Convenient asymmetric syntheses of anti-β-amino alochols

Article abstract of DOI:10.1021/jo9522062

Condensation of allylborane reagents 9 and 12 with aldehydes gave anti-3-[(diphenylmethylene)-amino]-1-alken-4-ols 10 and 13 with high relative and absolute stereocontrol. Subsequent deprotection gave the corresponding free anti-3-amino-1-alken-4-ols 11 and 14. Alternatively, reaction of imines 13a, 13f, and 13g with trifluoromethanesulfonic anhydride and acidic methanol gave, via rearrangement, double inversion, and hydrolysis, the isomeric anti-4-amino-1-alken-3-ols 22, 38a, and 38b in good yield. The stereochemistry of the rearrangement products has been established by a single crystal X-ray study of compound 37 and by chemical correlation.

Full text of DOI:10.1021/jo9522062

J . Org. Chem. 1996, 61, 2677-2685
2677
Con ven ien t Asym m etr ic Syn th eses of a n ti-â-Am in o Alcoh ols
Anthony G. M. Barrett,* Mark A. Seefeld, Andrew J . P. White, and David J . Williams
Imperial College of Science, Technology & Medicine, London SW7 2AY, England
Received December 13, 1995X
Condensation of allylborane reagents 9 and 12 with aldehydes gave anti-3-[(diphenylmethylene)-
amino]-1-alken-4-ols 10 and 13 with high relative and absolute stereocontrol. Subsequent
deprotection gave the corresponding free anti-3-amino-1-alken-4-ols 11 and 14. Alternatively,
reaction of imines 13a , 13f, and 13g with trifluoromethanesulfonic anhydride and acidic methanol
gave, via rearrangement, double inversion, and hydrolysis, the isomeric anti-4-amino-1-alken-3-
ols 22, 38a , and 38b in good yield. The stereochemistry of the rearrangement products has been
established by a single crystal X-ray study of compound 37 and by chemical correlation.
Sch em e 1
In tr od u ction
2-Amino alcohols are common structural subunits that
occur in diverse biologically active natural products and
related fine chemicals.1 Many methods have been em-
ployed to construct compounds containing such function-
ality, yet relatively few concise strategies exist to gen-
erate vicinal aminols stereoselectively. Generally, two
distinct methods are employed to introduce such units.
Firstly, amino alcohol entities may be introduced without
altering the carbon skeleton of a molecule. Such a
process is exemplified by the ring opening of epoxides
with a nitrogen centered nucleophile.2 Alternatively, the
vicinal amino alcohol array may be elaborated with the
simultaneous construction of the interconnecting C-C
bond.3 This process can be much more valuable since it
leads to an increase in the complexity of the carbon
skeleton in addition to the introduction of heteroatoms.
We have recently reported4,5 an example of this second
strategy. In an extension of allylborane chemistry,6 we
showed that the antipodal B-[(E)-3-(diphenylamino)allyl]-
diisopinocampheylboranes 1 and 4 were useful reagents
for masked aldol chemistry. Condensation of aldehydes
with boranes 1 and 4 gave â-hydroxy-N,N-dipheny-
lamines 2 and 5 with high anti-diastereoselectivity and
high enantioselectivity. Unfortunately, there were seri-
ous limitations associated with this methodology. The
product â-hydroxy N,N-diphenylamines 2 and 5 could not
be easily deprotected to reveal the parent â-hydroxy
primary amines. Additionally significant quantities of
cyclopropane side products 3 and 6 were also formed
(Scheme 1). Prior to this work, Hoffmann and Metter-
nich reported the formation of related cyclopropane
systems in allylboration reactions.7 Subsequently we
reported8 the use of B-[(E)-3-[(diphenylmethylene)amino]-
allyl]diisopinocampheylboranes 9 and 12 in asymmetric
synthesis. Condensation of boranes 9 and 12 with
aldehydes and deprotection gave the amino alcohols 11
and 14. Herein we report full experimental details of
this improved methodology and describe an unexpected
rearrangement reaction that proceeds with double inver-
sion and is also useful in asymmetric synthesis.
Resu lts a n d Discu ssion
In principle, deprotonation of a suitably protected
derivative of allylamine9 and condensation with (-)- or
(+)-(chloro)diisopinocampheylborane should provide the
corresponding protected (amino-1-propen-3-yl)diisopi-
nocampheylborane derivatives such as 9 and 12 respec-
tively. Such reagents should react with aldehydes to
provide protected 3-amino-1-alken-4-ol derivatives such
as 10 and 13. Clearly for this chemistry to be viable the
choice of protecting group on nitrogen is crucial. The
protecting group must be removable under mild condi-
tions yet withstand strongly basic reagents. Secondly,
the allyl amine system should stereoselectively produce
E-allyl metal derivatives upon deprotonation and remain
configurationally stable upon lithium to boron trans-
metalation. This is essential to ensure good anti-stereo-
control. Finally, the protecting group must mask the
X Abstract published in Advance ACS Abstracts, April 1, 1996.
(1) Dictionary of Antibiotics and Related Substances, Bycroft, B. W.,
Ed.; Chapman and Hall: London, 1988.
(2) Mitsunobu, O. Synthesis of Amines and Ammonium Salts. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Winter-
feldt, E., Eds.; Pergamon Press: Oxford, 1991; Vol. 6, pp 88-93.
(3) (a) Yamamoto, H.; Hattori, K. Tetrahedron 1994, 50, 2785. (b)
Ito, Y.; Ito, H.; Murakami, M. J . Org. Chem. 1993, 58, 6766. (c) Taguchi,
T.; Ito, H.; Hanzawa, Y. Tetrahedron Lett. 1992, 33, 4469.
(4) Barrett, A. G. M.; Seefeld, M. A. J . Chem. Soc., Chem. Commun.
1993, 339.
(5) Barrett, A. G. M.; Seefeld, M. A. Tetrahedron 1993, 49, 7857.
(6) (a) Roush, W. R. Allyl Organometallics. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Heathcock, C. H., Eds.;
Pergamon Press: Oxford, 1991; Vol. 2, pp 1-53. (b) Brown, H. C.;
J adhav, P. K., Bhat, K. S. J . Am. Chem. Soc. 1988, 110, 1535. (c)
J adhav, P. K.; Bhat, K. S.; Perumal, P. T., Brown, H. C. J . Org. Chem.
1986, 51, 432. (d) Brown, H. C., Bhat, K. S. J . Am. Chem. Soc. 1986,
108, 5919.
(7) Hoffmann, R. W.; Metternich, R. J ustus Liebigs Ann. Chem.
1985, 2390.
(8) Barrett, A. G. M.; Seefeld, M. A., Williams, D. J . J . Chem. Soc.,
Chem. Commun. 1994, 1053.
(9) (a) Barluenga, J .; Gonza´lez, R.; Fan˜ana´s, F. J .; Yus, M., Foubelo,
F. J . Chem. Soc., Perkin Trans. 1 1994, 1069. (b) Beak, P., Resek, J .
E. Tetrahedron Lett. 1993, 34, 3043. (c) Eisch, J . J ., Shah, J . H. J .
Org. Chem. 1991, 56, 2955. (d) Biellmann, J .-F.; Ducep, J .-B.; Org.
React. 1982, 27, ch. 1.
0022-3263/96/1961-2677$12.00/0 © 1996 American Chemical Society

2678 J . Org. Chem., Vol. 61, No. 8, 1996
Barrett et al.
Sch em e 2
tection of 13a furnished the free amine 14a in 98% yield.
Several other aldehydes were reacted under similar
conditions to give the corresponding anti-â-hydroxy-
imines 10 and 13 (Table 1).
The relative and absolute stereochemistries of the
product imines requires substantiation. Examination of
1H NMR and 13C NMR spectra showed the diastereose-
lectivity of the reaction to be at least 95% anti in all cases.
The enantioselectivities were determined by converting
each pair of vicinal imino alcohols 10 and 13 into their
corresponding Mosher esters 15 and 16.12 The enantio-
Ta ble 1. Rea ction of Ald eh yd es w ith Bor a n es 9 a n d 12
1
meric excesses were measured to be g90% by H NMR
in all cases except in those resulting from mismatched
stereochemical biases between reagent and substrate
(entries 8 and 9). The stereochemistry of one anti-â-
imino alcohol has been formally established by carrying
out an X-ray crystallographic study of 10d .7 This study
unequivocally established the relative and hence the
absolute stereochemistry of alcohol 10d and, by implica-
tion, all the other imino alcohols in Table 1. These
results are in full accord with the established stereose-
lectivities of other Brown allylborane and aldehyde
condensation reactions.5,6
amine in such a manner that enamine reactivity is
reduced to suppress the formation of cyclopropane prod-
ucts such as 3 and 6. The requirements of reduced
nucleophilicity and ease of removal should be both
fulfilled using an imine protection strategy. Wu¨rthwein
and Wolf10 have shown that 1,1-diphenyl-2-aza-1,4-pen-
tadiene (7) upon deprotonation with LDA in THF at -78
°C gave an all trans-W-anionic species 8 (Scheme 2). The
reaction of carbanion 8 with electrophiles resulted pri-
marily in γ-substitution; however, this was dependent
on several variables including solvent polarity and elec-
trophile reactivity.11 The ability of carbanion 8 to react
regiospecifically at the distal carbon and maintain an all
trans-W-configuration upon addition of a chiral borane
had not been investigated prior to our preliminary
communication.8
Following the Wu¨rthwein precedent,10 1,1-diphenyl-2-
aza-1,4-pentadiene (7) was deprotonated with LDA in
THF at -78 °C to give, upon reaction with (-)-B-
chlorodiisopinocampheylborane [(-)-(Ipc)2BCl], an ad-
duct, presumably the E-allylborane 9. In situ reaction
with cyclohexanecarboxaldehyde gave, on basic hydrogen
peroxide workup, the anti-â-hydroxy amine 10a (R )
c-C6H11) in 56% yield (Scheme 3). Deprotection of imine
10a gave the corresponding amino alcohol 11a in 98%
yield. In the same manner, reaction of the imine 7 with
LDA in THF at -78 °C, followed by metathetic exchange
with (+)-B-chlorodiisopinocampheylborane [(+)-(Ipc)2BCl]
and reaction with cyclohexanecarboxaldehyde gave the
antipodal imine 13a (R ) c-C6H11). Subsequent depro-
We sought to convert the product imino alcohols 13
stereospecifically into aziridines 19 via activation of the
hydroxyl group as derivative 17, cyclization via an SN2
manifold, and nucleophilic addition to the resultant
iminium species 18 (Scheme 4).13 Unfortunately, all our
attempts to convert imino alcohols 13 directly into
aziridines 19 met with failure giving intractable polym-
erized material. However, these studies led to the
discovery of an unexpected rearrangement reaction. The
addition of 2,6-lutidine and trifluoromethanesulfonic
anhydride to alcohol 13a in CH2Cl2 at 0 °C resulted in
the formation of a single low molecular weight substance
1
(Scheme 5). The H NMR spectrum of the new product
21 showed what appeared to be a 1:1 mixture of imino
alcohols isomeric with the starting material 13a . Ini-
tially, we suspected that the unknown product may have
contained the syn-isomer 20 although this expectation
was later proven unfounded. A sample of the syn-isomer
20 admixed with 13a was prepared by carrying out the
allylboration reaction at -50 °C rather than -78 °C
(Scheme 6). This provided an inseparable mixture of the
imino alcohol 13a and the corresponding syn-diastereoi-
somer 20 (9:1). The decrease in diastereoselectivity at
elevated temperatures, which presumably takes place via
reversible allylboron migration and E,Z isomerization of
(12) (a) Dale, J . A.; Mosher, H. S. J . Am. Chem. Soc. 1973, 95, 512.
(b) Dale, J . A.; Dull, D. L.; Mosher, H. S. J . Org. Chem. 1969, 34, 2543.
(13) For similar examples, see: (a) De Kimpe, N.; De Smaele, D.
Tetrahedron Lett. 1994, 35, 8023. (b) De Kimpe, N.; Boelens, M.;
Piqueur, J .; Baele, J . Tetrahedron Lett. 1994, 35, 1925. (c) De Kimpe,
N.; Boelens, M. J . Chem. Soc., Chem. Commun. 1993, 916.
(10) Wu¨rthwein, E.-U.; Wolf, G. Chem. Ber. 1991, 124, 655.
(11) Wu¨rthwein, E.-U.; Wolf, G. Tetrahedron Lett. 1988, 29, 3647.

Asymmetric Syntheses of anti-â-Amino Alcohols
J . Org. Chem., Vol. 61, No. 8, 1996 2679
Sch em e 3
Sch em e 4
Sch em e 6
corresponding benzamide 25 by hydrogenation/hydro-
genolysis and benzoylation. Samples of the racemic syn
and anti benzamido alcohols 29, 30, 34, and 35 were
synthesized independently from nitropropane 26 and
(nitromethyl)cyclohexane 3114 using the Seebach modi-
fication of the Henry reaction15 (Scheme 7). The relative
stereochemistries of the nitro alcohol products 27, 28, 32,
and 33 were assigned based on comparative 13C NMR
shift correlations for the (CNO2) and (COH) peaks as
described by Seebach.15 The resultant nitroaldol isomers
were chromatographically separated, hydrogenated over
10% palladium on carbon, and subsequently benzoylated
to provide the racemic amides 29, 30, 34, and 35.
Comparison of the 1H and 13C NMR spectra of each
racemic compound with products 23 and 25 showed the
constitution and relative stereochemistry of benzamide
23 to be the same as that of structure 34.
Sch em e 5
The relative stereochemistry of compound 21 was also
determined by converting the amino alcohol 22 into the
oxazolidinone 36 using bis(trichloromethyl) carbonate
and Hunig’s base (Scheme 8). Irradiation of the H-5
proton resonance (δ 4.47) of oxazolidinone 36 produced
a large NOE (8.6%) of the signal for H-4 (δ 3.56). In
addition, the coupling constant between H-4 and H-5
protons (J 7.1 Hz) was consistent with the cis structure
36.16 These results are in agreement with the assign-
ment of the stereochemistry of the amino alcohol precur-
sor 22 as anti. The determination of enantiomeric purity
of the amino alcohol 22 was confirmed by analysis of the
the intermediate allylborane derivative, is well estab-
lished with crotonylborane systems.6 The 1H NMR
spectrum of the diastereoisomeric mixture {δ 3.45 [1H,
m, CH(NR)], syn and 3.62 [1H, m, CH(OH)], syn} showed
that the rearranged product 21 in Scheme 6 was neither
alcohol 13a nor 20.
Hydrolysis of imino alcohol 21 with 1 M hydrogen
chloride in methanol, hydrogenation over 5% palladium
on carbon and benzoylation (BzCl, Et3N) gave, surpris-
ingly, a single diastereoisomeric benzamido alcohol 23.
The imino alcohol 13a was also converted into the
(14) Kornblum, N.; Larson, H. O.; Blackwood, R. K.; Mooberry, D.
D.; Oliveto, E. P.; Graham, G. E. J . Am. Chem. Soc. 1956, 78, 1497.
(15) Seebach, D.; Beck, A. K.; Mukhopadhyay, T.; Thomas, E. Helv.
Chim. Acta 1982, 65, 1101.
(16) For a similar analysis, see: Bergmeier, S. C.; Stanchina, D. M.
Tetrahedron Lett. 1995, 36, 4533 and references therein.

2680 J . Org. Chem., Vol. 61, No. 8, 1996
Barrett et al.
F igu r e 1.
Sch em e 7
Sch em e 9
1H NMR spectrum of 21 which indicated a 1:1 mixture
of products. It is reasonable to postulate that the position
now occupied by the diphenylmethylene group (C-1) in
the rearranged product 21 is sterically encumbered by
the cyclohexyl ring and that imine 21 thus exists as a
mixture of rotamers. This hypothesis was consistent
with the result of converting imino alcohol 21 into amino
alcohol 22. Free rotation about the C-N bond of depro-
tected amine 22 showed the product to be in fact a single
diastereoisomer. An X-ray crystallographic study of
ester19 37 confirmed its relative and absolute stereo-
chemistry as a doubly inverted product (Figure 1). The
results suggest that the stereospecific formation of
product 21 may involve the intermediacy of an aziri-
dinium species 18 and SN2 ring opening without allylic
rearrangement (Scheme 4).
Sch em e 8
Further examples of this novel rearrangement were
sought by treating both compounds 10d and 13b with
trifluoromethanesulfonic anhydride. Unfortunately, this
gave only a complex intractable mixture of products. In
contrast, reaction of the simple alkylimino alcohol deriva-
tive 13f with trifluoromethanesulfonic anhydride and
subsequent acidification (1 M HCl in methanol) gave the
amino alcohol hydrochloride 38a in 38% yield (Scheme
9). 1H NMR analysis of the corresponding oxazolidinone
39a showed the coupling constant of protons H-4 and H-5
(J 7.9 Hz) to be fully consistant with the cis-stereochem-
istry. The parent imino alcohol 13f was also converted
into the corresponding oxazolidinone 41a by hydrolysis
and condensation with bis(trichloromethyl) carbonate.
Again analysis of the 1H NMR spectrum (J 7.8 Hz)
further confirmed the cis geometry of oxazolidinone 39a
(Table 2). Final confirmation was achieved by hydroge-
nating both oxazolidinones 39a and 41a to give the
1H and 13C NMR spectra of the dinitrobenzoyl (R)-O-
methylmandelate derivative 37. These analyses revealed
the diastereomeric purity of 37 to be ∼90%. This result
is consistent with retention of the enantiomeric purity
of the initial imino alcohol 13a , but inconsistent with the

Asymmetric Syntheses of anti-â-Amino Alcohols
J . Org. Chem., Vol. 61, No. 8, 1996 2681
Ta ble 2. Vicin a l Cou p lin g Con sta n ts of
4.92 (dd, 1H, J 17.3, 1.2 Hz), 3.95 (dd, 1H, J 6.7, 4.6 Hz), 3.34
(dd, 1H, J 6.6, 4.6 Hz), 1.84-0.84 (m, 11H); 13C NMR (67.5
MHz, CDCl3) δ 168.3, 139.8, 136.9, 136.3, 130.5, 128.8, 128.6,
128.3, 128.0, 127.9, 117.3, 78.6, 67.6, 39.7, 29.1, 28.5, 26.8, 26.3,
26.1; MS (EI) m/ z (rel intensity) 333 (M + , 2), 315 [(M -
H2O)+, 1], 256 (20), 220 (100), 165 (40), 55 (41); HRMS (EI, 70
eV) m/ z calcd for C23H27NO (M + ) 333.2093, found 333.2086.
Anal. Calcd for C23H27NO: requires C, 82.84; H, 8.16; N 4.20.
Found: C, 82.56; H, 8.13; N, 4.15. A sample of 10a (15 mg,
0.04 mmol), (R)-Mosher acid (23 mg, 0.10 mmol) and 4-(dim-
ethylamino)pyridine (5 mg) were dissolved in CH2Cl2 (10 mL).
1,3-Dicyclohexylcarbodiimide (21 mg, 0.10 mmol) in CH2Cl2
was added, and the course of the reaction was monitored by
TLC (silica gel, CH2Cl2). After 2 h, the entire mixture was
directly chromatographed on silica gel and eluted with CH2-
Cl2. Evaporation of the solvent gave the crude ester 15a (37
mg, 96%) as a light yellow oil. This material was used directly
without any further purification, for the determination of the
enantioselectivity of the reaction. 1H NMR (500 MHz, CDCl3)
δ 7.70-7.13 (m, 15H), 6.01 (m, 1H), 5.13 (m, 1H), 5.11 (m, 2H),
4.90 (d, 1H, J 17.3 Hz), 4.13 (m, 1H), 3.64 (s, 3H), 1.64-0.75
(m, 11H).
cis-Oxa zolid in on es
Sch em e 10
P r ep a r a tion of Im in es 10 a n d 13. Condensation of
various aldehydes with boranes 9 and 12 following the general
procedure above were used to prepare the following deriva-
tives. In several cases esterification with (R)-Mosher acid was
used to determine the enantioselectivity of reaction.
identical dihydro derivative 42 (Scheme 10). One other
imino alcohol compound 10g was investigated in this
regard. Rearrangement of the imino alcohol 13g with
trifluoromethanesulfonic anhydride and Hunig’s base
followed by acid hydrolysis gave the amino alcohol 38b
in 31% yield.
(+)-(1S,2R)-1-Cycloh exyl-2-d ip h en ylm eth ylen ea m in o-
3-bu ten -1-ol (13a ). Imino alcohol 13a (72 mg, 61%) was
obtained as a white solid: mp 92-93 °C (hexane-EtOAc); TLC
Rf 0.51 (hexane-EtOAc, 4:1); [R]24 +27.0° (c 0.7, CHCl3); IR
D
(CHCl3) 3513 (OH), 3080, 3059, 2927, 2851, 1621 (CdN), 1446,
1103 cm-1; 1H NMR (270 MHz, CDCl3) δ 7.66-7.14 (m, 10H),
6.06 (ddd, 1H, J 17.4, 9.4, 6.7 Hz), 5.16 (dd, 1H, J 9.4, 1.0 Hz),
4.95 (dd, 1H J 17.4, 1.0 Hz), 3.97 (dd, 1H, J 6.5, 4.7 Hz), 3.37
(dd, 1H, J 6.7, 4.7 Hz), 1.90-0.93 (m, 11H); 13C NMR (67.5
MHz, CDCl3) 168.3, 139.8, 136.8, 136.2, 130.4, 128.8, 128.5,
128.3, 128.0, 127.9, 117.4, 78.6, 67.5, 39.6, 29.0, 28.5, 26.7, 26.3,
26.1; MS (EI) m/ z (rel intensity) 333 (M+, 1), 315 [(M - H2O)+,
2], 256 (22), 220 (100), 165 (45), 54 (40); HRMS (EI, 70 eV)
m/ z calcd for C23H27NO (M+) 333.2093, found 333.2078. Anal.
Calcd for C23H27NO: C, 82.84; H, 8.16; N, 4.20. Found: C,
82.60; H, 7.78; N, 4.25. Mosher ester 16a : 1H NMR (270 MHz,
CDCl3) δ 7.83-7.12 (m, 15H), 5.84 (m, 1H), 5.26 (dd, 1H, J
7.5, 4.9 Hz), 4.95 (d, 1H, J 10.5 Hz), 4.84 (d, 1H, J 17.3 Hz),
4.06 (app t, 1H, J 6.6 Hz), 3.51 (s, 3H), 1.67-0.89 (m, 11H).
(+)-(1R,2S)-2-[(Dip h en ylm et h ylen e)a m in o]-1-p h en yl-
3-bu ten -1-ol (10b). Imino alcohol 10b (96 mg, 53%) was
obtained as a white solid: mp 97-98 °C (hexane-EtOAc); TLC
The enantioselective production of vicinal amino alco-
hols via a one-pot procedure should be applicable to
synthesis of natural products. In addition, the stereospe-
cific rearrangement of the product imino alcohols should
provide a complementary procedure for amino alcohol
synthesis.
Exp er im en ta l Section
All solvents were redistilled prior to use. (Nitromethyl)-
cyclohexane (31),14 2,3-O-isopropylidene-D-glyceraldehyde,17
and 1,1-dimethylethyl (S)-4-formyl-2,2-dimethyl-3-oxazolidi-
necarboxylate18 were prepared according to reported proce-
dures. All other reagents were purchased from commercial
sources and used without further purification.
(-)-(1R,2S)-1-Cycloh exyl-2-[(d ip h en ylm eth ylen e)a m i-
n o]-3-bu ten -1-ol (10a ) (Gen er a l P r oced u r e). To a stirred
solution of diisopropylamine (0.70 mL, 5.0 mmol) in THF (30
mL) under N2 at -78 °C was added n-BuLi in hexane (2.5 M,
2.0 mL). The solution was kept at -78 °C for 25 min. 1,1-
Diphenyl-2-aza-1,4-pentadiene (7) (1.11 g, 5.0 mmol) in THF
(2 mL) was added with stirring at -78 °C. After 3 h, (-)-B-
chlorodiisopinocampheylborane (1.60 g, 5.0 mmol) in THF (5
mL) was added to the dark red mixture which was maintained
at -78 °C for 2 h. To this solution was added cyclohexan-
ecarboxaldehyde (0.45 g, 4.0 mmol) in THF (1 mL). The
reaction mixture was maintained at -78 °C for 3 h after which
aqueous NaOH (2 mL, 2.5 M) and 30% H2O2 (2 mL) were
added. The reaction mixture was stirred at room temperature
for 12 h and diluted with ether (40 mL), and the organic phase
was separated and dried (MgSO4). Evaporation and chroma-
tography (silica gel, hexane-EtOAc, 4:1) gave imine 10a (0.75
g, 56%) as a white solid: mp 92-93 °C (hexane-EtOAc); TLC
Rf 0.33 (hexane-EtOAc, 4:1); [R]24 +34.3° (c 0.7, CHCl3); IR
D
(CHCl3) 3441 (OH), 3080, 3059, 3027, 2888, 1623 (CdN), 1445,
1150 cm-1 1H NMR (500 MHz, CDCl3) δ 7.50 (d, 2H, J 6.5
;
Hz), 7.42-7.17 (m, 11H), 6.85 (m, 2H), 6.01 (ddd, 1H, J 17.4,
10.4, 6.6 Hz), 5.15 (d, 1H, J 10.4 Hz), 4.99 (d, 1H, J 17.4 Hz),
4.81 (d, 1H, J 5.9 Hz), 4.00 (app t, 1H, J 6.4 Hz); 13C NMR
(125.8 MHz, CDCl3) δ 169.0, 141.1, 139.8, 136.7, 136.6, 130.4,
128.8, 128.7, 128.4, 128.3, 128.2, 127.8, 127.6, 127.0, 117.8,
76.7, 72.2; MS (CI, NH3) m/ z 328 (M + H)+, 310 (M + H-H2O)+,
220, 165, 146, 117; HRMS (CI, NH3) m/ z calcd for C23H22NO
(M + H)+ 328.1701, found 328.1700; Anal. Calcd for C23H21
-
NO: C, 84.37; H, 6.46; N, 4.28. Found: C, 84.77; H, 6.19; N,
4.18. Mosher ester 15b: 1H NMR (500 MHz, CDCl3) δ 7.50-
7.10 (m, 18H), 6.78 (d, 2H, J 6.9 Hz), 6.16 (d, 1H, J 7.2 Hz),
6.08 (ddd, 1H, J 17.3, 10.4, 6.9 Hz), 5.19 (d, 1H, J 10.4 Hz),
5.07 (d, 1H, J 17.3 Hz), 4.25 (app t, 1H, J 7.0 Hz), 3.57 (s,
3H).
Rf 0.51 (hexane-EtOAc, 4:1); [R]24 -27.3° (c 1.0, CHCl3); IR
D
(-)-(1S,2R)-2-[(Dip h en ylm et h ylen e)a m in o]-1-p h en yl-
3-bu ten -1-ol (13b). Imino alcohol 13b (67 mg, 52%) was
obtained as a white solid: mp 97-98 °C (hexane-EtOAc); TLC
(CHCl3) 3503 (OH), 3079, 3059, 2924, 2851, 1623 (CdN), 1446,
1106 cm-1; 1H NMR (500 MHz, CDCl3) δ 7.61-7.12 (m, 10H),
6.05 (ddd, 1H, J 17.3, 9.4, 6.7 Hz), 5.15 (dd, 1H, J 9.4, 1.2 Hz),
Rf 0.33 (hexane-EtOAc, 4:1); [R]24 -35.0° (c 0.8, CHCl3); IR
D
(CHCl3) 3566 (OH), 3059, 3027, 2890, 1622 (CdN), 1598, 1491,
1
1151 cm-1; H NMR (270 MHz, CDCl3) δ 7.55 (m, 2H), 7.41-
(17) Schmid, C. R.; Bryant, J . D. Org. Synth. 1993, 72, 6.
(18) Garner, P.; Park, J . M. J . Org. Chem. 1987, 52, 2361.
(19) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
7.21 (m, 11H), 6.84 (m, 2H), 6.01 (ddd, 1H, J 16.1, 10.0, 6.0
Hz), 5.17 (d, 1H, J 10.0 Hz), 5.00 (d, 1H, J 16.1 Hz), 4.83 (d,
1H, J 5.9 Hz), 4.01 (app t, 1H, J 6.1 Hz); 13C NMR (125.8 MHz,
CDCl3) δ 169.0, 141.1, 139.8, 136.8, 136.7, 130.4, 128.8, 128.7,

2682 J . Org. Chem., Vol. 61, No. 8, 1996
Barrett et al.
128.4, 128.3, 128.2, 127.8, 127.6, 127.0, 117.8, 76.7, 72.2; MS
(CI, NH3) m/ z 328 (M + H)+, 220, 165, 146, 117; HRMS (CI,
NH3) m/ z calcd for C23H22NO (M + H)+ 328.1701, found
328.1720. Anal. Calcd for C23H21NO: C, 84.37; H, 6.46; N,
4.28. Found: C, 84.67; H, 6.31; N, 4.10. Mosher ester 16b:
1H NMR (500 MHz, CDCl3) δ 7.47-7.26 (m, 18H), 6.72 (d, 2H,
J 7.0 Hz), 6.24 (d, 1H, J 8.0 Hz), 5.91 (ddd, 1H, J 17.3, 10.3,
6.9 Hz), 5.02 (d, 1H, J 10.3 Hz), 4.93 (d, 1H, J 17.3 Hz), 4.22
(app t, 1H, J 6.9 Hz), 3.44 (s, 3H).
5H), 1.42 (s, 6H), 1.38 (s, 9H); MS (CI, NH3) m/ z 451 (M +
H)+, 395, 250, 221, 167; HRMS (CI, NH3) m/ z calcd for
C
27H35N2O4 (M + H)+ 451.2597, found 451.2628.
(-)-ter t-Bu tyl 4(S)-[2(R)-[(Dip h en ylm eth ylen e)a m in o]-
1(S)-h yd r oxy-3-b u t en -1-yl]-2,2-d im et h yl-3-oxa zolid in e-
ca r boxyla te (13e). Imino alcohol 13e (89 mg, 40%) was
obtained as a yellow solid: mp 90-92 °C (hexane-EtOAc);
TLC Rf 0.68 (hexane-EtOAc, 2:1); [R]24D -25.2° (c 1.1, CHCl3);
IR (CHCl3) 3452 (OH), 3041, 2977, 2876, 1693 (NCO2), 1662
1
(CdN), 1447 cm-1; H NMR (500 MHz, CDCl3) δ 7.59 (d, 2H,
(+)-(1S,2S)-2-[(Dip h en ylm eth ylen e)a m in o]-1-(2-p yr id i-
n yl)-3-bu ten -1-ol (10c). Imino alcohol 10c (116 mg, 49%) was
obtained as a yellow oil: TLC Rf 0.32 (hexane-EtOAc, 1:1);
[R]24D +41.1° (c 0.7, CHCl3); IR (CHCl3) 3480 (OH), 3281, 3080,
3022, 2922, 1623 (CdN), 1592, 1472 cm-1; 1H NMR (500 MHz,
CDCl3) δ 8.49 (m, 1H), 7.77-7.23 (m, 10H), 6.70 (m, 2H), 6.13
(ddd, 1H, J 17.2, 10.4, 6.0 Hz), 5.18 (d, 1H, J 10.5 Hz), 4.97
J 7.2 Hz), 7.38-7.08 (m, 8H), 6.04 (m, 1H), 5.09 (d, 1H, J 9.8
Hz), 5.00 (d, 1H, J 17.4 Hz), 4.14-4.07 (m, 3H), 3.95 (m, 1H),
3.81 (m, 1H), 1.47 (s, 3H), 1.42 (s, 3H), 1.37 (s, 9H); 13C NMR
(125.8 MHz, CDCl3) δ 168.6, 152.1, 139.3, 136.9, 136.2, 130.2,
128.5, 128.4, 128.3, 128.0, 127.5, 116.4, 93.3, 79.9, 74.4, 67.6,
63.9, 58.1, 28.4, 28.3, 27.9, 26.3, 25.9; MS (CI, NH3) m/ z 451
(M + H)+, 250, 221, 183, 167; HRMS (CI, NH3) m/ z calcd for
(d, 1H, J 17.2 Hz), 4.90 (m, 1H), 4.03 (app t, 1H, J 6.3 Hz); 13
C
C
27H35N2O4 (M + H)+ 451.2597, found 451.2610. Anal. Calcd
NMR (125.8 MHz, CDCl3) δ 168.8, 159.9, 148.3, 139.6, 137.2,
136.5, 134.2, 130.2, 128.6, 128.4, 128.1, 127.5, 126.4, 122.5,
116.6, 76.2, 71.4; MS (CI, NH3) m/ z 329 (M + H)+, 311, 220,
183, 165, 145, 77; HRMS (CI, NH3) m/ z calcd for C22H21N2O
(M + H)+ 329.1654, found 329.1674. Mosher ester 15c: 1H
NMR (500 MHz, CDCl3) δ 8.45 (d, 1H, J 4.9 Hz), 7.54-6.97
(m, 18H), 6.24 (d, 1H, J 5.6 Hz), 5.99 (m, 1H), 5.09 (d, 1H, J
10.5 Hz), 4.88 (d, 1H, J 17.2 Hz), 4.54 (m, 1H), 3.57 (s, 3H).
(-)-(1R,2R)-2-[(Dip h en ylm et h ylen e)a m in o]-1-(2-p yr i-
d in yl)-3-bu ten -1-ol (13c). Imino alcohol 13c (88 mg, 51%)
was obtained as a yellow oil: TLC Rf 0.32 (hexane-EtOAc,
1:1); [R]24D -40.6° (c 0.9, CHCl3); IR (CHCl3) 3436 (OH), 3080,
3022, 2923, 1623 (CdN), 1592, 1474 cm-1; 1H NMR (250 MHz,
CDCl3) δ 8.51 (m, 1H), 7.79-7.13 (m, 11H), 6.70 (m, 2H), 6.13
(ddd, 1H, J 17.1, 10.5, 5.9 Hz), 5.19 (d, 1H, J 10.5 Hz), 4.98
(d, 1H, J 17.1 Hz), 4.91 (d, 1H, J 6.4 Hz), 4.04 (app t, 1H, J
6.2 Hz); 13C NMR (125.8 MHz, CDCl3) δ 168.8, 159.9, 148.3,
139.6, 137.2, 136.5, 134.2, 130.2, 128.6, 128.4, 128.3, 128.1,
127.5, 126.4, 122.5, 116.6, 76.2, 71.4; MS (CI, NH3) m/ z 329
(M + H)+, 311, 220, 183, 165, 145; HRMS (CI, NH3) m/ z calcd
for C22H21N2O (M + H)+ 329.1654, found 329.1669. Mosher
ester 16c: 1H NMR (500 MHz, CDCl3) δ 8.50 (d, 1H, J 4.9
Hz), 7.62-7.14 (m, 17H), 6.81 (d, 1H, J 7.1 Hz), 6.20 (d, 1H, J
7.2 Hz), 5.82 (m, 1H), 4.96 (d, 1H, J 10.4 Hz), 4.84 (d, 1H, J
17.4 Hz), 4.49 (app t, 1H, J 6.8 Hz), 3.44 (s, 3H).
for C27H34N2O4: C, 71.97; H, 7.61; N, 6.22. Found C, 71.96;
H, 7.85; N, 6.01.
(+)-(3R,4S)-3-[(Dip h en ylm eth ylen e)a m in o]-1-h exen -4-
ol (13f). Imino alcohol 13f (42 mg, 48%) was obtained as a
colorless oil: TLC Rf 0.27 (hexane-EtOAc, 4:1); [R]24 +19.1°
D
(c 0.8, CHCl3); IR (neat) 3512 (OH), 3060, 2966, 2877, 1660
(CdN), 1128 (CsO) cm-1; 1H NMR (500 MHz, CDCl3) δ 7.82-
7.45 (m, 10H), 5.97 (ddd, 1H, J 17.5, 10.1, 8.2 Hz), 5.49 (d,
1H, J 17.5 Hz), 5.46 (d, 1H, J 10.1 Hz), 3.97-3.85 (m, 2H),
1.44 (m, 2H), 0.95 (t, 3H, J 7.3 Hz); 13C NMR (300 MHz, CDCl3)
δ 168.4, 137.7, 136.4, 132.4, 130.3, 128.3, 128.1, 127.8, 126.5,
125.6, 117.4, 80.5, 70.2, 26.0, 10.8; MS (CI, NH3) m/ z 280 (M
+ H)+, 221, 200, 183, 105; HRMS (CI, NH3) m/ z calcd for
C
19H22NO (M + H)+ 280.1701, found 280.1701.
(+)-(3R,4S)-3-[(Dip h en ylm et h ylen e)a m in o]-6-m et h yl-
1-h ep t en -4-ol (13g). Imino alcohol 13g (47 mg, 41%) was
obtained as a colorless oil: TLC Rf 0.32 (hexane-EtOAc, 4:1);
[R]24 +23.4° (c 0.7, CHCl3); IR (neat) 3524 (OH), 3060, 2965,
D
2876, 1660 (CdN), 1077 (CsO) cm-1
;
1H NMR (500 MHz,
CDCl3) δ 7.79-7.45 (m, 10H), 5.95 (ddd, 1H, J 16.3, 10.0, 7.5
Hz), 5.47 (d, 1H, J 16.3 Hz), 5.45 (d, 1H, J 10.0 Hz), 4.18 (m,
1H), 3.78 (m, 1H), 1.74 (m, 1H), 1.40 (m, 1H), 1.11 (m, 1H),
0.91 (d, 3H, J 6.4 Hz), 0.88 (d, 3H, J 6.4 Hz); 13C NMR (125.8
MHz, CDCl3) δ 162.9, 137.5, 132.4, 130.0, 129.2, 128.2, 122.8,
68.4, 58.9, 42.0, 24.3, 23.2, 21.9, MS (CI, NH3) m/ z 308 (M +
(-)-(4R)-2,2-Dim et h yl-4-[2(S)-[(d ip h en ylm et h ylen e)-
a m in o]-1(S)-h yd r oxy-3-bu ten -1-yl]-1,3-d ioxola n e (10d ).
Imino alcohol 10d (67 mg, 43%) was obtained as a white
solid: mp 136-137 °C (CH3OH); TLC Rf 0.49 (hexane-EtOAc,
2:1); [R]24D -18.7° (c 1.7, CHCl3); IR (CHCl3) 3179 (OH), 3080,
2988, 2905, 1621 (CdN) 1122 cm-1; 1H NMR (500 MHz, CDCl3)
δ 7.62-7.12 (m, 10H), 6.01 (ddd, 1H, J 17.3, 10.5, 6.3 Hz), 5.15
(dd, 1H, J 10.5, 1.5 Hz), 5.01 (dd, 1H, J 17.3, 1.5 Hz), 4.17-
3.93 (m, 4H), 3.80 (app t, 1H, J 5.0 Hz), 1.31 (s, 3H), 1.30 (s,
3H); 13C NMR (125.8 MHz, CDCl3) δ 169.2, 139.6, 136.5, 136.0,
130.5, 128.8, 128.6, 128.5, 128.3, 127.8, 117.3, 108.7, 76.2, 74.2,
66.8, 66.1, 26.9, 25.5; MS (CI, NH3) m/ z 352 (M + H)+, 220,
165, 117; HRMS (CI, NH3) m/ z calcd for C22H26NO3 (M + H)+
352.1913, found 352.1923. Anal. Calcd for C22H25NO3: C,
75.19; H, 7.17; N, 3.99. Found: C, 74.94; H, 6.94; N, 4.24.
(4R)-2,2-Dim eth yl-4-[2(R)-[(diph en ylm eth ylen e)am in o]-
1(R)-h yd r oxy-3-bu ten -1-yl]-1,3-d ioxola n e (13d ). Imino al-
cohol 13d (59 mg, 41% as a 30:11 diastereoisomeric ratio of
10d and 13d ) was obtained as a white solid: mp 96-98 °C
(hexane-EtOAc); TLC Rf 0.48 (hexane-EtOAc, 2:1); IR (CHCl3)
3176, 3080, 2988, 2904, 1621 (CdN), 1121 cm-1; 1H NMR (500
MHz, CDCl3) δ 7.69-7.12 (m, 10H), 6.05 (m, 1H), 5.13 (d, 1H,
J 10.4 Hz), 4.92 (d, 1H, J 17.3 Hz), 4.11-3.81 (m, 4H), 3.85
(app t, 1H, J 6.2 Hz), 1.37 (s, 3H), 1.32 (s, 3H); MS (CI, NH3)
m/ z 352 (M + H)+, 274, 250, 220, 182; HRMS (CI, NH3) m/ z
calcd for C22H26NO3 (M + H)+ 352.1913, found 352.1933.
ter t-Bu tyl4(S)-[2(S)-[(Dip h en ylm eth ylen e)a m in o]-1(R)-
h yd r oxy-3-bu ten -1-yl]-2,2-d im eth yl-3-oxa zolid in eca r box-
yla te (10e). Imino alcohol 10e (50 mg, 38% as a 17:21 dia-
stereoisomeric ratio of 10e and 13e) was obtained as a yellow
oil: TLC Rf 0.68 (hexane-EtOAc, 2:1); IR (CHCl3) 3452 (OH),
H)+, 222, 200, 182, 105; HRMS (CI, NH3) m/ z calcd for C21H26
NO (M + H)+ 308.2014, found 308.2003.
-
P r ep a r a t ion of (-)-(1R,2S)-2-Am in o-1-cycloh exyl-3-
bu ten -1-ol (11a ). Imine 10a (66 mg, 0.2 mmol) in MeOH (1
mL) was added to 10 mL of a 1 M HCl/CH3OH solution (1:1
v/v) at 0 °C, and the mixture was stirred for 15 min. The
reaction solution was concentrated under reduced pressure and
washed with ether (2 × 10 mL) and the aqueous residue
basified with NaOH (5 mL, 2.5 M in H2O). Extraction with
ethyl acetate (3 × 10 mL), drying (K2CO3), and concentration
in vacuo gave 11a (33mg, 98%) as a white solid: mp 65-66
°C (CHCl3); [R]24D -19.2° (c 0.8, CHCl3); IR (CHCl3) 3374 (OH),
3298, 3073, 2922, 2851, 1574, 1449, 1105 cm-1; 1H NMR (500
MHz, CDCl3) δ 5.87 (ddd, 1H, J 17.0, 9.1, 7.3 Hz), 5.20 (d, 1H,
J 17.0 Hz), 5.18 (d, 1H, J 9.1 Hz), 3.51 (m, 1H), 3.20 (dd, 1H,
J 8.1, 3.4 Hz), 1.91-1.00 (m, 11H); 13C NMR (125.8 MHz,
CDCl3) δ 137.8, 117.0, 78.3, 55.8, 40.4, 29.4, 29.0, 26.7, 26.2,
26.1; MS (CI, NH3) m/ z 170 (M + H)+, 152, 57; HRMS (CI,
NH3) m/ z calcd for C10H20NO (M + H)+ 170.1545, found
170.1538.
(+)-(1S,2R)-2-Am in o-1-cycloh exyl-3-b u t en -1-ol (14a ).
Amino alcohol 14a (33 mg, 97%), prepared from 13a using the
procedure for 11a , was obtained as a white solid: mp 65-66
°C (CHCl3); [R]24D +19.1° (c 1.0, CHCl3); IR (CHCl3) 3347, 3297,
3074, 3005, 2922, 2851, 1573, 1449, 1105 cm-1; 1H NMR (500
MHz, CDCl3) δ 5.89 (ddd, 1H, J 17.0, 9.2, 7.4 Hz), 5.20 (d, 1H,
J 17.0 Hz), 5.17 (d, 1H, J 9.2 Hz), 3.50 (m, 1H), 3.20 (dd, 1H,
J 8.3, 3.6 Hz), 1.99-0.96 (m, 11H); 13C NMR (125.8 MHz,
CDCl3) δ 137.8, 116.9, 78.3, 55.8, 40.4, 29.4, 29.0, 26.7, 26.2,
26.0; MS (CI, NH3) m/ z 170 (M + H)+, 152, 57; HRMS (CI,
NH3) m/ z calcd for C10H20NO (M + H)+ 170.1545, found
170.1544.
3060, 2978, 2879, 1692 (NCO2), 1662 (CdN), 1447 cm-1 1H
;
NMR (500 MHz, CDCl3) δ 7.74-7.09 (m, 10H), 6.07 (m, 1H),
5.13 (d, 1H, J 17.0 Hz), 4.91 (d, 1H, J 10.4 Hz), 4.17-3.48 (m,

Asymmetric Syntheses of anti-â-Amino Alcohols
J . Org. Chem., Vol. 61, No. 8, 1996 2683
P r ep a r a tion of (-)-(1R,2S)-1-Cycloh exyl-1-[(d ip h en yl-
m eth ylen e)a m in o]-3-bu ten -2-ol (21). To a stirred solution
of iminol 13a (50 mg, 0.15 mmol) and 2,6-lutidine (35 µL, 0.30
mmol) in CH2Cl2 (15 mL) at 0 °C was added trifluoromethane-
sulfonic anhydride (29 µL, 0.17 mmol) dropwise. After 12 h
at 0 °C under N2, H2O (1 mL) was added and the organic phase
separated, concentrated under reduced pressure, and chro-
matographed on silica (hexane-Et2O, 4:1) to give 21 (22 mg,
26.3, 25.9, 25.8, 20.8, 10.8; MS (CI, NH3) m/ z 551 (2M + H)+,
276 (M + H)+, 258, 216, 139, 122; HRMS (CI, NH3) m/ z calcd
for C17H26NO2 (M + H)+ 276.1963, found 276.1942; Anal.
Calcd for C17H25NO2: C, 74.14, H, 9.15; N, 5.09. Found: C,
73.84; H, 8.85; N, 4.94.
P r ep a r a tion of (1S*,2R*)-1-Cycloh exyl-2-n itr obu ta n -
1-ol (27) a n d (1R*,2R*)-1-Cycloh exyl-2-n it r ob u t a n -1-ol
(28). Nitro alcohols 27 and 28 were synthesized from cyclo-
hexanecarboxaldehyde and nitropropane (26) using the pro-
cedure reported by Seebach15 et al. giving syn-28 (0.70 g, 39%)
as a yellow oil and anti-27 (0.34 g, 20%) as an orange solid.
anti-Isomer 27: mp 65-67 °C (CHCl3); TLC Rf 0.20 (hexane-
EtOAc, 4:1); IR (neat) 3536 (OH), 3455, 2973, 2928, 2882, 1552
(C-NO2), 1450, 1101 (CsO) cm-1; 1H NMR (300 MHz, CDCl3)
δ 4.47 (ddd, 1H, J 11.1, 4.8, 4.5 Hz), 3.72 (dd, 1H, J 7.4, 4.5
Hz), 2.12-0.98 (m, 13H), 0.92 (t, 3H, J 7.4 Hz); 13C NMR (75.1
MHz, CDCl3) δ 91.9, 76.8, 40.6, 29.7, 28.3, 26.5, 26.3, 26.0,
21.7, 10.9; MS (CI, NH3) m/ z 219 (M + NH4)+, 184, 172, 154,
137, 95, 81, 58; HRMS (CI, NH3) m/ z calcd for C10H23N2O3 (M
44%) as a yellow oil. TLC Rf 0.41 (hexane-EtOAc, 4:1); [R]24
D
-35.8° (c 1.0, CHCl3); IR (neat) 3451 (OH), 3060, 3020, 2926,
2851, 1621 (CdN), 1446, 1197 (CsO) cm-1; 1H NMR (300 MHz,
CDCl3) δ 7.8-7.0 (m, 10H), 6.04 (m, 1H), 5.06 (app t, 1H, J
10.5Hz), 4.90 (2d, 1H, J 17.3 Hz), 4.37, 4.09, 3.96 (3m, 2H),
1.68-0.71 (m, 11H); 13C NMR (75.1 MHz, CDCl3) δ 168.8,
168.6, 140.1, 140.0, 138.0, 137.5, 137.1, 136.9, 132.8, 130.4,
129.1, 128.9, 128.7, 128.6, 128.4, 128.0, 117.6, 117.2, 83.1, 82.7,
66.8, 66.7, 39.6, 39.2, 30.8, 30.1, 28.0, 27.4, 26.7, 26.6, 26.5,
26.2; MS (CI, NH3) m/ z 334 (M + H)+, 222, 200, 183, 168,
105, 83; HRMS (CI, NH3) m/ z calcd for C23H28NO (M + H)+
334.2172, found 334.2172.
+ NH4)+ 219.1709, found 219.1713. Anal. Calcd for C10H19
-
P r ep a r a tion of (-)-(1R,2S)-1-Am in o-1-cycloh exylbu -
ta n -2-ol (22). Imino alcohol 21 (60 mg, 0.18 mmol), MeOH
(10 mL), and 3 M HCl (1 mL) were allowed to react for 10 min
when 5% Pd/C (20 mg) was added, and the mixture was
hydrogenated at 1 atm for 12 h. The reaction slurry was
filtered through celite and concentrated under reduced pres-
sure. The residual aqueous phase was washed with Et2O (2
× 10 mL), basified with aqueous 10% NaOH (3 mL), and
extracted with EtOAc (4 × 15 mL). The EtOAc fractions were
combined, dried over K2CO3, and concentrated in vacuo to 21
(28 mg, 0.16 mmol, 90%) as a white solid: mp 75-77 °C
(CHCl3); [R]24D -12.2° (c 0.25, CH3OH); IR (CHCl3) 3424 (OH),
3294, 2925, 2874, 1571, 1449, 1105 (CsO) cm-1; 1H NMR (300
MHz, CD3OD) δ 3.39 (m, 1H), 2.36 (m, 1H), 1.80-1.02 (m,
13H), 0.99 (t, 3H, J 7.4 Hz); 13C NMR (75.1 MHz, CD3OD) δ
74.1, 60.8, 41.6, 31.7, 29.1, 28.1, 27.8, 27.6, 27.5, 10.6; MS (CI,
NH3) m/ z 172 (M + H)+, 151, 137, 98, 58; HRMS (CI, NH3)
m/ z calcd for C10H22NO (M + H)+ 172.1701, found 172.1701.
(-)-(1R,2S)-1-Ben za m id o-1-cycloh exylbu ta n -2-ol (23).
To a stirred solution of amino alcohol 22 (20 mg, 0.12 mmol)
and Et3N (25 µL, 0.20 mmol) in CH2Cl2 at room temperature
was added benzoyl chloride (18 µL, 0.15 mmol). After 12 h
the reaction mixture was concentrated under reduced pressure
and chromatographed on silica (hexane-EtOAc, 4:1) to afford
23 (27 mg, 0.10 mmol, 83%) as a white solid: mp 191-192 °C
NO3: C, 59.66; H, 9.52; N, 6.96. Found: C, 59.62; H, 9.33; N,
6.85. syn-Isomer 28: TLC Rf 0.25 (hexane-EtOAc, 4:1); IR
(neat) 3544, 3446, 2973, 2929, 2882, 1552 (CsNO2), 1449, 1101
(CsO) cm-1 1H NMR (300 MHz, CDCl3) δ 4.58 (ddd, 1H, J
;
5.8, 4.9, 4.5 Hz), 3.62 (dd, 1H, J 5.9, 5.8 Hz), 2.11-1.13 (m,
13H), 0.99 (t, 3H, J 7.4 Hz); 13C NMR (75.1 MHz, CDCl3) δ
92.2, 76.3, 40.7, 30.2, 27.2, 26.5, 26.4, 26.1, 24.4, 10.6; MS (CI,
NH3) m/ z 219 (M + NH4)+, 184, 172, 154, 137, 95, 81, 58;
HRMS (CI, NH3) m/ z calcd for C10H23N2O3 (M + NH4)+
219.1709, found 219.1702.
P r ep a r a t ion of (1S*,2R*)-2-Ben za m id o-1-cycloh exyl-
b u t a n -1-ol (29). (1S*,2R*)-1-Cyclohexyl-2-nitrobutan-1-ol
(27)(0.70 g, 3.50 mmol) in MeOH (50 mL), 3 M HCl (1 mL),
and 10% Pd/C (∼100 mg) were hydrogenated at 600 psi for 16
h at 70 °C. The reaction slurry was filtered through Celite
and concentrated under reduced pressure. The remaining
aqueous fraction was washed with Et2O (2 × 10 mL) and
basified with aqueous 10% NaOH. Extraction of the basic
residue with EtOAc (4 × 25 mL), drying over K2CO3, and in
vacuo concentration afforded a white solid. This solid was
dissolved in CH2Cl2 (10 mL) and added to a stirred solution of
Et3N (0.46 mL, 3.50 mmol) in CH2Cl2 (15 mL). Benzoyl
chloride (0.29 mL, 2.5 mmol) was added dropwise to the
reaction solution at 0 °C. After 12 h the solution was
concentrated in vacuo and chromatographed on silica (hex-
ane-EtOAc, 1:1) to afford 29 (0.50 g, 57%) as white solid: mp
161-163 °C (CHCl3); TLC Rf 0.46 (hexane-EtOAc, 1:1); IR
(CHCl3); TLC Rf 0.47 (hexane-EtOAc, 1:1); [R]24 -34.3° (c
D
1.0, CHCl3); IR (CHCl3) 3326, 2928, 2853, 1637 (CdO), 1531,
1
1102 (C-O) cm-1; H NMR (300 MHz, CDCl3) δ 7.79 (m, 2H),
(CHCl3) 3327, 2928, 2853, 1632 (CdO), 1532, 1105 (CsO) cm-1
;
7.46 (m, 3H), 6.18 (d, 1H, J 9.4 Hz), 4.10 (m, 1H), 3.74 (m,
1H), 1.94-1.09 (m, 13H), 1.04 (t, 3H, J 7.4 Hz); 13C NMR (75.1
MHz, CDCl3) δ 168.5, 134.5, 131.6, 128.7, 127.0, 74.3, 59.1,
38.7, 30.9, 29.0, 26.2, 26.1, 25.9, 25.7, 10.5; MS (CI, NH3) m/ z
276 (M + H)+, 258, 216, 122; HRMS (CI, NH3) m/ z calcd for
C17H26NO2 (M + H)+ 276.1963, found 276.1950. Anal. Calcd
for C17H25NO2: C, 74.14; H, 9.15; N, 5.09. Found: C, 74.28;
H, 9.06; N, 4.99.
1H NMR (300 MHz, CDCl3) δ 7.80 (m, 2H), 7.46 (m, 3H), 6.49
(d, 1H, J 8.9 Hz), 4.26 (m, 1H), 3.44 (m, 1H), 1.99-1.11 (m,
13H), 1.04 (t, 3H, J 7.4 Hz); 13C NMR (75.1 MHz, CDCl3) δ
167.4, 134.9, 131,4, 128.6, 126.9, 78.8, 52.7, 40.8, 29.6, 28.9,
26.3, 25.9, 25.8, 20.8, 10.8; MS (CI, NH3) m/ z 276 (M + H)+,
258, 216, 139, 122; HRMS (CI, NH3) m/ z calcd for C17H26NO2
(M + H)+ 276.1963, found 276.1957. Anal. Calcd for C17H25
-
NO2: C, 74.13; H, 9.16; N, 5.09. Found: C, 74.29; H, 8.78; N,
4.97.
(+)-(1S,2R)-2-Am in o-1-cycloh exylbu tan -1-ol (24). Amino
alcohol 24 (62 mg, 81%), prepared from 13a according to the
procedure described for 22, was obtained as a white solid: mp
(1R*,2R*)-2-Ben za m id o-1-cycloh exylb u t a n -1-ol (30).
Amide 30 (0.24 g, 59%), prepared using the same procedure
as for 29, was obtained as a white solid: mp 137-139 °C
(CHCl3); TLC Rf 0.40 (hexane-EtOAc, 1:1); IR (CHCl3) 3327,
2928, 2853, 1637 (CdO), 1531, 1101 (CsO) cm-1; 1H NMR (300
MHz, CDCl3) δ 7.80 (m, 2H), 7.45 (m, 3H), 4.26 (m, 1H), 3.44
(m, 1H), 2.06-1.07 (m, 13H), 1.01 (t, 3H, J 7.4 Hz); 13C NMR
(75.1 MHz, CDCl3) δ 167.3, 134.5, 131.4, 128.6, 126.9, 78.8,
52.7, 40.8, 29.6, 28.9, 26.3, 25.9, 25.8, 20.8, 10.8; MS (CI, NH3)
m/ z 276 (M + H)+, 258, 216, 174, 153; HRMS (CI, NH3) m/ z
calcd for C17H26NO2 (M + H)+ 276.1963, found 276.1962. Anal.
Calcd for C17H25NO2: C, 74.13; H, 9.16; N, 5.09. Found: C,
74.24; H, 9.00; N, 5.09.
P r ep a r a tion of (1R*,2S*)-1-Cycloh exyl-1-n itr obu ta n -
2-ol (32) a n d (1R*,2R*)-1-Cycloh exyl-1-n it r ob u t a n -2-ol
(33). Nitro alcohols 32 and 33 were prepared from (nitrom-
ethyl)cyclohexane (31)14 and propanal according to the proce-
dure reported by Seebach15 et al. giving anti-32 (0.25 g, 12%)
as a colorless oil and syn-33 (0.65 g, 32%) as a colorless oil.
167-169 °C (CHCl3); [R]24 +6.9° (c 0.5, CH3OH); IR (CHCl3)
D
3364 (OH), 3295, 2924, 2875, 1577 (C-N), 1462, 1103 (CsO)
cm-1 1H NMR (300 MHz, CDCl3) δ 3.13 (dd, 1H, J 8.0, 4.0
;
Hz), 2.76 (m, 1H), 1.96-0.81 (m, 16H); 13C NMR (75.1 MHz,
CD3OD) δ 75.5, 53.6, 39.2, 28.2, 28.1, 25.4, 24.9, 24.8, 19.4,
8.6; MS (CI, NH3) m/ z 172 (M + H)+, 154, 88, 58; HRMS (CI,
NH3) m/ z calcd for C10H22NO (M + H)+ 172.1701, found
172.1699.
(+)-(1S,2R)-2-Ben za m id o-1-cycloh exylbu ta n -1-ol (25).
Amide 25 (72 mg, 90%), prepared using the same method as
for 23, was obtained as a white solid: mp 185-187 °C (CHCl3);
TLC Rf 0.46 (hexane-EtOAc, 1:1); [R]24D +26.8° (c 1.0, CHCl3);
IR (CHCl3) 3327, 2928, 2853, 1632 (CdO), 1532, 1105 (CsO)
cm-1; 1H NMR (300 MHz, CDCl3) δ 7.80 (m, 2H), 7.45 (m, 3H),
6.49 (d, 1H, J 8.9 Hz), 4.27 (m, 1H), 3.46 (m, 1H), 2.07-1.06
(m, 13H), 0.98 (t, 3H, J 7.4 Hz); 13C NMR (75.1 MHz, CDCl3)
δ 167.4, 134.9, 131.4, 128.5, 126.9, 78.8, 52.7, 40.8, 29.6, 28.9,

2684 J . Org. Chem., Vol. 61, No. 8, 1996
Barrett et al.
anti-Isomer 32: TLC Rf 0.12 (hexane-Et2O, 4:1); IR (neat) 3550
(OH), 3480, 2974, 2928, 2882, 1552 (C-NO2), 1450, 1108
(C-O) cm-1; 1H NMR (300 MHz, CDCl3) δ 4.34 (dd, 1H, J 6.4,
5.7 Hz), 3.97 (m, 1H), 2.12-1.04 (m, 13H), 1.00 (t, 3H, J 7.4
Hz); 13C NMR (75.1 MHz, CDCl3) δ 97.2, 72.0, 38.0, 30.3, 29.1,
26.7, 26.4, 26.3, 26.1, 10.2; MS (CI, NH3) m/ z 219 (M + NH4)+,
172, 154, 137, 58; HRMS (CI, NH3) m/ z calcd for C10H23N2O3
(M + NH4)+ 219.1709, found 219.1727. syn-Isomer 33: TLC
Rf 0.15 (hexane-Et2O, 4:1); IR (neat) 3550 (OH), 3479, 2974,
182-184 °C (CH3OH); TLC Rf 0.46 (hexane-EtOAc, 4:1); [R]24
D
-10.2° (c 0.7, CHCl3); IR (CHCl3) 3096, 2929, 2852, 1737
(CdO), 1673 (CdO), 1543 cm-1; 1H NMR (300 MHz, CDCl3) δ
9.20 (s, 1H), 8.91 (s, 2H), 7.45-7.31 (m, 5H), 6.49 (d, 1H, J
9.8 Hz), 5.00 (m, 1H), 4.81 (s, 1H), 4.31 (m, 1H), 3.49 (s, 3H),
1.77-0.90 (m, 13H), 0.71 (t, 3H, J 7.4 Hz); 13C NMR (75.1 MHz,
CDCl3) δ 171.3, 162.6, 148.7, 138.1, 136.1, 128.8, 128.6, 127.1,
127.0, 121.0, 82.7, 57.6, 38.3, 30.8, 28.5, 26.0, 25.9, 25.8, 23.9,
9.7; MS (CI, NH3) m/ z 531 (M + NH4)+, 484, 454, 348, 318,
184, 121; HRMS (CI, NH3) m/ z calcd for C26H35N4O8 (M +
1
2929, 2882, 1552 (C-NO2), 1450, 1103 (C-O) cm-1; H NMR
(300 MHz, CDCl3) δ 4.18 (dd, 1H, J 7.2, 4.1 Hz), 3.77 (m, 1H),
2.16-0.98 (m, 13H), 0.95 (t, 3H, J 7.4 Hz); 13C NMR (75.1 MHz,
CDCl3) δ 97.3, 70.6, 38.0, 29.5, 27.7, 26.4, 26.2, 26.0, 25.8, 10.5;
MS (CI, NH3) m/ z 219 (M + NH4)+, 172, 154, 137, 58; HRMS
(CI, NH3) m/ z calcd for C10H23N2O3 (M + NH4)+ 219.1709,
found 219.1730.
NH4)+ 531.2455, found 531.2474. Anal. Calcd for C26H31
-
N3O8: C, 59.99;H, 6.04; N, 8.40. Found: C, 60.26; H, 6.09; N,
8.41.
(-)-(3S,4R)-4-Am in o-1-h exen -3-ol Hyd r och lor id e (38a ).
To a stirred solution of imino alcohol 13f (60 mg, 0.22 mmol)
and 2,6-lutidine (52 µL, 0.45 mmol) in CH2Cl2 (10 mL) at 0 °C
was added trifluoromethanesulfonic anhydride (56 µL, 0.33
mmol) dropwise. The mixture was stirred for 8 h, filtered
through silica, concentrated in vacuo, and acidified (1 M HCl
in MeOH). The resulting aqueous residue was washed with
EtOAc (3 × 10 mL) and concentrated under reduced pressure
to afford amino alcohol 38a (12 mg, 38%) as a colorless viscous
oil: [R]24D -8.9° (c 0.35, H2O); IR (neat) 3390, 2969, 2930, 1605
(CdC), 1505, 992 (CsO) cm-1; 1H NMR (500 MHz, D2O) δ 5.84
(ddd, 1H, J 17.3, 10.6, 6.0 Hz), 5.40 (d, 1H, J 17.3 Hz), 5.37
(d, 1H, J 10.6 Hz), 4.38 (dd, 1H, J 5.2, 4.4 Hz), 3.25 (m, 1H),
1.67 (m, 1H), 1.55 (m, 1H), 0.96 (t, 3H, J 7.5 Hz); 13C NMR
(100 MHz, D2O) δ 134.3, 119.9, 71.7, 57.6, 21.8, 10.0; FABMS
(3-NBA) m/ z 267 [2(M + H) + H]+, 231 [2(M - Cl)+H]+, 116
(1S*,2R*)-1-Ben za m id o-1-cycloh exylb u t a n -2-ol (34).
Amide 34 (0.17 g, 56%), prepared using the same procedure
as for 29, was obtained as a white solid: mp 168-169 °C
(CHCl3); TLC Rf 0.45 (hexane-EtOAc, 1:1); IR (CHCl3) 3326,
2928, 2853, 1637 (CdO), 1531, 1102 (CsO) cm-1; 1H NMR (300
MHz, CDCl3) δ 7.79 (m, 2H), 7.46 (m, 3H), 6.20 (d, 1H, J 9.4
Hz), 4.10 (m, 1H), 3.72 (m, 1H), 1.94-1.09 (m, 13H), 1.04 (t,
3H, J 7.4 Hz); 13C NMR (75.1 MHz, CDCl3) δ 168.5, 134.5,
131.6, 128.7, 127.0, 74.3, 59.0, 38.7, 30.9, 29.0, 26.2, 26.1, 25.9,
25.7, 10.5; MS (CI, NH3) m/ z 276 (M + H)+, 258, 216, 163,
122; HRMS (CI, NH3) m/ z calcd for C17H26NO2 (M + H)+
276.1963, found 276.1948. Anal. Calcd for C17H25NO2: C,
74.13; H, 9.16; N, 5.09. Found: C, 74.37; H, 8.92; N, 4.98.
(1R*,2R*)-1-Ben za m id o-1-cycloh exylb u t a n -2-ol (35).
Amide 35 (0.18 g, 51%), prepared using the same procedure
as for 29, was obtained as a white solid: mp 144-145 °C
(CHCl3); TLC Rf 0.49 (hexane-EtOAc, 1:1); IR (CHCl3) 3326,
2928, 2853, 1637 (CdO), 1531, 1104 (CsO) cm-1; 1H NMR (300
MHz, CDCl3) δ 7.72 (m, 2H), 7.36 (m, 3H), 6.39 (d, 1H, J 9.0
Hz), 3.79 (m, 2H), 1.92-1.00 (m, 13H), 0.94 (t, 3H, J 7.4 Hz);
13C NMR (75.1 MHz, CDCl3) δ 168.0, 134.8, 131.4, 128.6, 126.9,
72.0, 57.3, 39.7, 30.2, 29.9, 28.0, 26.4, 26.3, 26.2, 10.2; MS (CI,
NH3) m/ z 258 (M + H - H2O)+, 216, 174, 167, 122; HRMS
(CI, NH3) m/ z calcd for C17H24NO (M + H-H2O)+ 258.1858,
found 258.1854. Anal. Calcd for C17H25NO2: C, 74.13; H, 9.16;
N, 5.09. Found: C, 74.31; H, 8.90; N, 4.85.
(M + H - Cl)+, 57; HRFABMS (3-NBA) m/ z calcd for C6H14
NO (M + H - Cl)+ 116.1075, found 116.1081.
-
(-)-(3S,4R)-4-Am in o-6-m et h yl-1-h ep t en -3-ol H yd r o-
ch lor id e (38b). Amine hydrochloride 38b (14 mg, 31%),
prepared from 13g as for 38a , was obtained as a colorless oil
using the procedure described for 38b: [R]24 -11.3° (c 0.20,
D
H2O); IR (neat) 3360, 2957, 2932, 1602, 1501, 1050 (CsO)
1
cm-1; H NMR (500 MHz, D2O) δ 5.85 (ddd, 1H, J 17.2, 10.7,
5.7 Hz), 5.42 (d, 1H, J 17.2 Hz), 5.37 (d, 1H, J 10.7 Hz), 4.40
(app t, 1H, J 5.4 Hz), 3.42 (m, 1H), 1.69-1.10 (m, 3H), 0.91
(d, 3H, J 6.5 Hz), 0.88 (d, 3H, J 6.5 Hz); 13C NMR (100 MHz,
D2O) δ 134.2, 119.8, 72.0, 54.2, 37.3, 24.4, 22.8, 21.5; FABMS
(3-NBA) m/ z 323 [2(M + H) - Cl]+, 287 [2(M - Cl) + H]+,
144 (M + H - Cl)+, 85; HRFABMS (3-NBA) m/ z calcd for
C8H18NO (M + H - Cl)+ 144.1388, found 144.1389.
(-)-cis-(4R,5S)-4-Cycloh exyl-5-et h yl-1,3-oxa zolid in -2-
on e (36). To a stirred solution of amino alcohol 22 (21 mg,
0.12 mmol) and diisopropylethylamine (47 µL, 0.27 mmol) in
CH2Cl2 (5 mL) at 0 °C was added triphosgene (18 mg, 0.06
mmol). The reaction solution was allowed to warm to room
temperature with stirring for 12 h. H2O (1 mL) and EtOAc
(15 mL) were added to the mixture, and the organic phase was
separated, dried over Na2SO4, concentrated under reduced
pressure, and chromatographed on silica (EtOAc) to afford 36
(21 mg, 85%) as colorless crystals: mp 143-144 °C (CHCl3);
(-)-cis-(4R ,5S )-5-E t h e n yl-4-e t h yl-1,3-oxa zolid in -2-
on e (39a ). Oxazolidinone 39a (12 mg, 77%), prepared from
38a using the same procedure as for 36, was obtained as a
yellow oil: TLC Rf 0.55 (EtOAc); [R]24 -40.6° (c 0.7, CHCl3);
D
IR (CHCl3) 2929, 2879, 1751 (CdO), 1127 (CsO) cm-1
;
1H
NMR (300 MHz, CDCl3) δ 6.32 (br s, 1H), 5.91 (ddd, 1H, J
17.1, 10.5, 7.9 Hz), 5.46 (d, 1H, J 17.1 Hz), 5.38 (d, 1H, J 10.5
Hz), 5.05 (app t, 1H, J 7.9 Hz), 3.81 (m, 1H), 1.52 (m, 2H),
0.96 (t, 3H, J 7.4 Hz); 13C NMR (75.1 MHz, CDCl3) δ 159.3,
131.0, 118.8, 80.6, 57.5, 24.1, 10.3; MS (CI, NH3) m/ z 159 (M
+ NH4)+, 142 (M + H)+, 98; HRMS (CI, NH3) m/ z calcd for
C7H15N2O2 (M + NH4)+ 159.1134, found 159.1136; Anal. Calcd
for C7H11NO2: C, 59.56; H, 7.85; N, 9.92. Found: C, 59.82;
H, 7.96; N, 9.89.
TLC Rf 0.62 (EtOAc); [R]24 -17.8° (c 1.0, CHCl3); IR (CHCl3)
D
1
2928, 2854, 1750 (CdO) cm-1; H NMR (300 MHz, CDCl3) δ
6.57 (s, 1H), 4.47 (m, 1H), 3.56 (app t, 1H, J 7.1 Hz), 1.86-
1.11 (m, 13H), 1.07 (t, 13H, J 7.4 Hz); 13C NMR (75.1 MHz,
CDCl3) δ 160.3, 81.9, 61.1, 37.5, 30.4, 29.0, 26.0, 25.7, 25.5,
22.0, 10.5; MS (CI, NH3) m/ z 215 (M + H)+, 198, 72; HRMS
(CI, NH3) m/ z calcd for C11H23N2O2 (M + NH4)+ 215.1760,
found 215.1757. Anal. Calcd for C11H19NO2: C, 66.96; H, 9.71;
N, 7.10. Found: C, 66.93; H, 9.45; N, 6.83.
(-)-cis-(4R,5S)-5-Eth en yl-4-(2-m eth ylp r op yl)-1,3-oxa zo-
lid in -2-on e (39b). Oxazolidinone 39b (16 mg, 80%), prepared
from 38b using the same procedure as for 36, was obtained
as a yellow oil: TLC Rf 0.58 (EtOAc); [R]24 -37.1° (c 0.3,
(-)-(1R,2S)-1-Cycloh exyl-1-(3,5-d in it r ob en za m id o)-2-
[2(R)-m eth oxyp h en yla cetoxy] bu ta n e (37). To a stirred
solution of amino alcohol 22 (34 mg, 0.20 mmol) in CH2Cl2 (10
mL) was added 2,6-lutidine (31 µL, 0.27 mmol) and 3,5-
dinitrobenzoyl chloride (46 mg, 0.21 mmol). After stirring for
12 h at room temperature the reaction was filtered through
silica and concentrated in vacuo. The crude solid was redis-
solved in dry CH2Cl2 (10 mL) and placed under an atmosphere
of nitrogen. To the reaction solution was added dicyclohexy-
lcarbodiimide (82 mg, 0.40 mmol), (R)-O-methylmandelic acid
(66 mg, 0.40 mmol), and 4-(dimethylamino)pyridine (5 mg).
After 3 h the mixture was concentrated under reduced pres-
sure and directly chromatographed on silica (hexane-EtOAc,
4:1) to give 37 (72 mg, 70% overall) as a white solid. Recrys-
tallization (CH3OH, -10 °C) gave 37 as colorless needles: mp
D
CHCl3); IR (CHCl3) 2955, 2871, 1747 (CdO), 1120 (CsO) cm-1
;
1H NMR (300 MHz, CDCl3) δ 5.89 (ddd, 1H, J 17.2, 10.5, 6.5
Hz), 5.45 (d, 1H, J 17.2 Hz), 5.38 (d, 1H, J 10.5 Hz), 5.34 (br
s, 1H), 5.06 (app t, 1H, J 7.6 Hz), 3.97 (m, 1H), 1.80-1.15 (m,
3H), 0.98 (d, 3H, J 6.5 Hz), 0.92 (d, 3H, J 6.5 Hz); 13C NMR
(75.1 MHz, CDCl3) δ 159.3, 131.0, 120.1, 80.6, 53.9, 39.7, 25.1,
23.4, 21.4; MS (CI, NH3) m/ z 187 (M + NH4)+, 170 (M + H)+,
126; HRMS (CI, NH3) m/ z calcd for C9H19N2O2 (M + NH4)+
187.1446, found 187.1446.
(+)-(3R,4S)-3-Am in o-1-h exen -4-ol Hyd r och lor id e (40a ).
Imino alcohol 13f (76 mg, 0.27 mmol) was added with stirring
to (6 mL) of 1 M HCl/CH3OH solution (1:1, v/v). After 15 min,
the solution was concentrated in vacuo, and the aqueous
residue was washed with EtOAc (3 × 10 mL) and concentrated

Asymmetric Syntheses of anti-â-Amino Alcohols
J . Org. Chem., Vol. 61, No. 8, 1996 2685
under reduced pressure to give 40a (38 mg, 93%) as a colorless
17.2, 10.0, 7.6 Hz), 5.25 (d, 1H, J 17.2 Hz), 5.24 (d, 1H, J 10.0
Hz), 4.70 (m, 1H), 4.25 (app t, 1H, J 7.6 Hz), 1.81 (m, 1H),
1.56 (m, 1H), 1.24 (m, 1H), 0.93 (d, 3H, J 7.0 Hz), 0.89 (d, 3H,
J 7.0 Hz); 13C NMR (75.1 MHz, CDCl3) δ 159.9, 133.2, 119.0,
78.5, 58.4, 39.1, 24.8, 23.2, 21.7; MS (CI, NH3) m/ z 187 (M +
NH4)+, 170 (M + H)+, 126; HRMS (CI, NH3) m/ z calcd for
C9H19N2O2 (M + NH4)+ 187.1446, found 187.1439.
viscous oil: [R]24 +14.0° (c 0.4, H2O); IR (neat) 3376, 2968,
D
2937, 1602, 1503 cm-1; 1H NMR (300 MHz, D2O) δ 5.82 (ddd,
1H, J 17.3, 10.3, 8.1 Hz), 5.48 (d, 1H, J 10.3 Hz), 5.40 (d, 1H,
J 17.3 Hz), 3.83 (m, 1H), 3.73 (m, 1H), 1.46 (m, 2H), 0.89 (t,
3H, J 7.4 Hz); 13C NMR (75.1 MHz, D2O) δ 128.6, 122.7, 72.1,
57.5, 25.8, 9.4; FABMS (3-NBA) m/ z 267 [2(M + H) - Cl]+,
231 [2(M - Cl) + H]+, 116 (M + H - Cl)+, and 57; HRFABMS
(CI, NH3) m/ z calcd for C6H14NO (M + H - Cl)+ 116.1075,
found 116.1067.
(+)-cis-(4R,5S)-4,5-Dieth yl-1,3-oxazolidin -2-on e (42). Ox-
azolidinone 41a (30 mg, 0.20 mmol), 5% Pd/C (20 mg), and
MeOH (5 mL) were hydrogenated at 1 atm for 12 h and filtered
through Celite. The filtrate was concentrated under reduced
pressure to afford a colorless low melting solid (28 mg, 90%):
(+)-(3R,4S)-3-Am in o-6-m et h yl-1-h ep t en -4-ol H yd r o-
ch lor id e (40b). Amine hydrochloride 40b (18 mg, 96%),
prepared from 13g as for 40a , was obtained as a white solid:
mp 115-117 °C (EtOAc); [R]24D +17.3° (c 0.45, H2O); IR (KBr)
3330, 3052, 2952, 2897, 1603 (CdC), 1051 (C-O) cm-1; 1H NMR
(300 MHz, D2O) δ 5.76 (ddd, 1H, J 17.3, 10.5, 8.2 Hz), 5.39 (d,
1H, J 10.5 Hz), 5.33 (d, 1H, J 17.3 Hz), 3.87 (m, 1H), 3.70 (m,
1H), 1.61 (m, 1H), 1.26 (m, 1H), 1.13 (m, 1H), 0.80 (d, 3H, J
7.0 Hz), 0.77 (d, 3H, J 7.0 Hz); 13C NMR (300 MHz, D2O) δ
128.6, 122.6, 68.6, 58.0, 41.4, 23.7, 22.5, 20.9; FABMS (3-NBA)
m/ z 323 [2(M + H)-Cl]+, 287 [2(M - Cl) + H]+, 144 (M + H -
Cl)+, 85, 57; HRFABMS (3-NBA) m/ z calcd for C8H18NO (M
mp 33-34 °C (CHCl3); TLC Rf 0.43 (hexane-EtOAc, 1:1); [R]24
D
+11.6° (c 0.9, CHCl3); IR (CHCl3) 3258 (NH), 2972, 2881, 1748
(CdO), 1028 cm-1 1H NMR (300 MHz, CDCl3) δ 5.84 (br s,
;
1H), 4.52 (ddd, 1H, J 7.5, 4.3, 4.3 Hz), 3.67 (m, 1H), 1.84-
1.41 (m, 4H), 1.08 (t, 3H, J 7.4, Hz), 0.98 (t, 3H, J 7.4 Hz); 13
C
NMR (125.8 MHz, CDCl3) δ 159.4, 82.2, 57.5, 23.2, 22.7, 10.82,
10.79; MS (CI, NH3) m/ z 304 (2M + NH4)+, 287 (2M + H)+,
161 (M + NH4)+, 144 (M + H)+; HRMS (CI, NH3) m/ z calcd
for C7H17N2O2 (M + NH4)+ 161.1298, found 161.1294.
Compound 39a was reduced using the above procedure to
give 42 in 85% yield as a low melting colorless solid. Mp 32-
33 °C (hexane-EtOAc); mixed mp 32-33 °C (hexane-EtOAc);
+ H - Cl)+ 144.1388, found 144.1397. Anal. Calcd for C8H18
-
ClNO: C, 53.46; H, 10.10; N, 7.79. Found: C, 53.19; H, 10.33;
N, 7.62.
[R]24 +11.1° (c 0.75, CHCl3). All spectroscopic data were
D
(+)-cis-(4R ,5S )-4-E t h e n yl-5-e t h yl-1,3-oxa zolid in -2-
on e (41a ). Oxazolidinone 41a (71 mg, 76%), prepared from
40a using the same procedure as for 36, was obtained as a
identical with the above data.
Ack n ow led gm en t. We thank Glaxo Group Re-
search Ltd. for the most generous Glaxo endowment (to
A.G.M.B), the Wolfson Foundation for establishing the
Wolfson Centre for Organic Chemistry in Medical
Science, and the Engineering and Physical Sciences
Research Council, Rhoˆne-Poulenc Rorer Ltd. and Zeneca
Corporate Research and Technology for generous sup-
port of our program.
white solid: mp 55-56 °C (CHCl3); TLC Rf 0.48 (EtOAc); [R]24
D
+31.4° (c 0.7, CHCl3); IR (CHCl3) 2925, 2854, 1748 (CdO) cm-1
;
1H NMR (300 MHz, CDCl3) δ 5.83 (ddd, 1H, J 16.2, 10.5, 7.8
Hz), 5.77 (br s, 1H), 5.34 (d, 1H, J 10.5 Hz), 5.30 (d, 1H, J
16.2 Hz), 4.56 (m, 1H), 4.30 (app t, 1H, J 7.8 Hz), 1.73 (m,
1H), 1.60 (m, 1H), 1.03 (t, 3H, J 7.4 Hz); 13C NMR (75.1 MHz,
CDCl3) δ 159.3, 133.1, 119.3, 81.6, 58.3, 23.6, 10.1; MS (CI,
NH3) m/ z 159 (M + NH4)+, 142 (M + H)+, 74; HRMS (CI, NH3)
m/ z calcd for C7H15N2O2 (M + NH4)+ 159.1134, found 159.1135.
Anal. Calcd for C7H11NO2: C, 59.56; H, 7.85; N, 9.92.
Found: C, 59.74; H, 7.89; N, 9.95.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra for 10c, 11a , 13c, 13f, 13g, 14a , 21, 22, 24, 28,
29, 32, 33, 34, 35, 38a -b, 39b, 40a , 41b, 42, and a 9:1 mixture
of 13a and 20 (43 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
(+)-cis-(4R,5S)-4-Eth en yl-5-(2-m eth ylp r op yl)-1,3-oxa zo-
lid in -2-on e (41b). Oxazolidinone 41b (34 mg, 79%), prepared
from 40b using the same procedure as for 36, was obtained
as a yellow oil: TLC Rf 0.53 (EtOAc); [R]24 +25.5° (c 0.65,
D
CHCl3); IR (CHCl3) 2958, 2873, 1751 (CdO), 1124 (C-O) cm-1
;
1H NMR (300 MHz, CDCl3) δ 6.60 (br s, 1H), 5.78 (ddd, 1H, J
J O9522062