good yields between 50 and 57%, whereas (‡)-

Helvetica Chimica Acta ± Vol. 82 (1999)
991
Fig. 2. Assignment of the absolute configuration at C(8) in the novel Cinchona-alkaloid analogs based on NOEs
(aS,3R,4S,8R,9R)-6 was only obtained in very low yield (up to 12%). The presence of a
particularly sterically shielded and, therefore, poorly nucleophilic quinuclidine N-atom
in precursor (‡)-30 could explain this result. To support this hypothesis, a conforma-
tional analysis was undertaken.
Scheme 7. Formation of the Novel Phase-Transfer Catalysts by Quaternization
a) 4-F3CC6H4CH2Br, THF, reflux, 3 d.
2.3. Conformational Analysis of the Novel Cinchona-Alkaloid Analogs. The four
tertiary amines (‡)-29, (‡)-30, ( )-31, and (‡)-32 were each subjected to a 1000-step
pseudo-MCMM conformational search in CHCl3 using the MM2* force field and the
GB/SA solvation model implemented in MacroModel V. 6.0.

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Helvetica Chimica Acta ± Vol. 82 (1999)
Similarly to quinine and quinidine derivatives [19][46], the overall conformation of
the four new Cinchona-alkaloid analogs is largely determined by the freedom of
rotation around the C(8) C(9) and C(9) C(7') bonds (for the numbering, see Fig. 3)
which link the rigid quinuclidine and 1,1'-binaphthalene ring systems together. Four
preferred conformations, named ꢁclosed 1ꢀ, ꢁclosed 2ꢀ, ꢁopen 1ꢀ, and ꢁopen 2ꢀ, defined
after the orientation of the quinuclidine N-atom with respect to the binaphthalene
moiety [19][46], were obtained from the pseudo-MCMM calculations for each one of
the four diastereoisomers. They are shown in Fig. 3 for the particular case of (‡)-
(aS,3R,4S,8R,9R)-30, which proved so difficult to be quaternized. Two ꢁclosedꢀ
conformations, with a H C(8) C(9) H dihedral angle of ca. 608 (gauche-con-
formers), have the quinuclidine N-atom pointing towards the adjacent naphthalene
ring, while the two ꢁopenꢀ conformations have the quinuclidine N-atom pointing away
from the adjacent naphthalene ring, with H C(8) and H C(9) antiperiplanar
(dihedral angle of 1808). These conformations can be further distinguished according
to the rotation about the C(9) C(7') bond. Conformation ꢁclosed 1ꢀ, with proton
H
C(9) close to H C(8'), has the quinuclidine N-atom pointing inside the 1,1'-
binaphthalene major groove. When H C(9) is near H C(6') (ꢁclosed 2ꢀ), the
quinuclidine N-atom is directed towards the face of the adjacent naphthalene ring
outside the major groove. The ꢁopenꢀ conformations can be similarly distinguished: the
quinuclidine N-atom is located either on one side of the adjacent naphthalene ring
(H C(9) near H C(6')) for ꢁopen 1ꢀ or on the opposite side (H C(9) near H C(8'))
for ꢁopen 2ꢀ. By further rotation around the C(8) C(9) bond, two additional gauche-
conformations are theoretically possible. They are, however, presumably not found
among the calculated low-energy conformations because of unfavorable steric
repulsions between the 1,1'-binaphthalene and quinuclidine moieties.
In the two open and two closed conformations of the three other diastereoisomers,
the orientation of the quinuclidine N-atom with respect to the binaphthalene moiety is
similar to that shown in Fig. 3 for (‡)-30. However, due to differences in the
configuration at C(8) and C(9), the orientation of H C(9) with respect to H C(8)
and the naphthalene protons H C(6') and H C(8') varies among the diastereoisom-
ers. As an example, in the ꢁclosed 1ꢀ conformation, both ꢁpseudo-enantiomersꢀ (‡)-29
and (‡)-30 feature H C(9) and H C(8) in a gauche-relationship; however, in the
former, H C(9) is located near H C(6'), whereas, in the latter, H C(9) is near
H
C(8'). Also, H C(8) and H C(9) in (‡)-29 and (‡)-30 adopt an anti-orientation
in the ꢁopen 1ꢀ and ꢁopen 2ꢀ conformations, whereas, in ( )-31 and (‡)-32, they feature
the anti-orientation in the ꢁclosed 1ꢀ and ꢁclosed 2ꢀ conformations.
We did not find the computational searches, which also included calculations in
vacuo and the use of the two other force fields AMBER* [47] and OPLS* [48]
implemented in MacroModel, of sufficient accuracy to predict conformational
1
preferences that matched the experimental H-NMR spectroscopic data. They were,
however, quite helpful for the interpretation of these data. Among the different
1
calculated conformations, we searched for those matching the H-NMR coupling
constants and NOEs. On this basis, we deduced that diastereoisomer (‡)-30 adopts a
ꢁclosed 1ꢀ conformation, as indicated by the NOE between H C(9) and H C(8'), and
3
the J(8,9) coupling constant of 9.6 Hz (compatible with a dihedral angle of 608). In
the case of compound (‡)-29, a similar vicinal coupling constant and the NOE between

Helvetica Chimica Acta ± Vol. 82 (1999)
993
Fig. 3. Newman projections of the C(8) C(9) bond for the four possible conformations of diastereoisomer (‡)-
30. The MeO and MeOCH2 substituents on the 1,1'-binaphthalene were omitted for clarity. The three other
diastereoisomers (‡)-29, ( )-31, and (‡)-32 also adopt these four conformations; however, due to differences in
the configuration at C(8) and C(9), the orientation of H C(9) with respect to H C(8) and with respect to the
naphthalene protons H C(6') and H C(8') may vary.
H
C(9) and H C(8') suggest a preference for the ꢁclosed 2ꢀ conformation, although
some ꢁclosed 1ꢀ conformation is also present in the equilibrium, as indicated by a
weaker NOE between H C(9) and H C(6'). For compound ( )-31, the ꢁopen 1ꢀ
1
conformation, with a 908 H C(8) C(9) H dihedral angle, matched the H-NMR
coupling constant (3J ˆ 6.7 Hz) and the NOE signal between H C(9) and H C(8').
Aweak NOE between H C(9) and H C(6') indicated that ꢁopen 2ꢀ is also present as a
minor conformer. Finally, compound (‡)-32 prefers the ꢁclosed 1ꢀ and ꢁclosed 2ꢀ
conformations. Thus, the spectra of (‡)-32 show a large coupling constant (3J(8,9) ˆ
13.4 Hz) in agreement with an antiperiplanar orientation of H C(8) and H C(9) as
well as NOEs on H C(6') and H C(8') upon irradiation of H C(9).
1
The conformational analysis by H-NMR spectroscopy, aided by the computer
modeling, clearly revealed that diastereoisomer (‡)-30 is the only one adopting
exclusively ꢁclosed 1ꢀ as a preferred conformation. Since this conformation is the one in
which the quinuclidine N-atom is the most hindered, it possibly accounts for the low
yield obtained in the quaternization reaction. It should, however, be noted that the
quaternization was carried out in THF at reflux, whereas the Monte-Carlo minimiza-
tion and the NMR experiments were performed in chloroform.
2.4. Catalysis Experiments. The conditions reported to give the highest enantiose-
lectivity in the asymmetric methylation of phenylindanone 1 in the presence of (‡)-
(3R,4S,8R,9S)-2 as the chiral phase-transfer agent [10] were used for the catalysis
experiments with the novel 1,1'-binaphthalene-derived quats (‡)-(aS,3R,4S,8R,9S)-4,
(‡)-(aS,3R,4S,8S,9S)-5, (‡)-(aS,3R,4S,8R,9R)-6, and ( )-(aS,3R,4S,8S,9R)-7. The high

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toxicity of gaseous MeCl, however, prompted us to change the alkylating agent to allyl
chloride. The phase-transfer catalyzed allylation was first carried out with the achiral
catalyst Bu4NBr, affording racemic indanone ( Æ )-3b in 43% yield (Table). Catalysis
by the cinchonine quat (‡)-(3R,4S,8R,9S)-2 afforded indanone (‡)-(S)-3b in 59%
yield and 74% ee. Both the chemical and optical yields were lower than those reported
for the methylation reaction (95% yield, 92% ee) [10a]. The lower yield, together with
the recovery of some starting material, indicated that the allylation is slower than the
methylation.
Table. Enantiomeric Excess (ee [%]) Obtained in the Phase-Transfer-Catalyzed Allylation of Phenylindanone 1
Catalyst
Yield [%]
(‡)-(S)-3b [%]
(
)-(R)-3b [%]
eea) [%]
Bu4NBr
43
59
57
13
45
38
50
87
66
53
39
42
50
13
34
47
61
58
0
(‡)-(3R,4S,8R,9S)-2
(‡)-(aS,3R,4S,8R,9S)-4
(‡)-(aS,3R,4S,8S,9S)-5
(‡)-(aS,3R,4S,8R,9R)-6
74 (S)
32 (S)
6 (S)
22 (R)
16 (R)
(
)-(aS,3R,4S,8S,9R)-7
a) The ee values were determined by analytical HPLC on a ꢁPirkle Covalent d-Phenylglycineꢀ chiral stationary
1
phase with 0.1% EtOH in hexane as the mobile phase and a flow rate of 3 ml min
.
The allylation of phenylindanone 1 was then carried out with the four new quats
(‡)-4, (‡)-5, (‡)-6, and ( )-7 as catalysts. Diastereoisomer (‡)-5 afforded indanone
(‡)-(S)-3b in 13% yield in a slow reaction and with a poor ee of 6% (Table). Catalysts
(‡)-6 and ( )-7 were more efficient and yielded indanone ( )-(R)-3b in 22% and 16%
ee, and 45% and 38% yield, respectively. The best result was obtained with the
designed catalyst (‡)-(aS,3R,4S,8R,9S)-4, which afforded (‡)-(S)-3b in 57% yield and
32% ee. The predominant formation of this enantiomer is in accordance with the ion-
pair model on which the catalyst design was based (Fig. 1). It should be noted that, at
this stage, no optimization of the reaction conditions was attempted, which is usually
necessary to achieve high ee and yield. We consider the 32% ee obtained in a first,
reproducible attempt a very encouraging result, and the accurate prediction of which
enantiomer is preferentially formed underlines the potential of molecular modeling as
a tool in the development of enantioselective catalysts.
The structures of the ion-pair complexes formed by the three other 1,1'-
binaphthalene quats were now calculated with the computational protocol described
in Section 2.1 in order to rationalize the obtained enantioselectivities. To reject
structures lacking the H-bond between the OH group of the catalyst and the enolate O-
atom, a maximal O H ´´´ O distance of 2.0 Š was defined as a constraint. This H-bond
is largely responsible for stereoselective ion-pair formation, and the constraint
therefore allows selection only for structures which might explain the enantioselec-
tivity.
The calculated, most stable ion-pair complex formed by ( )-(aS,3R,4S,8S,9R)-7
(Fig. 4, A) displays a set of intermolecular interactions (i.e., a reasonably short O H´´´O
H-bond, p-p stacking interactions in the 1,1'-binaphthalene major groove, and edge-to-
face interactions between the 4-(trifluoromethyl)benzyl ring and the Ph ring of the

Helvetica Chimica Acta ± Vol. 82 (1999)
995
enolate) similar to those seen in the complex formed by (‡)-(aS,3R,4S,8R,9S)-4
(Fig. 1). Due to the change in configuration at C(8) and C(9), however, the enolate
approaches the catalyst ( )-7 with its opposite face (as compared to the ion-pair
complex of (‡)-4) in order to undergo these three major interactions. Hence, allylation
from the open side of the enolate generates the enantiomeric indanone ( )-(R)-3b.
In the calculated most stable complex of (‡)-(aS,3R,4S,8R,9R)-6, the required H-
bond and the p-p stacking interactions between the two Ph rings are effective, whereas
the indanone moiety hardly interacts at all with the 1,1'-binaphthalene moiety
(Fig. 4, B). The calculated ion-pair structure, however, correctly predicts the prefer-
ential formation of indanone ( )-(R)-3b.
In the case of catalyst (‡)-5, no ion-pair complex with the required H-bond was
obtained, and all generated structures were rejected by the constraint. Although one
should be careful when interpreting negative results, it is perhaps noteworthy that this
modeling result matches the low ee (6%) experimentally obtained.
3. Conclusion. ± Covalent attachment of quinuclidinemethanol moieties to C(7') in
the major groove of a 1,1'-binaphthalene derivative afforded the novel unnatural
Cinchona-alkaloid analogs (‡)-(aS,3R,4S,8S,9S)-29, (‡)-(aS,3R,4S,8R,9R)-30, ( )-
(aS,3R,4S,8S,9R)-31, and (‡)-(aS,3R,4S,8R,9S)-32. A detailed conformational analysis,
1
combining H-NMR spectroscopy and molecular-mechanics computations, revealed
that the four diastereoisomers displayed different conformational preferences. Com-
pound (‡)-30 exclusively adopts the ꢁclosed 1ꢀ conformation in which the quinuclidine
N-atom points into the major groove of the 1,1'-binaphthalene moiety. As a result of
this steric hindrance, N-alkylation of this diastereoisomer proved to be very difficult.
Diastereoisomers (‡)-29 and (‡)-32 exist at room temperature in both the ꢁclosed 1ꢀ
and the less sterically hindered ꢁclosed 2ꢀ conformation, in which the quinuclidine
N-atom points towards the adjacent naphthalene ring, whereas ( )-31 prefers the ꢁopen
1ꢀ conformation with the N-atom turned away from the binaphthalene moiety. These
unnatural Cinchona-alkaloid analogs are now being tested as catalysts in various
asymmetric syntheses, such as the Sharpless dihydroxylation reaction [20]. Further-
more, a new series of hybrid compounds, in which quinuclidinemethanol moieties are
attached to C-atoms in the minor groove of 1,1'-binaphthalene derivatives, are
currently under construction.
The four diastereoisomeric Cinchona-alkaloid analogs were quaternized with 4-
(trifluoromethyl)benzyl bromide and the resulting phase-transfer agents used for the
enantioselective allylation of phenylindanone 1. ee Values ranging from 6 to 32% (13 to
57% yield) were obtained without optimization of the reaction conditions. Although
the yields and enantioselectivities remain to be improved, this research demonstrates
the potential of incorporating 1,1'-binaphthalene moieties into Cinchona-alkaloid
analogs for obtaining stereoselective catalysts. A remarkable performance of computer
modeling both in the catalyst design and the rationalization of the PTC results was
obtained. The designed catalyst (‡)-4 showed the best performance, as predicted, and
the computer calculations could rationalize the enantioselectivity observed with two of
the other catalysts and predict which enantiomer would be preferentially formed. We,
therefore, believe that this study demonstrates the potential of molecular modeling in
asymmetric catalysis, and expect that modeling strategies will be generalized over the

Helvetica Chimica Acta ± Vol. 82 (1999)
997
next few years to allow for a more systematic, less empirical approach to the design of
new catalysts.
Experimental Part
General. Solvents and reagents were of reagent-grade, purchased from commercial suppliers, and used
without further purification unless otherwise stated. Quinuclidine derivative (‡)-9 was purchased from Buchler
GmbH, Braunschweig. THF and Et2O were freshly distilled from sodium benzophenone ketyl. Evaporation in
vacuo was conducted at H2O aspirator pressure. Column chromatography (CC): SiO2 60 (230 ± 400 mesh,
0.040 ± 0.063 mm) from Fluka. M.p.: Büchi SMP-20; uncorrected. IR Spectra [cm 1]: Perkin-Elmer 1600-FT IR.
NMR Spectra: Bruker AMX 500 and Varian Gemini 300 or 200 at 296 K, with solvent peak as reference. MS
(m/z (%)): EI and DEI: VG TRIBRID spectrometer at 70 eV; FAB: VG ZAB2-SEQ spectrometer with
3-nitrobenzyl alcohol as matrix. Elemental analyses were performed by the Mikrolabor at the Laboratorium für
Organische Chemie, ETH-Zürich.
(3R,4S,8R)-N-Methoxy-N-methyl-3-vinyl-1-azabicyclo[2.2.2]octane-8-carboxamide ((‡)-10). To a soln. of
(‡)-9 (130 mg, 0.78 mmol) in acetone (10 ml) cooled to 08, CrO3 (94 mg, 0.94 mmol) and conc. H2SO4 (0.42 ml,
7.78 mmol), were added and the soln. was stirred at r.t. for 5 h. The mixture was neutralized with 1m aq. NaOH
(ca. 8 ml), washed with CH2Cl2 (50 ml), filtered, and purified by ion-exchange chromatography (H2O, then 1m
‡
aq. NH4OH) on Dowex ion-exchange resin 50WX4 (H form). To the residue, CH2Cl2 (100 ml) and PCl5
(145 mg, 0.72 mmol) were added, and the soln. was heated at reflux for 4 h. The soln. was then cooled to 08,
MeHNOMe ´ HCl (68 mg, 0.72 mmol) was added, followed by Et3N (dropwise up to pH 9), and the soln. was
stirred at r.t. for 3 h. The mixture was quenched with a sat. aq. NaHCO3 soln. (100 ml), the org. phase separated,
and the aq. phase extracted with CH2Cl2 (2 Â 100 ml). The combined org. extracts were dried (Na2SO4),
evaporated in vacuo, and purified by CC (SiO2; CH2Cl2/MeOH/NH4OH 90 : 9 : 1) to give (‡)-10 (76 mg, 44%).
Yellow oil. [a]Dr:t: ˆ ‡ 121.1 (c ˆ 1.00, CHCl3). IR (CHCl3): 2939m, 1658s, 1456w, 1178w, 1136w, 909m. 1H-NMR
(200 MHz, CDCl3): 6.11 ± 5.94 (m, 1 H); 5.10 ± 5.04 (m, 1 H); 5.00 (d, J ˆ 0.8, 1 H); 3.83 ± 3.71 (m, 1 H); 3.75
(s, 3 H); 3.22 (s, 3 H); 3.02 ± 2.77 (m, 4 H); 2.32 ± 2.16 (m, 2 H); 1.84 ± 1.77 (m, 1 H); 1.68 ± 1.58 (m, 2 H); 1.53 ±
1.38 (m, 1 H). 13C-NMR (75 MHz, CDCl3): 140.7; 114.9; 61.4; 55.3; 49.0; 48.7; 40.2; 27.7; 26.5; 22.6. EI-MS: 224
‡
‡
‡
‡
(10, M ), 193 (34, [M OMe] ), 164 (21, [M N(Me)OMe] ), 136 (100, [M CON(Me)OMe] ). EI-HR-
‡
MS: 224.1531 (M , C12H20N2O2; calc. 224.1525).
(3R,4S,8R)-N-Methoxy-N-methyl-3-ethyl-1-azabicyclo[2.2.2]octane-8-carboxamide ((‡)-8).
A soln. of
(‡)-10 (90 mg, 0.40 mmol) in EtOH (10 ml) was treated with 10% Pd/C (10 mg) under H2 (2 bar) for 3 h.
The mixture was filtered through Celite and evaporated in vacuo to give (‡)-8 (90 mg, 99%). Colorless oil.
[a]rD:t: ˆ ‡ 111.5 (c ˆ 1.00, CHCl3). IR (CHCl3): 2937s, 2873m, 1657s, 1456m, 983m. 1H-NMR (200 MHz,
CDCl3): 3.75 (s, 3 H); 3.75 ± 3.65 (m, 1 H); 3.22 (s, 3 H); 2.98 ± 2.40 (m, 4 H); 2.28 ± 2.10 (m, 1 H); 1.74 ± 1.26
(m, 7 H); 0.86 (t, J ˆ 7.1, 3 H). 13C-NMR (75 MHz, CDCl3): 61.4; 55.3; 50.7; 48.9; 37.5; 27.5; 25.8; 25.3; 22.4;
‡
‡
‡
12.0. EI-MS: 226 (2, M ), 195 (41, [M OMe] ), 166 (51, [M N(Me)OMe] ), 138 (100, [M
‡
‡
CON(Me)OMe] ). EI-HR-MS: 226.1681 (M , C12H22N2O2; calc. 226.1682).
Methyl 3-Hydroxynaphthalene-2-carboxylate (13). To a stirred soln. of 12 (20.00 g, 106.28 mmol) in MeOH
(100 ml) cooled to 08, dry HCl gas was added until no more absorption could be observed. The soln. was then
heated to reflux for 2 h, left to stand at r.t. for 12 h, and evaporated in vacuo to give 13 (21.27 g, 99%). Light-
brown solid. M.p. 74 ± 758 ([49]: 728). 1H-NMR (200 MHz, CDCl3): 10.43 (s, 1 H); 8.50 (s, 1 H); 7.83 ± 7.79
(m, 1 H); 7.72 ± 7.67 (m, 1 H); 7.55 ± 7.47 (m, 1 H); 7.37 ± 7.29 (m, 1 H); 7.32 (s, 1 H); 4.04 (s, 3 H).
7-Bromonaphthalen-2-ol (15). To a mechanically stirred soln. of Ph3P (14.41 g, 54.94 mmol) in MeCN
(12.5 ml), Br2 (2.82 ml, 54.94 mmol) was added dropwise at 08. The soln. was allowed to reach r.t., and 14 (8.00 g,
45.95 mmol) in MeCN (10 ml) was added in one portion. The mixture was heated to 60 ± 708 for 30 min, then the
solvent was distilled under reduced pressure. The mixture was heated to 2508 for 1 h, cooled down to r.t., and
dissolved in CH2Cl2 (200 ml). The soln. was washed with 1m aq. NaOH (200 ml), acidified with 1m aq. HCl
(250 ml), and extracted with CH2Cl2 (3 Â 200 ml). The combined org. extracts were dried (MgSO4), evaporated
in vacuo, and purified by CC (SiO2; CH2Cl2) to give 15 (7.11 g; 64%). Colorless solid. M.p. 130 ± 1328 ([50]:
1
132 ± 1338). H-NMR (200 MHz, CDCl3): 7.84 (d, J ˆ 1.9, 1 H); 7.72 (d, J ˆ 8.7, 1 H); 7.63 (d, J ˆ 8.7, 1 H);
7.40 (dd, J ˆ 8.7, 1.9, 1 H); 7.11 (dd, J ˆ 8.7, 2.3, 1 H); 7.06 (d, J ˆ 2.3, 1 H); 5.14 (br. s, 1 H).
( Æ )-Methyl 7'-Bromo-2,2'-dihydroxy-1,1'-binaphthalene-3-carboxylate (( Æ )-17). To a degassed soln. of 13
(4.53 g, 22.41 mmol), 15 (5.00 g, 22.41 mmol), and CuCl2 (12.05 g, 89.64 mmol) in MeOH (800 ml), t-BuNH2
(37.84 ml, 358.56 mmol) was slowly added, and the soln. was heated to 508 for 2 h. The mixture was then allowed
to cool to r.t., 1m aq. HCl (400 ml) was added, and MeOH was evaporated in vacuo. H2O (100 ml) was added

998
Helvetica Chimica Acta ± Vol. 82 (1999)
and the soln. extracted with CH2Cl2 (500 ml). The org. phase was washed with H2O (300 ml) and sat. aq.
NaHCO3 soln. (300 ml), dried (MgSO4), evaporated in vacuo, and purified by CC (SiO2; CH2Cl2) to give ( Æ )-
17 (7.46 g, 79%). Light-yellow solid. M.p. 229 ± 2328. IR (CHCl3): 1684m, 1616w, 1503m, 1445w, 1433w, 1340m,
1322m, 1279w, 1183m, 1156s, 1136s. 1H-NMR (200 MHz, CDCl3): 10.88 (s, 1 H); 8.76 (s, 1 H); 7.99 ± 7.94
(m, 1 H); 7.89 (d, J ˆ 8.7, 1 H); 7.74 (d, J ˆ 8.7, 1 H); 7.44 ± 7.35 (m, 4 H); 7.22 ± 7.13 (m, 2 H); 4.98 (s, 1 H);
4.10 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 170.6; 155.4; 152.5; 137.5; 135.1; 134.5; 130.7; 130.4; 130.3; 130.2;
‡
128.0; 127.7; 127.1; 126.9; 124.9; 124.6; 121.5; 118.4; 114.7; 113.7; 111.2; 53.0. DEI-MS: 424/422 (100/96, M ),
‡
348/346 (48/50, [M COOMe OH] ), 239(49), 226(88). Anal. calc. for C22H15BrO4 (423.3): C 62.43,
H 3.57, Br 18.88; found: C 62.31, H 3.34, Br 18.96.
Methyl 7'-Bromo-2,2'-bis[(1S)-camphor-10-(sulfonyloxy)]-1,1'-binaphthalene-3-carboxylates ((‡)-19) and
(( )-20). To a soln. of ( Æ )-17 (100 mg, 0.23 mmol) in CH2Cl2 (10 ml), Et3N (0.08 ml, 0.58 mmol) was added at
08, followed by (‡)-(1S)-camphor-10-sulfonyl chloride (128 mg, 0.51 mmol). The soln. was stirred at 08 for 3 h
and then at r.t. for 2 h. The reaction was quenched with H2O (50 ml) and the mixture extracted with CH2Cl2
(3 Â 50 ml). The combined org. extracts were dried (MgSO4), evaporated in vacuo, and purified by CC (SiO2;
CH2Cl2/AcOEt 99 : 1) to yield (‡)-19 and ( )-20.
Data of (‡)-(aS)-19: 80 mg, 40%. Colorless solid. M.p. 105 ± 1078. [a]rD:t: ˆ ‡ 29.1 (c ˆ 1.00, CHCl3). IR
1
(CHCl3): 2961m, 1746s, 1496m, 1453m, 1378s, 1365s, 1290m, 1189m, 1167s. H-NMR (200 MHz, CDCl3): 8.66
(s, 1 H); 8.07 ± 8.01 (m, 2 H); 7.86 ± 7.80 (m, 2 H); 7.65 ± 7.46 (m, 3 H); 7.39 ± 7.36 (m, 1 H); 7.32 ± 7.27
(m, 1 H); 4.01 (s, 3 H); 3.05, 2.58 (AB, JAB ˆ 15.0, 2 H); 3.02, 2.87 (AB, JAB ˆ 14.7, 2 H); 2.31 ± 1.72
(m, 10 H); 1.53 ± 1.14 (m, 4 H); 0.88 (s, 3 H); 0.77 (s, 3 H); 0.66 (s, 3 H); 0.59 (s, 3 H). 13C-NMR (75 MHz,
CDCl3): 213.8; 213.7; 166.1; 147.2; 143.0; 134.9; 134.6; 131.2; 131.0; 130.3; 130.1 (2Â); 129.9; 129.5; 128.5; 127.8;
126.9; 126.2; 125.2; 122.6; 122.2; 121.5; 58.0; 57.8; 52.8; 49.3; 49.2; 47.8; 47.7; 42.8; 42.8; 42.3; 42.3; 26.8; 26.7;
‡
‡
24.9; 24.8; 19.6; 19.4; 19.3 (2Â). DEI-MS: 852/850 (1/1, M ), 821/819 (1/1, [M OMe] ), 638/636 (80/75), 424/
422 (100/99). Anal. calc. for C42H43BrO10S2 (851.8): C 59.22, H 5.09, S 7.53, Br 9.38; found: C 59.08, H 5.11, S
7.28, Br 9.10.
Data of ( )-(aR)-20: 80 mg, 40%. Colorless solid. M.p. 101 ± 1048. [a]Dr:t:
ˆ
36.6 (c ˆ 1.00, CHCl3). IR
1
(CHCl3): 2962w, 1747s, 1496w, 1454w, 1376m, 1367m, 1290w, 1189m, 1167s. H-NMR (200 MHz, CDCl3): 8.66
(s, 1 H); 8.08 ± 8.03 (m, 2 H); 7.89 ± 7.81 (m, 2 H); 7.63 ± 7.42 (m, 3 H); 7.34 ± 7.33 (m, 1 H); 7.22 ± 7.18
(m, 1 H); 4.02 (s, 3 H); 3.32, 2.46 (AB, JAB ˆ 14.9, 2 H); 3.19, 2.36 (AB, JAB ˆ 14.5, 2 H); 2.28 ± 1.73
(m, 10 H); 1.42 ± 1.19 (m, 4 H); 0.80 (s, 3 H); 0.74 (s, 3 H); 0.54 (s, 3 H); 0.48 (s, 3 H). 13C-NMR (75 MHz,
CDCl3): 213.8; 213.6; 166.2; 147.0; 143.1; 134.9; 134.5; 131.2 (2Â); 130.4; 130.3; 130.2; 129.8; 129.5; 128.5; 127.7;
126.9; 126.0; 125.5; 122.6; 122.5; 121.7; 58.0; 57.8; 52.8; 49.5; 49.3; 47.7; 47.5; 42.8 (2Â); 42.3 (2Â); 26.7 (2Â);
‡
‡
24.8; 24.6; 19.5; 19.4; 19.2; 19.2. DEI-MS: 852/850 (1/1, M ), 821/819 (1/1, [M OMe] ), 638/636 (97/87), 424/
422 (96/100). Anal. calc. for C42H43BrO10S2 (851.8): C 59.22, H 5.09, S 7.53, Br 9.38; found: C 58.94, H 5.27,
S 7.28, Br 9.11.
(aS)-Methyl 2,2'-Dihydroxy-1,1'-binaphthalene-3-carboxylate (( )-21) [39c]. To (‡)-19 (165 mg, 0.19 mmol)
in dry THF (10 ml) at 788 under Ar, BuLi (1.6m soln. in hexanes, 0.36 ml, 0.58 mmol) was added, and the soln.
was stirred at r.t. for 2 h. The reaction was quenched with MeOH (0.5 ml) and 1m aq. HCl (50 ml), and the
mixture was extracted with CH2Cl2 (3 Â 50 ml). The combined org. extracts were dried (Na2SO4) and
evaporated in vacuo. The residue was dissolved in MeOH (25 ml) and 1m aq. NaOH (25 ml), and the soln. was
heated at reflux for 12 h. MeOH was evaporated in vacuo, 1m aq. HCl (50 ml) added, and the soln. extracted
with CH2Cl2 (3 Â 50 ml). The combined org. extracts were dried (Na2SO4) and evaporated in vacuo. The residue
was diluted with MeOH (50 ml), treated with dry HCl gas at 08 for 15 min, and left to stand at r.t. for 12 h.
MeOH was evaporated in vacuo and the product purified by CC (SiO2; CH2Cl2) to give ( )-21 (40 mg, 60%).
Yellow, amorphous solid. [a]Dr:t:
ˆ
48.0 (c ˆ 1.00, CHCl3),
126.0 (c ˆ 1.00, THF). 1H-NMR (200 MHz,
CDCl3): 10.88 (s, 1 H); 8.76 (s, 1 H); 7.99 ± 7.87 (m, 2 H); 7.74 (d, J ˆ 8.7, 1 H); 7.44 ± 7.13 (m, 7 H); 4.99
(s, 1 H); 4.10 (s, 3 H).
(aS)-Methyl 7'-Bromo-2,2'-dimethoxy-1,1'-binaphthalene-3-carboxylate (( )-22).
A
soln. of (‡)-19
(760 mg, 0.89 mmol) in MeOH (50 ml) and 1m aq. NaOH (25 ml) was heated to reflux for 20 h. MeOH was
evaporated in vacuo, 1m aq. HCl (60 ml) added, and the soln. extracted with CH2Cl2 (3 Â 60 ml). The combined
org. extracts were dried (MgSO4) and evaporated in vacuo. The residue was dissolved in acetone (100 ml), and
KOH (400 mg, 7.12 mmol) was added. After stirring for 30 min, (MeO)2SO2 (0.51 ml, 5.34 mmol) was added
and the soln. heated to reflux for 3 h. The reaction was quenched with 1m aq. HCl (50 ml), the acetone was
evaporated in vacuo, and the soln. was extracted with CH2Cl2 (3 Â 50 ml). The combined org. extracts were
dried (Na2SO4), evaporated in vacuo, and purified by CC (SiO2; hexane/AcOEt 8 : 2) to afford ( )-22 (389 mg,
97%). Colorless, amorphous solid. [a]Dr:t:
ˆ
43.5 (c ˆ 1.00, CHCl3). IR (CHCl3): 1705s, 1257m, 1175m, 1150m,

Helvetica Chimica Acta ± Vol. 82 (1999)
999
1139m. 1H-NMR (200 MHz, CDCl3): 8.55 (s, 1 H); 8.00 ± 7.96 (m, 2 H); 7.74 (d, J ˆ 8.7, 1 H); 7.50 ± 7.30
(m, 4 H); 7.23 (d, J ˆ 1.7, 1 H); 7.12 ± 7.07 (m, 1 H); 4.01 (s, 3 H); 3.79 (s, 3 H); 3.49 (s, 3 H). 13C-NMR
(75 MHz, CDCl3): 167.3; 155.9; 154.7; 135.9; 135.5; 133.6; 130.2; 130.0; 129.9; 129.4; 128.7; 127.6; 127.4; 127.2;
‡
126.6; 125.8; 125.5; 125.0; 121.7; 118.1; 113.8; 61.9; 56.5; 52.5. DEI-MS: 452/450 (100/100, M ). Anal. calc. for
C24H19BrO4 (451.3): C 63.87, H 4.24, Br 17.70; found: C 63.93, H 4.22, Br 17.59.
(aS)-7'-Bromo-2,2'-dimethoxy-1,1'-binaphthalene-3-methanol ((‡)-23). To ( )-22 (360 mg, 0.80 mmol) in
CH2Cl2 (30 ml) at 788 under Ar, DIBAL-H (1m soln. in hexane, 3.19 ml, 3.19 mmol) was added, and the soln.
was stirred at r.t. for 2.5 h. The reaction was quenched with a sat. aq. NaCl soln. (50 ml), the org. phase
separated, and the aq. phase extracted with CH2Cl2 (2 Â 50 ml). The combined org. extracts were dried
(MgSO4), evaporated in vacuo, and purified by CC (SiO2; CH2Cl2/MeOH 99 : 1) to give (‡)-23 (243 mg, 72%).
1
Colorless, amorphous solid [a]rD:t: ˆ ‡ 63.2 (c ˆ 1.00, CHCl3). IR (CHCl3): 3422m, 1611m, 1500m, 1255s. H-
NMR (200 MHz, CDCl3): 8.76 ± 7.88 (m, 3 H); 7.75 (d, J ˆ 8.7, 1 H); 7.51 ± 7.37 (m, 3 H); 7.30 ± 7.21 (m, 2 H);
7.11 ± 7.07 (m, 1 H); 5.04 ± 4.88 (m, 2 H); 3.80 (s, 3 H); 3.41 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 156.0; 155.0;
135.5; 134.0; 133.8; 131.0; 130.2; 129.9; 128.5; 128.3; 127.7; 127.5; 127.4; 126.5; 125.3; 125.3; 124.0; 121.7; 118.6;
‡
‡
113.9; 62.5; 60.8; 56.6. DEI-MS: 424/422 (97/100, M ). DEI-HR-MS: 422.0516 (M , C23H19BrO3; calc.
422.0518).
(aS)-7'-Bromo-2,2'-dimethoxy-3-(methoxymethyl)-1,1'-binaphthalene (( )-11). To (‡)-23 (180 mg,
0.43 mmol) in acetone (20 ml), (MeO)2SO2 (0.12 ml, 1.29 mmol) was added, followed by NaH (41 mg,
1.72 mmol), and the soln. was stirred at r.t. for 1 h. The reaction was quenched with 1m aq. HCl (50 ml) and the
mixture extracted with CH2Cl2 (3 Â 50 ml). The combined org. extracts were dried (Na2SO4), evaporated in
vacuo, and purified by CC (SiO2; hexane/AcOEt 90 : 10) to give ( )-11 (180 mg, 97%). Colorless, amorphous
solid. [a]rD:t:
ˆ
14.6 (c ˆ 1.00, CHCl3). IR (CHCl3): 1499m, 1257s, 1150s, 1136s, 1111s. 1H-NMR (200 MHz,
CDCl3): 8.05 (s, 1 H); 7.99 (d, J ˆ 8.7, 1 H); 7.93 (d, J ˆ 8.3, 1 H); 7.76 (d, J ˆ 8.7, 1 H); 7.51 ± 7.39 (m, 3 H);
7.29 ± 7.23 (m, 2 H); 7.12 ± 7.07 (m, 1 H); 4.78 (s, 2 H); 3.80 (s, 3 H); 3.59 (s, 3 H); 3.41 (s, 3 H). 13C-NMR
(75 MHz, CDCl3): 156.0; 155.0; 135.7; 133.8; 131.7; 131.0; 130.1; 129.9; 129.1; 128.4; 127.7; 127.4 (2Â); 126.4;
‡
125.3; 125.1; 124.2; 121.6; 118.9; 114.0; 70.6; 61.1; 58.7; 56.6. DEI-MS: 438/436 (100/100, M ), 407/405 (16/16,
‡
[M OMe] ). Anal. calc. for C24H21BrO3 (437.3): C 65.91, H 4.84, Br 18.27; found: C 65.97, H 4.87, Br 18.35.
(aRS)-2,2'-Dimethoxy-3-(methoxymethyl)-1,1'-binaphthalene (( Æ )-24). Colorless solid, M.p. 132 ± 1348
(AcOEt). IR (CHCl3): 3007m, 1359m, 1266s, 1248s, 1148m, 1112s, 1089m. 1H-NMR (200 MHz, CDCl3): 8.04 ±
8.00 (m, 2 H); 7.92 ± 7.86 (m, 2 H); 7.47 (d, J ˆ 9.1, 1 H); 7.43 ± 7.10 (m, 6 H); 4.77 (s, 2 H); 3.80 (s, 3 H); 3.57
(s, 3 H); 3.38 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 155.3; 154.9; 134.3; 134.0; 131.7; 130.9; 130.0; 129.3; 128.6;
‡
128.2; 128.1; 126.9; 126.2; 125.6; 125.5; 125.0; 123.9; 119.4; 113.8; 70.6; 61.0; 58.7; 56.7. DEI-MS: 358 (100, M ).
Anal. calc. for C24H22O3 (358.4): C 80.42, H 6.19; found: C 80.40, H 6.30.
(aRS)-Tributyl[2,2'-dimethoxy-3'-(methoxymethyl)-1,1'-binaphthalen-7-yl]stannane (( Æ )-26). To hexabu-
tyldistannane (1.35 ml, 2.70 mmol) in dry THF (10 ml) at 08 under Ar, BuLi (1.6m soln. in hexanes, 1.56 ml,
2.50 mmol) was added, and the soln. was stirred at 08 for 15 min to afford a 0.17m soln. of Bu3SnLi [44]. A
portion of this soln. (5.56 ml, 0.95 mmol) was added at 08 under Ar to ( Æ )-11 (277 mg, 0.63 mmol) in dry THF
(20 ml), and the soln. was stirred at 08 for 30 min. The reaction was quenched with a sat. aq. NH4Cl soln.
(50 ml), and the mixture was extracted with AcOEt (2 Â 50 ml). The combined org. extracts were dried
(Na2SO4), evaporated in vacuo, and purified by CC (SiO2; hexane/AcOEt 90 : 10) to give ( Æ )-26 (209 mg,
51%). Colorless oil. IR (CHCl3): 2973s, 2928s, 1247s, 1139m, 1111m, 1047s. 1H-NMR (200 MHz, CDCl3): 8.00
(s, 1 H); 7.97 (d, J ˆ 9.1, 1 H); 7.88 (d, J ˆ 8.3, 1 H); 7.81 (d, J ˆ 7.9, 1 H); 7.46 ± 7.32 (m, 3 H); 7.23 ± 7.09
(m, 3 H); 4.77 (s, 2 H); 3.79 (s, 3 H); 3.55 (s, 3 H); 3.35 (s, 3 H); 1.37 ± 1.01 (m, 12 H); 0.84 ± 0.69 (m, 15 H).
13C-NMR (75 MHz, CDCl3): 155.2; 154.9; 140.7; 134.4; 134.0; 133.8; 131.4; 131.1; 130.9; 129.8; 129.2; 128.4;
128.2; 126.9; 126.1; 125.7; 124.8; 119.1; 114.0; 70.6; 60.9; 58.5; 56.9; 28.9; 27.2; 13.6; 9.5. DEI-MS: 648/646 (4/3,
‡
‡
‡
M
(
120Sn/118Sn)), 561/559 (100/73, [M OMe Bu ‡ H] ), 447/445 (49/39, [M OMe 3 Bu ‡ H ),
282(36). Anal. calc. for C36H48O3Sn (647.5): C 66.78, H 7.47; found: C 66.51, H 7.47.
(aS,3R,4S,8R)- and (aS,3R,4S,8S)-[2,2'-Dimethoxy-3'-(methoxymethyl)-1,1'-binaphthalen-7-yl](3-ethyl-1-
azabicyclo[2.2.2]oct-8-yl)methanone (27/28). To ( )-11 (250 mg, 0.57 mmol) and (‡)-8 (258 mg, 1.14 mmol) in
dry THF (25 ml) at 788 under Ar, BuLi (1.6m soln. in hexanes, 0.71 ml, 1.14 mmol) was added dropwise, and
the soln. was stirred at this temp. for 10 min. The reaction was quenched with sat. aq. NaHCO3 soln. (50 ml) and
the mixture extracted with CH2Cl2 (3 Â 50 ml). The combined org. extracts were dried (Na2SO4), evaporated in
vacuo, and purified by CC (SiO2; AcOEt) to afford 27/28 (137 mg, 46%) as an inseparable 1 : 1 mixture.
Colorless oil. IR (CHCl3): 2956s, 2935s, 1683w, 1459m, 1136vs. 1H-NMR (200 MHz, CDCl3): 8.05 ± 7.85
(m, 6 H); 7.56 (dd, J ˆ 9.1, 1.7, 1 H); 7.43 ± 7.36 (m, 1 H); 7.23 ± 7.04 (m, 2 H); 4.78 ± 4.77 (m, 2 H); 3.83
(s, 1.5 H); 3.82 (s, 1.5 H); 3.82 ± 3.69 (m, 1 H); 3.58 (s, 1.5 H); 3.57 (s, 1.5 H); 3.38 (s, 1.5 H); 3.35 (s, 1.5 H);

1000
Helvetica Chimica Acta ± Vol. 82 (1999)
2.95 ± 2.04 (m, 4 H); 1.68 ± 0.91 (m, 8 H); 0.82 (t, J ˆ 6.9, 1.5 H); 0.76 (t, J ˆ 6.9, 1.5 H). 13C-NMR (75 MHz,
CDCl3): [199.4; 199.3]; [155.8; 155.7]; [155.1; 155.0]; 134.3; 134.1; 133.9; 133.9; 133.6; 133.5; 131.8; 131.5; 131.3;
131.2; 130.9; 129.8; 129.7; 128.9; 128.9; 128.8; 128.8; 128.4 (2Â); 128.2; [126.4; 126.3]; 125.7; 125.5; [125.1;
125.0]; [124.3; 124.3]; 122.6; 122.5; 121.2; 116.1; 116.0; [70.7; 70.6]; [61.2; 61.1]; 60.5; [58.7; 58.7]; [56.8; 56.7];
‡
50.8; 48.2; 42.8; [37.5; 37.5]; 28.1; 27.7; 27.5; 25.9; 25.4; 25.3; 22.6; 22.5; 21.8. DEI-MS: 523 (14, M ), 508 (20,
‡
‡
‡
‡
[M Me] ), 357 (13, [M COC9H16N] ), 138 (100, [C9H16N] ). DEI-HR-MS: 523.2713 (M , C34H37NO4;
calc. 523.2722).
Four Diastereoisomers of [2,2'-Dimethoxy-3'-(methoxymethyl)-1,1'-binaphthalen-7-yl](3-ethyl-1-azabicy-
clo[2.2.2]oct-8-yl)methanol ((‡)-29, (‡)-30, ( )-31, and (‡)-32). To the 1:1 mixture 27/28 (120 mg, 0.23 mmol)
in benzene (50 ml) at 08, DIBAL-H (1m soln. in hexane, 0.69 ml, 0.69 mmol) was added, and the soln. was stirred
at r.t. for 4 h. The reaction was quenched with a sat. aq. NaHCO3 soln. (50 ml) and the mixture extracted with
CH2Cl2 (3 Â 50 ml). The combined org. extracts were dried (Na2SO4), evaporated in vacuo, and purified by CC
(SiO2; CH2Cl2/MeOH/NH4OH 90 : 9 : 1) to give the pure four diastereoisomers.
Data of (‡)-(aS,3R,4S,8S,9S)-29: 12 mg, 10%. Yellow, highly viscous oil. [a]rD:t: ˆ ‡ 36.7 (c ˆ 0.50, CHCl3).
2
IR (CHCl3): 2925w, 1133vs. 1H-NMR (300 MHz, CDCl3) ): 8.02 (s, H C(4'')); 7.98 (d, J ˆ 9.0, H C(4')); 7.90
(d, J ˆ 7.4, H C(5'')); 7.88 (d, J ˆ 8.7, H C(5')); 7.47 ± 7.45 (m, H C(6')); 7.44 (d, J ˆ 9.0, H C(3')); 7.40 ±
7.35 (m, H C(6'')); 7.22 ± 7.17 (m, H C(7'')); 7.08 (d, J ˆ 8.4, H C(8'')); 7.04 (s, H C(8')); 4.79 (d, J ˆ 12.5,
1 H C(12)); 4.73 (d, J ˆ 12.5, 1 H C(12)); 4.13 (d, J ˆ 9.7, H C(9)); 3.77 (s, MeO); 3.55 (s, MeO); 3.33
(s, MeO); 3.08 (dd, J ˆ 13.5, 10.1, 1 H C(2)); 2.96 ± 2.84 (m, 1 H C(6)); 2.64 ± 2.52 (m, 2 H, H C(8),
H
C(6)); 2.38 ± 2.31 (m, 1 H C(2)); 1.57 ± 1.53 (m, H C(4)); 1.48 ± 1.30 (m, H C(3), CH2(5)); 1.21 ± 1.10
(m, 1 H C(7), CH2(10)); 0.78 (t, J ˆ 7.3, CH3(11)); 0.73 ± 0.66 (m, 1 H C(7)). 13C-NMR (75 MHz, CDCl3):
155.5; 155.1; 139.3; 134.1; 134.0; 131.5; 130.9; 129.8; 129.1; 128.7; 128.6; 128.2; 126.3; 125.7; 125.0; 124.7; 124.6;
123.1; 119.6; 113.9; 74.9; 70.6; 61.8; 61.0; 58.6; 57.2; 56.8; 40.7; 37.7; 28.3; 27.6; 25.0; 24.2; 12.1. DEI-MS: 525 (39,
‡
‡
‡
‡
M ), 510 (30, [M Me] ), 495 (31, [M 2 Me] ), 386 (49, [M C9H16N H] ), 356 (38, [M
‡
‡
‡
CH(OH)C9H16N H] ), 302(76), 139 (100, [C9H16N ‡ H] ). DEI-HR-MS: 525.2875 (M , C34H39NO4; calc.
525.2879).
Data of (‡)-(aS,3R,4S,8R,9R)-30: 12 mg, 10%. Yellow, highly viscous oil. [a]rD:t: ˆ ‡ 33.2 (c ˆ 0.50,
2
CHCl3). IR (CHCl3): 2935w, 1261w, 1136vs, 1111s. 1H-NMR (300 MHz, CDCl3) ): 8.03 (s, H C(4'')); 7.98
(d, J ˆ 9.2, H C(4')); 7.90 (d, J ˆ 8.4, H C(5')); 7.87 (d, J ˆ 9.3, H C(5'')); 7.50 (dd, J ˆ 8.4, 1.6, H C(6'));
7.46 (d, J ˆ 9.2, H C(3')); 7.33 ± 7.28 (m, H C(6'')); 7.12 ± 7.07 (m, H C(7'')); 7.01 (d, J ˆ 8.4, H C(8''));
6.88 (s, H C(8')); 4.80 (d, J ˆ 12.5, 1 H C(12)); 4.75 (d, J ˆ 12.5, 1 H C(12)); 4.28 (d, J ˆ 9.6, H C(9));
3.80 (s, MeO); 3.72 (s, MeO); 3.59 (s, MeO); 3.10 ± 2.89 (m, 1 H C(2), CH2(6), H C(8)); 2.51 ± 2.44
(m, 1 H C(2)); 1.64 ± 1.56 (m, 1 H C(5)); 1.54 ± 1.50 (m, 1 H C(4)); 1.47 ± 1.37 (m, 1 H C(3)); 0.90 ± 0.68
(m, 1 H C(5), CH2(7), CH2(10)); 0.71 (t, J ˆ 7.1, CH3(11)). 13C-NMR (75 MHz, CDCl3): 155.8; 155.2; 138.1;
133.8; 133.8; 132.0; 131.0; 129.8; 129.2; 129.1; 128.6; 128.3; 125.8; 125.7; 124.9; 124.6; 124.5; 121.8; 119.4; 114.4;
‡
73.2; 70.6; 63.8; 61.1; 58.9; 57.0; 48.4; 48.0; 36.1; 25.5; 25.2; 24.7; 23.2; 11.7. DEI-MS: 525 (5, M ), 510 (5, [M
‡
‡
‡
‡
Me] ), 495 (5, [M 2 Me] ), 386 (9, [M C9H16N H] ), 139 (100, [C9H16N ‡ H] ). DEI-HR-MS:
‡
525.2881 (M , C34H39NO4; calc. 525.2879).
Data of ( )-(aS,3R,4S,8S,9R)-31: 12 mg, 10%. Yellow, highly viscous oil. [a]Dr:t:
ˆ
3.2 (c ˆ 0.50, CHCl3).
2
IR (CHCl3): 2964w, 1265s, 1136vs. 1H-NMR (300 MHz, CDCl3) ): 8.01 (s, H C(4'')); 7.96 (d, J ˆ 9.0,
H
C(4')); 7.87 (d, J ˆ 9.0, H C(5'')); 7.84 (d, J ˆ 8.7, H C(5')); 7.41 (d, J ˆ 9.0, H C(3')); 7.40 ± 7.36
(m, H C(6')); 7.37 ± 7.32 (m, H C(6'')); 7.19 ± 7.14 (m, H C(7'')); 7.09 (d, J ˆ 8.4,
(s, H C(8')); 4.77 (d, J ˆ 12.5, 1 H C(12)); 4.72 (d, J ˆ 12.5, 1 H C(12)); 4.57 (d, J ˆ 6.7, H C(9)); 3.76
(s, MeO); 3.56 (s, MeO); 3.34 (s, MeO); 2.93 ± 2.72 (m, 1 H C(2), 1 H C(6), C(8)); 2.31 ± 2.17
H C(8'')); 6.99
H
(m, 1 H C(2), 1 H C(6)); 1.66 ± 1.55 (m, H C(4), 1 H C(7)); 1.47 ± 1.16 (m, H C(3), CH2(5),
1 H C(7), CH2(10)); 0.80 (t, J ˆ 7.2, CH3(11)). 13C-NMR (75 MHz, CDCl3): 155.5; 154.9; 141.7; 134.1;
134.0; 131.5; 130.9; 129.8; 129.0; 129.0; 128.8; 128.7; 128.2; 126.2; 125.7; 124.9; 123.3; 122.3; 119.5; 113.8; 111.2;
‡
70.7; 61.0 (2Â); 58.7; 58.0; 56.7; 42.3; 37.4; 28.1; 27.5; 25.5; 23.8; 12.1. DEI-MS: 525 (20, M ), 510 (33, [M
‡
‡
‡
‡
Me] ), 495 (35, [M 2 Me] ), 138 (100, [C9H16N] ). DEI-HR-MS: 525.2874 (M , C34H39NO4; calc. 525.2879).
Data of (‡)-(aS,3R,4S,8R,9S)-32: 15 mg, 12%. Yellow, highly viscous oil. [a]rD:t: ˆ ‡ 38.0 (c ˆ 0.50,
2
CHCl3). IR (CHCl3): 2922w, 1139vs. 1H-NMR (300 MHz, CDCl3) ): 8.01 (s, H C(4'')); 7.97 (d, J ˆ 9.0,
H
C(4')); 7.89 (d, J ˆ 8.1, H C(5'')); 7.84 (d, J ˆ 8.4, H C(5')); 7.42 (d, J ˆ 9.0, H C(3')); 7.39 ± 7.32
(m, H C(6'), H C(6'')); 7.20 ± 7.15 (m, H C(7'')); 7.08 (d, J ˆ 9.0, H C(8'')); 7.04 (s, H C(8')); 5.28
(s, CH2(12)); 4.72 (d, J ˆ 13.4, C(9)); 3.77 (s, MeO); 3.55 (s, MeO); 3.35 (s, MeO); 2.84 ± 2.76
H
(m, H C(8)); 2.69 ± 2.26 (m, CH2(2), CH2(6)); 1.63 ± 1.06 (m, H C(3),
H C(4), CH2(5), CH2(7),
CH2(10)); 0.74 (t, J ˆ 7.3, CH3(11)). 13C-NMR (75 MHz, CDCl3): 155.5; 155.0; 141.1; 134.1; 134.0; 131.6;

Helvetica Chimica Acta ± Vol. 82 (1999)
1001
131.0; 129.8; 128.9; 128.7; 128.3; 128.2; 126.1; 125.7; 124.8; 123.2; 122.7; 119.5; 113.8; 75.2; 70.6; 61.3; 61.0; 58.6;
‡
‡
56.7; 50.4; 49.6; 37.1; 26.7; 26.0; 24.9; 22.7; 11.8. DEI-MS: 525 (12, M ), 510 (17, [M Me] ), 495 (17, [M
‡
‡
‡
‡
2 Me] ), 168 (25, [CH(OH)C9H16N] ), 138 (100, [C9H16N] ). DEI-HR-MS: 525.2875 (M , C34H39NO4; calc.
525.2879).
General Procedure (GP) for the Quaternization. A soln. of (‡)-29, (‡)-30, ( )-31, or (‡)-32 (0.50 mmol)
and 4-(trifluoromethyl)benzyl bromide (0.50 mmol) in THF (10 ml) was heated to reflux for 72 h. The mixture
was then evaporated in vacuo and purified by CC (SiO2; CH2Cl2/MeOH 95 :5).
(aS,2S,4S,5R)-1-[4-(Trifluoromethyl)benzyl]-2-[(S)-2,2'-dimethoxy-3'-(methoxymethyl)-1,1'-binaphthalen-
7-yl)hydroxymethyl]-5-ethylazoniabicyclo[2.2.2]octane Bromide ((‡)-5). Conversion of (‡)-29 (11 mg,
0.02 mmol) afforded (‡)-5 (9 mg, 56%). Colorless solid. [a]rD:t: ˆ ‡ 4.1 (c ˆ 0.25, CHCl3). IR (CHCl3):
2
3456s, 1461w, 1322s, 1250w, 1167w, 1122m, 1067m. 1H-NMR (500 MHz, CDCl3) ): 8.03 (s, H C(4'')); 7.99
(d, J ˆ 9.0, H C(4')); 7.87 (d, J ˆ 8.4, 1 arom. H); 7.84 (d, J ˆ 8.0, 1 arom. H); 7.78, 7.51 (AA'BB', J ˆ 7.9,
H
C(15), H C(16), H C(18), H C(19)); 7.48 (d, J ˆ 9.0, H C(3')); 7.47 ± 7.45 (m, H C(6')); 7.34 ± 7.29
(m, H C(6'')); 7.17 ± 7.13 (m, H C(7'')); 7.08 ± 7.05 (m, H C(8'), H C(8'')); 5.52 (d, J ˆ 12.8, 1 H C(13));
5.28 (d, J ˆ 10.0, 1 H); 5.09 (d, J ˆ 12.8, 1 H C(13)); 4.75 (d, J ˆ 12.3, 1 H C(12)); 4.69 (d, J ˆ 12.3,
1 H C(12)); 4.45 ± 4.39 (m,1 H); 3.95 ± 3.89 (m, 1 H); 3.80 (s, MeO); 3.56 ± 3.51 (m, 1 H); 3.53 (s, MeO); 3.33
(s, MeO); 2.32 ± 2.26 (m, 1 H); 2.02 ± 1.95 (m, 1 H); 1.92 ± 1.80 (m, 2 H); 1.80 ± 1.75 (m, H C(4)); 1.32 ± 0.80
(m, 5 H); 0.76 (t, J ˆ 7.4, CH3(11)). 13C-NMR (125 MHz, CDCl3): 155.5; 154.8; 138.1; 134.0; 133.7; 133.6; 132.1
([q, J ˆ 31.5], C(17)); 131.9; 131.5; 130.7; 129.8; 129.1; 128.9; 128.2; 125.9; 125.8; 125.8; 125.3; 124.6; 124.0;
124.0; 123.9; 123.7 ([q, J ˆ 273.0], CF3); 119.1; 114.2; 70.6; 66.6; 65.3; 63.2; 61.0; 58.7; 56.5; 51.2; 35.3; 29.7; 25.6;
‡
‡
24.7; 24.6; 24.3; 11.1. FAB-MS: 684 (100, (M Br] ). FAB-HR-MS: 684.3304 ([M Br] , C42H45F3NO4, calc.
684.3300).
(aS,2R,4S,5R)-1-[4-(Trifluoromethyl)benzyl]-2-[(R)-(2,2'-dimethoxy-3'-(methoxymethyl)-1,1'-binaphthalen-
7-yl)hydroxymethyl]-5-ethylazoniabicyclo[2.2.2]octane Bromide ((‡)-6). Conversion of (‡)-30 (11 mg,
0.02 mmol) afforded (‡)-6 (2 mg, 12%). Colorless solid. [a]rD:t: ˆ ‡ 3.9 (c ˆ 0.25, CHCl3). IR (CHCl3):
2
3422s, 1461w, 1322s, 1250w, 1167w, 1122m, 1067m. 1H-NMR (300 MHz, CDCl3) ): 8.03 (s, H C(4'')); 7.92
(d, J ˆ 8.9, H C(4')); 7.90 (d, J ˆ 6.5, H C(5'')); 7.76 (d, J ˆ 8.1, H C(5')); 7.74, 7.56 (AA'BB', J ˆ 7.9,
H
C(15), H C(16), H C(18), H C(19)); 7.67 ± 7.63 (m, H C(6')); 7.44 (d, J ˆ 8.9, H C(3')); 7.39 ± 7.26
(m, H C(6''), H C(7'')); 7.10 (d, J ˆ 8.4, H C(8'')); 6.99 (s, H C(8')); 6.00 ± 5.96 (m, 1 H); 5.72 (d, J ˆ 12.1,
1 H C(13)); 4.80 ± 4.65 (m, CH2(12), 1 H C(13)); 4.28 ± 4.16 (m, 1 H); 3.80 (s, MeO); 3.62 ± 3.57 (m, 1 H);
3.55 (s, MeO); 3.31 (s, MeO); 3.24 ± 3.14 (m, 1 H); 3.06 ± 2.94 (m, 1 H); 2.74 ± 2.66 (m, 1 H); 2.18 ± 0.83
‡
‡
(m, 8 H); 0.77 (t, J ˆ 7.3, CH3(11)). FAB-MS: 684 (100), [M Br] ). FAB-HR-MS: 684.3302 ([M Br] ,
C42H45F3NO4; calc. 684.3300).
(aS,2S,4S,5R)-1-[4-(Trifluoromethyl)benzyl]-2-[(R)-(2,2'-dimethoxy-3'-(methoxymethyl)-1,1'-binaphthalen-
7-yl)hydroxymethyl]-5-ethylazoniabicyclo[2.2.2]octane Bromide (( )-7). Conversion of
0.03 mmol) afforded ( )-7 (11 mg, 54%). Colorless solid. [a]Dr:t:
1.4 (c ˆ 0.25, CHCl3). IR (CHCl3):
3444s, 1461w, 1328s, 1250w, 1172w, 1117m, 1067m. 1H-NMR (300 MHz, CDCl3) ): 8.02 (s, H C(4'')); 7.88
(d, J ˆ 7.8, C(5'')); 7.86 (d, J ˆ 8.9, C(4')); 7.66, 7.46 (AA'BB', J ˆ 7.9, C(15), C(16),
( )-31 (14 mg,
ˆ
2
H
H
H
H
H
C(18), H C(19)); 7.64 (d, J ˆ 6.7, H C(5')); 7.56 ± 7.52 (m, H C(6')); 7.42 (d, J ˆ 8.9, H C(3'));
7.39 ± 7.34 (m, H C(6'')); 7.24 ± 7.19 (m, H C(7'')); 7.11 (d, J ˆ 8.4, H C(8'')); 7.03 (s, H C(8')); 5.95 ± 5.92
(m, 1 H); 5.56 (d, J ˆ 12.9, 1 H C(13)); 4.99 (d, J ˆ 12.9, 1 H C(13)); 4.76 (d, J ˆ 12.5, 1 H C(12)); 4.70
(d, J ˆ 12.5, 1 H C(12)); 4.63 ± 4.52 (m, 1 H); 3.79 (s, MeO); 3.52 (s, MeO); 3.29 (s, MeO); 3.22 ± 2.96
(m, 3 H); 2.82 ± 2.74 (m, 1 H); 1.88 ± 0.80 (m, 8 H); 0.75 (t, J ˆ 7.3, CH3(11)). 13C-NMR (75 MHz, CDCl3):
155.5; 155.2; 138.1; 134.2; 133.9; 133.7; 132.4 ([q, J ˆ 33.0], C(17)); 131.9; 131.5; 130.9; 129.9; 128.9; 128.7;
128.7; 128.4; 126.0; 125.9; 125.6; 124.8; 124.5; 123.8 ([q, J ˆ 272.0], CF3); 122.4; 122.1; 119.2; 114.0; 70.7; 69.9;
‡
67.2; 63.0; 62.2; 61.0; 58.7; 56.8; 36.3; 29.7; 26.3; 25.5; 24.1; 20.7; 11.4. FAB-MS: 684 (100, [M Br] ). FAB-
‡
HR-MS: 684.3300 ([M Br] , C42H45F3NO4; calc. 684.3300).
(aS,2R,4S,5R)-1-[4-(Trifluoromethyl)benzyl]-2-[(S)-(2,2'-dimethoxy-3'-(methoxymethyl)-1,1'-binaphthalen-7-
yl)hydroxymethyl]-5-ethylazoniabicyclo[2.2.2]octane Bromide ((‡)-4). Conversion of (‡)-32 (11 mg,
0.02 mmol) afforded (‡)-4 (8 mg, 50%). Colorless solid. [a]rD:t: ˆ ‡ 15.2 (c ˆ 0.25, CHCl3). IR (CHCl3):
2
3433s, 1461w, 1322s, 1250w, 1167w, 1117m, 1067m. 1H-NMR (300 MHz, CDCl3) ): 8.06 (s, H C(4'')); 7.88
(d, J ˆ 7.8, H C(5'')); 7.60, 7.35 (AA'BB', J ˆ 8.3, H C(15), H C(16), H C(18), H C(19)); 7.49 (d, J ˆ
9.0, H C(4')); 7.38 (d, J ˆ 9.0, H C(3')); 7.29 ± 7.24 (m, H C(5'), H C(6')); 7.20 ± 7.16 (m, H C(6''));
7.04 ± 6.99 (m, H C(7'')); 6.91 ± 6.87 (m, H C(8'), H C(8'')); 5.97 (d, J ˆ 11.7, 1 H C(13)); 5.87 ± 5.83
(m, 1 H); 5.03 (d, J ˆ 11.7, 1 H C(13)); 4.87 (s, CH2(12)); 4.26 ± 4.17 (m, 1 H); 4.13 ± 4.01 (m, 1 H); 3.83 ± 3.73
(m, 1 H); 3.81 (s, MeO); 3.63 (s, MeO); 3.62 (s, MeO); 3.01 ± 2.94 (m, 1 H); 2.48 ± 2.36 (m, 1 H); 1.80 ± 1.22

1002
Helvetica Chimica Acta ± Vol. 82 (1999)
(m, 5 H); 0.98 ± 0.83 (m, 3 H); 0.65 (t, J ˆ 7.2, CH3(11)). 13C-NMR (75 MHz, CDCl3): 155.5; 155.3; 137.4;
134.2; 134.0; 132.2 ([q, J ˆ 33.0], C(17)); 132.0; 132.0; 131.1; 129.7; 128.7; 128.3; 128.1; 125.9; 125.6; 125.6;
125.3; 124.8; 124.4; 123.6 ([q, J ˆ 271.5], CF3); 123.0; 121.9; 119.5; 114.1; 70.7; 68.4; 68.2; 61.5; 60.2; 58.8; 57.1;
‡
55.8; 36.0; 29.7; 24.5; 24.5; 23.6; 20.8; 11.4. FAB-MS: 684 (100, [M Br] ). FAB-HR-MS: 684.3324 ([M
‡
Br] , C42H45F3NO4; calc. 684.3300).
6,7-Dichloro-5-methoxy-2-phenyl-2-(prop-2-enyl)-indan-1-one (3b). A suspension of 1 (50 mg, 0.16 mmol),
phase-transfer catalyst (0.02 mmol, 10 mol-%), and allyl chloride (0.07 ml, 0.80 mmol) in PhMe (2.5 ml), and
50% aq. NaOH soln. (0.5 ml) was shaken at r.t. for 20 h. After addition of H2O (10 ml) and AcOEt (10 ml), the
org. phase was separated, washed with 1m aq. HCl soln. (2 Â 10 ml) and H2O (10 ml), dried (Na2SO4),
evaporated in vacuo, and purified by CC (SiO2; hexane/Et2O 8 : 2) to give 3b (for yields, see the Table).
Colorless solid. M.p. 118 ± 1218. IR (KBr): 1700s, 1578s, 1300m, 1267w, 1156m, 1067m. 1H-NMR (200 MHz,
CDCl3): 7.42 ± 7.18 (m, 5 H); 6.91 (s, 1 H); 5.70 ± 5.50 (m, 1 H); 5.18 ± 5.08 (m, 1 H); 5.07 ± 5.01 (m, 1 H); 4.01
(s, 3 H); 3.49 (dd, J ˆ 17.7, 0.8, 1 H); 3.36 (dd, J ˆ 17.7, 1.0, 1 H); 2.86 ± 2.82 (m, 2 H). 13C-NMR (75 MHz,
CDCl3): 202.6; 161.4; 154.7; 142.0; 133.8; 132.4; 128.9; 127.2; 126.7; 126.1; 123.3; 119.3; 106.7; 57.7; 57.0; 42.7;
‡
‡
39.2. EI-MS: 348/346 (21/32, M ), 307/305 (66/100, [M C3H5] ). Anal. calc. for C19H16Cl2O2 (347.2): C 65.72,
H 4.64, Cl 20.42; found: C 65.65, H 4.87, Cl 20.33.
This work was supported by the TEMA grant from the ETH research council. The authors are indebted to
Dr. U.-H. Dolling, Merck, Rahway, New Jersey, for providing generous amounts of phenylindanone 1 and to Dr.
Monica Sebova for NMR measurements.
REFERENCES
[1] G. R. Stephenson, ꢁAdvanced Asymmetric Synthesisꢀ, Chapman & Hall, London, 1996.
[2] D. J. Ager, M. B. East, ꢁAsymmetric Synthetic Methodologyꢀ, CRC Press, Boca Raton, 1995.
Â
[3] R. E. Gawley, J. Aube, ꢁPrinciples of Asymmetric Synthesisꢀ, Eds. J. E. Baldwin, P. D. Magnus, Pergamon,
Oxford, 1996.
[4] R. S. Atkinson, ꢁStereoselective Synthesisꢀ, Wiley, Chichester, 1995.
[5] M. J. OꢀDonnell in ꢁCatalytic Asymmetric Synthesisꢀ, Ed. I. Ojima, VCH, New York, 1993, pp. 389 ± 411.
[6] T. Shioiri in ꢁ Handbook of Phase Transfer Catalysisꢀ, Ed. Y. Sasson and R. Neumann, Blackie Academic &
Professional, London, 1997, pp. 462 ± 479.
[7] R. Noyori in ꢁAsymmetric Catalysis in Organic Chemistryꢀ, Wiley, New York, 1994, pp. 333 ± 341.
[8] T. Shioiri, A. Ando, M. Masui, T. Miura, T. Tatematsu, A. Bohsako, M. Higashiyama, C. Asakura in ꢁPhase-
Transfer Catalysis Mechanism and Synthesisꢀ, Ed. M. E. Halpern, ACS Symposium Series 659, Washington,
D.C., 1997, pp. 136 ± 147.
[9] C. M. Starks, C. L. Liotta, M. Halpern in ꢁPhase-Transfer Catalysis Fundamentals, Applications, and
Industrial Perspectives,ꢀ Chapman & Hall, New York, 1994, pp. 576 ± 593.
[10] a) U.-H. Dolling, P. Davis, E. J. J. Grabowski, J. Am. Chem. Soc. 1984, 106, 446; b) A. Bhattacharya, U.-H.
Dolling, E. J. J. Grabowski, S. Karady, K. M. Ryan, L. M. Weinstock, Angew. Chem. 1986, 98, 442; ibid., Int.
Ed. 1986, 25, 476; c) D. L. Hughes, U.-H. Dolling, K. M. Ryan, E. F. Schoenewaldt, E. J. J. Grabowski, J.
Org. Chem. 1987, 52, 4745; d) U.-H. Dolling, D. L. Hughes, A. Bhattacharya, K. M. Ryan, S. Karady, L. M.
Weinstock, E. J. J. Grabowski in ꢁPhase-Transfer Catalysisꢀ, Ed. C. M. Starks, ACS Symposium Series 326,
Washington D.C., 1987, pp. 67 ± 81.
[11] M. J. OꢀDonnell, J. Am. Chem. Soc. 1989, 111, 2353; K. B. Lipkowitz, M. W. Cavanaugh, B. Baker, M. J.
OꢀDonnell, J. Org. Chem. 1991, 56, 5181; M. J. OꢀDonnell, S. Wu, Tetrahedron: Asymmetry 1992, 3, 591;
M. J. OꢀDonnell, S. Wu, J. C. Huffman, Tetrahedron 1994, 50, 4507; M. J. OꢀDonnell, F. Delgado, C.
Hostettler, R. Schwesinger, Tetrahedron Lett. 1998, 39, 8775.
[12] E. J. Corey, F. Xu, M. C. Noe, J. Am. Chem. Soc. 1997, 119, 12414; E. J. Corey, M. C. Noe, F. Xu,
Tetrahedron Lett. 1998, 39, 5347; see also: E. J. Corey, Y. Bo, J. Busch-Petersen, J. Am. Chem. Soc. 1998,
120, 13000.
[13] B. Lygo, J. Crosby, J. A. Peterson, Tetrahedron Lett. 1999, 40, 1385; B. Lygo, ibid. 1999, 40, 1389.
[14] A. Ando, T. Miura, T. Tatematsu, T. Shioiri, Tetrahedron Lett. 1993, 34, 1507; C. M. Gasparski, M. J. Miller,
Tetrahedron 1991, 47, 5367.
[15] R. S. E. Conn, A. V. Lovell, S. Karady, L. M. Weinstock, J. Org. Chem. 1986, 51, 4710; A. Loupy, J.
Sansoulet, A. Zaparucha, C. Merienne, Tetrahedron Lett. 1989, 30, 333; S. Colonna, H. Hiemstra, H.
Wynberg, J. Chem. Soc., Chem. Commun. 1978, 238.

Helvetica Chimica Acta ± Vol. 82 (1999)
1003
[16] a) Y. Harigaya, H. Yamaguchi, M. Onda, Chem. Pharm. Bull. 1981, 29, 1321; b) H. Takahashi, Y. Kobuta,
H. Miyazaki, M. Onda, Chem. Pharm. Bull. 1984, 32, 4852; c) R. Helder, J. C. Hummelen, R. W. P. M.
Laane, J. S. Wiering, H. Wynberg, Tetrahedron Lett. 1976, 1831; d) H. Wynberg in ꢁTopics in Stereo-
chemistryꢀ, Vol. 16, Eds. E. L. Eliel, S. H. Wilen, N. L. Allinger, Wiley, New York, 1986, pp. 87 ± 129.
[17] M. Masui, A. Ando, T. Shioiri, Tetrahedron Lett. 1988, 29, 2835.
Â
Â
[18] S. Colonna, R. Fornasier, Synthesis 1975, 531; S. Julia, A. Ginebreda, J. Guixer, J. Masana, A. Tomas, S.
Colonna, J. Chem. Soc., Perkin Trans. 1 1981, 574.
[19] B. Winter-Werner, F. Diederich, V. Gramlich, Helv. Chim. Acta 1996, 79, 1338.
[20] R. A. Johnson, K. B. Sharpless in ꢁCatalytic Asymmetric Synthesisꢀ, Ed. I. Ojima, VCH, New York, 1993,
pp. 227 ± 272; H. C. Kolb, M. S. VanNieuwenhze, K. B. Sharpless, Chem. Rev. 1994, 94, 2483.
[21] S. H. Wilen, ꢁTables of Resolving Agents and Optical Resolutionsꢀ, Ed. E. L. Eliel, University of Notre
Dame Press, Notre Dame, 1972; J. Jacques, A. Collet, S. H. Wilen in ꢁEnantiomers, Racemates and
Resolutionꢀ, Wiley, New York, 1981.
[22] J. Reeder, P. P. Castro, C. B. Knobler, E. Martinborough, L. Owens, F. Diederich, J. Org. Chem. 1994, 59,
3151.
[23] C. Rosini, L. Franzini, A. Raffaelli, P. Salvadori, Synthesis 1992, 503; L. Pu, Chem. Rev. 1998, 2405; H.
Brunner and W. Zettlmeier, ꢁ Handbook of Enantioselective Catalysis with Transition Metal Compoundsꢀ,
VCH, Weinheim, 1993, Vols. 1 and 2; R. Noyori, ꢁAsymmetric Catalysisꢀ Wiley, New York, 1994.
[24] G. W. Gokel, ꢁCrown Ethers and Cryptands, Monographs in Supramolecular Chemistryꢀ, Ed. J. F. Stoddart,
The Royal Society of Chemistry, Cambridge, 1991; D. J. Cram, J. M. Cram, Acc. Chem. Res. 1978,
11, 8.
[25] S. Anderson, U. Neidlein, V. Gramlich, F. Diederich, Angew. Chem. 1995, 107, 1722; ibid., Int. Ed 1995, 34,
1596; U. Neidlein, F. Diederich, J. Chem. Soc., Chem. Commun. 1996, 1493; A. Bähr, A. S. Droz, M.
Püntener, U. Neidlein, S. Anderson, P. Seiler, F. Diederich, Helv. Chim. Acta 1998, 81, 1931.
[26] E. Martinborough, T. Mordasini Denti, P. P. Castro, T. B. Wyman, C. B. Knobler, F. Diederich, Helv. Chim.
Acta 1995, 78, 1037; P. Lustenberger, E. Martinborough, T. Mordasini Denti, F. Diederich, J. Chem. Soc.,
Perkin Trans. 2 1998, 747; P. P. Castro, T. M. Georgiadis, F. Diederich, J. Org. Chem. 1989, 54, 5835.
[27] H.-Y. Li, T. Nehira, M. Hagiwara, N. Harada, J. Org. Chem. 1997, 62, 7222; T. Hattori, K. Sakurai, N. Koike,
S. Miyano, H. Goto, F. Ishiya, N. Harada, J. Am. Chem. Soc. 1998, 120, 9086.
[28] E. J. Corey, A. Guzman-Perez, Angew. Chem. 1998, 110, 402; ibid., Int. Ed. 1998, 37, 388.
[29] T. Horiuchi, T. Ohta, M. Stephan, H. Takaya, Tetrahedron: Asymmetry 1994, 5, 325.
[30] N. L. Allinger, J. Am. Chem. Soc. 1977, 99, 8127.
[31] W. C. Still, A. Tempczyk, R. C. Hawley, T. Hendrickson, J. Am. Chem. Soc. 1990, 112, 6127.
[32] F. Mohamadi, N. G. J. Richards, W. C. Guida, R. Liskamp, M. Lipton, C. Caufield, G. Chang, T.
Hendrickson, W. C. Still, J. Comput. Chem. 1990, 11, 440.
[33] A. Baiker, C. A. Müller, F. Diederich, L. Ducry, unpublished results.
[34] M. Schneider, A. Baiker, Cat. Rev.-Sci. Eng. 1995, 37, 515; N. Hüsing, U. Schubert, Angew. Chem. 1998, 110,
22; ibid., Int. Ed. 1998, 37, 22; R. J. P. Corriu, D. Leclercq, Angew. Chem. 1996, 108, 1524; ibid., Int. Ed.
1996, 35, 1420.
[35] a) M. Uskokovic, J. Gutzwiller, T. Henderson, J. Am. Chem. Soc. 1970, 92, 203; b) J. Gutzwiller, M.
Uskokovic, J. Am. Chem. Soc. 1970, 92, 204; c) M. Uskokovic, C. Reese, H. L. Lee, G. Grethe, J.
Gutzwiller, J. Am. Chem. Soc. 1971, 93, 5902; d) G. Grethe, H. L. Lee, T. Mitt, M. R. Uskokovic, J. Am.
Chem. Soc. 1971, 93, 5904; e) G. Grethe, H. L. Lee, T. Mitt, M. R. Uskokovic, Helv. Chim. Acta 1973, 56,
1485; f) J. Gutzwiller, M. R. Uskokovic, Helv. Chim. Acta 1973, 56, 1494; g) M. R. Uskokovic, T.
Henderson, C. Reese, H. L. Lee, G. Grethe, J. Gutzwiller, J. Am. Chem. Soc. 1978, 100, 571; h) J.
Gutzwiller, M. R. Uskokovic, J. Am. Chem. Soc. 1978, 100, 576; i) G. Grethe, H. L. Lee, T. Mitt, M. R.
Uskokovic, J. Am. Chem. Soc. 1978, 100, 581; j) G. Grethe, H. L. Lee, T. Mitt, M. R. Uskokovic, J. Am.
Chem. Soc. 1978, 100, 589.
[36] S. Nahm, S. M. Weinreb, Tetrahedron Lett. 1981, 22, 3815; J.-A. Fehrentz, B. Castro, Synthesis 1983, 676.
Â
Â
[37] M. Hovorka, J. Günterova, J. Zavada, Tetrahedron Lett. 1990, 31, 413.
Â
Â
[38] a) M. Hovorka, J. Zavada, Org. Prep. Proc. Int. 1991, 23, 200; b) M. Hovorka, R. Scigel, J. Gunterova, M.
Â
Tichy, J. Zavada, Tetrahedron 1992, 48, 9503.
[39] a) M. Smrcina, M. Lorenc, V. Hanus, P. Kocovsky, Synlett 1991, 231; b) M. Smrcina, M. Lorenc, V. Hanus, P.
Â
Â
Sedmera, P. Kocovsky, J. Org. Chem. 1992, 57, 1917; c) M. Smrcina, J. Polakova, S. Vyskocil, P. Kocovsky, J.
Org. Chem. 1993, 58, 4534.
Â
[40] M. Hovorka, J. Zavada, Tetrahedron 1992, 48, 9517.

1004
Helvetica Chimica Acta ± Vol. 82 (1999)
Â
Â
[41] M. Smrcina, S. Vyskocil, B. Maca, M. Polasek, T. A. Claxton, A. P. Abbott, P. Kocovsky, J. Org. Chem. 1994,
59, 2156.
[42] J. P. Schaefer, J. Higgins, P. K. Shenoy, Org. Synth. 1969, 49, 6.
[43] H.-F. Chow, C.-W. Wan, M.-K. Ng, J. Org. Chem. 1996, 61, 8712.
[44] W. C. Still, J. Am. Chem. Soc. 1978, 100, 148.
[45] A. Loupy, B. Tchoubar ꢁSalt Effects in Organic and Organometallic Chemistryꢀ, VCH, Weinheim, 1992,
Chapt. 7, pp. 241 ± 288.
[46] G. D. H. Dijkstra, R. M. Kellogg, H. Wynberg, J. S. Svendsen, I. Marko, K. B. Sharpless, J. Am. Chem. Soc.
1989, 111, 8069; G. D. H. Dijkstra, R. M. Kellogg, H. Wynberg, J. Org. Chem. 1990, 55, 6121; F. I. Carroll, P.
Abraham, K. Gaetano, S. W. Mascarella, R. A. Wohl, J. Lind, K. Petzoldt, J. Chem. Soc., Perkin Trans. 1
1991, 3017; U. Berg, M. Aune, O. Matsson, Tetrahedron Lett. 1995, 36, 2137.
[47] S. J. Weiner, P. A. Kollman, D. A. Case, U. C. Singh, C. Ghio, G. Alagona, S. Profeta, Jr., P. Weiner, J. Am.
Chem. Soc. 1984, 106, 765; D. Q. McDonald, W. C. Still, Tetrahedron Lett. 1992, 33, 7743.
[48] W. L. Jorgensen, J. Tirado-Rives, J. Am. Chem. Soc. 1988, 110, 1657.
[49] H. Meyer, Monatsh. Chem. 1901, 22, 777.
[50] M. Jakes, Collect. Czech. Chem. Commun. 1929, 100, 573.
Received March 19, 1999