Enantiospecific Synthesis of N-9-Phenylfluoren-9-yl-α-amino Ketones

Article abstract of DOI:10.1021/jo9707646

Enantiomerically pure N-(9-phenylfluoren-9-yl)-α-amino ketones were prepared in excellent yields by acylation of organolithium reagents with N-(9-phenylfluoren-9-yl)-α-amino acid-derived oxazolidinones. The method is not applicable for the acylation of Grignard reagents as they attack the methylenic carbon of the oxazolidinone to give the corresponding N-alkylated amino acids 13 in excellent yields. The resulting N-(9-phenylfluoren-9-yl)-α-amino ketones 8 could be stereoselectively reduced to the corresponding syn- or anti-β-amino alcohols depending upon the nature of the reducing agent.

Full text of DOI:10.1021/jo9707646

6862
J . Org. Chem. 1997, 62, 6862-6869
En a n tiosp ecific Syn th esis of N-(9-P h en ylflu or en -9-yl)-r-a m in o
Keton es†
M. Rita Paleo, M. Isabel Calaza, and F. J avier Sardina*
Departamento de Quı´mica Orga´nica, Universidad de Santiago de Compostela,
15706 Santiago de Compostela, Spain
Received April 30, 1997
Enantiomerically pure N-(9-phenylfluoren-9-yl)-R-amino ketones were prepared in excellent yields
by acylation of organolithium reagents with N-(9-phenylfluoren-9-yl)-R-amino acid-derived oxazo-
lidinones. The method is not applicable for the acylation of Grignard reagents as they attack the
methylenic carbon of the oxazolidinone to give the corresponding N-alkylated amino acids 13 in
excellent yields. The resulting N-(9-phenylfluoren-9-yl)-R-amino ketones 8 could be stereoselectively
reduced to the corresponding syn- or anti-â-amino alcohols depending upon the nature of the
reducing agent.
In tr od u ction
provide R-amino aryl ketones. The Dakin-West reac-
tion10 and other reported methods that do not use amino
acids as starting materials, such as the Neber rearrange-
ment,11 the reaction of R-halo ketones with amines,12 and
the reaction of metalated R-amino nitriles with alde-
hydes,13 do not afford enantiomerically pure compounds
and/or suffer from unsatisfactory yields and lack of
regioselectivity.
We now report an alternative synthesis of enantio-
merically pure N-protected R-amino ketones 8 based on
the reaction of N-(9-phenylfluoren-9-yl)amino acid-
derived oxazolidinones 6 with organolithium reagents,14
which avoids the use of difficult-to-remove N-protecting
groups and expensive carboxyl activation schemes.
The synthesis of enantiomerically pure R-amino ke-
tones is of general interest and wide applicability in
asymmetric organic synthesis as it provides a direct route
to the preparation of a large variety of heterocyclic
systems, as well as natural and pharmacologically in-
teresting products.1 In this regard the preparation of
R-amino aryl ketones is particularly important.2 Several
different methods for the synthesis of R-amino ketones
have been reported.3 A number of them use R-amino
acids as precursors since they are generally inexpensive
compounds and readily available in many structural
types and in enantiomerically pure form. An attractive
approach for the preparation of enantiomerically pure
R-amino ketones is the reaction of suitably N-protected
(with benzenesulfonyl, ethoxycarbonyl, acetyl, or benzoyl
groups) R-amino acids with alkyllithium or Grignard
reagents,4 although the removal of the N-protecting group
usually requires harsh conditions. N-Blocked R-amino
ketones can also be prepared by acylation of organome-
tallic reagents with carboxyl-activated R-amino acid
derivatives: isoxazolidides,5 N-methyl-N-methoxyamides,6,7
thiopyridyl esters,8 and acid chlorides.4a Intra- and
intermolecular versions of the Friedel-Crafts acylation4a,9
Resu lts a n d Discu ssion
We have shown recently that treatment of certain
cyclic N-(9-phenylfluoren-9-yl)-R-amino esters, such as 1,
with organolithium reagents afforded the corresponding
enantiomerically pure R-amino ketones in high yields.15
We attribute the success of this transformation to the
unusual stability of the intermediate 2, which would stem
from the electron-withdrawing effect of the R-nitrogen
and the lithium-complexing ability of the fluorenyl ring
of the Pf group.14 If it were possible to extend such
transformation to acyclic N-Pf-R-amino esters, then a
very convenient synthesis of R-amino ketones would be
in hand. To study the feasibility of this proposal, we
studied the acylation of alkyllithium reagents with N-Pf-
R-amino esters, and even with N-Pf-R-amino acids, but
to no avail: only when the acids were treated with 300
mol % of alkyllithium were the corresponding ketones
isolated in moderate yields (<50%). All other nucleo-
phile-electrophile combinations afforded low yields, at
best, of the desired ketones. These failures were possibly
* Corresponding author. Fax: +34-81-595012. E-mail: qojskd@
usc.es.
† Dedicated to the memory of Prof. Ignacio Ribas.
X Abstract published in Advance ACS Abstracts, September 1, 1997.
(1) (a) Coppola, G.; Schuster, H. Asymmetric Synthesis: Construction
of Chiral Molecules Using Amino Acids; Wiley: New York, 1987. (b)
Reetz, M. T. Angew. Chem., Int. Ed. Engl. 1991, 30, 1531. (c) Sardina,
F. J .; Rapoport, H. Chem. Rev. 1996, 96, 1825.
(2) (a) Musso, D. L.; Mehta, N. B.; Soroko, F. E. Bioorg. Med. Chem.
Lett. 1997, 7, 1. (b) Bartroli, J .; Turmo, E.; Belloc, J .; Forn, J . J . Org.
Chem. 1995, 60, 3000. (c) Wolf, J .-P.; Pfander, H. Helv. Chim. Acta
1986, 69, 918.
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22, 399. (b) Pace, R. D.; Kabalka, G. W. J . Org. Chem. 1995, 60, 4838.
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Rapoport, H. J . Org. Chem. 1989, 54, 1866. (f) Klix, R. C.; Chamberlin,
S. A.; Bhatia, A. V.; Davis, D. A.; Hayes, T. K.; Rojas, F. G.; Koops, R.
W. Tetrahedron Lett. 1995, 36, 1791.
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1990, 55, 3511.
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Holdgru¨n, X. Tetrahedron: Asymmetry 1990, 1, 375. (b) Hamby, J . M.;
Hodges, J . C. Heterocycles 1993, 35, 843.
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2533.
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Chem. 1981, 46, 2431.
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981.
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1288.
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(14) Paleo, M. R.; Sardina, F. J . Tetrahedron Lett. 1996, 37, 3403.
(15) (a) Ferna´ndez-Meg´ıa, E.; Iglesias-Pintos, J . M.; Sardina, F. J .
J . Org. Chem. 1997, 62, 4770. (b) Blanco, M.-J .; Sardina, F. J . J . Org.
Chem. 1996, 61, 4748.
S0022-3263(97)00764-0 CCC: $14.00 © 1997 American Chemical Society

N-(9-Phenylfluoren-9-yl)-R-amino Ketones
J . Org. Chem., Vol. 62, No. 20, 1997 6863
Ta ble 1
Sch em e 1
entry
R
R
compound yield (%)
due to the acidic hydrogen of the NH group, which could
be transferred to the alkoxide intermediate, leading to
its collapse and the subsequent formation of tertiary
alcohols, the major reaction products observed. Thus we
turned our attention toward other aminoacylating elec-
trophiles that would lack the offending NH group.
Oxazolidinones 6 were an obvious alternative: N,N-
diprotected R-amino esters which were obtained in excel-
lent yields by treatment of the corresponding N-Pf- amino
acid 5 with aqueous formaldehyde in the presence of
p-TsOH.16
To our delight, when alanine-derived oxazolidinone 6a
was treated with MeLi (150 mol %, THF, -78 °C), methyl
ketone 8a was isolated in 92% yield after purification
Sch em e 2
1
(Table 1). Detailed analysis of the H NMR spectrum of
the crude reaction mixture showed no traces of the
corresponding tertiary alcohol. Remarkably, the addition
of MeLi to 6a to provide ketone 8a could be carried out
successfully even at 0 °C (72% yield, no tertiary alcohol
detected in the crude reaction mixture), attesting to the
robustness of the addition intermediate 7.
The question of whether the reaction had occurred
without racemization was addressed by transforming 8a
into the tertiary alcohol 9 (MeLi, -78 °C, 62% yield)
followed by reaction with (R)- and (S)-phenylethyl iso-
cyanate (Scheme 2). 1H NMR analysis of the crude
diastereomeric carbamates 10a ,b and of mixtures of them
of known composition showed that their ratios of dia-
stereomers (dr) were >99/1; thus the ratios of enanti-
omers (er) of 9 and 8a must be >99/1.
As can be seen from Table 1, other alkyllithium,
aryllithium, and vinyllithium reagents were successfully
added to oxazolidinone 6a to provide the corresponding
ketones in excellent yields (entries 2-6).
The stability of the intermediate 7, the key factor that
determines the output of these nucleophilic additions, is
partly due to the Pf group, since the reaction of the Cbz-
protected analogue of oxazolidinone 6a with MeLi gave
a complex mixture of products, none of them being the
expected amino ketone. The beneficial effect of the Pf
group probably stems from its ability to act as a Li+
ligand in intermediate 7, through a cation-π interac-
tion.17 In fact, semiempirical calculations on 7 (R ) R′
) Me, monomeric species, Li+ coordinated to two mol-
ecules of dimethyl ether, PM3) showed that its most
stable conformation places the Li+ snugly within the
fluorenyl π cloud.18
To test the scope of this R-amino ketone preparation,
we studied the reaction of lithium reagents with oxazo-
lidinones derived from leucine, phenylglycine, phenyl-
alanine, cyclohexylalanine, and serine19 (6b-f). Starting
from leucine oxazolidinone 6b, the corresponding methyl
(17) (a) Kumpf, R. A.; Dougherty, D. A. Science 1993, 261, 1708. (b)
Posner, G. H.; Lentz, C. M. J . Am. Chem. Soc. 1979, 101, 934.
(18) The intramolecular acylation of N-Pf-o-lithiophenylalanine-
derived oxazolidinones to give (N-Pf-amino)indanones has been re-
ported.16 In this case extremely low temperatures (-90 °C) and strict
stoichiometric control had to be employed to avoid overaddition of the
organolithium reagent (used to generate the o-lithiophenylalanine) to
the carboxyl group. MNDO calculations on these systems showed that
the Li+ in the corresponding intermediates cannot bind to the fluorenyl
ring of the Pf group.
(16) Paleo, M. R.; Castedo, L.; Dom´ınguez, D. J . Org. Chem. 1993,
58, 2763.
(19) Lubell, W.; Rapoport, H. J . Org. Chem. 1989, 54, 3824.

6864 J . Org. Chem., Vol. 62, No. 20, 1997
Paleo et al.
Ta ble 2
Sch em e 3
entry
R
compound yield (%)
R
and phenyl ketones 8g,h were obtained in excellent yields
(91% and 96%, respectively) using the same reaction
conditions as for alanine. Next we investigated the
reaction with R-ethoxyvinyllithium,20 a readily prepared
acyl anion equivalent of considerable synthetic value.
When 6b was treated with this lithium reagent at -78
°C and then stirred at 0 °C for 4 h, the amino ketone 8i
was isolated in 85% yield.
The acylation of serine-derived oxazolidinone 6f was
particularly interesting, since the resulting ketones are
precursors of chloramphenicol and its analogues23 and
of dopamine agonists.24 6f was prepared by benzylation
of N-Pf-serine19 (BnBr, NaH, DMF) followed by reaction
of the resulting acid with aq formaldehyde and p-TsOH.
Treatment of a THF solution of 6f with PhLi at -78 °C
for 2 h afforded the amino ketone 8o in 87% yield.
The reaction of the oxazolidinones 6 with Grignard
reagents was also studied, since they are often more
convenient to prepare than the equivalent lithium re-
agents. Addition of MeMgBr or PhMgBr to a cold
solution (-78 °C) of the corresponding oxazolidinone in
THF proceeded smoothly to give new products which
were isolated in very good yield and unambiguously
identified as the amino acids 13 (Table 2). Surprisingly,
no amino ketones 8 were detected in the crude reaction
mixture. This behavior resembles the Lewis acid-
promoted ring opening of chiral oxazolidines.25 This
reaction is quite general, as can be seen from Table 2.
The same mode of addition was obtained when a solution
of oxazolidinone was treated with reducing agents such
as DIBALH or LiBH4 (entry 5).
A natural corollary to any new method of preparation
of N-protected R-amino ketones is to study the stereose-
lectivity of their reductions to â-amino alcohols26 (Scheme
4). To study this transformation we chose the amino
ketones 8d , since they should provide the ephedrine-type
systems, and 8f, a chiral ferrocene derivative which could
be seen as a precursor of chiral ferrocenyl catalysts.27
After extensive optimization of the reaction conditions
(reducing agent, solvent, and temperature), we found that
both 8d ,f could be stereodivergently reduced to give
either 14d ,f or 15d ,f.
The addition of organolithium compounds to D-phen-
ylglycine oxazolidinone provided a more stringent test
of our methodology, due to the highly sensitive nature of
the resulting benzyl ketones to acidic or basic conditions.
Unfortunately, attempted acylations of MeLi and n-BuLi
with 6c gave complex mixtures of products, among which
was 9-phenylfluorene (PfH). The presence of this com-
pound indicated that the hydrogen of the chiral center
was being abstracted by these highly basic nucleophiles.21
In stark contrast, the reaction of 6c with the less basic
PhLi (THF, -40 °C) afforded ketone 8j in 85% yield.
When phenylalanine-derived oxazolidinone 6d was
treated with PhLi at -40 °C for 4 h, the corresponding
ketone 8k was isolated in 91% yield, but when 6d was
treated with R-ethoxyvinyllithium at 0 °C for 4 h, the
amino ketone 8l was isolated only in a modest 58% yield.
In the crude product from this reaction, a very unstable
byproduct was detected and tentatively identified as 12.
A plausible mechanism for its formation is shown in
Scheme 3. Molecular mechanics (MM3) calculations
showed that in the lowest energy conformation of 6d the
carbonyl oxygen lies very close to one of the benzylic
hydrogens, which has an antiperiplanar relationship with
the N-Pf group. Complexation of the organolithium
nucleophile to the carbonyl oxygen prior to addition
should place the basic reagent very close to the afore-
mentioned hydrogen and lead to elimination to give
amide 11.22 Ring reclosure in 11 would lead to the
observed compound. 12 was also detected when 6d was
treated with LDA (150 mol %) at -40 °C, which argues
in favor of the base-promoted elimination mechanism
shown above.
Our MM calculations suggested that bulky nucleo-
philes should be less prone to give this side reaction.
Thus, while MeLi failed to give any of the corresponding
methyl ketone, when we used a more basic but also
bulkier reagent such as t-BuLi, at -20 °C for 1.5 h, the
corresponding amino ketone 8m was isolated in 57%
yield.
The configurational assignment of 14d and 15d was
carried out as follows: treatment of the â-amino alcohols
14d and 15d with aqueous formaldehyde and catalytic
p-TsOH in THF afforded the oxazolidines 16 and 17 in
92% and 96% yield, respectively. 16 showed a strong
Cyclohexylalanine oxazolidinone 6e afforded the cor-
responding ketone 8n in 85% yield when treated with
R-ethoxyvinyllithium in THF at 0 °C, showing that the
problems encountered with phenylalanine-derived ox-
azolidinone 6d were not due to steric hindrance.
(23) Hill, R. K.; Nugara, P. N.; Holt, E. M.; Holland, K. P. J . Org.
Chem. 1992, 57, 1045 and references therein.
(24) DeWald, H. A.; Heffner, T. G.; J aen, J . C.; Lustgarten, D. M.;
McPhail, A. T.; Meltzer, L. T.; Pugsley, T. A.; Wise, L. D. J . Med. Chem.
1990, 33, 445.
(25) (a) Burgess, L. E.; Meyers, A. I. J . Am. Chem. Soc. 1991, 113,
9858. (b) Andre´s, C.; Maestro, A.; Pedrosa, R.; Pe´rez-Encabo, A.;
Vicente, M. Synlett 1992, 45.
(26) (a) Tramontini, M. Synthesis 1982, 605. (b) Fujita, M.; Hiyama,
T. J . Org. Chem. 1988, 53, 5405. (c) Fujita, M.; Hiyama, T. J . Org.
Chem. 1988, 53, 5415 and references therein.
(20) (a) Oakes, F. T.; Sebastian, J . F. J . Org. Chem. 1980, 45, 4959.
(b) Angelastro, M. R.; Peet, N. P.; Bey, P. J . Org. Chem. 1989, 54, 3913.
(21) The removal of the R-carbon proton assures elimination of the
stabilized aromatic 9-phenylfluorenyl anion: Lubell, W. D.; Rapoport,
H. J . Am. Chem. Soc. 1987, 109, 236.
(27) (a) Togni, A. Angew. Chem., Int. Ed. Engl. 1996, 35, 1475. (b)
Sammakia, T.; Latham, H. A. J . Org. Chem. 1996, 61, 1629.
(22) Beak, P.; Meyers, A. I. Acc. Chem. Res. 1986, 19, 356.

N-(9-Phenylfluoren-9-yl)-R-amino Ketones
J . Org. Chem., Vol. 62, No. 20, 1997 6865
g, 120 mmol) was added, and the resulting solution was stirred
at rt for 24 h. Toluene (100 mL) was added, and the layers
were separated; the aqueous layer was acidified to pH 2 with
10% H3PO4 and extracted with EtOAc (3 × 80 mL). The
combined organic layer was washed with water (50 mL) and
brine (50 mL), dried, and concentrated. The residue was
purified by column chromatography (CH2Cl2-MeOH, 5%) or
crystallized from the appropriate solvent to give the product
as white crystals.
Sch em e 4
N-(9-P h en ylflu or en -9-yl)-L-leu cin e (5b): 4.23 g, 95%
yield; mp 165-167 °C (EtOAc-hexane); [R]20 -36 (c 1.0,
D
CHCl3); IR 1715 cm-1; H NMR δ 0.52 (d, J ) 6.5, 3H), 0.75
1
(d, J ) 6.5, 3H), 1.35 (m, 2H), 1.71 (m, 1H), 2.60 (dd, J ) 5.8,
7.9, 1H), 6.16 (bs, 1H), 7.14-7.44 (m, 11H), 7.69 (t, J ) 7.5,
2H); 13C NMR δ 21.8, 22.6, 24.3, 43.8, 54.2, 72.8, 120.0, 120.1,
125.0, 126.0, 126.2, 127.5, 127.8, 128.1, 128.5, 128.8, 128.9,
140.7, 140.8, 143.7, 147.4, 148.7, 178.6. Anal. Calcd for
C25H25NO2: C, 80.83; H, 6.78; N, 3.77. Found: C, 80.52; H,
6.92; N, 3.70.
N-(9-P h en ylflu or en -9-yl)-L-p h en ylglycin e (5c): 4.13 g,
88% yield; mp 150-153 °C (EtOH); [R]20D -131 (c 1.0, CH2Cl2);
IR 1735 cm-1 1H NMR δ 3.64 (s, 1H), 6.85-7.37 (m, 16H),
;
7.74 (t, J ) 6.4, 2H); 13C NMR δ 60.4, 73.0, 119.8, 119.9, 125.6,
125.7, 126.1, 127.3, 127.5, 127.7, 127.9, 128.2, 128.3, 128.4,
128.8, 139.2, 140.2, 141.0, 143.6, 147.6, 148.0, 176.7. Anal.
Calcd for C27H21NO2: C, 82.89; H, 5.42; N, 3.58. Found: C,
83.04; H, 5.68; N, 3.72.
NOE between H4 and H5, while 17b did not show an
NOE between H4 and H5; this allowed us to assign the
configurations shown for 14d and 15d . The stereochem-
istry of ferrocenyl alcohols 14d (J 1,2 ) 3.3 Hz) and 15d
N-(9-P h en ylflu or en -9-yl)-L-p h en yla la n in e (5d ): 4.71 g,
97% yield; mp 185 °C (EtOH); [R]20 +128 (c 1.1, CH2Cl2); IR
D
1702 cm-1
;
1H NMR δ 2.65-2.80 (m, 3H), 6.63 (d, J ) 7.5,
1H), 6.97-7.31 (m, 15H), 7.63 (d, J ) 7.5, 2H); 13C NMR δ
39.7, 57.1, 72.7, 119.8, 120.1, 124.6, 125.9, 126.0, 127.0, 127.4,
127.8, 128.0, 128.4, 128.5, 128.6, 128.8, 129.6, 136.4, 140.5,
140.6, 143.6, 147.2, 148.2, 177.9. Anal. Calcd for C28H23NO2:
C, 83.03; H, 5.73; N, 3.46. Found: C, 82.83; H, 5.82; N, 3.39.
1
(J 1,2 ) 7.0 Hz) was established by H NMR analysis and
comparison of coupling constants J 1,2 with those shown
by the closely related phenyl alcohols 14d (J 1,2 ) 3.1 Hz)
and 15d (J 1,2 ) 8.3 Hz).
In conclusion, we report a useful method for the
enantiospecific synthesis of R-amino ketones based on the
acylation of organolithium reagents by N-(9-phenylfluo-
ren-9-yl)amino acid-derived oxazolidinones. The reaction
proceeds with no detectable racemization. The method
is not applicable for the acylation of Grignard reagents
as they attack the methylenic carbon of the oxazolidinone
to give the corresponding N-alkylated amino acids 13 in
excellent yields. The resulting N-(9-phenylfluoren-9-yl)-
R-amino ketones 8 can be stereoselectively reduced to the
corresponding syn- or anti-â-amino alcohols depending
upon the nature of the reducing agent.
N-(9-P h en ylflu or en -9-yl)-L-cycloh exyla la n in e (5e): 4.1
g, 82% yield; mp 156-161 °C (EtOH); [R]20 +138 (c 1.3,
D
CH2Cl2); IR 1714 cm-1
;
1H NMR δ 0.52-0.7 (m, 1H), 0.74-
0.98 (m, 1H), 1.02-1.63 (m, 11H), 2.61 (m, 1H), 7.12-7.42 (m,
11H), 7.67 (t, J ) 7.9, 2H); 13C NMR δ 26.0, 26.2, 26.3, 32.3,
33.4, 33.5, 42.3, 53.4, 72.8, 120.1, 120.2, 124.8, 126.0, 126.2,
127.5, 127.8, 128.1, 128.5, 128.7, 128.9, 140.7, 140.8, 143.7,
147.3, 148.8, 178.7. Anal. Calcd for C28H29NO2: C, 81.72; H,
7.10; N, 3.40. Found: C, 81.67; H, 7.29; N, 3.43.
P r ep a r a tion of Oxa zolid in on es 6. Gen er a l P r oced u r e.
N-Pf-amino acid 5 (5.0 mmol), formaldehyde (26 wt % solution
in water, 100 mmol), and p-TsOH‚H2O (95 mg, 0.5 mmol) were
dissolved in THF (50 mL) and stirred at rt, under Ar, for 24
h. The reaction mixture was then partitioned between satd
NaHCO3 and CH2Cl2 (2 × 75 mL), and the combined organic
layer was washed with water (50 mL) and brine (50 mL), dried,
and then concentrated to give a white solid in quantitative
yield. The products were not stable under chromatographic
conditions, and the residues were recrystallized from the
appropriate solvents to give 6 as white crystals.
Exp er im en ta l Section
Gen er a l.15b N-Pf-L-alanine,21 N-Pf-L-aspartic acid â-methyl
ester,28 and N-Pf-L-serine19 were prepared as described in the
literature. J values are reported in hertz (Hz).
P r ep a r a tion of N-(9-P h en ylflu or en -9-yl)-L-a m in o Ac-
id s 5. Gen er a l P r oced u r e. Thionyl chloride (2.4 mL, 33.0
mmol) was added dropwise to a suspension of commercial
L-amino acid (25.0 mmol) in dry MeOH (25 mL) at 0 °C. The
bath was removed and the resulting solution allowed to stir
at rt for 20 h; then it was concentrated to an oily residue which
was triturated with ether, and the resulting white crystalline
solid was filtered, washed with cold ether, and dried to give 4
in 95-97% yield. To a stirred suspension of 4 (12 mmol) in
CH3CN (20 mL) were added sequentially anhydrous Pb(NO3)2
(3.18 g, 9.6 mmol), K3PO4 (5.35 g, 25.2 mmol), and a solution
of PfBr (4.81 g, 15 mmol) in CH3CN (10 mL). Additional PfBr
(320 mg, 1 mmol) in CH3CN (1 mL) was added after 24 h. After
being stirred for a total of 48 h, the reaction mixture was
filtered through a pad of Celite, and the residue was thor-
oughly washed with CH2Cl2 and MeOH. The combined filtrate
and washings were concentrated, and the residue was dis-
solved in a (1:1) dioxane:H2O mixture (200 mL); LiOH‚H2O (5
(4S)-4-Meth yl-3-N-(9′-p h en ylflu or en -9′-yl)oxa zolid in -5-
on e (6a ): recrystallization from CH2Cl2-hexane gave 1.6 g,
94% yield; mp 179-180 °C; [R]20 -92 (c 1.0, CHCl3); IR 1780
D
cm-1; H NMR δ 1.25 (d, J ) 7.3, 3H), 3.12 (q, J ) 7.3, 1H),
1
5.11 (d, J ) 7.5, 1H), 5.23 (d, J ) 7.5, 1H), 7.23-7.46 (m, 11H),
7.69 (m, 2H); 13C NMR δ 16.4, 54.7, 77.1, 82.8, 120.3, 125.5,
125.8, 127.0, 127.9, 128.2, 128.4, 128.8, 129.1, 129.4, 140.0,
141.1, 142.5, 145.9, 147.1, 177.6. Anal. Calcd for C23H19NO2:
C, 80.92; H, 5.61; N, 4.10. Found: C, 80.78; H, 6.00; N, 4.23.
(4S)-4-Isobu tyl-3-N-(9′-p h en ylflu or en -9′-yl)oxa zolid in -
5-on e (6b): recrystallization from EtOAc-hexane gave 1.84
g, 96% yield; mp 179-181 °C; [R]20 -260 (c 1.0, CHCl3); IR
D
1780 cm-1; H NMR δ 0.43 (d, J ) 6.5, 3H), 0.72 (d, J ) 6.5,
1
3H), 1.28-1.55 (m, 2H), 1.72 (m, 1H), 2.84 (dd, J ) 6.5, 8.2,
1H), 5.31 (d, J ) 7.9, 1H), 5.38 (d, J ) 7.9, 1H), 7.18-7.74 (m,
13H); 13C NMR δ 21.8, 22.4, 24.1, 39.3, 56.7, 77.3, 83.6, 120.0,
120.3, 125.9, 126.2, 127.0, 127.9, 128.2, 128.4, 128.8, 128.9,
129.6, 139.7, 141.5, 142.5, 144.9, 147.4, 177.4. Anal. Calcd
for C26H25NO2: C, 81.43; H, 6.57; N, 3.65. Found: C, 81.31;
H, 6.53; N, 3.59.
(28) Gmeiner, P.; Feldman, P. L.; Chu-Moyer, M. Y.; Rapoport, H.
J . Org. Chem. 1990, 55, 3068.

6866 J . Org. Chem., Vol. 62, No. 20, 1997
Paleo et al.
(4R)-4-P h en yl-3-N-(9′-p h en ylflu or en -9′-yl)oxa zolid in -
5-on e (6c): recrystallization from CH2Cl2-hexane gave 1.6
Calcd for C23H21NO: C, 84.37; H, 6.46; N, 4.28. Found: C,
84.31; H, 6.87; N, 4.40.
g, 80% yield; mp 160-162 °C; [R]20 -9.2 (c 1.0, CHCl3); IR
(2S)-2-[N-(9′-P h en ylflu or en -9′-yl)a m in o]h ep ta n -3-on e
D
1770 cm-1; 1H NMR δ 4.16 (s, 1H), 5.32 (d, J ) 7.7, 1H), 5.36
(d, J ) 7.7, 1H), 7.12-7.57 (m, 16H), 7.68 (d, J ) 7.5, 1H),
7.77 (d, J ) 7.5, 1H); 13C NMR δ 61.3, 77.4, 83.5, 120.1, 120.4,
125.5, 126.0, 126.5, 126.9, 128.0, 128.3, 128.5, 128.7, 128.9,
129.1, 129.6, 134.7, 139.7, 141.3, 142.2, 145.4, 146.9, 175.0.
Anal. Calcd for C28H21NO2: C, 83.35; H, 5.25; N, 3.47.
Found: C, 82.91; H, 5.20; N, 3.41.
(8b): 117 mg, 90% yield; mp 56-58 °C (lit.29 56-57 °C); [R]20
D
-200 (c 1.2, CHCl3); IR (CH2Cl2) 1710 cm-1; H NMR δ 0.78
1
(t, J ) 7.0, 3H), 1.00 (d, J ) 7.1, 3H), 1.13 (m, 4H), 1.53 (m,
1H), 2.06 (m, 1H), 2.70 (q, J ) 7.1, 1H), 7.13-7.48 (m, 11H),
7.70 (m, 2H); 13C NMR δ 13.6, 20.8, 22.0, 25.3, 39.4, 56.8, 73.1,
119.6, 119.8, 125.4, 126.1, 126.3, 127.1, 127.7, 127.9, 128.1,
128.2, 140.1, 141.0, 144.8, 149.8, 150.1, 214.2.
(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-on e (8c): 122 mg, 94%; mp 170-172 °C (CH2Cl2-
(4S)-4-Ben zyl-3-N-(9′-p h en ylflu or en -9′-yl)oxa zolid in -5-
on e (6d ): recrystallization from CH2Cl2-hexane gave 1.98 g,
hexane); [R]20 -227 (c 1.3, CHCl3); IR 1695 cm-1; 1H NMR δ
95% yield; mp 167-169 °C; [R]20 -205 (c 1.02, CHCl3); IR
D
D
1775 cm-1; 1H NMR δ 2.67 (dd, J ) 5.3, 13.4, 1H), 2.87 (dd, J
) 5.8, 13.4, 1H), 3.07 (t, J ) 5.5, 1H), 4.54 (d, J ) 7.5, 1H),
5.17 (d, J ) 7.5, 1H), 6.99-7.44 (m, 16H), 7.59 (d, J ) 7.5,
1H), 7.68 (d, J ) 7.5, 1H); 13C NMR δ 37.1, 60.1, 77.3, 84.1,
119.9, 120.2, 125.3, 125.7, 126.8, 126.9, 127.8, 128.1, 128.4,
128.5, 128.6, 128.8, 129.5, 129.8, 136.6, 139.3, 141.5, 142.6,
145.0, 147.0, 176.7. Anal. Calcd for C29H23NO2: C, 83.52; H,
5.57; N, 3.36. Found: C, 83.28; H, 5.54; N, 3.35.
0.63 (s, 9H), 1.01 (d, J ) 6.9, 3H), 3.10 (q, J ) 6.9, 1H), 3.58
(bs, 1H), 7.06-7.41 (m, 11H), 7.66 (d, J ) 7.3, 2H); 13C NMR
δ 22.7, 26.7, 42.8, 52.2, 73.0, 119.6, 119.8, 125.3, 126.1, 126.5,
127.0, 127.9, 128.0, 128.2, 139.9, 141.2, 145.3, 149.8, 150.2,
219.8. Anal. Calcd for C26H27NO‚1/2H2O: C, 82.50; H, 7.46;
N, 3.70. Found: C, 82.80; H, 7.15; N, 3.68.
(2S)-1-P h en yl-2-[N-(9′-p h en ylflu or en -9′-yl)a m in o]p r o-
p a n -1-on e (8d ). To a -78 °C solution of PhBr (72 µL, 0.7
mmol) in THF (0.5 mL) was added n-BuLi (2.5 M, 240 µL, 0.6
mmol); the reaction mixture was stirred for 30 min and then
transferred via cannula to a solution of 6a (0.35 mmol) in THF
(3 mL) at -78 °C. After 2 h at -78 °C, quenching and workup
were performed as above. Column chromatography (CH2Cl2-
hexane, 1:1) afforded 128 mg, 94% yield; mp 134-136 °C
(4S)-4-(Cycloh exylm et h yl)-3-N-(9′-p h en ylflu or en -9′-
yl)oxa zolid in -5-on e (6e): recrystallization from CH2Cl2-
hexane gave 1.9 g, 90% yield; mp 180-182 °C; [R]20 -232 (c
D
1.1, CH2Cl2); IR 1777 cm-1
;
1H NMR δ 0.55-1.67 (m, 13H),
2.92 (dd, J ) 5.6, 9.0, 1H), 5.34 (d, J ) 7.9, 1H), 5.42 (d, J )
7.9, 1H), 7.23-7.50 (m, 11H), 7.67 (d, J ) 7.5, 1H), 7.75 (d, J
) 7.9, 1H); 13C NMR δ 26.0, 26.1, 26.2, 32.2, 33.2, 33.3, 37.6,
56.0, 76.5, 77.0, 77.2, 77.5, 83.5, 119.9, 120.3, 125.8, 126.3,
127.0, 127.9, 128.2, 128.3, 128.7, 128.8, 129.5, 139.5, 141.5,
142.5, 144.8, 147.4, 177.6. Anal. Calcd for C29H29NO2: C,
82.24; H, 6.90; N, 3.30. Found: C, 81.95; H, 6.79; N, 3.24.
(Et2O-MeOH); [R]20 -288 (c 1.05, CHCl3); IR 1680 cm-1; 1H
D
NMR δ 0.99 (d, J ) 7.0, 3H), 3.55 (q, J ) 7.0, 1H), 3.61 (bs,
1H), 6.90-7.44 (m, 16H), 7.59 (d, J ) 7.4, 2H); 13C NMR δ
22.2, 52.4, 73.2, 119.5, 119.8, 125.5, 126.2, 126.5, 127.1, 127.7,
127.8, 128.0, 128.1, 128.3, 132.7, 135.2, 140.1, 140.8, 144.6,
149.5, 150.1, 205.2. Anal. Calcd for C28H23NO: C, 86.34; H,
5.95; N, 3.60. Found: C, 85.98; H, 5.94; N, 3.65.
(4S)-4-[(Ben zyloxy)m et h yl]-3-N-(9′-p h en ylflu or en -9′-
yl)oxa zolid in -5-on e (6f): recrystallization from Et2O-
(4S)-4-[N-(9′-P h en ylflu or en -9′-yl)a m in o]-1-(tr im eth yl-
sila n yl)p en t -1-en -3-on e (8e). A solution of (2-bromovin-
yl)trimethylsilane30 (90 µL, 0.58 mmol) in Et2O (1 mL) at -78
°C was treated with t-BuLi (0.5 mL, 0.75 mmol, 1.5 M in
pentane) and then warmed to -20 °C for 2 h. The reaction
mixture was cooled to -78 °C, treated with a solution of 6a
(100 mg, 0.29 mmol) in THF (4 mL), and slowly warmed to 10
°C over a period of 4 h. HCO2Et (60 µL, 0.75 mmol) was added
followed by AcOH (430 µL, 7.5 mmol) after 3 min; the resulting
mixture was stirred for 10 h. Workup as above followed by
column chromatography (CH2Cl2-hexane, 1:1, to CH2Cl2)
afforded 8e as a white foam in 92% yield (110 mg): [R]20D -190
CH2Cl2-hexane gave 2.06 g, 92% yield; mp 139-141 °C; [R]20
D
-120 (c 1.0, CHCl3); IR 1780 cm-1; 1H NMR δ 2.97 (t, J ) 2.7,
1H), 3.47 (dd, J ) 2.8, 9.5, 1H), 3.68 (dd, J ) 2.7, 9.4, 1H),
4.48 (d, J ) 12.3, 1H), 4.60 (d, J ) 12.3, 1H), 5.28 (d, J ) 6.7,
1H), 5.41 (d, J ) 6.7, 1H), 7.14-7.49 (m, 16H), 7.64 (d, J )
7.5, 1H), 7.71 (d, J ) 7.5, 1H); 13C NMR δ 59.7, 71.5, 73.3,
77.4, 85.5, 120.2, 120.3, 125.4, 125.7, 127.0, 127.6, 127.7, 127.9,
128.2, 128.4, 128.6, 128.8, 128.9, 129.5, 137.9, 139.6, 141.3,
142.5, 145.3, 147.3, 175.9. Anal. Calcd for C30H25NO3: C,
80.51; H, 5.63; N, 3.13. Found: C, 80.11; H, 5.67; N, 3.06.
(4S)-[5-Oxo-3-N-(9′-p h en ylflu or en -9′-yl)oxa zolid in -4-
yl]a cetic a cid m eth yl ester (6g): recrystallization from
1
(c 1.2, CHCl3); IR 1685 cm-1; H NMR δ 0.06 (s, 9H), 1.02 (d,
CH2Cl2-hexane gave 1.84 g, 92% yield; mp 169-171 °C; [R]20
D
J ) 7.0, 3H), 3.14 (q, J ) 7.0, 1H), 3.45 (bs, 1H), 6.10 (d, J )
19.1, 1H), 6.53 (d, J ) 19.1, 1H), 7.07-7.48 (m, 11H), 7.64 (d,
J ) 7.5, 1H), 7.70 (d, J ) 7.5, 1H); 13C NMR δ 1.4, 21.1, 53.6,
73.1, 119.5, 119.7, 124.8, 125.4, 126.2, 126.7, 127.1, 127.7,
128.0, 128.1, 128.3, 139.3, 140.2, 140.9, 144.6, 146.6, 149.6,
150.1, 204.0. Anal. Calcd for C27H29NOSi: C, 78.79; H, 7.10;
N, 3.40. Found: C, 78.63; H, 7.29; N, 3.52.
-258 (c 1.0, CHCl3); IR 1730, 1785 cm-1; 1H NMR δ 2.28 (dd,
J ) 5.0, 16.6, 1H), 2.63 (dd, J ) 4.0, 16.6, 1H), 3.06 (t, J )
4.5, 1H), 3.72 (s, 3H), 5.37 (s, 2H), 7.21-7.50 (m, 11H), 7.66
(d, J ) 7.5, 1H), 7.74 (d, J ) 7.5, 1H); 13C NMR δ 37.2, 52.0,
55.1, 77.5, 84.4, 120.3, 120.4, 125.5, 125.6, 126.9, 128.1, 128.2,
128.8, 129.0, 129.1, 129.7, 139.3, 141.8, 142.3, 144.8, 147.2,
171.0, 176.1. Anal. Calcd for C25H21NO4: C, 75.17; H, 5.30;
N, 3.51. Found: C, 75.02; H, 5.41; N, 3.43.
(2S )-1-F e r r o c e n y l-2-[N -(9′-p h e n y lflu o r e n -9′-y l)-
a m in o]p r op a n -1-on e (8f). A solution of (tri-n-butylstannyl-
)ferrocene31 (560 mg, 1.18 mmol) in THF (10 mL) at -78 °C
was treated with n-BuLi (2.5 M in hexane, 470 µL, 1.18 mmol)
and then stirred at -78 °C for 30 min as a precipitate of
monolithioferrocene appeared. A solution of 6a (350 mg, 1.0
mmol) in THF (12 mL) was then added via cannula, and the
reaction mixture was stirred for 1.5 h; then HCO2Et (95 µL,
1.18 mmol) and AcOH (300 µL, 5.2 mmol) were added, the
cooling bath was removed, and the mixture was allowed to
reach rt. EtOAc (30 mL) was added, and the organic layer
was washed with satd NaHCO3, water, and brine, dried, and
concentrated. Short column chromatography (CH2Cl2-hex-
ane, 1:1, to CH2Cl2) afforded the product as a brick-red solid
P r ep a r a t ion of N-(9-P h en ylflu or en -9-yl)a m in o Ke-
ton es 8. Gen er a l P r oced u r e. A solution of 6 (0.35 mmol)
in THF (4 mL) was cooled to -78 °C and treated with R′Li
(0.525 mmol). After the mixture stirred at -78 °C for 2 h,
the reaction was quenched by addition of HCO2Et (0.525
mmol), the resulting mixture was stirred for 2-3 min, and
then AcOH (5.25 mmol) was added. The cooling bath was
removed, the reaction mixture was further stirred for 12 h and
then partitioned between satd NaHCO3 and EtOAc (25 mL),
and the organic layer was washed with water (10 mL) and
brine (10 mL), dried, and concentrated. The residue was
purified by column chromatography (CH2Cl2-hexane, 1:1) to
give the product as a white solid.
in 84% yield (428 mg): mp 169-172 °C (EtOH); [R]20 -155
D
(c 1.0, CH2Cl2); IR 1660 cm-1; 1H NMR δ 1.16 (d, J ) 6.9, 3H),
3.16 (q, J ) 6.9, 1H), 3.72 (bs, 1H), 3.91 (s, 5H), 4.33 (m, 3H),
4.42 (s, 1H), 7.19-7.44 (m, 11H), 7.62 (d, J ) 7.1, 1H), 7.70
(3S)-3-[N-(9′-P h en ylflu or en -9′-yl)a m in o]b u t a n -2-on e
(8a ): 105 mg, 92% yield; mp 117-118 °C (CH2Cl2-hexane);
[R]20 -200 (c 1.0, CHCl3); IR 1710 cm-1; 1H NMR δ 0.98 (d, J
D
) 7.1, 3H), 1.62 (s, 3H), 2.70 (q, J ) 7.1, 1H), 3.40 (bs, 1H),
7.10-7.43 (m, 11H), 7.67 (bd, J ) 7.2, 2H); 13C NMR δ 20.5,
26.7, 57.6, 73.2, 119.7, 119.9, 125.4, 126.2, 126.3, 127.2, 127.8,
128.0, 128.3, 140.2, 141.0, 144.7, 149.8, 150.2, 212.0. Anal.
(29) Lubell, W. D.; Rapoport, H. J . Am. Chem. Soc. 1988, 110, 7447.
(30) Boeckman, R. K., J r.; Bruza, K. J . Tetrahedron Lett. 1974, 3365.
(31) Guillaneux, D.; Kagan, H. B. J . Org. Chem. 1995, 60, 2502.

N-(9-Phenylfluoren-9-yl)-R-amino Ketones
J . Org. Chem., Vol. 62, No. 20, 1997 6867
(d, J ) 7.3, 1H); 13C NMR δ 24.0, 54.6, 68.9, 69.6, 69.9, 71.5,
71.6, 72.8, 77.2, 119.7, 119.9, 125.8, 126.2, 127.0, 127.8, 128.1,
128.2, 128.4, 140.1, 140.9, 145.3, 150.1, 150.2, 208.0. Anal.
Calcd for C32H27FeNO: C, 77.27; H, 5.47; N, 2.82. Found: C,
77.31; H, 5.84; N, 2.65.
stirred for 4 h at -40 °C, and then the reaction was quenched
by addition of a pH 8.6 buffer solution. The resulting mixture
was partitioned between CH2Cl2 and H2O (10 mL). The
organic layer was washed with water and brine (10 mL), dried,
and concentrated. Column chromatography (CH2Cl2-hexane,
1:2) afforded 8k as a white solid (148 mg, 91% yield): mp 111-
(3S)-5-Meth yl-3-[N-(9′-ph en ylflu or en -9′-yl)am in o]h exan -
2-on e (8g): same procedure as for 6a but starting with 6b
(0.35 mmol) and with a reaction time of 5 h at -78 °C afforded
113 °C (CH2Cl2-hexane); [R]20 -249 (c 1.2, CHCl3); IR 1680
D
cm-1; 1H NMR δ 2.5-2.67 (m, 2H), 3.56 (bs, 1H), 3.66 (dd, J )
4.5, 8.5, 1H), 6.65 (d, J ) 7.5, 1H), 6.87-7.41 (m, 21H), 7.57
(d, J ) 7.4, 1H); 13C NMR δ 41.5, 58.2, 73.0, 119.3, 125.5, 126.2,
127.0, 127.1, 127.5, 127.7, 127.8, 127.9, 128.0, 128.1, 128.2,
129.9, 132.6, 135.5, 138.2, 139.7, 141.0, 144.7, 149.1, 149.2,
204.7. Anal. Calcd for C34H27NO: C, 87.70; H, 5.86; N, 3.01.
Found: C, 87.47; H, 5.84; N, 3.11.
118 mg, 91% yield; mp 88-90 °C (Et2O-EtOH); [R]20 -226
D
(c 1.0, CHCl3); IR 1710 cm-1; 1H NMR δ 0.27 (d, J ) 6.5, 3H),
0.73 (d, J ) 6.5, 3H), 0.81 (m, 1H), 1.07 (m, 1H), 1.33 (s, 3H),
1.75 (m, 1H), 2.51 (dd, J ) 3.1, 9.7, 1H), 3.18 (bs, 1H), 6.96-
7.60 (m, 13H); 13C NMR δ 21.2, 23.6, 24.1, 27.2, 43.1, 59.5,
73.0, 119.5, 119.6, 125.8, 126.2, 127.2, 127.4, 127.6, 128.1,
128.2, 128.3, 140.0, 141.2, 144.5, 149.7, 149.8, 213.3. Anal.
Calcd for C26H27NO: C, 84.51; H, 7.37; N, 3.79. Found: C,
84.23; H, 7.33; N, 3.88.
(4S)-2-E t h oxy-5-p h en yl-4-[N-(9′-p h en ylflu or en -9′-yl)-
a m in o]p en t-1-en -3-on e (8l). The same procedure as for 8i
was used but starting from 6d (0.25 mmol) and using HCO2Et
(60 µL, 0.75 mmol) and AcOH (100 µL) for the quench. The
reaction mixture was then stirred for 10 min followed by
aqueous workup as above. The residue was chromatographed
through a short column (CH2Cl2-hexane, 1:3 to 1:1) to give
(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-on e (8h ): same procedure as for 8d with a
stirring time in the presence of AcOH of only 4 h afforded 145
mg, 96% yield; mp 130-132 °C; [R]20 -332 (c 1.0, CHCl3); IR
D
8l in 58% yield (67 mg) as an oil: [R]20 -186 (c 1.0, CHCl3);
1680 cm-1; H NMR δ 0.37 (d, J ) 6.5, 3H), 0.80 (d, J ) 6.5,
1
D
IR 1708 cm-1; H NMR δ 1.11 (t, J ) 6.9, 3H), 2.39 (dd, J )
1
3H), 0.89 (m, 1H), 1.29 (m, 1H), 2.01 (m, 1H), 3.53 (dd, J )
2.6, 10.4, 1H), 3.63 (bs, 1H), 6.87-7.51 (m, 17H), 7.63 (d, J )
7.3, 1H); 13C NMR δ 21.0, 23.7, 24.3, 44.4, 54.4, 73.0, 119.3,
119.5, 126.1, 126.2, 127.1, 127.3, 127.4, 127.5, 128.0, 128.1,
128.3, 132.5, 135.3, 140.1, 141.0, 144.7, 149.3, 149.9, 205.6.
Anal. Calcd for C31H29NO: C, 86.27; H, 6.77; N, 3.24.
Found: C, 85.99; H, 7.06; N, 3.12.
9.2, 13.2, 1H), 2.62 (dd, J ) 4.1, 13.2, 1H), 3.29-3.55 (m, 4H),
3.99 (d, J ) 2.4, 1H), 4.64 (d, J ) 2.4, 1H), 6.49 (d, J ) 7.6,
1H), 6.80 (t, J ) 7.5, 1H), 6.99-7.37 (m, 14H), 7.55 (d, J )
7.4, 2H); 13C NMR δ 14.0, 40.7, 57.3, 63.2, 72.9, 90.9, 119.0,
119.2, 125.3, 126.0, 126.3, 127.0, 127.6, 127.8, 127.9, 128.0,
128.1, 129.9, 138.5, 139.7, 141.3, 144.7, 149.2, 149.3, 156.1,
201.9. Anal. Calcd for C32H29NO2‚2/3H2O: C, 81.49; H, 6.49;
N, 2.97. Found: C, 81.25; H, 6.53; N, 2.61.
(4S)-2-Eth oxy-6-m eth yl-4-[N-(9′-ph en ylflu or en -9′-yl)am i-
n o]h ep t-1-en -3-on e (8i). To a solution of ethyl vinyl ether
(72 µL, 0.75 mmol) in THF (1 mL) at -78 °C was added t-BuLi
(0.75 mmol); the resulting solution was stirred while slowly
warmed to 0 °C, stirred for 45 min at that temperature, cooled
to -78 °C, and treated via cannula with a solution of 6b (96
mg, 0.25 mmol) in THF (2 mL). The resulting solution was
stirred at 0 °C for 4 h, and then the reaction was quenched by
addition of a buffer solution of pH 8.6 (KH2PO4-NaOH). The
cooling bath was removed and the reaction mixture stirred for
30 min. The solution was partitioned between EtOAc (10 mL)
and water (10 mL); the organic layer was washed with water
(10 mL) and brine (10 mL), dried, and concentrated. The
residue was chromatographed through a short column of
alumina, grade III (CH2Cl2-hexane, 1:1), to give 8i in 85%
yield (90 mg): mp 85-86 °C (EtOH); [R]20D -285 (c 1.1, CHCl3);
(2S)-4,4-Dim et 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 -3-on e (8m ). To a solution of 6d (104 mg,
0.25 mmol) in THF (3 mL) at -20 °C was slowly added t-BuLi
(0.38 mmol). The resulting yellow solution was stirred for 90
min at -20 °C; then the reaction was quenched by addition of
HCO2Et (31 µL, 0.38 mmol) and AcOH (50 µL). The cooling
bath was removed and the reaction mixture stirred for an
additional 15 min. Workup as above and column chromatog-
raphy (CH2Cl2-hexane, 1:2) afforded 64 mg of 8m , 57% yield;
mp 158-160 °C (CH2Cl2-hexane); [R]20 -219 (c 1.1, CHCl3);
D
IR 1697 cm-1; 1H NMR δ 0.65 (s, 9H), 2.24 (dd, J ) 9.8, 13.2,
1H), 2.71 (dd, J ) 2.2, 13.2, 1H), 3.25 (dd, J ) 2.6, 9.8, 1H),
3.36 (bs, 1H), 6.09 (d, J ) 7.6, 1H), 6.71 (t, J ) 7.5, 1H), 7.08-
7.29 (m, 14H), 7.54 (d, J ) 7.5, 1H), 7.62 (d, J ) 7.2, 1H); 13
C
1
IR 1700 cm-1; H NMR δ 0.31 (d, J ) 6.5, 3H), 0.81 (d, J )
NMR δ 26.8, 41.6, 43.1, 58.5, 72.7, 119.1, 119.5, 125.4, 126.1,
126.3, 126.9, 127.1, 127.6, 127.8, 127.9, 128.1, 128.2, 130.3,
138.8, 139.2, 141.4, 145.8, 148.9, 149.1, 218.9. Anal. Calcd
for C32H31NO: C, 86.24; H, 7.03; N, 3.14. Found: C, 86.03;
H, 7.03; N, 3.04.
6.7, 3H), 0.85 (m, 1H), 1.08 (t, J ) 6.8, 3H), 1.14 (m, 1H), 1.91
(m, 1H), 3.26-3.53 (m, 4H), 3.97 (d, J ) 2.3, 1H), 4.61 (d, J )
2.3, 1H), 6.97 (d, J ) 7.5, 1H), 7.08-7.48 (m, 10H), 7.58 (d, J
) 7.5, 1H), 7.63 (d, J ) 7.5, 1H); 13C NMR δ 14.0, 20.8, 23.7,
24.3, 43.7, 53.4, 63.1, 73.0, 90.5, 119.2, 119.3, 125.9, 126.3,
127.1, 127.4, 127.6, 127.9, 128.1, 128.2, 140.2, 141.4, 144.7,
149.5, 149.9, 156.0, 202.9. Anal. Calcd for C29H31NO2: C,
81.83; H, 7.36; N, 3.29. Found: C, 81.53; H, 7.57; N, 3.24.
(2R)-1,2-Dip h en yl-2-[N-(9′-p h en ylflu or en -9′-yl)a m in o]-
1-eth a n on e (8j). To a solution of PhBr (57 µL, 0.56 mmol)
in THF (0.8 mL) at -78 °C was added n-BuLi (2.5 M, 208 µL,
0.52 mmol), and the reaction mixture was stirred for 30 min
and then transferred via cannula to a solution of 6c (0.35
mmol) in THF (1.5 mL) at -40 °C. After 3 h the reaction was
quenched by addition of a pH 8.6 buffer solution, and then
workup was done as above. Column chromatography (CH2Cl2-
(4S)-5-Cycloh exyl-2-et h oxy-4-[N-(9′-p h en ylflu or en -9′-
yl)a m in o]-1-p en ten -3-on e (8n ). To a solution of ethyl vinyl
ether (74 µL, 0.77 mmol) in THF (1 mL) at -78 °C was added
t-BuLi (0.75 mmol); the resulting solution was stirred while
allowed to warm slowly to 0 °C, stirred for 45 min at that
temperature, then cooled to -78 °C, and treated via cannula
with a solution of 6e (106 mg, 0.25 mmol) in THF (2 mL). The
resulting solution was stirred at 0 °C for 4 h and then the
reaction quenched by addition of a buffer solution of pH 8.6
(KH2PO4-NaOH). The cooling bath was removed and the
reaction mixture stirred for 45 min. The solution was parti-
tioned between EtOAc (10 mL) and water (10 mL); the organic
layer was washed with water (10 mL) and brine (10 mL), dried,
and concentrated. The residue was chromatographed through
a short column of alumina grade III (EtOAc-hexane, 1:6) to
hexane, 1:1) afforded 134 mg of 8j, 85%: mp 132-134 °C
1
(Et2O-hexane); [R]20 +142 (c 1.0, CHCl3); IR 1684 cm-1; H
D
NMR δ 4.2 (bs, 1H), 4.6 (s, 1H), 6.93-7.6 (m, 22H), 7.7 (d, J )
7.5, 1H); 13C NMR δ 61.4, 73.4, 119.5, 119.7, 126.0, 126.4,
126.5, 127.1, 127.2, 127.6, 127.7, 127.8, 127.9, 128.1, 128.2,
128.3, 128.4, 132.6, 135.7, 140.0, 140.3, 141.1, 144.5, 149.2,
149.6, 201.2. Anal. Calcd for C33H25NO: C, 87.88; H, 5.60;
N, 3.12. Found: C, 87.88; H, 5.58; N, 3.10.
give 8n as an oil in 85% yield (99 mg): [R]20 -218 (c 1.2,
D
CH2Cl2); IR 1708 cm-1; H NMR δ 0.35-0.41 (m, 1H), 0.76-
1
1.64 (m, 14H), 3.29-3.49 (m, 4H), 3.98 (d, J ) 2.4, 1H), 4.61
(d, J ) 2.4, 1H), 6.98 (d, J ) 7.5, 1H), 7.09-7.49 (m, 10H),
7.57 (d, J ) 7.5, 1H), 7.62 (d, J ) 7.5, 1H); 13C NMR δ 14.0,
26.1, 26.5, 26.6, 31.5, 33.6, 34.5, 42.0, 52.6, 63.1, 73.0, 90.6,
119.1, 119.2, 125.8, 126.2, 127.0, 127.3, 127.5, 127.7, 127.8,
127.9, 128.1, 140.0, 141.2, 144.5, 149.3, 149.8, 155.8. Anal.
Calcd for C32H35NO2‚1/4H2O: C, 81.74; H, 7.62; N, 2.98.
Found: C, 81.96; H, 7.53; N, 3.09.
(2S )-1,3-D i p h e n y l-2-[N -(9′-p h e n y lflu o r e n -9′-y l)-
a m in o]p r op a n -1-on e (8k ). To a solution of PhBr (68 µL, 0.66
mmol) in THF (3 mL) at -78 °C was added n-BuLi (2.5 M,
252 µL, 0.63 mmol); the reaction mixture was stirred for 30
min and then transferred via cannula to a solution of 6d (0.35
mmol) in THF (6 mL) at -40 °C. The reaction mixture was
(2S)-3-(Ben zyloxy)-1-p h en yl-2-[N-(9′-p h en ylflu or en -9′-

6868 J . Org. Chem., Vol. 62, No. 20, 1997
Paleo et al.
yl)a m in o]p r op a n -1-on e (8o): same procedure as for 8d but
with a stirring time in the presence of AcOH of only 2 h
afforded 151 mg of 8o (87% yield) after chromatography
(CH2Cl2-hexane, 1:1); mp 63-64 °C (Et2O-EtOH); [R]20D -189
127.6, 127.9, 128.7, 129.0, 129.1, 129.3, 139.4, 141.3, 141.9,
144.9, 147.2, 175.3. Anal. Calcd for C24H23NO2: C, 80.64; H,
6.49; N, 3.92. Found: C, 80.49; H, 6.27; N, 3.92.
(2S)-2-[N-Ben zyl-N-(9′-p h en ylflu or en -9′-yl)a m in o]-4-
m eth ylp en ta n oic a cid (13b): 108 mg, 94% yield; [R]20D +179
(c 1.0, CHCl3); IR 1703 cm-1; 1H NMR δ 0.24 (d, J ) 6.5, 3H),
0.61 (d, J ) 6.5, 3H), 0.79 (m, 1H), 1.29 (m, 1H), 1.56 (m, 1H),
3.24 (dd, J ) 2.8, 10.0, 1H), 4.10 (d, J ) 13.8, 1H), 4.41 (d, J
) 13.8, 1H), 7.21-7.79 (m, 18H); 13C NMR δ 20.7, 23.4, 25.3,
37.3, 50.9, 57.9, 79.7, 120.0, 120.6, 126.3, 126.9, 127.1, 127.4,
127.5, 127.8, 127.9, 128.2, 128.6, 128.7, 128.8, 129.4, 138.7,
140.1, 141.3, 143.3, 146.1, 147.4, 177.1. Anal. Calcd for
C32H31NO2‚1/2H2O: C, 81.67; H, 6.85; N, 2.98. Found: C, 81.40;
H, 6.98; N, 2.83.
(c 1.0, CHCl3); IR 1680 cm-1 1H NMR δ 3.46 (m, 2H), 3.70
;
(bs, 1H), 3.80 (m, 1H), 4.25 (s, 2H), 6.90-7.45 (m, 22H), 7.65
(d, J ) 7.4, 1H); 13C NMR δ 56.1, 72.9, 73.0, 73.7, 119.5, 119.8,
125.6, 126.2, 126.4, 127.1, 127.2, 127.3, 127.7, 127.8, 127.9,
128.1, 128.3, 128.4, 132.5, 136.5, 138.0, 140.1, 140.9, 144.4,
149.3, 149.7, 204.4. Anal. Calcd for C35H29NO2: C, 84.82; H,
5.90; N, 2.83. Found: C, 84.63; H, 5.83; N, 2.83.
2-Met h yl-3-[N-(9-p h en ylflu or en -9-yl)a m in o]b u t a n -2-
ol (9). A solution of 8a (180 mg, 0.55 mmol) in THF (6 mL)
at -78 °C was treated with MeLi (690 mL, 1.1 mmol), the
reaction mixture was stirred for 2 h at that temperature, and
the reaction was quenched by addition of AcOH (500 µL, 8.7
mmol). EtOAc (10 mL) was added, the mixture was washed
with satd NaHCO3 (10 mL), H2O (10 mL), and brine (10 mL),
and the organic layer was dried, filtered and concentrated. The
residue was purified by column chromatography (EtOAc-
(2S)-3-(Ben zyloxy)-2-[N-et h yl-N-(9′-p h en ylflu or en -9′-
yl)a m in o]p r op a n oic a cid (13c): 97 mg, 84% yield; [R]20
D
+350 (c 1.0, CHCl3); IR 1710, 1760 cm-1; 1H NMR δ 1.21 (t, J
) 7.0, 3H), 3.11-3.32 (m, 4H), 3.49 (m, 1H), 4.07 (d, J ) 12.0,
1H), 4.19 (d, J ) 12.0, 1H), 7.09-7.47 (m, 16H), 7.61 (d, J )
7.5, 1H), 7.73 (d, J ) 7.5, 1H); 13C NMR δ 15.1, 42.6, 60.6,
66.2, 73.0, 79.9, 120.3, 120.6, 125.2, 126.1, 126.6, 127.5, 127.7,
127.9, 128.0, 128.2, 128.6, 129.0, 129.1, 129.2, 137.6, 139.5,
141.2, 142.2, 145.1, 146.5, 172.6. Anal. Calcd for C31H29NO3:
C, 80.32; H, 6.31; N, 3.02. Found: C, 80.13; H, 6.20; N, 2.87.
(2S)-2-[N-Eth yl-N-(9′-ph en ylflu or en -9′-yl)am in o]-3-[(m e-
th yloxy)ca r bon yl]p r op a n oic a cid (13d ): 94 mg, 90% yield;
[R]20D +341 (c 1.0, CHCl3); IR 1708, 1736, 1769 cm-1; 1H NMR
δ 1.11 (t, J ) 7.1, 3H), 1.62 (dd, J ) 2.6, 15.6, 1H), 2.48 (dd,
J ) 10.1, 15.6, 1H), 2.83 (m, 1H), 3.27 (m, 1H), 3.43 (s, 3H),
3.79 (dd, J ) 2.5, 10.0, 1H), 7.17-7.48 (m, 11H), 7.67 (d, J )
7.4, 1H), 7.75 (d, J ) 7.4, 1H); 13C NMR δ 13.9, 30.8, 41.8,
51.6, 55.7, 79.1, 120.4, 120.9, 124.9, 126.1, 127.4, 127.7, 128.6,
128.8, 129.1, 129.2, 139.6, 141.5, 142.2, 144.8, 147.2, 171.1,
175.7. Anal. Calcd for C26H25NO4: C, 75.16; H, 6.06; N, 3.37.
Found: C, 74.76; H, 6.16; N, 3.15.
hexane, 1:5) to give 9 as a colorless oil in 64% yield (121 mg):
1
[R]20 +285 (c 1.6, CHCl3); H NMR δ 0.52 (d, J ) 6.5, 3H),
D
0.98 (s, 3H), 1.13 (s, 3H), 2.13 (q, J ) 6.5, 1H), 7.21-7.45 (m,
11H), 7.70 (d, J ) 7.5, 1H), 7.74 (d, J ) 7.5, 1H); 13C NMR δ
18.2, 23.4, 26.5, 57.0, 71.9, 72.4, 119.9, 120.0, 125.2, 125.7,
125.9, 127.2, 127.7, 128.2, 128.3, 128.4, 140.1, 140.8, 145.4,
148.6, 151.4. Anal. Calcd for C24H25NO: C, 83.93; H, 7.34;
N, 4.08. Found: C, 83.99; H, 7.59; N, 3.87.
P r ep a r a tion of 10a ,b. A solution of 9 (85 mg, 0.25 mmol)
in THF (3 mL) was treated with CuBr‚SMe2 (155 mg, 0.75
mmol) and (R)-(+) or (S)-(-)-phenylethyl isocyanate (70 µL,
0.50 mmol) at rt. The resulting suspension was stirred at 40
°C for 24 h (10a ) or 14 h (10b), diluted with EtOAc (25 mL),
and washed with a pH 8 buffer solution (NH3/NH4Cl). The
organic phase was washed with brine (2 × 15 mL), dried, and
concentrated. The determination of the er was done with the
crude product, but for analytical purposes the residue was
purified by column chromatography. (R)-10a : column chro-
(2S)-2-[N-Meth yl-N-(9′-p h en ylflu or en -9′-yl)a m in o]p r o-
p a n oic Acid (13e). (a) A solution of 6a (50 mg, 0.15 mmol)
in THF (2 mL) was cooled to 0 °C, and LiBH4 (6.5 mg, 0.3
mmol) was added. The reaction mixture was stirred for 24 h
while warming to rt; then 1 M H3PO4 (0.5 mL) was slowly
added. The resulting mixture was partitioned between satd
NaHCO3 (10 mL) and EtOAc (2 × 10 mL); the combined
organic phase was washed with water (10 mL) and brine (10
mL), dried, and concentrated. The residue was purified by
column chromatography (CH2Cl2-MeOH, 2%) to give 13e in
92% yield (47 mg). (b) A solution of 6a (50 mg, 0.15 mmol) in
THF (2 mL) at -78 °C was treated with DIBALH (220 µL,
0.22 mmol). The reaction mixture was stirred for 2 h at -78
°C, and HCO2Et (20 mL, 0.25 mmol) was added; the resulting
mixture was stirred for 10 min and then diluted with CHCl3
(8 mL) and satd Na2CO3 (5 drops), stirring was continued until
the solution became cloudy, and then KH2PO4 and Na2SO4
were added. The resulting mixture was stirred at rt for 1 h
and then filtered. The residue was washed with CHCl3, the
combined clear filtrate and washings were concentrated, and
the residue was purified by chromatography (CH2Cl2-MeOH,
matography (CH2Cl2) afforded 91 mg, 74% yield; [R]20 +169
D
(c 1.0, CHCl3); IR 1702 cm-1; H NMR (338 K) δ 0.44 (d, J )
1
6.4, 3H), 1.38 (d, J ) 6.8, 3H), 1.40 (s, 3H), 1.44 (s, 3H), 1.99
(bs, 1H), 2.49 (q, J ) 6.4, 1H), 4.62 (m, 1H), 4.68 (m, 1H), 7.11-
7.38 (m, 16H), 7.64 (t, J ) 7.6, 2H); 13C NMR δ 17.3, 22.4,
22.8, 23.5, 50.3, 56.0, 72.6, 84.8, 119.8, 119.9, 125.5, 125.8,
125.9, 126.2, 127.0, 127.1, 127.4, 127.5, 128.0, 128.1, 128.2,
128.6, 140.2, 140.4, 144.0, 146.3, 149.0, 152.1, 155.0. Anal.
Calcd for C33H34N2O2‚H2O: C, 77.92; H, 7.13; N, 5.51.
Found: C, 77.93; H, 6.88; N, 5.41. (S)-10b: column chroma-
tography (EtOAc-hexane, 1:6) afforded 98 mg, 80% yield;
1
[R]20 +118 (c 0.9, CHCl3); IR 1700 cm-1; H NMR (338 K) δ
D
0.41 (bs, 3H), 1.41 (m, 9H), 2.09 (bs, 1H), 2.52 (q, J ) 6.5, 1H),
4.61 (bs, 1H), 4.70 (bm, 1H), 7.10-7.40 (m, 16H), 7.65 (t, J )
6.5, 2H); 13C NMR δ 17.2, 22.7, 23.5, 50.5, 55.8, 72.6, 84.9,
119.8, 119.9, 125.5, 125.8, 126.2, 126.3, 127.0, 127.1, 127.5,
127.6, 128.0, 128.1, 128.2, 128.6, 140.3, 140.4, 144.1, 146.5,
148.9, 152.2, 154.9. Anal. Calcd for C33H34N2O2‚3/4H2O: C,
78.62; H, 7.10; N, 5.55. Found: C, 78.30; H, 7.05; N, 5.21.
Rea ction of Oxa zolid in on es 6 w ith Gr ign a r d Re-
a gen ts. Gen er a l P r oced u r e. To a solution of oxazolidinone
6 (0.25 mmol) in THF (5 mL) at -78 °C was added a
commercial solution of RMgBr (0.5 mmol). After the mixture
was stirred for 6 h at -78 °C, glacial AcOH (85 µL, 1.5 mmol)
was added, the cooling bath was removed, and the reaction
mixture was stirred for 15 min. The solution was partitioned
between satd NaHCO3 (10 mL) and EtOAc (10 mL), and the
aqueous layer was extracted with EtOAc (2 × 10 mL). The
combined organic layer was washed with water (10 mL) and
brine (10 mL), dried, and concentrated. Column chromatog-
raphy (CH2Cl2-MeOH, 2%) provided 13 as a white foam.
(2S)-2-[N-E t h yl-N-(9′-p h en ylflu or en -9′-yl)a m in o]p r o-
p a n oic a cid (13a ): 82 mg, 92% yield; mp 169-171 °C
2%) to give 13e as a white foam (48 mg, 94% yield): [R]20
D
+383 (c 1.0, CHCl3); IR 1714, 1757 cm-1; 1H NMR δ 0.73 (d, J
) 7.1, 3H), 2.54 (s, 3H), 3.28 (q, J ) 7.1, 1H), 7.18-7.53 (m,
11H), 7.65 (d, J ) 7.6, 1H), 7.78 (d, J ) 7.6, 1H); 13C NMR δ
10.9, 32.0, 56.7, 77.7, 120.4, 120.9, 124.7, 126.6, 127.6, 128.0,
128.7, 128.9, 129.1, 129.3, 139.6, 140.9, 141.1, 145.1, 147.0,
174.5. Anal. Calcd for C23H21NO2‚1/2H2O: C, 78.38; H, 6.29;
N, 3.97. Found: C, 78.71; H, 6.43; N, 3.82.
(1 R ,2 S )-1 -P h e n y l -2 -[N -(9 ′-p h e n y l fl u o r e n -9′-y l )-
a m in o]p r op a n -1-ol (14d ). A solution of 8d (50 mg, 0.13
mmol) in THF (4 mL) at -78 °C was treated with BH3‚SMe2
(0.02 mL, 0.2 mmol) and stirred for 36 h while slowly warming
to rt. MeOH (0.3 mL) was slowly added to the reaction
mixture, and after stirring for 5 min, the resulting mixture
was concentrated to dryness and purified by column chroma-
tography (EtOAc-hexane, 1:6) to give 14d as a white foam
(49 mg, 98% yield): [R]20D +189 (c 1.0, CHCl3); 1H NMR δ 0.46
(d, J ) 6.0, 3H), 2.29 (m, 1H), 4.02 (d, J ) 3.1, 1H), 6.80 (d, J
) 7.4, 2H), 7.02-7.70 (m, 16H); 13C NMR δ 15.8, 53.9, 72.9,
74.9, 120.0, 120.1, 124.6, 125.5, 125.7, 126.0, 126.7, 127.4,
(CH2Cl2-hexane); [R]20 +486 (c 1.0, CHCl3); IR 1707, 1760
D
cm-1; H NMR δ 0.77 (d, J ) 7.2, 3H), 1.13 (t, J ) 7.2, 3H),
1
3.00 (m, 1H), 3.11 (q, J ) 7.2, 1H), 3.29 (m, 1H), 7.16-7.54
(m, 11H), 7.67 (d, J ) 7.5, 1H), 7.79 (d, J ) 7.6, 1H); 13C NMR
δ 10.1, 14.4, 40.7, 54.6, 79.2, 120.3, 120.8, 124.7, 126.0, 126.5,

N-(9-Phenylfluoren-9-yl)-R-amino Ketones
J . Org. Chem., Vol. 62, No. 20, 1997 6869
127.9, 128.0, 128.1, 128.5, 128.6, 128.7, 139.9, 141.3, 141.4,
145.0, 149.5, 150.0. Anal. Calcd for C28H25NO: C, 85.90; H,
6.44; N, 3.58. Found: C, 85.83; H, 6.29; N, 3.72.
119.8, 126.5, 126.9, 127.2, 127.3, 127.4, 127.6, 127.7, 128.0,
128.1, 128.2, 128.5, 128.7, 139.1, 139.3, 142.3, 145.3, 147.5,
148.9. Anal. Calcd for C29H25NO: C, 86.32; H, 6.24; N, 3.47.
Found: C, 86.33; H, 6.19; N, 3.52.
(1 S ,2 S )-1 -P h e n y l -2 -[N -(9 ′-p h e n y l fl u o r e n -9 ′-y l )-
a m in o]p r op a n -1-ol (15d ). A solution of 8d (50 mg, 0.13
mmol) in THF (5 mL) at -78 °C was treated with L-Selectride
(260 µL, 0.26 mmol) and stirred for 7 h; then the reaction was
quenched with AcOH (22 µL, 0.38 mmol). After 5 min of
stirring, the reaction mixture was allowed to warm up to rt.
LiOH‚H2O (27 mg, 0.64 mmol) and H2O2 (30%, 1 mL) were
added, and the resulting mixture was stirred for 30 min and
then partitioned between CH2Cl2 (15 mL) and H3PO4 (1 M, 15
mL). The aqueous phase was washed with CH2Cl2 (15 mL),
and the combined organic phase was washed with brine (20
mL), dried, and concentrated to give a residue that was
purified by short column chromatography (EtOAc-hexane,
(1R,2S)-1-F er r ocen yl-2-[N-(9′-p h en ylflu or en -9′-yl)a m i-
n o]p r op a n -1-ol (14f): same procedure as for 14d afforded
14f in 84% yield (42 mg) as an orange foam after short column
chromatography (CH2Cl2-hexane, 1:1 to 2:1); mp 139-140 °C
(Et2O-hexane); [R]20 -18 (c 1.0, CH2Cl2); 1H NMR (CDCl3 +
D
D2O) δ 0.52 (d, J ) 6.6, 3H), 2.23 (m, 1H), 3.58 (s, 1H), 3.85
(d, J ) 3.3, 1H), 3.95 (s, 1H), 4.04 (s, 6H), 4.21 (s, 1H), 7.18-
7.43 (m, 11H), 7.71 (d, J ) 7.0, 1H); 13C NMR δ 26.5, 63.5,
75.5, 78.4, 82.2, 82.5, 86.4, 86.9, 87.4, 99.1, 129.8, 129.9, 134.8,
135.4, 135.9, 137.1, 137.7, 137.8, 138.2, 138.3, 150.0, 150.8,
155.0, 159.6, 160.3. Anal. Calcd for C32H29FeNO‚H2O: C,
74.27; H, 6.04; N, 2.71. Found: C, 73.91; H, 5.81; N, 2.75.
(1S,2S)-1-F er r ocen yl-2-[N-(9′-p h en ylflu or en -9′-yl)a m i-
n o]p r op a n -1-ol (15f). A solution of 8f (200 mg, 0.4 mmol) in
THF (5 mL) at -78 °C was treated with L-Selectride (800 µL,
0.8 mmol) and stirred for 24 h while slowly warming to rt;
then it was quenched with AcOH (70 µL, 1.2 mmol). After 5
min of stirring, the reaction mixture was cooled to 0 °C,
LiOH‚H2O (85 mg, 2.0 mmol) and H2O2 (30%, 1.7 mL) were
added, and the resulting mixture was stirred for 20 min and
then partitioned between CH2Cl2 (15 mL) and H3PO4 (1 M, 15
mL). The aqueous phase was washed with CH2Cl2 (15 mL),
and the combined organic phase was washed with brine (20
mL), dried, and concentrated to give a residue that was
purified by short column chromatography (CH2Cl2-hexane, 1:1
1:6) to give 15d (49 mg, 98%) as a white foam: [R]20 +258 (c
D
1
1.0, CH2Cl2); H NMR δ 0.36 (d, J ) 6.3, 3H), 2.16 (m, 1H),
3.98 (d, J ) 8.3, 1H), 6.90-7.62 (m, 18H); 13C NMR δ 19.2,
55.0, 72.6, 78.6, 120.0, 120.1, 125.1, 125.8, 126.0, 127.2, 127.3,
127.5, 127.8, 128.1, 128.2, 128.4, 128.5, 140.3, 140.8, 142.3,
144.9, 148.7, 151.1. Anal. Calcd for C28H25NO: C, 85.90; H,
6.44; N, 3.58. Found: C, 85.78; H, 6.31; N, 3.62.
(4S,5R)-4-Met h yl-5-p h en yl-3-[N-(9′-p h en ylflu or en -9′-
yl)a m in o]oxa zolid in e (16). A solution of 14d (50 mg, 0.13
mmol) in THF (1 mL) was treated with H2CO (26%, 0.2 mL)
and p-TsOH (5 mg, 0.026 mmol). The reaction mixture was
stirred at rt for 48 h and then partitioned between satd
NaHCO3 (15 mL) and CH2Cl2 (15 mL); the organic phase was
washed with water (10 mL) and brine (10 mL), dried, and
concentrated to give a residue which was purified by short
column chromatography (EtOAc-hexane, 1:6) to give 16 as a
to 2:1) to give 15f (159 mg, 79%) as an orange foam: mp 148-
1
149 °C (Et2O-hexane); [R]20 +20 (c 1.0, CH2Cl2); H NMR δ
D
0.44 (d, J ) 6.3, 3H), 2.15 (quintuplet, J ) 6.5, 1H), 3.93 (d, J
) 7.0, 1H), 4.03 (m, 3H), 4.10 (s, 1H), 4.15 (s, 5H), 7.17-7.40
(m, 11H), 7.63 (m, 2H); 13C NMR δ 18.9, 54.4, 65.3, 67.3, 67.4,
68.4, 68.5, 72.6, 74.2, 90.5, 119.8, 119.9, 125.2, 125.7, 126.0,
127.1, 127.6, 127.8, 128.2, 128.3, 140.2,140.5, 145.4, 149.0,
151.2. Anal. Calcd for C32H29FeNO‚H2O: C, 74.27; H, 6.04;
N, 2.71. Found: C, 73.87; H, 5.77; N, 2.73.
white crystalline solid (47 mg, 92% yield): mp 142-144 °C
1
(EtOAc-hexane); [R]20 -420 (c 0.7, CHCl3); H NMR δ 0.48
D
(d, J ) 7.0, 3H), 2.98 (q, J ) 6.8, 1H), 4.23 (d, J ) 6.4, 1H),
5.01 (d, J ) 6.3, 1H), 5.09 (d, J ) 6.3, 1H), 6.97-7.71 (m, 18H);
13C NMR δ 17.1, 58.2, 77.1, 81.1, 83.4, 119.8, 119.9, 125.5,
125.9, 126.7, 126.8, 127.1, 127.3, 127.9, 128.0, 128.1, 128.2,
128.5, 128.8, 139.3, 140.0, 141.6, 144.5, 148.0, 149.7. Anal.
Calcd for C29H25NO‚1/2H2O: C, 84.43; H, 6.11; N, 3.39.
Found: C, 84.09; H, 6.22; N, 3.37.
Ack n ow led gm en t . Financial support from the
CICYT (Spain, Grant SAF96-0251) and the Xunta de
Galicia (Grant XUGA 20912B96) is gratefully acknowl-
edged as well as fellowships from the Spanish Ministerio
de Educacio´n y Ciencia (M.R.P.) and Xunta de Galicia
(M.I.C.). We also thank Prof. Rafael Suau (Universidad
de Ma´laga, Spain) for the elemental analyses.
(4S,5S)-4-Met h yl-5-p h en yl-3-[N-(9′-p h en ylflu or en -9′-
yl)a m in o]oxa zolid in e (17): same procedure as above but
with a reaction time of 24 h provided 17 in 96% yield (49 mg);
1
mp 120-121 °C (EtOH); [R]20 -440 (c 0.7, CHCl3); H NMR
D
δ 0.77 (d, J ) 6.2, 3H), 2.23 (m, 1H), 4.11 (d, J ) 8.0, 1H),
4.78 (d, J ) 7.3, 1H), 5.17 (d, J ) 7.3, 1H), 6.54 (m, 2H), 6.98-
7.69 (m, 16H); 13C NMR δ 19.4, 62.1, 77.1, 84.1, 88.7, 119.7,
J O9707646