Enantioselective synthesis of hydroxy-substituted DBN-type amidines as potential chiral catalysts

Article abstract of DOI:10.1002/(sici)1099-0690(200001)2000:1<105::aid-ejoc105>3.0.co;2-n

The synthesis and X-ray crystal structures of three enantiopure hydroxy- substituted amidines of the DBN-type are described. The key starting material, a 5-(phenylsulfonyl)pyrrolidin-2-one, was obtained by an oxazaborolidine-catalysed reductive desymmetrization of a meso-imide and was functionalized through N-acyliminium ion chemistry. The hydroxy groups were introduced by ozonolysis or reduction. Preliminary results on the use of the hydroxyamidines as chiral, bifunctional catalysts in selected Michael reactions are described.

Full text of DOI:10.1002/(sici)1099-0690(200001)2000:1<105::aid-ejoc105>3.0.co;2-n

FULL PAPER
Enantioselective Synthesis of Hydroxy-Substituted DBN-Type Amidines as
Potential Chiral Catalysts
Martin Ostendorf,[a] Sandor van der Neut,[a] Floris P. J. T. Rutjes,[a] and Henk Hiemstra*[a]
Keywords: Amidines / Chiral base / Enantioselective catalysis / Enantioselective synthesis / N-acyliminium ions /
Oxazaborolidines
The synthesis and X-ray crystal structures of three
enantiopure hydroxy-substituted amidines of the DBN-type
meso-imide and was functionalized through N-acyliminium
ion chemistry. The hydroxy groups were introduced by
ozonolysis or reduction. Preliminary results on the use of the
hydroxyamidines as chiral, bifunctional catalysts in selected
Michael reactions are described.
are described. The key starting material,
a
5-
(phenylsulfonyl)pyrrolidin-2-one, was obtained by an
oxazaborolidine-catalysed reductive desymmetrization of a
Introduction
Catalytic asymmetric synthesis is one of the most chal-
lenging topics in contemporary organic chemistry.[1]
A
great deal of research in this area has focused on the utiliz-
ation of transition-metal-containing catalysts. The appli-
cation of purely organic compounds as homogeneous cata-
lysts, however, has remained a relatively unexplored field.
The potential advantages of such a catalytic system include
low costs, a low level of toxicity, and high stability under
the reaction conditions. Notable examples are an (S)-pro-
line-catalysed aldol cyclization,[2] enantioselective reactions
catalysed by cinchonidine 1 and other members of the cin-
chona alkaloids,[3] and the addition of HCN to benzal-
dehyde, catalysed by the dipeptide 2.[4] More recently, Co-
rey and co-workers modified the structure of cinchonidine
to give the phase-transfer catalyst 3, which was applied in
the enantioselective alkylation of imino esters.[5] A very re-
cent example was reported by the same group; in this case
the C2-symmetric guanidine 4 was employed in catalytic
asymmetric Strecker reactions.[6] Alternatively, in the group
of Jacobsen, a combinatorial-chemistry approach was used
to develop the amino-acid-derived catalyst 5, which was
also applied in asymmetric Strecker reactions.[7] In ad-
dition, the topic of asymmetric conjugate addition reactions
has been covered in a recent review article.[8]
The excellent catalytic properties of bases 1 and 2 was
ascribed to their bifunctionality. In a base-catalysed pro-
cess, the basic moiety in the catalyst is believed to activate
the nucleophile, while, at the same time, the hydrogen-do-
nating group can activate the electrophile through hydrogen
bonding. In this way both the reaction partners are acti-
vated and held closely together to allow a successful and
enantioselective reaction. Amino alcohols such as 1 are,
however, limited in their applicability as catalysts due to the
relatively low basicity of the nitrogen atom. A more basic
functionality in the chiral catalyst might extend the scope
of organic base catalysis. The amidine function is an ex-
ample of such a stronger base.[9] The combination of an
amidine with an alcohol could, therefore, possibly lead to a
catalytic system possessing enantioselectivity-inducing
properties. Previous research from our group resulted in the
synthesis of hydroxy amidine 6, which was prepared in
eleven steps from (S)-pyroglutamic acid.[10]
Because hydroxy amidine 6 displayed only limited enanti-
oselectivity in base-catalysed reactions, we decided to de-
sign new types of hydroxy amidines (viz. 7Ϫ9). These en-
antiopure bases feature an additional six-membered ring,
which to some extent could block the top face of the basic
molecule. Furthermore, the six-membered ring renders the
system more hydrophobic than 6, so that better solubility in
apolar solvents is achieved. These features might positively
influence the asymmetry-inducing properties. This article
describes the synthesis of amidine 7, which contains an
ethyl side chain with a primary hydroxy group, and of the
diastereomeric amidines 8 and 9, which contain a phenyle-
thyl side chain with a secondary hydroxy group. Both dia-
[a]
Laboratory of Organic Chemistry, Institute of Molecular
Chemistry, University of Amsterdam
Nieuwe Achtergracht 129, NL-1018 WS Amsterdam,
The Netherlands
Fax: (internat.) ϩ 31-20/525-5670
E-mail: henkh@org.chem.uva.nl
Eur. J. Org. Chem. 2000, 105Ϫ113
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0101Ϫ105 $ 17.50ϩ.50/0
105

M. Ostendorf, S. van der Neut, F. P. J. T. Rutjes, H. Hiemstra
FULL PAPER
stereomers were synthesized in order to investigate a pos-
sible matched/mismatched selectivity.
Results and Discussion
A suitable intermediate to arrive at the targeted hydroxy-
amidines 7Ϫ9 was deemed to be sulfonyllactam 13 (Scheme
1). Lactam 13 was obtained from an oxazaborolidine-cata-
lysed reductive desymmetrization[11] of the corresponding
meso-imide 10 according to a recently published procedure
developed by our group.[12] Compared to this published
procedure, we have greatly improved the enantioselective
synthesis of lactam 12 by using neat BH3·Me2S instead of
BH3·THF.[12a] In this way, more reproducible results were
obtained without affecting yields and eeЈs. Thus, when im-
ide 10 was treated with a mixture of BH3·Me2S (0.60 equiv.)
and oxazaborolidine 11 (20 mol-%), the hydroxylactams 12
were obtained in 80% yield (Scheme 1). Rather than con-
verting the mixture of hydroxylactams into the ethoxylac-
tam,[12a] we treated it directly with benzenesulfinic acid and
CaCl2, to afford the sulfone 13 in 80% yield and 85% ee.
After a single recrystallization, enantiopure material was
obtained (> 99% ee, 32% overall yield from 10) as crystals
(m.p. 95Ϫ96.5°C) which were suitable for X-ray analysis
(Figure 1). The crystal structure clearly showed the trans
stereochemistry at C1 and C7a, and confirmed the (1S,3a-
S,7aR) absolute configuration that was determined pre-
viously by chemical correlation.[10]
Figure 1. Crystal structure of 13
the allylated lactam 14 in quantitative yield. This reaction,
which presumably proceeds via an N-acyliminium ion,[13]
took place in > 98% de, as shown by H- and 13C NMR
1
data. The alcohol group was introduced by ozonolysis of
the double bond and subsequent in situ reduction with
NaBH4 to afford 15 in 81% yield. The primary alcohol was
protected with a tert-butyldimethylsilyl group to give 16 in
95% yield, after which the amidine moiety could be intro-
duced with chemistry developed previously in our group.[10]
This involved a series of reactions, the first of which is re-
duction of the nitrile function. Treatment of 16 with CoCl2
(2 equiv.) and an excess of NaBH4 in MeOH/NH3 (to pre-
vent the formation of dimers)[14] resulted in the formation
of the amine which was not purified, but immediately pro-
tected with a tBoc group to afford 17 in 58% yield after
purification by column chromatography. Direct cyclization
to the lactam proved not possible at this stage. Therefore, a
mild cyclization route was followed.[10] Treatment of 16
with LawessonЈs reagent[15] afforded thiolactam 18 in 81%
yield. After the alcohol group was deprotected with TBAF,
19 was treated with neat MeI to give the methylthioiminium
salt. The tBoc group was then removed with trifluoroacetic
acid; cyclization of the resulting amine onto the activated
lactam was promoted by an excess of Et3N, with the
hydroxyamidine 7 forming in 81% yield. The product was
purified by recrystallization from benzene to afford crystals
suitable for X-ray analysis (Figure 2). The crystal structure
clearly showed the trans relationship between the cis-fused
six-membered ring and the two-carbon side chain. The Cϭ
˚
N bond length was found to be 1.28 A and the CϪN bond
˚
length 1.36 A.
Next, the syntheses of amidines 8 and 9 were investi-
gated. It was envisioned that both compounds might be de-
rived from ketone 21 (Equation 1). Extensive experiment-
ation eventually showed that the most efficient route to 21
involved treatment of sulfone 13 with the enol acetate of
acetophenone[16] in the presence of AlCl3; this reaction af-
forded 21 in 89% yield (for example reaction with the com-
mercially available trimethylsilyl enol ether of acetophenone
Scheme 1. Synthesis of sulfonyllactam 13
The synthesis of our first target molecule, hydroxyami- and BF3·OEt2 afforded 21 in only 21%). As expected, this
dine 7, is detailed in Scheme 2. Treatment of sulfone 13 with N-acyliminium ion mediated reaction occurred with com-
allyltrimethylsilane in the presence of BF3·OEt2 provided plete diastereoselectivity.
106
Eur. J. Org. Chem. 2000, 105Ϫ113

Enantioselective Synthesis of Hydroxy-Substituted DBN-Type Amidines
FULL PAPER
Scheme 2. Synthesis of hydroxyamidine 7
1
(30%) afforded alcohol 23a in > 98% de according to H-
and 13C NMR spectroscopy. The supposed (R) configura-
tion at the benzylic position could not be confirmed by
NMR data, but was proven later by the X-ray crystal struc-
ture of the corresponding hydroxyamidine (see Figure 3).
On the other hand, when ketone 21 was treated with
BH3·Me2S and oxazaborolidine 22b [derived from (R)-di-
phenylprolinol], the (S)-alcohol 22b was formed as a single
diastereomer, thus confirming the complete reagent control
of the oxazaborolidines.
Figure 2. Crystal structure of 7
Reduction of ketone 21 with NaBH4 afforded a 4:3 mix-
ture of diastereomers 23a and 23b, which could not be sepa-
rated by flash column chromatography or recrystallization.
Therefore, the application of a chiral reducing reagent in
Scheme 3. Reduction of ketone 21
Both alcohols 23a and 23b underwent the previously de-
this reaction was investigated. It was found that the combi- scribed chemical reactions that lead to amidines (Scheme
nation of borane and an oxazaborolidine was the best 4). The hydroxy groups were protected as tert-butyldimeth-
choice to obtain the desired products as single dia- ylsilyl ethers with TBDSMOTf; followed by an identical
stereomers. Whereas the B-H oxazaborolidine 11 was the series of events to afford the hydroxyamidines 8 and 9 in
reagent of choice for the enantioselective reduction of meso- comparable yields. Amidine 8 was obtained as a solid
imides (Scheme 1), we preferred to use the corresponding which, upon recrystallization, gave crystals that were ana-
B-Me catalysts 22a and 22b in this case (Scheme 3), because lysed by an X-ray crystal structure determination (m.p.
they are significantly more stable and display equal selec- 104Ϫ107°C). From this crystal structure (Figure 3) it be-
tivity.[11] The B-Me catalysts are nowadays commercially came clear that in the solid state, two molecules of 8 were
available, but can also be synthesized from the appropriate linked to one molecule of H2O through four hydrogen
diphenylprolinol enantiomer and trimethylboroxine.[17] bonds. Amidine 9 was obtained as a foam and, in our
Treatment of 21 with BH3·Me2S and oxazaborolidine 22a hands, could not be crystallized.
Eur. J. Org. Chem. 2000, 105Ϫ113
107

M. Ostendorf, S. van der Neut, F. P. J. T. Rutjes, H. Hiemstra
Table 1. Conjugate addition results
FULL PAPER
[a]
Determined from the known specific rotation.[3a]
tion 2). When 25% of 7 was used, product 29 was obtained
in 56% yield and 35% o.p.[18]
Figure 3. Crystal structure of 8
The hydroxy amidines 7Ϫ9 were tested for their catalytic
activity and enantioselectivity. A well-studied Michael-type
addition, the addition of thiophenol to cyclohexenone, was
chosen as an asymmetric test reaction.[3a] The results are
summarized in Table 1. The reaction proceeded well in the
presence of 1Ϫ5 mol-% of catalyst to give thioether 28 in
good yields (72Ϫ100%). The highest optical purity (23%)
was obtained with hydroxyamidine 7 that contains the pri-
Conclusion
In conclusion, three enantiopure hydroxyamidines were
mary alcohol group. Catalysts 8 and 9 gave the product in synthesized from the readily available sulfonyllactam 13 as
15% and 14% o.p., respectively. Remarkably, the sign of op- the starting material. These compounds belong to a struc-
tical rotation of product 28 was independent of the stereo- tural class of amidines which is virtually unknown in the
chemistry in the side chain.
literature. The structures of 7 and 8 were proven by X-ray
Carbon nucleophiles such as nitromethane, 2,4-pentane- crystal structure determinations. The most simple catalyst
dione, and dimethyl malonate also reacted with cyclohex- 7, containing a primary alcohol, effected slightly better en-
enone in the presence of catalyst 7. In all cases, the products antioselectivity than 8 and 9: The introduction of an extra,
were obtained in good yields (56Ϫ70%). An optically active phenyl-substituted secondary stereocentre did not lead to
product was obtained only with dimethyl malonate (Equa- higher selectivities. Moreover, both diastereomers of cata-
Scheme 4. Synthesis of hydroxyamidines 8 and 9
108
Eur. J. Org. Chem. 2000, 105Ϫ113

Enantioselective Synthesis of Hydroxy-Substituted DBN-Type Amidines
FULL PAPER
21.7, [t, Ϫ(CH2)4Ϫ], 16.1 (t, CH2CN). Ϫ HRMS (FABϩ) calcd.
lysts 8 and 9 gave the same enantiomer of the Michael-type
product 28; this implies that this stereocentre does not play
an essential role in the enantioselective catalysis. Despite
the fact that these amidines showed satisfactory catalytic
activity, it is evident that the enantioselectivity-inducing
properties are inferior compared to previously obtained
eeЈs. [3]
for C13H21N2O2 (M ϩ H) 237.1603, found 237.1598. Ϫ [α]D
Ϫ31.1 (c ϭ 1.0; CHCl3).
ϭ
3-{(1R,3aS,7aR)-1-[2-(tert-Butyldimethylsilyloxy)ethyl]-3-oxo-
octahydroisoindol-2-yl}propionitrile (16): To a solution of 15 (6.60 g,
28.0 mmol) in CH2Cl2 (40 mL) was added TBDMSCl (4.40 g,
29.4 mmol), imidazole (4.80 g, 70.0 mmol), and DMAP (324 mg,
2.8 mmol). After being stirred at room temperature for 3 h, the
Further studies towards new hydroxyamidines will focus
on the relative orientation of the amidine and the hydroxy reaction mixture was quenched with 5% aqueous HCl. After the
water layer was extracted (CH2Cl2, 4 ϫ), the combined organic
layers were dried (Na2SO4), and in vacuo concentration took place,
the product was obtained, after flash chromatography (EtOAc/PE,
1:1), as a white solid (9.3 g, 26.6 mmol, 95%), m.p. 44Ϫ45°C. Ϫ
functions in order to search for better enantioselectivity in
base-catalysed processes
1
IR (CHCl3): ν˜ ϭ 2250 cmϪ1, 1681. Ϫ H NMR (400 MHz): δ ϭ
Experimental Section
General: All reactions were carried out under dry nitrogen, unless
3.84Ϫ3.77 (dt, 1 H, J ϭ 13.9, 6.4 Hz, NCHH), 3.65Ϫ3.62 (t, 2 H,
J ϭ 5.5 Hz, CH2OSi), 3.29Ϫ3.25 (dd, 1 H, J ϭ 8.8, 4.1 Hz NCH),
3.19Ϫ3.13 (quint, 1 H, J ϭ 6.9 Hz, NCHH), 2.72Ϫ2.64 (m, 1 H,
described otherwise. Standard syringe techniques were applied for
transfer of dry solvents and air- or moisture-sensitive reagents. Ϫ NCH2CHH), 2.57Ϫ2.50 [m, 2 H, CHC(O) and NCH2CHH],
IR: Bruker IFS 28 (absorptions are reported in cmϪ1). Ϫ NMR:
2.17Ϫ2.14 (dt, 1 H, J ϭ 10.8, 5.7 Hz, NCHCH), 2.09Ϫ2.05 [br. d,
1 H, J ϭ 14.2 Hz, C(O)CHCHH], 1.76Ϫ1.41 (m, 6 H), 1.19Ϫ1.06
(m, 3 H), 0.84 [s, 9 H, SiC(CH3)3], 0.00 [s, 6 H, Si(CH3)2]. Ϫ 13C
NMR (100 MHz): δ ϭ 175.8 [s, C(O)], 117.9 (s, CN), 61.0 (d,
NCH), 59.7 (t, CH2OSi), 38.9 [d, C(O)CH], 37.4 (d, NCHCH),
Bruker AC 200, Bruker WM 250, Bruker ARX 400 (200, 250 or
1
400 MHz for H; 50, 63, or 100 MHz for 13C). NMR spectra were
obtained from CDCl3 solutions. Chemical shifts are reported in δ
relative to an internal standard of residual chloroform (δ ϭ 7.27
1
for H NMR and δ ϭ 77.0 for 13C NMR). Ϫ HRMS: JEOL JMS 37.3 (t, NCH2), 33.3 (t, CH2CH2OH), 25.7 (q, SiC(CH3)3), 28.9,
SX/SX102A, coupled to a JEOL MS-MP7000. Ϫ Elemental analy-
ses: Vario EL. Ϫ Optical rotations: PerkinϪElmer 241 (in the indi-
23.7, 22.9, 22.8 [t, Ϫ(CH2)4Ϫ], 18.0 [s, SiC(CH3)3], 16.1 (t,
CH2CN), Ϫ5.60, Ϫ5.62 [q, Si(CH3)2]. ϪC19H34N2O2Si (350.6):
cated solvent at ambient temerature). Ϫ Melting points and boiling calcd. C 65.09, H 9.78, N 7.99; found C 64.78, H 9.55, N, 8.11. Ϫ
points are uncorrected. Ϫ Ethyl acetate (EtOAc) and petroleum
ether 60Ϫ80 (PE) were distilled before use. Tetrahydrofuran (THF)
and diethyl ether (Et2O) were freshly distilled from sodium benzo-
phenone ketyl prior to use. CH2Cl2, toluene, CH3CN, EtOH, and
MeOH were dried and distilled from CaH2 or LiAlH4 and stored
over 4 A (MeOH over 3 A) molecular sieves under nitrogen. Et3N
and pyridine were dried and distilled from KOH pellets and stored
over KOH pellets under nitrogen. Ϫ Compounds 10؊14 were de-
scribed previously.[12a]
[α]D ϭ Ϫ26.2 (c ϭ 1.0; CHCl3).
{3-[(1R,3aS,7aR)-1-[2-(tert-Butyldimethylsilyloxy)ethyl]-3-oxo-
octahydroisoindol-2-yl]propyl}carbamic Acid tert-Butyl Ester (17):
To a vigorously stirred, purple solution of CoCl2·H2O (6.2 g,
26.2 mmol) in MeOH (20 mL) was added, at 0°C, NaBH4 (124 mg,
3.3 mmol). The deep-black solution was stirred for 15 min at room
temperature and cooled again. Then a solution of 16 (4.6 g,
13.1 mmol) in 2% NH3 in MeOH (40 mL) was added dropwise.
NaBH4 pellets (5.0 g, 131 mmol) were added in portions over 1.5 h;
hydrogen gas evolved. After being stirred another 1.5 h at 0°C, the
reaction mixture was quenched with H2O and filtered through Ce-
lite. The Celite was washed three times with MeOH/H2O, 9:1. The
solution was concentrated in vacuo and the residue was taken up
in 5% aqueous NH3. After extraction of the water layer (EtOAc, 5
ϫ), drying of the combined organic layers (Na2SO4) and concen-
tration in vacuo, the crude product was obtained as a purple oil
˚
˚
Crystallographic Data for 13: Orthorhombic crystals, P212121, a ϭ
3
˚
˚
8.4904(5), b ϭ 11.0928(5), c ϭ 17.4835(11) A, V ϭ 1646.6(2) A ,
Z ϭ 4, DX ϭ 1.34 g cmϪ3, λ (Cu-Kα) ϭ 1.5418 A, µ (Cu-Kα) ϭ
˚
18.9 cmϪ1, F(000) ϭ 704, Ϫ25°C. Final R ϭ 0.057 for 1870 ob-
served reflections.[19]
3-[(1R,3aS,7aR)-1-(2-Hydroxyethyl)-3-oxooctahydroisoindol-2-yl)]-
propionitrile (15): Ozone was bubbled through a solution of 13
(28.8 mg, 0.12 mmol) in MeOH (2 mL) at Ϫ78°C. After 2 min, the (4.1 g, 11.7 mmol, 89%). To a solution of this amine in CH2Cl2
solution turned blue. The ozone was replaced with nitrogen and
after 5 min, NaBH4 (47 mg, 1.2 mmol) was added in portions. Stir-
(40 mL) was added Boc2O (4.9 g, 22.6 mmol) and a catalytic
amount of DMAP. After being stirred for 3 h at room temperature,
ring was continued for 15 min at Ϫ78°C and 1 h at room temp. the reaction mixture was concentrated in vacuo and purified by
The reaction mixture was quenched with 5% aqueous HCl. The
water layer was extracted (CH2Cl2, 5 ϫ) and the combined organic
layers were dried (Na2SO4) and concentrated in vacuo. After flash
flash chromatography (EtOAc/PE, 1:1); the product was obtained
as a yellow oil (3.5 g, 7.6 mmol, 58% from 15). Ϫ IR (film): ν˜ ϭ
3400 cmϪ1, 1684. Ϫ 1H NMR (400 MHz): δ ϭ 5.55 (br. t, 1 H,
chromatography (EtOAc) 15 (23 mg, 0.10 mmol, 81%) was ob- NHBoc), 3.63 (m, 3 H, NCHH, CH2OSi), 3.24 (m, 1 H,
tained as a colourless oil. Ϫ IR (film): ν˜ ϭ 3410 cmϪ1, 2249, 1667.
CHHNHBoc), 3.09 (dd, 1 H, J ϭ 9.3, 3.2 Hz, NCH), 2.90 (m, 2
Ϫ 1H NMR (400 MHz): δ ϭ 3.85Ϫ3.79 (dt, 1 H, J ϭ 13.9, 6.5 Hz, H, NCHHCH2, CHHNHBoc), 2.56 [br. t, 1 H, J ϭ 5.6 Hz,
NCHH), 3.69Ϫ3.62 (m, 2 H, CH2OH), 3.33Ϫ3.30 (dd, 1 H, J ϭ C(O)CH], 2.14 [dt, 1 H, J ϭ 10.8, 6.4 Hz, C(O)CHCHH], 2.07 (br.
8.7, 4.2 Hz NCH), 3.25Ϫ3.18 (dt, 1 H, J ϭ 13.9, 6.7 Hz, NCHH),
2.73Ϫ2.65 (m, 1 H, NCH2CHH), 2.62Ϫ2.54 (m, 2 H, CHC(O) and CO2C(CH3)3], 1.1Ϫ0.9 (m, 3 H), 0.84 [s, 9 H, SiC(CH3)3], 0.00 [s,
NCH2CHH), 2.17Ϫ2.11 (dt, 1 H, J ϭ 10.5, 5.9 Hz, NCHCH),
6 H, Si(CH3)2]. Ϫ 13C NMR (100 MHz): δ ϭ 175.9 [s, NC(O)],
2.06Ϫ2.02 (br. d, 1 H, J ϭ 14.8 Hz, C(O)CHCHH), 1.80Ϫ1.73 (m, 156.0 [s, NHC(O)], 78.6 [s, CO2C(CH3)3], 60.3 (d, NCH), 59.8 (t,
d, 1 H, J ϭ 13.3 Hz, NCHCH), 1.7Ϫ1.4 (m, 8 H), 1.38 [s, 9 H,
2 H), 1.70Ϫ1.63 (m, 1 H), 1.57Ϫ1.40 (m, 3 H), 1.22Ϫ1.06 (m, 3
CH2OSi), 39.0 [d, C(O)CH], 37.4 (t, NCH2 and t, CH2NHBoc),
H). Ϫ 13C NMR (100 MHz): δ ϭ 176.2 [s, C(O)], 118.1 (s, CN), 37.1 (d, NCHCH), 32.8 and 27.3 (t, CH2CH2OH and t,
60.8 (d, NCH), 59.0 (t, CH2OH), 39.0 [d, C(O)CH], 37.4 (d, NCH2CH2CH2), 28.3 [q, CO2C(CH3)3], 25.7 [q, SiC(CH3)3], 29.2,
NCHCH), 37.3 (t, NCH2), 33.2 (t, CH2CH2OH), 28.8, 23.7, 22.9,
23.8, 23.1, 22.9 [t, Ϫ(CH2)4Ϫ], 18.0 [s, SiC(CH3)3], Ϫ5.58, Ϫ5.63
Eur. J. Org. Chem. 2000, 105Ϫ113
109

M. Ostendorf, S. van der Neut, F. P. J. T. Rutjes, H. Hiemstra
[t, Si(CH3)2]. Ϫ HRMS (FABϩ) calcd. for C24H47N2O4Si (M ϩ H) were dried (Na2SO4) and concentrated in vacuo. The amidine was
FULL PAPER
455.3305, found 455.3280. Ϫ [α]D ϭ ϩ30.0 (c ϭ 1.0; CHCl3).
obtained as a colourless oil (1.0 g, 4.5 mmol, 81%) which was crys-
tallized from benzene, m.p. 105Ϫ107°C. Ϫ 1H NMR (400 MHz,
C6D6): δ ϭ 3.80Ϫ3.77 (t, 2 H, J ϭ 6.2 Hz, CH2OH), 3.53Ϫ3.48
(m, 1 H, CϭNCHH), 3.36Ϫ3.30 (m, 1 H, CϭNCHH), 3.13Ϫ3.03
(m, 2 H, CϪNCHH, NCH), 2.86Ϫ2.81 (m, 1 H, CϪNCHH),
2.71Ϫ2.70 (m, 1 H, NϭCCH), 2.38Ϫ2.35 (m, 1 H, NϭCCHCHH),
{3-[(1R,3aS,7aR)-1-[2-(tert-Butyldimethylsilyloxy)ethyl]-3-thi-
oxooctahydroisoindol-2-yl]propyl}carbamic Acid tert-Butyl Ester
(18): To a solution of 17 (3.5 g, 7.7 mmol) in toluene (20 mL) was
added LawessonЈs reagent (1.7 g, 4.2 mmol). After being stirred at
80°C for 30 min, the reaction mixture was concentrated in vacuo.
After purification by flash chromatography (EtOAc/PE, 1:4), the
product was isolated as a yellow oil (2.9 g, 6.2 mmol, 81%). Ϫ IR
(film): ν˜ ϭ 3400 cmϪ1, 1609. Ϫ 1H NMR (400 MHz): δ ϭ 5.39 (br.
s, 1 H, NHBoc), 4.42Ϫ4.35 (dt, 1 H, J ϭ 13.5, 8.4 Hz, NCHH),
3.72Ϫ3.61 (m, 2 H, CH2OSi), 3.47Ϫ3.44 (dd, 1 H, J ϭ 9.6, 2.8 Hz,
NCH), 3.29Ϫ3.27 (m, 1 H, CHHNHBoc), 3.21Ϫ3.15 (dt, 1 H, J ϭ
13.6, 5.7 Hz, NCHH), 2.96Ϫ2.91 (m, 1 H, CHHNHBoc), 2.83 [br.
t, 1 H, C(S)CH], 2.49Ϫ2.45 (br. d, 1 H, J ϭ 13.6 Hz, NCHCH),
2.29Ϫ2.23 [quint, 1 H, J ϭ 6.0 Hz, C(S)CHCHH], 1.83Ϫ1.47 (m,
8 H), 1.41 [s, 9 H, CO2C(CH3)3], 1.25Ϫ1.02 (m, 3 H), 0.87 [s, 9 H,
SiC(CH3)3], 0.00 [s, 6 H, Si(CH3)2]. Ϫ 13C NMR (100 MHz): δ ϭ
1.94Ϫ1.91 (m,
1 H, CϪNCHCH), 1.84Ϫ1.75 (m, 1 H,
CϪNCHCHH), 1.67Ϫ1.47 (m, 8 H), 1.24Ϫ1.17 (m, 2 H). Ϫ 13C
NMR (100 MHz, C6D6): δ ϭ 160.7 (CϭN), 64.4 (CϪNCH), 58.5
(CH2CH2OH), 43.6 (CϭNCH2), 42.2 (CϪNCH2), 39.6 (NϭCCH),
39.2 (NϪCHCH), 34.7 (CH2CH2OH), 28.4 (NϪCHCHCH2), 24.2
[NϭCCHCH2), 24.1, 22.9 (NϭCCHCH2Ϫ(CH2)2Ϫ], 21.0 (Cϭ
NCH2CH2). Ϫ [α]D ϭ ϩ60.9 (c ϭ 1.0; CHCl3). Ϫ Crystallographic
data for 7: orthorhombic, P212121, a ϭ 7.1184(5), b ϭ 8.4949(4),
3
c ϭ 21.1830(8) A, V ϭ 1280.9(1) A , Z ϭ 4, DX ϭ 1.15 g cmϪ3, λ
˚
˚
(Cu-Kα) ϭ 1.5418 A, µ (Cu-Kα) ϭ 5.7 cmϪ1, F(000) ϭ 488, room
˚
temperature. Final R ϭ 0.057 for 1211 observed reflections.[19]
203.9 [s, NC(S)], 155.9 [s, NHC(O)], 78.8 [s, CO2C(CH3)3], 67.3 (d, α-Acetoxystyrene (20): A mixture of isopropenyl acetate (10 mL,
NCH), 59.8 (t, CH2OSi), 49.0 [d, C(S)CH], 42.9 (t, NCH2 and t, 90.8 mmol, 2 equiv), acetophenone (5.3 mL, 45.4 mmol) and
CH2NHBoc), 38.8 (d, NCHCH), 31.8 and 26.7 (t, CH2CH2OSi H2SO4 (cat) was heated at 90°C. Acetone was distilled from the
and t, NCH2CH2CH2), 28.4 [q, CO2C(CH3)3], 25.7 [q, SiC(CH3)3], reaction mixture for 7 h. The product was isolated together with
28.6, 26.1, 23.9 22.1 [t, Ϫ(CH2)4Ϫ], 18.1 [s, SiC(CH3)3], Ϫ5.50,
acetophenone, as a 3:1 mixture, after distillation (b.p. 90Ϫ110°C,
Ϫ5.56 [q, Si(CH3)2]. Ϫ HRMS (FABϩ) calcd. for C24H47N2O3SSi 20 Torr). This mixture could not be separated by distillation or
(M ϩ H) 471.3077, found 471.3115. Ϫ [α]D ϭ Ϫ31.4 (c ϭ 1.0; column chromatography. Ϫ 1H NMR (200 MHz): δ ϭ 7.6Ϫ7.2 (m,
CHCl3).
5 H, Ph), 5.5 (d, 1 H, CHHϭC), 5.0 (d, 1 H, CHHϭC), 2.6 (s, 3
H, CH3).
{3-[(1R,3aS,7aR)-1-(2-Hydroxyethyl)-3-thioxooctahydroisoindol-2-
yl]propyl}carbamic Acid tert-Butyl Ester (19): To a solution of 18
(300 mg, 0.64 mmol) in THF (5 mL) was added TBAF (0.70 mL,
3-[(1R,3aS,7aR)-1-Oxo-3-(2-oxo-2-phenylethyl)octahydroisoindol-2-
yl]propionitrile (21): To a solution of sulfonyllactam 13 (7.51 g,
0.76 mmol, 1.1  in THF). After being stirred at room temperature 22.6 mmol), in CH2Cl2 (50 mL), were slowly added, at Ϫ78°C, alu-
for 90 min, the reaction mixture was quenched with water. After minium trichloride (4.81 g, 36.1 mmol, 1.6 equiv) and α-acetoxys-
extraction of the water layer (CH2Cl2, 4 ϫ), drying of the combined tyrene (6.04 mL, 45.2 mmol, 2.0 equiv). After the reaction mixture
organic layers (Na2SO4) and concentration in vacuo, the product
was obtained, after flash chromatography (EtOAc/PE, 3:1), as a
was stirred for 15 min at Ϫ78°C, the temperature was allowed to
rise slowly to Ϫ20°C in 2 h. The reaction mixture was poured in
white solid (224 mg, 0.63 mmol, 98%). An analytical sample was ice-cold aqueous saturated NaCl. After extraction of the water
recrystallized from a 1:2:2 mixture of MeOH/EtOAc/pentane, m.p. layer (CH2Cl2, 5 ϫ), the combined organic layers were dried
157Ϫ158°C. Ϫ IR (CHCl3): ν˜ ϭ 3353 cmϪ1, 1684. Ϫ 1H NMR (Na2SO4) and concentrated in vacuo. The residue was chromato-
(250 MHz): δ ϭ 5.29 (br. s, 1 H, NHBoc), 4.44Ϫ4.32 (dt, 1 H, J ϭ graphed (EtOAc/PE, 1:1) to give the product (6.21 g, 20.0 mmol,
13.6, 7.5 Hz, NCHH), 3.82Ϫ3.64 (m, 2 H, CH2OH), 3.57Ϫ3.46 89%) as a white solid, which was recrystallized from EtOAc/pen-
(dd, 1 H, J ϭ 6.2, 2.9 Hz, NCH), 3.28Ϫ3.18 (m, 2 H, NCHH, tane as colourless crystals, m.p. 136Ϫ138°C. Ϫ IR (CHCl3): ν˜ ϭ
CHHNHBoc), 2.99 (m, 1 H, CHHNHBoc), 2.85 [br. t, 1 H,
2252 cmϪ1, 1697, 1674. Ϫ 1H NMR (400 MHz): δ ϭ 7.93Ϫ7.90
C(S)CH], 2.49Ϫ2.44 (br. d, 1 H, J ϭ 13.9 Hz, NCHCH), 2.29Ϫ2.19 (m, 2 H, o-phenyl), 7.60Ϫ7.55 (m, 1 H, p-phenyl), 7.48Ϫ7.44 (m,
[quint, 1 H, J ϭ 6.1 Hz, C(S)CHCHH], 1.88Ϫ1.36 (m, 8 H), 1.42 2 H, m-phenyl), 3.86Ϫ3.79 (m, 2 H, NCH, NCHH), 3.31Ϫ3.14 [m,
[s, 9 H, CO2C(CH3)3], 1.25Ϫ1.02 (m, 3 H). Ϫ 13C NMR (50 MHz):
δ ϭ 203.7 [s, NC(S)], 156.0 [s, NHC(O)], 78.7 [s, CO2C(CH3)3],
3 H, PhC(O)CH2, NCHH], 2.71Ϫ2.58 [m, 3 H, CH2CN, C(O)CH],
2.13Ϫ2.06 [m, 2 H, NCHCH, C(O)CHCHH], 1.95Ϫ1.91 (m, 1 H,
67.0 (d, NCH), 59.3 (t, CH2OH), 49.4 [d, C(S)CH], 42.9 (t, NCH2 NCHCHCHH), 1.60Ϫ1.44 (m,
and t, CH2NHBoc), 38.9 (d, NCHCH), 31.8, (t, CH2CH2OH), 28.3 1.25Ϫ1.11 [m, H, NC(O)CHCHCHCH].
(t, NCHCHCH2), 28.2 [q, CO2C(CH3)3], 26.6, 25.9, 23.7, 21.9 [t, (100 MHz): δ ϭ 197.8 [s, PhC(O)], 176.0 [s, NC(O)], 136.2 (s, Ph-
3
H, NCHCHCHCHCH),
3
Ϫ
13C NMR
Ϫ(CH2)4Ϫ]. Ϫ C18H32N2O3S (356.5): calcd. C 60.64, H 9.05, N Cq), 133.7 (d, p-phenyl), 128.7 (d, m-phenyl), 127.9 (d, o-phenyl),
7.86; found C 60.88, H 8.99, N 7.71. Ϫ [α]D ϭ Ϫ52.3 (c ϭ 1.2; 118.0 (s, CN), 58.9 (d, NCH), 40.1 [t, PhC(O)CH2], 39.1 [d,
CHCl3).
NC(O)CH], 38.7 (d, NCHCH), 37.7 (t, NCH2), 28.4, 23.5, 22.9,
22.7 [t, Ϫ(CH2)4Ϫ], 16.1 (t, CH2CN). Ϫ C19H22N2O2 (310.4):
calcd. C 73.52, H 7.14, N 9.03; found C 73.65, H 7.04, N 9.10. Ϫ
[α]D ϭ Ϫ13.7 (c ϭ 1.0; CHCl3).
2-[(4bS,8aR,9R)-1,2,3,4b,5,6,7,8,8a,9-Decahydro-4,9a-diazafluoren-
9-yl]ethanol (7): A solution of 19 (1.9 g, 5.6 mmol) in MeI (15 mL)
was stirred for 17 h at room temperature in the dark. After concen-
tration in vacuo, a pale yellow foam was obtained. This methylated 3-{(1R,3aS,7aR)-1-[2-(R)-Hydroxy-2-phenylethyl]-3-oxoocta-
compound was dissolved in CH2Cl2 (20 mL), then TFA (3 mL) was hydroisoindol-2-yl}propionitrile (23a): To a solution of ketone 21
added at 0°C and the yellow solution was stirred for 2 h. At the (3.79 g, 12.2 mmol) in toluene (60 mL), and the (S)-oxazaborolid-
same temperature, Et3N (9.2 mL) was slowly added. The mixture
decolorized; stirring was continued for 2 h. The reaction mixture
ine catalyst 22a (7.4 mL, 3.7 mmol, 0.5  solution in toluene, 0.3
equiv), was slowly added BH3·Me2S (0.73 mL, 7.3 mmol). After
was extracted with 5% aqueous HCl (3 ϫ), and solid NaOH was being stirred for 45 min, the reaction mixture was poured into 5%
added at 0°C until the water layer was basic. The basic aqueous
solution was extracted (CH2Cl2, 5 ϫ). The combined organic layers
aqueous HCl. After the water layer (CH2Cl2, 5 ϫ) was extracted,
the combined organic layers were dried (Na2SO4) and concentrated
110
Eur. J. Org. Chem. 2000, 105Ϫ113

Enantioselective Synthesis of Hydroxy-Substituted DBN-Type Amidines
FULL PAPER
in vacuo. The residue was chromatographed (EtOAc/PE, 1:1) to
give the product (3.14 g, 10.0 mmol, 82%) as a colourless oil and a
single diastereomer. Ϫ IR (CHCl3): ν˜ ϭ 3400 cmϪ1, 2250, 1685. Ϫ
1H NMR (200 MHz): δ ϭ 7.40Ϫ7.23 (m, 5 H, Ph), 4.78Ϫ4.72 (dd,
3.13Ϫ3.10 (dd, 1 H, J ϭ 9.5, 2.4 Hz, NCH), 3.08Ϫ3.01 (dt, 1 H,
J ϭ 13.9, 7.0 Hz, NCHH), 2.66Ϫ2.58 (dt, 1 H, J ϭ 16.8, 7.1 Hz,
CHHCN), 2.55Ϫ2.52 [br. t, 1 H, J ϭ 6.0 Hz, C(O)CH], 2.50Ϫ2.43
(dt, 1 H, J ϭ 16.8, 6.2 Hz, CHHCN), 2.12Ϫ2.09 (m, 1 H, NCHCH)
1 H, J ϭ 14.3, 7.1 Hz, PhCHOH), 3.87Ϫ3.73 (dt, 1 H, J ϭ 13.9, 1.99Ϫ1.91 [m, 2 H, C(O)CHCHH, CHHC(OSi]), 1.80Ϫ1.75 [m, 1
6.5 Hz, NCHH), 3.50Ϫ3.44 (dd, 1 H, J ϭ 9.6, 2.6 Hz, NCH), H, CHHC(OSi)], 1.63Ϫ1.01 (m, 8 H), 0.89 [s, 9 H, SiC(CH3)3],
3.24Ϫ3.11 (dt, 1 H, J ϭ 13.8, 6.8 Hz, NCHH), 2.75Ϫ2.45 (m, 4 0.04, Ϫ0.19, [2 ϫ s, 6 H, Si(CH3)2]. Ϫ 13C NMR (100 MHz): δ ϭ
H), 2.25Ϫ1.07 (m, 11 H). δ ϭ 13C NMR (50 MHz): δ ϭ 175.7 [s,
175.6 [s, NC(O)], 143.9 (s, Ph), 128.3, 127.5, 125.6 (d, Ph), 117.8
NC(O)], 144.2 (s, Ph), 128.4, 127.6, 125.2 (d, Ph), 117.9 (s, CN), (s, CN), 73.0 (d, PhCHOSi), 60.6 (d, NCH), 40.8 [t, PhC(OSi)CH2],
71.2 (d, CHOH), 60.6 (d, NCH), 39.5 [t, PhC(O)CH2], 38.7, 37.4 38.8, 38.2 [d, C(O)CHCH], 37.0 (t, NCH2), 25.7 [q, SiC(CH3)3],
[d, C(O)CHCH], 36.8 (t, NCH2), 28.8, 23.5, 22.8, 22.6 [t, 28.6, 23.7 22.8, 22.8 [t, Ϫ(CH2)4Ϫ], 18.0 [s, SiC(CH3)3], 16.0 (t,
Ϫ(CH2)4Ϫ], 15.9 (t, CH2CN).
Ϫ
HRMS (EIϩ) calcd. for
CH2CN) Ϫ4.7, Ϫ5.0 [q, Si(CH3)2]. Ϫ HRMS (EIϩ) calcd. for
C19H24N2O2 312.1838, found 312.1826. Ϫ [α]D ϭ ϩ2.0 (c ϭ 1.0; C25H38N2O2Si 426.2703, found 426.2703. Ϫ [α]D ϭ Ϫ4.7 (c ϭ
CHCl3).
1.0; CHCl3).
3-{(1R,3aS,7aR)-1-[2-(S)-Hydroxy-2-phenylethyl]-3-oxoocta-
hydroisoindol-2-yl}propionitrile (23b): According to the procedure
described for 23a, 2.50 g (8.1 mmol) of ketone 21 was reduced with
(R)-catalyst 22b (4.0 mL, 2.0 mmol, 0.5  solution in toluene, 0.25
equiv.) to give the product (1.76 g, 10.0 mmol, 70%, colourless oil).
Ϫ IR (CHCl3): ν˜ ϭ 3400 cmϪ1, 2250, 1685. Ϫ 1H NMR
(3-{(1R,3aS,7aR)-1-[2-(R)-(tert-Butyldimethylsilanyloxy)-2-phen-
ylethyl]-3-oxooctahydroisoindol-2-yl}propyl)carbamic Acid tert-Bu-
tyl Ester (25a): According to the procedure described for 16, 3.93 g
(9.2 mmol) of 24a was transformed into the corresponding amine
(3.45 g, 8.0 mmol, 87%), which was transformed into 2.85 g of 25a
(5.4 mmol, 58% from 24a, colourless oil). Ϫ IR (CHCl3): ν˜ ϭ 3400
1
(200 MHz): δ ϭ 7.41Ϫ7.12 (m, 5 H, Ph), 4.79Ϫ4.72 (dd, 1 H, J ϭ cmϪ1, 1669. Ϫ H NMR (200 MHz): δ ϭ 7.33Ϫ7.24 (m, 5 H, Ph),
5.4, 2.3 Hz, PhCHOH), 3.91Ϫ3.78 (dt, 1 H, J ϭ 13.8, 6.5 Hz,
5.50 (br. s, 1 H, NHBoc), 4.75Ϫ4.70 (dd, 1 H, J ϭ 8.5, 2.9 Hz,
NCHH), 3.27Ϫ3.13 [m, 3 H, NCH, NCHH and NC(O)CH] PhCHOSi), 3.70Ϫ3.55 (m, 1 H, NCHH), 3.35Ϫ3.20 (m, 1 H,
2.88Ϫ2.41 (m, 3 H), 2.12Ϫ1.08 (m, 11 H). Ϫ 13C NMR (50 MHz): CHHNHBoc), 3.18Ϫ3.12 (dd, 1 H, J ϭ 10.2, 2.0 Hz, NCH),
δ ϭ 178.1 [s, NC(O)], 143.9 (s, Ph), 128.4, 127.7, 125.4 (d, Ph), 2.95Ϫ2.73 (m, 2 H, NCHH, CHHNHBoc), 2.62Ϫ2.52 [m, 1 H,
117.9 (s, CN), 71.6 (d, CHOH), 60.5 (d, NCH), 40.1 [t, C(O)CH], 2.29Ϫ2.07 [m, 2 H, NCHCH, C(O)CHCHH], 1.9Ϫ1.5
PhC(OH)CH2], 38.8, 38.3 [d, C(O)CHCH], 37.5 (t, NCH2), 28.5, (m, 8 H), 1.43 [s, 9 H, CO2C(CH3)3], 1.2Ϫ0.9 (m, 3 H), 0.90 [s, 9
23.6, 22.7, 22.6 [t, Ϫ(CH2)4Ϫ], 15.8 (t, CH2CN). Ϫ HRMS (EIϩ) H, SiC(CH3)3], 0.04, Ϫ0.22, [2 ϫ s, 6 H, Si(CH3)2]. Ϫ 13C NMR
calcd. for C19H24N2O2 312.1838 found, 312.1838. Ϫ [α]D ϭ Ϫ29.3
(c ϭ 1.0; CHCl3).
(100 MHz): δ ϭ 176.0 [s, NC(O)], 156.0 [s, NHC(O)], 144.3 (s, Ph),
128.2, 127.3, 125.5 (d, Ph), 79.3 [s, CO2C(CH3)3], 72.4 (d,
PhCHOSi), 59.5 (d, NCH), 40.5 [t, PhC(OSi)CH2], 38.9, 37.5 [d,
NC(O)CHCH], 37.1 (t, NCH2), not observed (t, CH2NHBoc), 28.3
[q, CO2C(CH3)3], 27.3 (t, CH2CH2NHBoc), 25.6 [q, SiC(CH3)3],
29.3, 24.0, 23.0, 22.9 [t, Ϫ(CH2)4Ϫ], 17.9 [s, SiC(CH3)3], Ϫ4.7, Ϫ5.2
[q, Si(CH3)2]. Ϫ HRMS (FABϩ) calcd. for C30H51N2O4Si (M ϩ
H) 531.3618, found 531.3618. Ϫ [α]D ϭ ϩ65.4 (c ϭ 1.1; CHCl3).
3-{(1R,3aS,7aR)-1-[2-(R)-(tert-Butyldimethylsilanyloxy)-2-phenyl-
ethyl]-3-oxooctahydroisoindol-2-yl}propionitrile (24a): To a solution
of alcohol 23a (3.0 g, 9.6 mmol) in CH2Cl2 (30 mL) was added, at
0°C, TBDMSOTf (6.6 mL, 28.8 mmol, 3 equiv) and 2,6-lutidine
(4.4 mL, 38.5 mmol, 4 equiv.). After being stirred for 10 min at
0°C, and for 4 h at room temperature, the reaction mixture was
poured into 5% aqueous HCl. After the water layer (CH2Cl2, 5 ϫ) (3-{(1R,3aS,7aR)-1-[2-(S)-(tert-Butyldimethylsilanyloxy)-2-phenyl-
was extracted, the combined organic fractions were dried (Na2SO4)
and concentrated in vacuo. The residue was chromatographed
(EtOAc/PE, 1:3) to give the product (3.93 g, 9.2 mmol, 96%) as a
ethyl]-3-oxooctahydroisoindol-2-yl}propyl)carbamic Acid tert-Butyl
Ester (25b): According to the procedure described for 16, 2.40 g
(5.6 mmol) of 24b was transformed into the corresponding amine
(1.9 g, 4.4 mmol, 79%), which was transformed into 1.1 g of 25b
1
colourless oil. Ϫ IR (CHCl3): ν˜ ϭ 2220 cmϪ1, 1681. Ϫ H NMR
(400 MHz): δ ϭ 7.35Ϫ7.24 (m, 5 H, Ph), 4.76Ϫ4.74 (dd, 1 H, J ϭ
(2.1 mmol, 50% from 24b, colourless oil). Ϫ IR (CHCl3): ν˜ ϭ 3400
1
8.3, 3.0 Hz, PhCHOSi), 3.79Ϫ3.72 (dt, 1 H, J ϭ 13.5, 6.5 Hz, cmϪ1, 1668. Ϫ H NMR (250 MHz): δ ϭ 7.34Ϫ7.24 (m, 5 H, Ph),
NCHH), 3.33Ϫ3.30 (dd, 1 H, J ϭ 10.2, 2.1 Hz, NCH), 3.05Ϫ2.98 5.54 (br. s, 1 H, NHBoc), 4.79Ϫ4.74 (t, 1 H, J ϭ 5.7 Hz,
(dt, 1 H, J ϭ 13.8, 6.9 Hz, NCHH), 2.66Ϫ2.56 [m, 2 H, CHHCN,
C(O)CH], 2.49Ϫ2.42 (dt, 1 H, J ϭ 16.8, 6.4 Hz, CHHCN),
PhCHOSi), 3.66Ϫ3.54 (m, 1 H, NCHH), 3.26Ϫ3.21 (m, 1 H,
CHHNHBoc), 2.93Ϫ2.78 (m, 3 H, NCH, NCHH, CHHNHBoc),
2.27Ϫ2.23 [m, 1 H, C(O)CHCHH], 2.19Ϫ2.15 (m, 1 H, NCHCH), 2.54Ϫ2.52 [m, 1 H, C(O)CH], 1.9Ϫ1.4 (m, 8 H), 1.41 [s, 9 H,
1.86Ϫ1.10 (m, 9 H), 0.91 [s, 9 H, SiC(CH3)3], 0.06, Ϫ0.20, [2 ϫ s, CO2C(CH3)3], 1.2Ϫ0.9 (m, 3 H), 0.87 [s, 9 H, SiC(CH3)3], 0.03,
6 H, Si(CH3)2]. Ϫ 13C NMR (100 MHz): δ ϭ 176.0 [s, NC(O)], Ϫ0.12, [2 ϫ s, 6 H, Si(CH3)2]. Ϫ 13C NMR (100 MHz): δ ϭ 175.7
144.2 (s, Ph), 128.3, 127.4, 125.2 (d, Ph), 117.9 (s, CN), 72.2 (d,
[s, NC(O)], 156.0 [s, NHC(O)], 144.0 (s, Ph), 128.3, 127.4, 125.6 (d,
PhCHOSi), 60.3 (d, NCH), 40.9 [t, PhC(OSi)CH2], 38.8, 37.7 [d, Ph), 78.7 [s, CO2C(CH3)3], 73.1 (d, PhCHOSi), 59.7 (d, NCH), 40.4
C(O)CHCH], 37.0 (t, NCH2), 25.7 [q, SiC(CH3)3], 29.0, 24.0, 22.9,
22.8 [t, Ϫ(CH2)4Ϫ], 18.0 [s, SiC(CH3)3], 16.0 (t, CH2CN), Ϫ4.7,
[t, PhC(OSi)CH2], 38.9, 37.5 [d, NC(O)CHCH], 37.1 (t, NCH2),
not observed (t, CH2NHBoc), 28.3 [q, CO2C(CH3)3], 28.0 (t,
Ϫ5.0 [q, Si(CH3)]. Ϫ HRMS (FABϩ) calcd. for C25H39N2O2Si (M CH2CH2NHBoc), 25.7 [q, SiC(CH3)3], 29.3, 23.8, 22.9, 22.9 [t,
ϩ H) 427.2781, found 427.2781. Ϫ [α]D ϭ ϩ1.2 (c ϭ 0.64; CHCl3).
Ϫ(CH2)4Ϫ], 18.0 [s, SiC(CH3)3], Ϫ4.7, Ϫ5.0 [q, Si(CH3)2]. Ϫ
HRMS (FABϩ) calcd. for C30H51N2O4Si (M ϩ H) 531.3618, found
531.3629. Ϫ [α]D ϭ Ϫ4.7 (c ϭ 1.0; CHCl3).
3-{(1R,3aS,7aR)-1-[2-(S)-(tert-Butyldimethylsilanyloxy)-2-phenyl-
ethyl]-3-oxooctahydroisoindol-2-yl}propionitrile (24b): According to
the procedure described for 24a, 1.76 g (5.6 mmol) of alcohol 23b
was transformed into 2.39 g (5.6 mmol, 100%, colourless oil) of
24b. Ϫ IR (CHCl3): ν˜ ϭ 2225 cmϪ1, 1681. Ϫ 1H NMR (400 MHz):
(3-{(1R,3aS,7aR)-1-[2-(R)-(tert-Butyldimethylsilanyloxy)-2-phenyl-
ethyl]-3-thioxooctahydroisoindol-2-yl}propyl)carbamic Acid tert-Bu-
tyl Ester (26a): According to the procedure described for 17, 2.75 g
δ ϭ 7.35Ϫ7.24 (m, 5 H, Ph), 4.81Ϫ4.78 (t, 1 H, J ϭ 5.8 Hz, of 25a (5.2 mmol) was transformed into 2.76 g of the product
PhCHOSi), 3.83Ϫ3.76 (dt, 1 H, J ϭ 13.4, 6.4 Hz, NCHH),
Eur. J. Org. Chem. 2000, 105Ϫ113
(5.1 mmol, 97%, colourless oil). ؊ IR (CHCl3): ν˜ ϭ 2275 cmϪ1
,
111

M. Ostendorf, S. van der Neut, F. P. J. T. Rutjes, H. Hiemstra
FULL PAPER
1
1699, 1683. Ϫ H NMR (200 MHz): δ ϭ 7.38Ϫ7.25 (m, 5 H, Ph),
3.9 Hz, NCH), 3.27Ϫ3.16 (m, 2 H, NCHH and CHHNHBoc),
2.97Ϫ2.86 [m, 2 H, CHHNHBoc, C(S)CH], 2.51Ϫ2.47 [m, 1 H,
5.37 (br. s, 1 H, NHBoc), 4.79Ϫ4.73 (dd, 1 H, J ϭ 7.8, 3.6 Hz,
PhCHOSi), 4.38Ϫ4.31 (m, 1 H, NCHH), 3.50Ϫ3.44 (dd, 1 H, J ϭ C(S)CHCHH], 2.35Ϫ2.17 (m, 2 H), 2.06Ϫ1.88 (m, 2 H), 1.80Ϫ1.50
9.4, 2.7 Hz, NCH), 3.31Ϫ3.21 (m, 1 H, CHHNHBoc), 3.06Ϫ2.81 (m, 5 H), 1.44 [s, 9 H, CO2C(CH3)3], 1.20Ϫ1.10 (m, 2 H),
[m, 3 H, NCH, CHHNHBoc, C(S)CH], 2.61Ϫ2.54 (m, 1 H,
0.99Ϫ0.80 (m, 2 H). Ϫ 13C NMR (100 MHz): δ ϭ 203.7 [s, NC(S)],
NCHCH), 2.39Ϫ2.27 [m, 1 H, C(S)CHCHH], 1.9Ϫ1.4 (m, 8 H), not observed [CO2C(CH3)3], 143.5 (s, Ph), 128.8, 128.2, 125.5 (d,
1.45 [s, 9 H, CO2C(CH3)3], 1.3Ϫ1.1 (m, 3 H), 0.91 [s, 9 H, Ph), 79.0 [s, CO2C(CH3)3], 72.3 (d, PhCHOH), 67.0 (d, NCH), 49.4
SiC(CH3)3], 0.05, Ϫ0.20, [2 ϫ s, 6 H, Si(CH3)2]. Ϫ 13C NMR
[d, C(S)CH], 43.2 (t, NCH2), 40.0 (d, NCHCH), 38.0 [t,
(100 MHz): δ ϭ not observed [s, NC(S), CH2NHCO2C(CH3)3], CH2C(OH)], 37.3 (t, CH2NHBoc) 28.3 [q, CO2C(CH3)3], 26.4 (t,
143.8 (s, Ph), 128.3, 127.5, 125.4 (d, Ph), 72.4 (d, PhCHOSi), 66.4 CH2CH2NHBoc), 28.3, 25.9 23.8, 22.0, [t, Ϫ(CH2)4Ϫ]. Ϫ HRMS
(d, NCH), 49.2 [d, C(S)CH], 42.6 (d, NCH2), 39.4 (d, NCHCH), (FABϩ) calcd. for C24H36N2O3S (M ϩ H) 433.2525 found
39.4 [t, C(OSi)CH2], 28.3 [q, CO2C(CH3)3], 26.6 (t, 433.2525. Ϫ [α]D ϭ Ϫ5.4 (c ϭ 0.32; CHCl3).
CH2CH2NHBoc), 25.7 [q, SiC(CH3)3], 28.6, 24.0, 22.0, 22.0 [t,
Ϫ(CH2)4Ϫ], 17.9 [s, SiC(CH3)3] Ϫ4.8, Ϫ5.0 [q, Si(CH3)2]. Ϫ
HRMS (FABϩ) calcd. for C30H50N2O4Si (M ϩ H) 547.3390, found
547.3390. Ϫ [α]D ϭ Ϫ0.2 (c ϭ 0.4; CHCl3).
(1R)-2-[(4bS,8aR,9R)-1,2,3,4b,5,6,7,8,8a,9-Decahydro-4,9a-diaza-
fluoren-9-yl]-1-phenylethanol (8):
A solution of 25a (1.40 g,
3.3 mmol) in MeI (10 mL) was stirred for 17 h at room temperature
and in the dark. After concentration in vacuo, the iodine salt was
obtained as a pale yellow foam (1.89 g, 3.3 mmol, 100%). This iod-
ine salt (250 mg, 0.44 mmol) was dissolved in CH2Cl2 (3 mL). TFA
(1 mL) was added at 0°C and the resulting yellow solution was
stirred for 2 h at room temp., after which the reaction mixture was
concentrated in vacuo. This concentrated reaction mixture was re-
dissolved in CH2Cl2 (4 mL), and at 0°C, Et3N (122 mL, 0.87 mmol,
2 equiv.) was added. The mixture decolorized; stirring was con-
tinued for 2 h. The reaction mixture was extracted with 5% aqueous
HCl (3 ϫ), and solid NaOH was added at 0°C until the water layer
was basic. The basic aqueous solution was extracted (CH2Cl2, 5
ϫ). The combined organic layers were dried (Na2SO4) and concen-
trated in vacuo. The amidine was obtained as a white foam
(106 mg, 0.36 mmol, 82%). After purification by crystallization
from benzene/2-propanol, the product was obtained as a colourless
crystalline compound (65.7 mg, 52%), m.p. 104Ϫ107°C. Ϫ IR
(CHCl3): ν˜ ϭ 3400 cmϪ1, 1652. Ϫ 1H NMR (400 MHz): δ ϭ
7.35Ϫ7.24 (m, 5 H, Ph), 4.74Ϫ4.72 (dd, 1 H, J ϭ 9.4, 3.5 Hz,
PhCHOH), 3.38Ϫ3.06 (m, 5 H), 2.71 (m, 1 H), 2.10Ϫ1.95 (m, 3
H), 1.76Ϫ1.64 (m, 4 H), 1.53Ϫ1.44 (m, 3 H), 1.27Ϫ1.16 (m, 4 H).
(3-{(1R,3aS,7aR)-1-[2-(S)-(tert-Butyldimethylsilanyloxy)-2-phen-
ylethyl]-3-thioxooctahydroisoindol-2-yl}propyl)carbamic Acid tert-
Butyl Ester (26b): According to the procedure described for 17,
1.71 g (3.2 mmol) of lactam 25b was transformed into 1.36 g of the
product (2.5 mmol, 80%, colourless oil). Ϫ IR (CHCl3): ν˜ ϭ 2275
cmϪ1, 1692, 1681. Ϫ 1H NMR (400 MHz): δ ϭ 7.35Ϫ7.25 (m, 5
H, Ph), 5.30 (br. s, 1 H, NHBoc), 4.84Ϫ4.81 (t, 1 H, J ϭ 5.6 Hz,
PhCHOSi), 4.38Ϫ4.34 (m, 1 H, NCHH), 3.28Ϫ3.26 (m, 2 H, NCH,
NCHH), 3.09Ϫ3.06 (m, 1 H, CHHNHBoc), 2.89Ϫ2.78 [m, 2 H,
CHHNHBoc, C(S)CH], 2.50Ϫ2.47 [m,
1 H, C(S)CHCHH],
1.98Ϫ1.40 (m, 9 H), 1.43 [s, 9 H, CO2C(CH3)3], 1.25Ϫ1.10 (m, 3
H), 0.90 [s, 9 H, SiC(CH3)3], 0.05, Ϫ0.16, [2 ϫ s, 6 H, Si(CH3)2].
Ϫ
13C NMR (100 MHz): δ ϭ 203.7 [s, NC(S)], not observed
[CH2NCO2C(CH3)3], 143.6 (s, Ph), 128.3, 127.6, 125.5 (d, Ph), 72.8
(d, PhCHOSi), 66.5 (d, NCH), 49.2 [d, C(S)CH], 42.6 (t, NCH2),
39.9 (d, NCHCH), 39.3 [t, C(OSi)CH2], 28.2 [q, CO2C(CH3)3], 26.6
(t, CH2CH2NHBoc), 25.7 [q, SiC(CH3)3], 28.3, 25.9, 23.8, 22.0 [t,
Ϫ(CH2)4Ϫ], 18.0 [s, SiC(CH3)3], Ϫ4.8, Ϫ5.0 [q, Si(CH3)2]. Ϫ
HRMS (FABϩ) calcd. for C30H50N2O4Si (M ϩ H) 547.3390, found
547.3390. Ϫ [α]D ϭ Ϫ5.2 (c ϭ 0.5; CHCl3).
Ϫ
13C NMR (100 MHz): δ ϭ 161.5 (s, CϭN), 144.6 (s, Ph), 128.5,
127.7, 125.5, (d, Ph), 71.5 (d, CHOH), 64.5 (d, NCH), 41.7, 39.9,
(t, CϭNCH2 and NCH2), 39.4, 38.9, (d, NϭCCH and NCHCH),
28.4, 23.9, 23.9, 22.6, 22.6, 20.5. Ϫ [α]D ϭ ϩ66.9 (c ϭ 0.13; CHCl3).
(3-{(1R,3aS,7aR)-1-[2-(R)-Hydroxy-2-phenylethyl]-3-thioxoocta-
hydroisoindol-2-yl}propyl)carbamic Acid tert-Butyl Ester (27a): Ac-
cording to the procedure described for 18, 2.35 g of 26a (4.3 mmol)
was transformed into 1.66 g of 27a (3.8 mmol, 90%, colourless oil).
Ϫ IR (CHCl3): ν˜ ϭ 3452 cmϪ1, 2360, 1703. Ϫ 1H NMR
(200 MHz): δ ϭ 7.35Ϫ7.26 (m, 5 H, Ph), 4.81Ϫ4.75 (dd, 1 H, J ϭ
9.6, 2.9 Hz, PhCHOH), 4.45Ϫ4.31 (dt, 1 H, J ϭ 13.4, 8.2 Hz,
NCHH), 3.72Ϫ3.68 (dd, 1 H, J ϭ 9.7, 2.7 Hz, NCH), 3.37Ϫ3.14
(m, 2 H, CH2NHBoc), 3.03Ϫ2.87 [m, 2 H, C(S)CHCHH],
2.57Ϫ2.50 (m, 1 H, NCHCH), 2.35Ϫ2.25 (m, 1 H), 2.0Ϫ1.5 (m, 8
H), 1.44 [s, 9 H, CO2C(CH3)3], 1.2Ϫ1.0 (m, 3 H). Ϫ 13C NMR
(50 MHz): δ ϭ 203.5 [s, NC(S)], 155.9 [s, NHC(O)], 143.7 (s, Ph),
128.5, 127.8, 125.2 (d, Ph), 79.0 [s, CO2C(CH3)3], 71.5 (d,
PhCHOH), 66.9 (d, NCH), 49.2 [t, C(S)CH], 42.6 (t, NCH2), 38.9
(d, NCHCH), 38.0 [t, PhC(OH)CH2], 37.3 (t, CH2NHBoc), 28.2
[q, CO2C(CH3)3], 26.7 (t, CH2CH2NHBoc), 28.6, 25.8, 23.8, 21.9
[t, Ϫ(CH2)4Ϫ]. Ϫ HRMS (FABϩ) calcd. for C24H36N2O3S (M ϩ
H) 433.2525, found 433.2525. Ϫ [α]D ϭ Ϫ33.8 (c ϭ 1.0; CHCl3).
Ϫ Crystallographic data for 8: P21, a ϭ 10.070(1), b ϭ 17.244(5),
3
˚
˚
c ϭ 10.508(1) A, β ϭ 106.720(6)°, V ϭ 1747.7(5) A , Z ϭ 2, DX ϭ
1.17 g cmϪ3, λ (Cu-Kα) ϭ 1.5418 A, µ (Cu-Kα) ϭ 5.47 cm
,
Ϫ1
˚
F(000) ϭ 668, Ϫ25°C. Final R ϭ 0.059 for 2326 observed reflec-
tions. There is one H2O molecule between two molecules which are
connected by four hydrogen bonds. N1aϪO1s 2.708(8), N1bϪO1s
[19]
˚
2.723(7), O1bϪO1s 2.725(7), O1aϪO1s 2.752(7) A.
2-(S)-[(4bS,8aR,9R)-1,2,3,4b,5,6,7,8,8a,9-Decahydro-4,9a-diaza-
fluoren-9-yl]-1-phenylethanol (9):
A solution of 25b (1.05 g,
2.4 mmol) in MeI (10 mL) was stirred for 17 h at room temperature
in the dark. After concentration in vacuo, the iodine salt was ob-
tained as a pale yellow foam (1.42 g, 2.4 mmol, 100%). This iodine
salt (250 mg, 0.44 mmol) was dissolved in CH2Cl2 (3 mL). TFA
(1 mL) was added at 0°C and the yellow solution was stirred for
2 h at room temp., after which the reaction mixture was concen-
trated in vacuo. This concentrated reaction mixture was redissolved
in CH2Cl2 (4 mL) and, at 0°C, Et3N (122 mL, 0.87 mmol, 2 equiv.)
was added. The mixture decolorized; stirring was continued for 2 h.
The reaction mixture was extracted with 5% aqueous HCl (3 ϫ),
and solid NaOH was added at 0°C until the water layer was basic.
(3-{(1R,3aS,7aR)-1-[2-(S)-Hydroxy-2-phenylethyl]-3-thioxoocta-
hydroisoindol-2-yl}propyl)carbamic Acid tert-Butyl Ester (27b): Ac-
cording to the procedure described for 18, 1.36 g of 26b
(2.50 mmol) was transformed into 1.05 g of 27b (2.40 mmol, 96%,
colourless oil). Ϫ IR (CHCl3): ν˜ ϭ 3500 cmϪ1, 3300, 1699. Ϫ H The basic aqueous solution was extracted (CH2Cl2, 5 ϫ). The com-
1
NMR (400 MHz): δ ϭ 7.40Ϫ7.26 (m, 5 H, Ph), 5.28 (br. s, 1 H,
NHBoc) 4.83Ϫ4.80 (t, 1 H, J ϭ 6.2 Hz, PhCHOH), 4.44Ϫ4.36 (dt, cuo. The amidine was obtained as
1 H, J ϭ 14.8, 7.8 Hz, NCHH), 3.37Ϫ3.34 (dd, 1 H, J ϭ 8.4, 0.43 mmol, 98% crude). The product could not be purified by crys-
bined organic layers were dried (Na2SO4) and concentrated in va-
a
white foam (126 mg,
112
Eur. J. Org. Chem. 2000, 105Ϫ113

Enantioselective Synthesis of Hydroxy-Substituted DBN-Type Amidines
FULL PAPER
[3b]
417Ϫ430. Ϫ
H. Wynberg, E. G. J. Staring, J. Am. Chem.
tallization and was washed with benzene. Ϫ IR (CHCl3): ν˜ ϭ 3400
[3c]
Soc. 1982, 104, 166Ϫ168. Ϫ
G. D. H. Dijkstra, R. M. Kel-
1
cmϪ1, 1651. Ϫ H NMR (400 MHz): δ ϭ 7.32Ϫ7.22 (m, 5 H, Ph),
logg, H. Wynberg, Recl. Trav. Chim. Pays-Bas 1989, 108,
195Ϫ204.
4.74Ϫ4.71 (dd, 1 H, J ϭ 7.9, 5.2 Hz, CHOH), 3.37Ϫ2.98 (m, 5 H),
2.68 (m, 1 H), 2.01Ϫ1.05 (m, 14 H). Ϫ 13C NMR (100 MHz): δ ϭ
161.3 (s, CϭN), 145.5 (s, Ph), 128.2, 127.2, 125.7, (d, Ph), 71.4 (d,
CHOH), 64.5 (d, NCH), 42.7, 41.1, (d, NϭCCH and NCHCH),
39.7, 39.3, (t, CϭNCH2 and NCH2), 28.1, 24.0, 23.8, 22.9, 22.6,
20.7. Ϫ HRMS (FABϩ) calcd. for C19H27N2O (M ϩ H) 299.2123,
found 299.2125. Ϫ [α]D ϭ ϩ21.1 (c ϭ 0.9; CHCl3).
K. Tanaka, A. Mori, S. Inoue, J. Org. Chem. 1990, 55,
[4] [4a]
[4b]
181Ϫ185. Ϫ
M. N. Iyer, K. M. Gigstad, N. D. Namdev, M.
Lipton, J. Am. Chem. Soc. 1996, 118, 4910Ϫ4911.
E. J. Corey, F. Xu, M. C. Noe, J. Am. Chem. Soc. 1997, 119,
12414Ϫ12415.
[5]
[6]
[7]
E. J. Corey, M. J. Grogan, Org. Lett. 1999, 1, 157Ϫ160.
M. S. Sigman, E. N. Jacobsen, J. Am. Chem. Soc. 1998, 120,
4901Ϫ4902.
[8]
J. Leonard, E. Diez-Barra, S. Merino, Eur. J. Org. Chem.
1998, 2051Ϫ2061.
Thiophenol Addition Product 28: A mixture of thiophenol (51.0 mL,
0.29 mmol) and amidine 6 (5.0 mg, 0.015 mmol) was dissolved in
toluene (1 mL). Cyclohexenone (43.7 mL, 0.29 mmol) was added
and after being stirred for 20 min at room temperature, the reaction
mixture was diluted with toluene and washed (5% aqueous HCl, 2
ϫ). The organic layer was dried (MgSO4) and concentrated in va-
cuo, yielding the product (66.6 mg, 0.32 mmol, 72%) as a colourless
oil. Spectral data was as reported previously.[3a] Ϫ [α]D ϭ ϩ21.3
(c ϭ 0.70; CCl4). [α]578 ϭ ϩ22.4. Ϫ O.p. 23%.[3a]
[9] [9a]
[9b]
R. Schwesinger, Chimia 1985, 39, 269Ϫ273. Ϫ
R. W.
[9c]
Alder, Chem. Rev. 1989, 89, 1215Ϫ1223. Ϫ
R. Schwesinger,
Nachr. Chem. Tech. Lab. 1990, 38, 1214Ϫ1224.
[10]
[11]
J. Dijkink, K. Goubitz, M. N. A. van Zanden, H. Hiemstra,
Tetrahedron: Asymmetry 1996, 7, 515Ϫ524.
E. J. Corey, C. J. Helal, Angew. Chem. Int. Ed. 1998, 37, 1987.
[12] [12a] M. Ostendorf, R. Romagnoli, I. Cabeza Pereiro, E. C. Roos,
M. J. Moolenaar, W. N. Speckamp, H. Hiemstra, Tetrahedron:
[12b]
Asymmetry 1997, 8, 1773Ϫ1789. Ϫ
R. Romagnoli, E. C.
Roos, H. Hiemstra, M. J. Moolenaar, W. N. Speckamp, B.
Kaptein, H. E. Schoemaker, Tetrahedron Lett. 1994, 35,
1087Ϫ1090.
Malonate Addition Product 29: A mixture of dimethyl malonate
(20.0 mL, 0.18 mmol) and amidine 7 (9.6 mg, 0.043 mmol) was dis-
solved in toluene (1 mL). Cyclohexenone (16.7 mL, 0.17 mmol) was
added and after being stirred for 24 h at room temp., the reaction
mixture was diluted with toluene and washed (5% aqueous HCl, 2
ϫ). The organic layer was dried (MgSO4) and concentrated in va-
cuo, yielding the product (27 mg, 0.12 mmol, 70%) as a colourless
oil. Spectral data was as reported previously.[18] Ϫ [α]D ϭ ϩ1.4
(c ϭ 0.5; CHCl3). Ϫ O.p. [18] 35%.
[13]
For a review see: H. Hiemstra, W. N. Speckamp in Comprehen-
sive Organic Synthesis (Eds.: B. M. Trost, I. Fleming), Pergamon
Press, Oxford, 1991, vol. 2, p. 1047Ϫ1082.
[14] [14a] A. G. M. Barrett in Comprehensive Organic Synthesis (Eds.:
B. M. Trost, I. Fleming), Pergamon Press, Oxford, 1991, vol. 8,
[14b]
´
A. Echavarren, A. Galan, J. de Mendoza,
p. 251Ϫ252. Ϫ
´
A. Salmeron, J.-M. Lehn, Helv. Chim. Acta 1988, 71, 685Ϫ693.
[14c]
Ϫ
J. O. Osby, S. W. Heinzman, B. Ganem, J. Am. Chem.
Soc. 1986, 108, 67Ϫ72.
[15]
B. Yde, N. M. Yousif, U. Pedersen, I. Thomsen, S. -O. Lawes-
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[16] [16a]
Methoden der Organischen Chemie (Houben-Weyl) (Eds.:
O. Bayer, H. Meerwein, K. Ziegler), Georg Thieme Verlag,
Acknowledgments
[16b]
Stuttgart, 1952, vol. 8, p. 531Ϫ531. Ϫ
D. S. Noyce, R. M.
This research was financially supported by the Council for Chemi-
cal Sciences of the Netherlands Organization for Scientific Re-
search (CWϪNWO). We kindly thank K. Goubitz and J. Fraanje
(Laboratory of Crystallography, University of Amsterdam) for the
X-ray crystal structure determinations.
Pollack, J. Am. Chem. Soc. 1969, 91, 119Ϫ124.
[17]
[18]
[19]
L. C. Xavier, J. J. Mohan, D. J. Mathre, A. S. Thompson, J. D.
Carroll, E. G. Corly, R. Desmond, Org. Synth. 1996, 74, 50Ϫ70.
Determined from the known specific rotation: H. Sasai, T. Arai,
M. Shibasaki, J. Am. Chem. Soc. 1994, 116, 1571Ϫ1572.
Experimental details of the X-ray structure determinations and
tables of fractional atomic coordinates, thermal parameters,
and interatomic distances and angles of 7, 8 and 13 were de-
posited by the authors at the Cambridge Crystallographic Data
Centre as supplementary publication nos. CCDC-114104 (7),
-114106 (8), and -114105 (13). Copies of the data can be ob-
tained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [Fax: (internat.) ϩ 44-1223/336-033;
E-mail: deposit@ccdc.cam.ac.uk].
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113