Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by N-(9-Phenylfluoren-9-yl) β-Amino Alcohols

Article abstract of DOI:10.1021/jo9917083

A set of secondary N-phenylfluorenyl β-amino alcohols have been prepared and evaluated as catalysts for the enantioselective addition of diethylzinc to benzaldehyde. The influence of the substituents on the stereogenic centers of the ligand has been studied, and enantioselectivities up to 97% have been obtained. Those ligands with bulky groups in the carbinol stereocenter and small groups α to the nitrogen atom displayed the best catalytic activity and enantioselectivity. The most enantioselective ligand (4e) was found to possess general applicability for the enantioselective addition of diethylzinc to a variety of aromatic and aliphatic aldehydes.

Full text of DOI:10.1021/jo9917083

2108
J . Org. Chem. 2000, 65, 2108-2113
En a n tioselective Ad d ition of Dieth ylzin c to Ald eh yd es Ca ta lyzed
by N-(9-P h en ylflu or en -9-yl) â-Am in o Alcoh ols
M. Rita Paleo, Isabel Cabeza, and F. J avier Sardina*
Departamento de Quı´mica Orga´nica. Facultad de Quı´mica. Universidad de Santiago de Compostela.
15706 Santiago de Compostela, Spain
Received November 1, 1999
A set of secondary N-phenylfluorenyl â-amino alcohols have been prepared and evaluated as
catalysts for the enantioselective addition of diethylzinc to benzaldehyde. The influence of the
substituents on the stereogenic centers of the ligand has been studied, and enantioselectivities up
to 97% have been obtained. Those ligands with bulky groups in the carbinol stereocenter and small
groups R to the nitrogen atom displayed the best catalytic activity and enantioselectivity. The most
enantioselective ligand (4e) was found to possess general applicability for the enantioselective
addition of diethylzinc to a variety of aromatic and aliphatic aldehydes.
In tr od u ction
also been used as catalysts for this reaction. The mech-
anism of the process has been discussed for tertiary
â-amino alcohols,5b,16 and it has been shown that the
absolute configurations of the products correlate with the
configuration of the hydroxyl-bearing stereocenter of the
ligand, and that anti tertiary â-amino alcohols are
usually better ligands than the corresponding syn
stereoisomers.1c,10a Although less intensively investigated,
there have appeared some reports describing the suc-
cessful use of secondary â-amino alcohols,17 which showed
that the secondary amine group present in the catalyst
is not deprotonated under the reaction conditions. The
flow of reports in the literature dealing with new cata-
lysts for the enantioselective addition of organozinc
reagents to aldehydes continues unabated, showing the
importance and interest of this reaction nowadays. But,
despite this continued interest, there have been no
general studies on the combined influence of the substit-
uents on the amino- and hydroxyl-bearing carbons of the
catalyst in the outcome of the reaction, probably due to
the lack of an efficient and versatile method for the
systematic preparation of chiral, enantiomerically pure
â-amino alcohols. This situation is specially poignant
since the model proposed to account for the rate accelera-
tion in this reaction implicates a five-membered ring
Zn(II) aminoalkoxide complex 1 as the actual catalyst,
and, as Figure 1 clearly shows, the influence of the
The enantioselective addition of diorganozinc reagents
to aldehydes in the presence of catalytic amounts of a
chiral ligand provides an excellent method for the
preparation of enantiomerically enriched secondary al-
cohols.1 The discovery that certain â-amino alcohols can
promote the ethylation of benzaldehyde by Et2Zn initi-
ated a search for efficient chiral auxiliaries for this type
of reaction.2 A myriad of â-tertiary amino alcohols have
been investigated as catalysts; among them derivatives
of natural products such as ephedrine,3 norephedrine,4
camphor,5 proline,6 pinane,7 and cinchona alkaloids8 have
attracted widespread attention. The catalytic abilities of
nonnaturally occurring â-amino alcohols have been probed
as well, and the results were used to study the effects of
the substituents on the nitrogen atom9 and the hydroxyl-
bearing carbon of the ligand on the enantioselectivity of
the addition.10,11 Ferrocenyl amino alcohols,9 chiral pip-
erazines,12 γ-amino alcohols,13 δ-amino alcohols,14 and
derivatives of 2-amino-2′-hydroxy-1,1′-binaphthyls15 have
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis; J ohn
Wiley & Sons: New York, 1994, Chapter 5. (b) Soai, K.; Niwa, S. Chem.
Rev. 1992, 92, 833. (c) Noyori, R.; Kitamura, M. Angew. Chem., Int.
Ed. Engl. 1991, 30, 49. (d) Seyden-Penne, J . Chiral Auxiliaries and
Ligands in Asymmetric Synthesis; J ohn Wiley & Sons: New York,
1995.
(2) (a) Mukaiyama, T.; Soai, K.; Sato, T.; Shimizu, H.; Suzuki, K. J .
Am. Chem. Soc. 1979, 101, 1455. (b) Oguni, N.; Omi, T. Tetrahedron
Lett. 1984, 25, 2823.
(3) (a) Chaloner, P. A.; Perera, S. A. R. Tetrahedron Lett. 1987, 28,
3013. (b) Chaloner, P. A.; Langadianou, E. Tetrahedron Lett. 1990, 31,
5185. (c) Corey, E. J .; Hannon, F. J . Tetrahedron Lett. 1987, 28, 5233.
(d) Corey, E. J .; Hannon, F. J . Tetrahedron Lett. 1987, 28, 5237. (e)
Soai, K.; Nishi, M.; Ito, Y. Chem. Lett. 1987, 2405. (f) Itsuno, S.;
Fre´chet, J . M. J . J . Org. Chem. 1987, 52, 4140.
(4) (a) Soai, K.; Yokoyama, S.; Ebihara, K.; Hayasaka, T. J . Chem
Soc., Chem. Commun. 1987, 1690. (b) Soai, K.; Yokoyama, S.; Ha-
yasaka, T. J . Org. Chem. 1991, 56, 4264.
(5) (a) Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J . Am. Chem.
Soc. 1986, 108, 6071. (b) Kitamura, M.; Okada, S.; Suga, S.; Noyori,
R. J . Am. Chem. Soc. 1989, 111, 4028.
(6) (a) Soai, K.; Ookawa, A.; Ogawa, K.; Kaba, T. J . Chem Soc.,
Chem. Commun. 1987, 467. (b) Soai, K.; Ookawa, A.; Kaba, T.; Ogawa,
K. J . Am. Chem. Soc. 1987, 109, 7111. (c) Asami, M.; Inoue, S. Chem.
Lett. 1991, 685.
(10) (a) Vidal-Ferran, A.; Moyano, A.; Perica`s, M. A.; Riera, A. J .
Org. Chem. 1997, 62, 4970. (b) Sola`, L.; Reddy, K. S.; Vidal-Ferran,
A.; Moyano, A.; Perica`s, M. A.; Riera, A.; Alvarez-Larena, A.; Piniella,
J .-F. J . Org. Chem. 1998, 63, 7078. (c) Reddy, K. S.; Sola`, L.; Moyano,
A.; Perica`s, M. A.; Riera, A. J . Org. Chem. 1999, 64, 3969.
(11) (a) Wilken, J .; Gro¨ger, H.; Kossenjans, M.; Martens, J . Tetra-
hedron: Asymmetry 1997, 8, 2761. (b) Sibi, M. P.; Chen, J .; Cook, G.
R. Tetrahedron Lett. 1999, 40, 3301.
(12) Shono, T.; Kise, N.; Shirakawa, E.; Matsumoto, H.; Okazaki,
E. J . Org. Chem. 1991, 56, 3063.
(13) Oppolzer, W.; Radinov, R. N. Tetrahedron Lett. 1988, 29, 5645.
(14) Genov, M.; Dimitrov, V.; Ivanova, V. Tetrahedron: Asymmetry
1997, 8, 3703.
(15) Vyskocˇil, S.; J aracz, S.; Smrcˇina, M.; Sˇt´ıcha, M.; Hanusˇ, V.;
Pola´sˇek, M.; Kocˇovsky´, P. J . Org. Chem. 1998, 63, 7727.
(16) Yamakawa, M.; Noyori, R. J . Am. Chem. Soc. 1995, 117, 6327.
(17) (a) Tanaka, K.; Ushio, H.; Suzuki, H. J . Chem Soc., Chem.
Commun. 1989, 1700. (b) Corey, E. J .; Yuen, P.-W.; Hannon, F. J .;
Wierda, D. A. J . Org. Chem. 1990, 55, 784. (c) Soai, K.; Watanabe, M.;
Yamamoto, A.; Yamashita, T. J . Mol. Catal. 1991, 64, L27.
(7) Cherng, Y.-J .; Fang, J .-M.; Lu, T.-J . J . Org. Chem. 1999, 64, 3207.
(8) Smaardijk, A. A.; Wynberg, H. J . Org. Chem. 1987, 52, 135.
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Chem. 1991, 56, 2218.
10.1021/jo9917083 CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/04/2000

Enantioselective Addition of Diethylzinc to Aldehydes
J . Org. Chem., Vol. 65, No. 7, 2000 2109
Sch em e 1. Syn th esis of â-Am in o Alcoh ols 4 a n d 5
F igu r e 1.
substituents R1-R6 on the â-amino alcohol must be
paramount on the feasibility of complexation with the Zn
atom.1,16
Sch em e 2. En a n tioselective Ad d ition of Et2Zn to
Ben za ld eh yd e: Effect of RN a n d RO Su bstitu en ts
Resu lts a n d Discu ssion
We have recently reported18 a method for the prepara-
tion of N-(9-phenylfluoren-9-yl) secondary amino alcohols
4, 5 which possess the structure present in most of the
catalysts used for the addition of diorganozinc reagents
to aldehydes. The bulky phenylfluorenyl group (Pf)
present in these molecules should act as a conformational
lock at the aminoalkoxide catalyst stage, thus allowing
the effects of the interactions among the R3-R6 groups
on the enantioselectivity of the additions to come to the
fore. Herein we present the results obtained when a
series of Pf-amino alcohols were used as catalysts for the
addition of Et2Zn to aldehydes.
â-Amino alcohols 4 and 5 were easily obtained from
R-amino ketones 3 using a variety of reducing agents.
The R-amino ketones were obtained from oxazolidinones
2, which were prepared from the corresponding amino
acid by N-phenylfluorenylation followed by reaction with
aq formaldehyde. Treatment of 2 with a variety of
organolithium reagents afforded R-amino ketones 3 in
excellent yields and without loss of enantiomeric purity.18
By using this route, both the syn and anti epimers of the
desired â-amino alcohols could be prepared, which al-
lowed us to study the influence of the substituents at the
amino- (RN) and hydroxyl-bearing carbons (RO), as well
as the importance of the configuration of the hydroxyl-
bearing stereocenter on the outcome of the addition.1
Alanine and leucine were chosen as the starting amino
acids since they provide RN groups with very different
steric demands. The introduction of six different RO
aliphatic and aromatic groups, covering a wide range of
sizes, provided the 18 ligands used for this study.
The stereochemistries of the amino alcohols 4 and 5
were determined as follows: the configuration of the
carbon bearing the amino group was fixed by the starting
amino acid (S), and the configuration of the carbinol
stereocenter was established by analysis of the coupling
constants between the hydrogens of the stereocenters.18
The assignments were corroborated by NOE experiments
on the oxazolidines18 derived from amino alcohols 4a ,b,f
and 5a ,b,f (RO ) Ph, ferrocenyl, and trityl, respectively).
No diagnostic NOE enhancements were observed for the
tert-butyl-substituted oxazolidinones 6e and 7e, and their
relative stereochemistries were determined by X-ray
crystallography.19
ligand in toluene at room temperature. The amino
alcohols were prepared (Scheme 1), and the enantiose-
lectivities and configuration of the products resulting
from the Et2Zn addition to benzaldehyde are shown in
Scheme 2.
Perusal of the data shown in the table (Scheme 2)
points to some interesting trends. With regards to the
syn ligands, 4, it can be seen that increasing the size of
RN (Me2CHCH2 vs Me), while keeping the same RO group,
is detrimental for the enantioselectivity of the catalyst
(compare entries 1 and 8, 3 and 7, 5 and 9). On the other
hand, the % ee values obtained when the RO group was
varied, while holding constant RN, increased in the
following order, 1-naphthyl < 2-naphthyl < ferrocenyl
∼ phenyl < trityl < tert-butyl, showing that bulky RO
groups combined with small RN substituents favored the
enantioselectivity of the process. (S)-Selectivity was
always favored with syn ligands.
Amino alcohols 4 and 5 were studied as catalysts for
the addition of Et2Zn to benzaldehyde, using 3 mol % of
(18) (a) Paleo, M. R.; Sardina, F. J . Tetrahedron Lett. 1996, 37, 3403.
(b) Paleo, M. R.; Calaza, M. I.; Sardina, F. J . J . Org. Chem. 1997, 62,
6862.
(19) See Supporting Information for details.

2110 J . Org. Chem., Vol. 65, No. 7, 2000
Paleo et al.
Sch em e 3
to explain the lack of clear trends in the enantioselectivity
displayed by the reactions catalyzed by these ligands. In
these systems there should exist a strong steric interac-
tion between RO () R2) and RN, which would lead to
destabilization of the chelate. The fact that ligands 5 in
which the RO group is very bulky (trityl or tert-butyl) give
products with S configuration, instead of the expected R
alcohols, might even indicate that the formation of the
chelate does not take place and that the true catalyst is
a Zn alkoxide in which the N atom remains uncomplexed.
In the case of the transition structures derived from
syn amino alcohols 4 (12, R1 ) RO, R2 ) H) this steric
repulsion is absent, and thus the Et2Zn addition should
proceed exclusively through the chelated form of the
catalyst. The transition structures 12-pro-S, the favored
ones, can provide an explanation for the decrease in
enantioselectivity observed for catalysts bearing bulky
RN groups: the steric interacions of RN with the Et2Zn
and PhCHO groups should result in the elongation of
both O-Zn bonds, thus isolating the reactants from the
influence of the chiral centers of the catalyst. The
increased enantioselectivity observed with the increasing
bulkiness of RO could be the result of steric compression
by this group onto the Et bound to the Zn to which the
PhCHO is attached; this effect should reduce the Et-
Zn-O angle and thus bring the Et group in closer
proximity to one of the carbonyl substituents, thus
increasing the enantiodifferentiation between 12-pro-S
and 12-pro-R.
Once we had developed a ligand (4e) that promoted
the highly enantioselective addition of Et2Zn to benzal-
dehyde very efficiently, we decided to explore its general
applicability, and thus we used it to induce the addition
of Et2Zn to a series of aromatic and aliphatic aldehydes
(Scheme 4). The reactions were performed using 3 mol
% of the catalyst in toluene at different temperatures,
and very good enantioselectivities were obtained in most
cases. We observed that, in the majority of cases, lower
temperatures favored the enantioselectivity of the reac-
tion; thus, when the reactions were carried out at 40 °C,
lower ee values were obtained compared to room tem-
perature or 0 °C. In these two latter cases the ee values
were high and quite similar but slightly better for the
reactions carried out at 0 °C. With regard to the additions
to aromatic aldehydes, we observed that steric hindrance
plays an important role in determining the degree of
enantioselection of the reaction: ortho-substituted ben-
zaldehydes underwent addition with lower enantioselec-
tivities compared to their meta or para analogues, and
1-naphthaldehyde (86% ee) gave lower enantioselectivity
compared to 2-naphthaldehyde (97% ee), although the
effect for the bromobenzaldehydes is less dramatic (94
vs 96% ee, entries 11 and 13). Electronic effects of the
aromatic ring substituents do not appear to have a large
influence on the enantioselectivity of the addition, with
the notable exception of the dialkoxybenzaldehydes where
the ee obtained were only moderate-to-good. Linear and
branched aliphatic aldehydes underwent Et2Zn addition
catalyzed by 4e in a highly enantioselective fashion
(entries 24 and 25) as well.
Anti amino alcohols 5 showed a different, more erratic
behavior and, overall, they gave poorer enantioselectivi-
ties than their trans counterparts. The (R)-ethyl carbinol
(R)-9 was the predominant product in most cases, the
exception being the reactions catalyzed by the ligands
possessing bulky RO groups (tert-butyl and trityl, 5e, 5f,
5i), where (S)-9 was the main product.
Theoretical calculations have been used to study the
mechanism of the addition of dialkylzinc compounds to
aldehydes and the origin of the enantioselectivity of the
process.16,20 These studies have established the nature
of the intermediates, transition states, and the energetics
of the reaction profile. The mechanistic picture that
emerged from this work is depicted in Scheme 3. Com-
plexation of the reactants with the true catalyst, ethylzinc
aminoalkoxide 10, leads to a di-zinc complex (11) which
undergoes intramolecular ethyl migration, through tran-
sition state 12, to give a catalyst/product complex (13);
regeneration of the catalyst 10 and liberation of the
product take place in a subsequent step.16,20d The energy
differences, calculated at ab initio or semiempirical levels,
of the corresponding transition states leading to the R-
and S-reaction products have been used to explain the
enantioselectivies displayed by the different catalysts.20
The interaction of the substituents of the carbonyl group
with the ethyl group attached to the aminoalkoxide Zn
atom in the transition state appears to be the cause of
the observed enantioselection (compare transition states
12-pro-S and 12-pro-R).20c,d
Analysis of the transition structures 12 (R1 ) H, R2 )
RO) originated from anti amino alcohols 5 provided a clue
Con clu sion
(20) (a) Vidal-Ferran, A.; Moyano, A.; Perica`s, M. A.; Riera, A.
Tetrahedron Lett. 1997, 38, 8773. (b) Nakano, H.; Kumagai, N.;
Matsuzaki, H.; Kabuto, C.; Hongo, H. Tetrahedron: Asymmetry 1997,
8, 1391. (c) Goldfuss, B.; Houk, K. N. J . Org. Chem. 1998, 63, 8998.
(d) Yamakawa, M.; Noyori, R. Organometallics 1999, 18, 128.
Our studies have shown that the nature and stereo-
chemistry of the substituents in a series of N-phenylfluo-
renyl â-amino alcohols have a profound influence in their

Enantioselective Addition of Diethylzinc to Aldehydes
J . Org. Chem., Vol. 65, No. 7, 2000 2111
125.3, 125.8, 126.0, 127.0, 127.5, 128.2, 128.3, 128.4, 128.5,
128.6, 128.9, 129.8, 133.2, 136.5, 140.2, 141.3, 144.8, 149.4,
149.5. Anal. Calcd for C32H27NO: C, 87.04; H, 6.16; N, 3.17.
Found: C, 86.81; H, 5.97; N, 3.08.
Sch em e 4. Ca ta lytic En a n tioselective Ad d ition of
Et2Zn to Ald eh yd es Med ia ted by 4e
(1S,2S)-1-(2-Na p h t h yl)-2-[N-(9′-p h en ylflu or en -9′-yl)-
a m in o]p r op a n -1-ol (4d ) a n d (1R,2S)-1-(2-Na p h th yl)-2-[N-
(9′-p h en ylflu or en -9′-yl)a m in o]p r op a n -1-ol (5d ). To a -78
°C solution of 3d (200 mg, 0.45 mmol) in THF (5 mL) was
added L-Selectride (0.9 mL, 0.9 mmol) and stirred for 4 h at 0
°C, and then it was quenched with AcOH (0.1 mL, 1.76 mmol).
After 5 min of stirring, LiOH‚H2O (95 mg, 2.26 mmol) and
H2O2 (2.6 mL) were added, and the resulting mixture was
stirred for 25 min and then partitioned between CH2Cl2 (15
mL) and 1 M H3PO4 (15 mL). The aqueous phase was extracted
with CH2Cl2 (15 mL), and the combined organic phase was
washed with brine (20 mL), dried, and concentrated to give a
residue which was purified by column chromatography (CH2-
Cl2/hexane 1/1) to give 4d (150 mg, 74%) and 5d (49 mg, 25%
1
yield). 4d : [R]20 ) + 172 (c 1.0, CH2Cl2); H NMR δ 0.45 (d,
D
J ) 6.2, 3H), 2.31 (m, 1H), 3.46 (bs, 2H), 4.19 (d, J ) 8.6, 1H),
6.99 (dd, J ) 1.9, 8.5, 1H), 7.15-7.71 (m, 19H); 13C NMR δ
19.3, 54.8, 72.6, 78.4, 120.0, 120.1, 124.8, 125.1, 125.6, 125.8,
125.9, 126.0, 126.4, 127.3, 127.5, 127.8, 128.1, 128.4, 132.9,
139.7, 140.1, 140.6, 144.6, 148.4, 150.7. Anal. Calcd for C32H27
-
NO: C, 87.04; H, 6.16; N, 3.17. Found: C, 87.14; H, 5.97; N,
2.97. 5d : [R]20 ) + 151 (c 1.0, CH2Cl2); 1H NMR δ 0.56 (d, J
D
) 6.5, 3H), 1.90 (bs, 1H), 2.49 (m, 1H), 3.58 (bs, 1H), 4.28 (d,
J ) 2.8, 1H), 6.85 (d, J ) 8.8, 1H), 7.23-7.50 (m, 14H), 7.62
(d, J ) 8.5, 1H), 7.76 (m, 4H); 13C NMR δ 15.9, 53.9, 72.9,
74.8, 120.0, 120.1, 124.0, 124.2, 124.6, 125.3, 125.5, 125.8,
126.0, 127.3, 127.4, 127.5, 127.8, 128.0, 128.1, 128.4, 128.5,
128.7, 132.4, 133.0, 138.7, 139.9, 141.2, 144.7, 149.1, 149.7.
Anal. Calcd for C32H27NO: C, 87.04; H, 6.16; N, 3.17. Found:
C, 86.91; H, 6.07; N, 3.33.
(3S,4S)-2,2-Dim eth yl-4-[N-(9′-p h en ylflu or en -9′-yl)a m i-
n o]p en ta n -3-ol (4e) a n d (3R,4S)-2,2-Dim eth yl-4-[N-(9′-
p h en ylflu or en -9′-yl)a m in o]p en ta n -3-ol (5e). Method A: To
a -78 °C solution of ketone 3e (200 mg, 0.54 mmol) in THF (6
mL) was added Li(tBuO)3AlH (0.91 mL, 1.08 mmol, 1.19 M in
cyclohexane). The resulting solution was stirred for 3 h at -78
°C and 40 h at room temperature, and then it was cooled to 0
°C and quenched by addition of EtOAc (1 mL). After 3 min,
the cooling bath was removed and CH2Cl2 (9 mL) was added
followed successively by saturated aqueous Na2CO3, KH2PO4,
and Na2SO4. The resulting suspension was stirred for 30 min,
ability to act as catalysts for the enantioselective addition
of diethylzinc to aldehydes. Those ligands with bulky
groups in the carbinol stereocenter and small groups R
to the nitrogen atom displayed the best catalytic activity
and enantioselectivity.
1
filtered, and concentrated in vacuo. The H NMR spectrum of
the crude product showed a mixture of 3e/4e/5e in a 2.8/24/1
ratio. Purification by column chromatography afforded 171 mg
of amino alcohol 4e (85% yield) as a white foam. Method B: A
0 °C solution of 3e (50 mg, 0.13 mmol) in THF (1.5 mL) was
treated with LiBH4 (3 × 6 mg, 0.27 mmol) at intervals of 1.5
h each. After 4.5 h the reaction was quenched by addition of
10% H3PO4 (0.5 mL). The reaction mixture was partitioned
between EtOAc and saturated aqueous NaHCO3. The aqueous
layer was extracted with EtOAc (10 mL), and the combined
organic layer was washed with water and brine, dried, filtered,
and concentrated to give a residue which was purified by
column chromatography (CH2Cl2/hexane 3/2) to give 4e (15 mg,
Exp er im en ta l Section
Gen er a l Meth od s. General experimental aspects have
been published elsewhere.18 Amino ketones 3 and amino
alcohols 4a ,b and 5a ,b were prepared according to the
published procedure.18
(1S,2S)-1-(1-Na p h t h yl)-2-[N-(9′-p h en ylflu or en -9′-yl)-
a m in o]p r op a n -1-ol (4c) a n d (1R,2S)-1-(1-Na p h th yl)-2-[N-
(9′-p h en ylflu or en -9′-yl)a m in o]p r op a n -1-ol (5c). A 0 °C
solution of 3c (240 mg, 0.55 mmol) in MeOH/THF (6/2 mL)
was treated with NaBH4 (31 mg, 0.825 mmol). After stirring
for 4 h under Ar, the reaction mixture was quenched by slow
addition of 10% HCl. The resulting solution was extracted with
EtOAc, and the organic layer was washed with water and
brine, dried, filtered, and evaporated. Column chromatography
(CH2Cl2/hexane 1/1) afforded 4c (157 mg, 65% yield) and 5c
(77 mg, 32% yield). 4c: mp 156-158 °C (EtOH); [R]20D ) +235
29%) and 5e (34 mg, 67% yield). 4e: [R]20 ) +292 (c 1.0,
D
CHCl3); 1H NMR δ 0.55 (s, 9H), 0.82 (d, J ) 6.3, 3H), 2.13 (m,
1H), 2.75 (d, J ) 7.1, 1H), 7.19-7.79 (m, 13H); 13C NMR δ
24.8, 26.0, 34.4, 47.8, 72.6, 81.1, 119.6, 120.0, 125.3, 125.7,
126.3, 127.3, 127.5, 128.1, 128.3, 128.4, 139.8, 141.1, 144.5,
148.0, 149.8. Anal. Calcd for C26H29NO: C, 84.06; H, 7.87; N,
3.77. Found: C, 83.80; H, 7.63; N, 3.64. 5e : [R]20 ) + 155 (c
1
(c 1.0, CHCl3); H NMR δ 0.48 (d, J ) 6.3, 3H), 2.80 (m, 1H),
D
3.35 (bs, 1H), 4.74 (d, J ) 8.8, 1H), 7.19-7.94 (m, 20H); 13C
NMR δ 20.2, 53.4, 72.6, 78.3, 120.0, 120.1, 124.6, 124.9, 125.1,
125.2, 125.3, 125.7, 125.9, 126.4, 127.3, 127.7, 128.1, 128.2,
128.3, 128.4, 131.1, 134.0, 136.9, 140.3, 140.7, 144.7, 148.7,
150.7. Anal. Calcd for C32H27NO: C, 87.04; H, 6.16; N, 3.17.
Found: C, 86.78; H, 5.77; N, 3.11. 5c: mp 213-214 °C (EtOAc);
1.9, CHCl3); 1H NMR δ 0.52 (s, 9H), 0.83 (d, J ) 6.7, 3H), 1.85
(bs, 1H), 2.27 (m, 1H), 2.80 (d, J ) 1.9, 1H), 7.16-7.43 (m,
11H), 7.65 (d, J ) 7.6, 1H), 7.72 (d, J ) 7.2, 1H); 13C NMR δ
17.2, 26.6 (3C), 33.3, 49.8, 73.2, 81.1, 119.8, 119.9, 124.6, 125.8,
126.0, 127.2, 127.6, 127.8, 128.3, 139.9, 141.2, 145.0, 149.3,
149.7. Anal. Calcd for C26H29NO: C, 84.06; H, 7.87; N, 3.77.
Found: C, 83.83; H, 8.02; N, 3.80.
[R]20 ) +174 (c 1.0, CHCl3); 1H NMR δ 0.58 (d, J ) 6.7, 3H),
D
2.28 (bs, 1H), 2.69 (m, 1H), 3.70 (bs, 1H), 4.96 (d, J ) 2.7, 1H),
6.31 (d, J ) 8.5, 1H), 7.04-7.91 (m, 19H); 13C NMR δ 15.6,
52.1, 71.6, 73.2, 120.1, 120.2, 122.6, 123.0, 124.5, 124.9, 125.2,
(2S,3S)-1,1,1-Tr ip h en yl-3-[N-(9′-p h en ylflu or en -9′-yl)-
a m in o]bu ta n -2-ol (4f) a n d (2R,3S)-1,1,1-Tr ip h en yl-3-[N-
(9′-p h en ylflu or en -9′-yl)a m in o]bu ta n -2-ol (5f). A solution

2112 J . Org. Chem., Vol. 65, No. 7, 2000
Paleo et al.
of Ph3CH (175 mg, 0.72 mmol) in THF (7 mL) was cooled to 0
°C and treated with nBuLi (300 mL, 0.67 mmol). The dark red
solution was stirred for 2 h at 0 °C, and then a solution of
N-Pf-alaninal (140 mg, 0.45 mmol) was added. After 4 h of
stirring at 0 °C, the reaction was quenched by addition of
AcOH (0.5 mL). The cooling bath was removed, and after 3
min the mixture was partitioned between EtOAc and saturated
aqueous NaHCO3. The organic layer was washed with satu-
rated aqueous NaHCO3, water, and brine, dried, filtered, and
evaporated. The residue was purified to give 4f (77 mg, 31%
with EtOAc (15 mL) and the combined organic phase was
washed with brine (20 mL), dried, and concentrated to give a
residue which was purified by column chromatography (CH2-
Cl2/hexane 1/1) to give 4h (196 mg, 65%) and 5h (100 mg, 33%
yield). 4h : [R]20 ) +209 (c 1.0, CH2Cl2); 1H NMR δ 0.07 (d, J
D
) 6.1, 3H), 0.37 (d, J ) 6.1, 3H), 0.79 (m, 1H), 1.24 (t, J ) 8.8,
1H), 2.31 (m, 1H), 4.24 (d, J ) 5.8, 1H), 6.95-7.39 (m, 16 H),
7.65 (d, J ) 7.5, 1H), 7.69 (d, J ) 7.5, 1H); 13C NMR δ 20.9,
23.3, 24.4, 44.0, 56.6, 72.6, 76.0, 119.6, 120.0, 125.4, 125.9,
126.0, 126.8, 127.1, 127.2, 127.6, 127.9, 128.2, 128.3, 140.1,
140.9, 143.0, 144.9, 148.2, 150.4. Anal. Calcd for C31H31NO:
C, 85.87; H, 7.21; N, 3.23. Found: C, 86.06; H, 6.95; N, 3.33.
yield) and 5f (74 mg, 30% yield). 4f: [R]20 ) -96 (c 1.0, CH2-
D
Cl2); 1H NMR δ 0.63 (d, J ) 6.6, 3H), 1.34 (m, 1H), 3.05 (bd, J
) 6.1, 1H), 5.16 (bs, 1H), 6.94-7.39 (m, 26 H), 7.63 (d, J )
7.5, 1H), 7.69 (d, J ) 7.5, 1H); 13C NMR δ 19.8, 53.4, 61.7,
71.1, 76.1, 120.1, 124.7, 124.9, 125.4, 125.7, 125.9, 127.0, 127.2,
127.3, 127.6, 127.7, 127.9, 128.1, 128.2, 129.5, 138.8, 140.2,
145.1, 148.0, 150.8. Anal. Calcd for C41H35NO: C, 84.06; H,
5h : [R]20 ) +101 (c 1.3, CHCl3); 1H NMR δ 0.23 (d, J ) 6.4,
D
3H), 0.61 (d, J ) 6.6, 3H), 0.81 (m, 1H), 1.08 (m, 1H), 1.34 (m,
1H), 2.20 (bs, 1H), 2.49 (m, 1H), 3.25 (bs, 1H), 4.04 (d, J )
2.7, 1H), 6.87 (d, J ) 7.1, 2H), 7.09-7.55 (m, 14H), 7.77 (d, J
) 7.6, 1H), 7.82 (d, J ) 7.6, 1H); 13C NMR δ 21.4, 23.3, 24.0,
38.5, 56.4, 72.5, 73.1, 119.8, 120.0, 125.2, 125.3, 126.0, 126.2,
127.3, 127.7, 127.9, 128.1, 128.3, 128.4, 128.6, 139.7, 141.1,
141.3, 145.0, 149.4, 149.9. Anal. Calcd for C31H31NO: C, 85.87;
H, 7.21; N, 3.23. Found: C, 85.96; H, 7.27; N, 3.06.
7.87; N, 3.77. Found: C, 84.07; H, 7.63; N, 3.76. 5f : mp 196
1
°C (EtOH); [R]20 ) +75 (c 1.0, CHCl3); H NMR δ 0.11 (d, J
D
) 6.6, 3H), 1.53 (bs, 1H), 2.66 (bd, J ) 5.2, 1H), 3.29 (bd, J )
2.3, 1H), 4.46 (bs, 1H), 7.04-7.35 (m, 26H), 7.50 (d, J ) 6.6,
1H), 7.55 (d, J ) 7.5, 1H); 13C NMR δ 17.5, 51.3, 60.4, 72.6,
76.1, 120.1, 120.2, 124.4, 125.2, 125.7, 125.8, 127.2, 127.3,
127.7, 127.8, 127.9, 128.2, 128.3, 130.1, 139.5, 140.8, 144.9,
145.4, 149.0, 150.0. Anal. Calcd for C41H35NO: C, 84.06; H,
7.87; N, 3.77. Found: C, 84.17; H, 7.58; N, 3.76.
(3S,4S)-2,2,6-Tr im et h yl-4-[N-(9′-p h en ylflu or en -9′-yl)-
a m in o]h ep ta n -3-ol (4i) a n d (3R,4S)-2,2,6-Tr im eth yl-4-[N-
(9′-p h en ylflu or en -9′-yl)a m in o]h ep ta n -3-ol (5i). LiAlH4 (28
mg, 0.73 mmol) in THF (5 mL) was cooled to 0 °C and treated
with a solution of 3i (150 mg, 0.36 mmol) in THF (5 mL), the
cooling bath was removed, and the resulting mixture was
stirred for 30 min. Then it was quenched by slow addition of
EtOAc (1 mL) followed by CH2Cl2, saturated aqueous NaHCO3
(1 mL), KH2PO4, and anhyd Na2SO4. The resulting mixture
was stirred at room temperature for 1 h and then filtered. The
residue was washed with CH2Cl2, the combined clear filtrate
and washings were concentrated, and the residue was purified
by short column chromatography (CH2Cl2/hexane 1/1) to give
(1S,2S)-4-Meth yl-1-(1-n aph th yl)-2-[N-(9′-ph en ylflu or en -
9′-yl)a m in o]p en ta n -1-ol (4g) a n d (1R,2S)-4-Meth yl-1-(1-
n a p h th yl)-2-[N-(9′-p h en ylflu or en -9′-yl)a m in o]p en ta n -1-
ol (5g). A 0 °C solution of 3g (200 mg, 0.4 mmol) in THF (1
mL) was treated with LiBH4 (3 × 20 mg, 0.85 mmol) at
intervals of 1.5 h each. After 4 h the reaction was quenched
by slow addition of 10% H3PO4 (0.5 mL). The reaction mixture
was partitioned between EtOAc and saturated aqueous NaH-
CO3. The aqueous layer was extracted with EtOAc (10 mL),
and the combined organic layer was washed with water and
brine, dried, filtered, and concentrated to give a residue which
was purified by column chromatography (CH2Cl2/hexane 1/1)
4i (97 mg, 64%) and 5i (48 mg, 32%). 4i: [R]22 ) +160 (c 2.3,
D
CHCl3); 1H NMR δ 0.38 (d, J ) 6.5, 3H), 0.50 (d, J ) 6.5, 3H),
0.61 (m, 1H), 0.70 (s, 9H), 0.99 (m, 1H), 1.25 (m, 1H), 2.47 (q,
J ) 3.8, 1H), 2.92 (d, J ) 3.9, 1H), 3.12 (bs, 2H), 7.17-7.38
(m, 11H), 7.67 (m, 2H); 13C NMR δ 21.7, 23.4, 24.3, 26.4, 34.9,
43.9, 50.9, 72.3, 79.0, 119.9, 125.2, 125.8, 126.6, 127.1, 127.7,
128.2, 128.3, 128.4, 140.4, 140.5, 145.5, 148.1, 151.5. Anal.
to give 4g (70 mg, 35%) and 5g (126 mg, 63% yield). 4g: [R]20
D
) +235 (c 1.0, CHCl3); 1H NMR δ -0.09 (d, J ) 6.5, 3H), 0.26
(d, J ) 6.5, 3H), 0.52 (m, 1H), 0.78 (m, 1H), 1.35 (m, 1H), 2.64
(m, 1H), 3.21 (bs, 2H), 4.93 (d, J ) 5.6, 1H), 6.46 (d, J ) 7.5,
1H), 6.70 (t, J ) 7.5, 1H), 7.05-7.75 (m, 18H); 13C NMR δ 20.7,
23.4, 24.5, 44.3, 54.8, 72.5, 75.1, 119.3, 119.9, 123.4, 124.8,
125.0, 125.2, 125.3, 125.4, 125.7, 125.9 (2C), 127.0, 127.4,
127.5, 127.8, 128.0, 128.2 (3C), 128.5, 130.8, 133.9, 137.7,
140.0, 140.8, 145.0, 148.2, 150.4. Anal. Calcd for C35H33NO:
C, 86.92; H, 6.88; N, 2.90. Found: C, 86.81; H, 7.13; N, 3.17.
Calcd for C29H35NO: C, 84.22; H, 8.53; N, 3.39. Found: C,
1
84.12; H, 8.76; N, 3.27. 5i: [R]22 ) +12 (c 1.5, CH2Cl2); H
D
NMR δ 0.48 (s, 9H), 0.50 (d, J ) 6.6, 3H), 0.91 (d, J ) 6.6,
3H), 1.27 (m, 2H), 1.76 (m, 1H), 2.05 (m, 1H), 2.16 (m, 1H),
2.44 (dd, J ) 1.7, 9.8, 1H), 2.64 (d, J ) 1.2, 1H), 7.21-7.74
(m, 13H); 13C NMR δ 21.4, 24.4, 24.5, 27.0, 33.4, 39.8, 52.5,
72.6, 79.3, 119.7, 119.9, 125.6, 126.1, 127.1, 127.7, 127.8, 128.2,
5g: [R]20 ) +69 (c 1.0, CHCl3); 1H NMR δ -0.13 (d, J ) 6.3,
128.3, 139.9, 141.0, 145.6, 149.3, 150.6. Anal. Calcd for C29H35-
NO: C, 84.22; H, 8.53; N, 3.39. Found: C, 84.33; H, 8.21; N,
3.35.
D
1H), 0.38 (d, J ) 6.3, 1H), 1.02 (m, 3H), 2.81 (m, 1H), 3.74 (bs,
1H), 4.70 (bs, 1H), 6.37 (d, J ) 9.5, 1H), 6.99-7.87 (m, 19H);
13C NMR δ 21.3, 23.2, 24.3, 39.0, 54.7, 70.5, 72.8, 120.0, 120.1,
122.6, 123.1, 124.8, 125.0, 125.1, 125.5, 125.6, 126.0, 126.9,
127.4, 128.2, 128.3, 128.5, 128.7, 128.9, 129.7, 133.1, 136.5,
139.9, 141.3, 149.8. Anal. Calcd for C35H33NO: C, 86.92; H,
6.88; N, 2.90. Found: C, 86.90; H, 6.98; N, 2.95.
P r ep a r a tion of Oxa zolid in es 6/7e,f. Gen er a l P r oce-
d u r e. A solution of amino alcohol 4e,f or 5e,f (0.15 mmol),
p-TsOH (6 mg, 0.03 mmol), and aq formaldehyde (0.2 mL, 1.5
mmol) in THF (2 mL) was stirred at room temperature for 24
h. The reaction mixture was partitioned between CH2Cl2 and
saturated aqueous NaHCO3. The organic layer was washed
with water and brine, dried, filtered, and evaporated. The
residue was purified by column chromatography (EtOAc/
hexane 1/20 for 6/7e and EtOAc/hexane 1/10 for 6/7f) to give
the product as a white solid.
(1S,2S)-4-Met h yl-1-p h en yl-2-[N-(9′-p h en ylflu or en -9′-
yl)a m in o]p en ta n -1-ol (4h ) a n d (1R,2S)-4-Meth yl-1-p h en -
yl-2-[N-(9′-p h en ylflu or en -9′-yl)a m in o]p en t a n -1-ol (5h ).
Method A: A solution of 3h (250 mg, 0.58 mmol) in THF (5
mL) at -78 °C was treated with BH3‚SMe2 (1.16 mL, 1.16
mmol, 1 M in THF) and stirred for 48 h while slowly warming
to room temperature. MeOH (1 mL) was slowly added to the
reaction mixture, and after stirring for 5 min, the resulting
mixture was concentrated to dryness and the residue purified
by column chromatography (CH2Cl2/hexane 1/1) to give 4h /
5h in a ratio 1/12. Method B: To a -78 °C solution of 3h (300
mg, 0.7 mmol) in THF (7 mL) was added L-Selectride (1.4 mL,
1.4 mmol, 1 M in THF) and stirred for 16 h while slowly
warming to room temperature, and then it was quenched with
AcOH (0.1 mL, 1.76 mmol). After 3 min of stirring, the reaction
mixture was cooled to 0 °C, LiOH‚H2O (146 mg, 3.5 mmol)
and H2O2 (3 mL) were added, and the resulting mixture was
stirred for 20 min and then partitioned between EtOAc (15
mL) and 1 M H3PO4 (15 mL). The aqueous phase was extracted
(4S,5R)-5-(ter t-Bu tyl)-4-m eth yl-3-[N-(9′-p h en ylflu or en -
9′-yl)a m in o]oxa zolid in e (6e): mp 129-130 °C (EtOH); [R]20
D
1
) -423 (c 1.0, CHCl3); H NMR δ 0.67 (s, 9H), 0.91 (d, J )
6.6, 3H), 2.61 (m, 1H), 2.69 (d, J ) 5.6, 1H), 4.68 (d, J ) 5.3,
1H), 4.85 (d, J ) 5.3, 1H), 7.10-7.65 (m, 13H); 13C NMR δ
18.3, 27.0 (3C), 32.8, 56.1, 76.6, 82.3, 86.9, 119.6, 119.7, 125.6,
126.6, 126.9, 127.0, 127.2, 127.6, 127.7, 128.0, 128.2, 128.3,
128.6, 139.2, 141.3, 144.3, 148.1, 149.5. Anal. Calcd for C27H29
-
NO: C, 84.55; H, 7.62; N, 3.65. Found: C, 84.23; H, 7.67; N,
3.70.
(4S,5S)-5-(ter t-Bu tyl)-4-m eth yl-3-[N-(9′-p h en ylflu or en -
9′-yl)a m in o]oxa zolid in e (7e): mp 127-128 °C (EtOH); [R]20
D
1
) -489 (c 1.0, CHCl3); H NMR δ 0.47 (s, 9H), 0.86 (d, J )
6.1, 3H), 2.22 (m, 1H), 3.00 (d, J ) 7.5, 1H), 4.66 (d, J ) 7.2,

Enantioselective Addition of Diethylzinc to Aldehydes
J . Org. Chem., Vol. 65, No. 7, 2000 2113
1H), 4.99 (d, J ) 7.2, 1H), 7.07-7.69 (m, 13H); 13C NMR δ
22.7, 26.1 (3C), 32.4, 54.2, 76.9, 82.4, 94.0, 119.2, 119.6, 126.6,
126.9, 127.0, 127.2, 127.8, 127.9, 128.0, 128.3, 128.4, 139.1,
141.8, 145.7, 147.6, 149.0. Anal. Calcd for C27H29NO: C, 84.55;
H, 7.62; N, 3.65. Found: C, 84.32; H, 7.81; N, 3.62.
by comparison of the known optical rotation of (S)-1-phenyl-
propan-1-ol. 1-(2-Naphthyl)-1-propanol: â-DEX 120 column,
160 °C, tR R isomer 58.3 min, tR S isomer 60.6 min. 1-(1-
Naphthyl)-1-propanol: â-DEX 120 column, 160 °C, tR R isomer
52.0 min, tR S isomer 53.0 min. 1-(4-Phenylphenyl)-1-pro-
(4S,5R)-4-Meth yl-3-[N-(9′-p h en ylflu or en -9′-yl)a m in o]-
panol: â-DEX 120 column, 180 °C, tR R isomer 60.7 min, tR S
5-tr ityloxa zolid in e (6f): mp 201-202 °C (EtOH); [R]20
)
isomer 62.0 min. 1-(2-Bromophenyl)-1-propanol: â-DEX 120
column, 140 °C, tR R isomer 37.5 min, tR S isomer 40.8 min.
1-(4-Bromophenyl)-1-propanol: â-DEX 120 column, 140 °C, tR
R isomer 47.9 min, tR S isomer 49.2 min. 1-(4-Chlorophenyl)-
1-propanol: â-DEX 120 column, 140 °C, tR R isomer 32.5 min,
tR S isomer 33.8 min. 1-(4-Methoxyphenyl)-1-propanol: â-DEX
120 column, 145 °C, tR R isomer 26.2 min, tR S isomer 26.9
min. 1-(3-Methoxyphenyl)-1-propanol: â-DEX 120 column, 135
°C, tR R isomer 39.8 min, tR S isomer 40.7 min. 1-(3,4-
Methylenedioxyphenyl)-1-propanol: â-DEX 120 column, 150
°C, tR R isomer 40.6 min, tR S isomer 41.4 min. 1-(3,4-
Dimethoxyphenyl)-1-propanol: â-DEX 120 column, 140 °C, tR
R isomer 103.6 min, tR S isomer 106.5 min. 1-Cyclohexyl-1-
propanol: R-DEX 120 column, 90 °C, tR R isomer 32.4 min, tR
S isomer 33.1 min. 3-Dodecanol: R-DEX 120 column, 90 °C,
tR R isomer 36.7 min, tR S isomer 37.7 min. The absolute
configuration was established by comparison of the optical
rotation of the products with the reported values.10b
D
+207 (c 1.0, CH2Cl2); 1H NMR δ 0.23 (d, J ) 6.9, 3H), 3.16 (d,
J ) 6.9, 3H), 4.27 (d, J ) 5.7, 2H), 4.75 (d, J ) 6.6, 1H), 4.80
(d, J ) 6.6, 1H), 6.8-7.68 (m, 28H); 13C NMR δ 18.2, 29.7,
58.2, 59.4, 81.7, 83.2, 119.6, 119.7, 125.3, 125.9, 126.8, 127.0,
127.2, 127.3, 127.5, 127.7, 128.0, 128.2, 128.3, 128.9, 130.4,
139.2, 141.5, 144.1, 148.1, 149.5. Anal. Calcd for C42H35NO:
C, 88.54; H, 6.19; N, 2.46. Found: C, 88.32; H, 6.39; N, 2.31.
(4S,5S)-4-Met h yl-3-[N-(9′-p h en ylflu or en -9′-yl)a m in o]-
5-tr ityloxa zolid in e (7f): mp 201 °C (Et2O-EtOH); [R]20
)
D
+187 (c 1.0, CH2Cl2); 1H NMR δ 0.38 (d, J ) 6.0, 3H), 3.22 (m,
1H), 4.40 (d, J ) 2.5, 3H), 4.71 (d, J ) 2.5, 3H), 5.11 (d, J )
4.4, 3H), 6.77 (d, J ) 7.9, 3H), 6.93-7.37 (m, 25H), 7.52 (d, J
) 7.6, 3H), 7.62 (d, J ) 7.1, 3H); 13C NMR δ 17.9, 54.8, 61.0,
72.5, 79.1, 88.8, 119.6, 120.1, 126.0, 126.1, 126.5, 126.7, 127.0,
127.2, 127.4, 127.5, 127.6, 127.9, 128.1, 130.4, 138.7, 141.0,
143.9, 145.1, 147.6, 148.7. Anal. Calcd for C42H35NO: C, 88.54;
H, 6.19; N, 2.46. Found: C, 88.35; H, 6.39; N, 2.40.
Gen er a l P r oced u r e for th e En a n tioselective Am in o
Alcoh ol-Ca ta lyzed Ad d ition of Dieth ylzin c to Ald eh yd es.
A solution of the amino alcohol 4 or 5 (0.027 mmol) and the
aldehyde 8 or 14a -l (0.9 mmol) in anhydrous toluene (1 mL)
was cooled to the desired temperature and treated with Et2-
Zn (100 or 250 mol %, 1 M in hexane), and the mixture was
stirred under Ar and monitored by TLC. The reaction was
cooled to 0 °C, quenched by careful addition of 10% HCl, and
extracted with EtOAc (2 × 10 mL), and the combined organic
layer was washed with water and brine, dried, and evaporated.
The residue was purified by bulb to bulb distillation. Enan-
tiomeric excesses were determined by chiral GC using a
Supelco R- or â-DEX 120 column, isotherm temperature
program, and He as carrier gas (1.3 mL/min). 1-Phenylpro-
Ack n ow led gm en t . Financial support from the
CICYT (Spain, grants SAF96-0251 and SAF99-0127)
and the Xunta de Galicia (grant XUGA 20912B96) is
gratefully acknowledged as well as a fellowship from
the Xunta de Galicia (I.C.). We also thank Prof. Rafael
Suau (Universidad de Ma´laga, Spain) for the elemental
analyses and Prof. Miquel A. Perica`s (Universidad de
Barcelona, Spain) for advice.
Su p p or tin g In for m a tion Ava ila ble: ORTEP drawings
and crystal and structural data of compounds 6e and 7e. This
material is available free of charge via the Internet at
http://pubs.acs.org.
panol: â-DEX 120 column, 120 °C, tR R isomer 20.8 min, tR
S
isomer 21.2 min. The absolute configuration was determined
J O9917083