Stereoselective deprotonation of chiral and achiral 2-aminoalkyl carbamates: Synthesis of optically active β-amino alcohols via 1-oxy- substituted alkyllithium intermediates

Article abstract of DOI:10.1055/s-1999-3575

A facile protocol for the electrophilic C-substitution (methylation, acylation, α-hydroxyalkylation, and carboxylation) of several 2-(N,N- dibenzylamino)alkan-1-ols via the carbamates 10 is reported. The stereochemistry of the lithiation is greatly influenced by the complexing diamine. The substrate-directed selection between the diastereotopic a-pro-R and pro-S protons in the TMEDA-assisted deprotonation is largely shifted towards pro-S-selectivity in the presence of (-)-sparteine (4). Each of both diastereomeric series is readily accessible in several cases.

Full text of DOI:10.1055/s-1999-3575

PAPER
1573
Stereoselective Deprotonation of Chiral and Achiral 2-Aminoalkyl
Carbamates: Synthesis of Optically Active b-Amino Alcohols via 1-Oxy-
Substituted Alkyllithium Intermediates
Jörg Schwerdtfeger, Sabine Kolczewski, Berthold Weber, Roland Fröhlich, Dieter Hoppe*
Institut für Organische Chemie der Westfälischen Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany
Fax +49(251)8339772; E-mail: dhoppe@uni-muenster.de
Received 25 February 1999; revised 11 May 1999
Dedicated to Professor Werner Tochtermann on the occasion of his 65th birthday.
tion at the adjacent carbon atom8,9 and may be enforced by
remote chelating ligands in R.10 The b-N,N-dibenzylami-
no group, which is not able to complex alkyllithium under
our reaction conditions, plays an outstanding role when
Abstract: A facile protocol for the electrophilic C-substitution (me-
thylation, acylation, a-hydroxyalkylation, and carboxylation) of
several 2-(N,N-dibenzylamino)alkan-1-ols via the carbamates 10 is
reported. The stereochemistry of the lithiation is greatly influenced
by the complexing diamine. The substrate-directed selection be- placed at a stereogenic carbon atom.6,11 In the work pre-
tween the diastereotopic a-pro-R and pro-S protons in the TMEDA-
assisted deprotonation is largely shifted towards pro-S-selectivity in
the presence of (-)-sparteine (4). Each of both diastereomeric series
is readily accessible in several cases.
sented here, we investigated the lithiation, substitution,
and the stereoselectivity in several 2-(N,N-dibenzyl-
amino)alkyl carbamates 10.
Key words: 2-amino-1-hydroxy carbanions, stereoselective depro-
tonation, chiral 2-aminoalkan-1-ols, (-)-sparteine, substituted iso-
serines
Introduction
Earlier methods for the generation of chiral, nonracemic
synthetic equivalents of 1-hydroxyalkanides B are based
on the lithiodestannylation of (a-oxyalkyl)stannanes.1 Ex-
amples for the preparation of B by simple deprotonation
from non-activated alkanols A, in which R is a group not
suitable for mesomeric stabilization of an adjacent nega-
tive charge, were unknown before 1990 (Scheme 1).
Thus, this attractive route for the connective synthesis of
secondary alcohols C via the introduction of electrophiles
onto the a-carbon atom had been limited to synthetic
equivalents of achiral lithiomethyl derivatives such as
(tert-butoxy)methyllithium (B, R = H),2 and lithiomethyl
2,4,6-trialkylbenzoates,3 to the corresponding racemic 2-
(dimethylamino)lithioethyl ester (R = Me2NCH2),3c be-
fore we found a general solution by applying sterically
shielded carbamate esters of type 1 to be smoothly depro-
tonated by sec-butyllithium in the presence of a chelating
diamine such as N,N,N’,N’-tetramethylethylenediamine
(TMEDA).4 Moreover, if (-)-sparteine (4) is used, an ef-
ficient selection between the enantiotopic protons in 1
with high preference for the pro-S-H is observed, giving
rise to the essentially enantiomerically pure esters 3 after
stereospecific substitution with retention.4,5
Scheme 1
Results and Discussion
Starting Materials
The carbamates 10 and ent-104,12 were obtained by acyla-
tion of the 2-(N,N-dibenzylamino)alkan-1-ols 7 or ent-7
with
2,2,4,4-tetramethyl-1,3-oxazolidine-3-carbonyl
chloride (8)4a via the sodium alkoxides (Scheme 2,
Table 1). The alcohols 7 or ent-7 were prepared by the
standard procedure13 from the (S)- or (R)-amino acids
with the exception of 7a, 7c, ent-7c and ent-7g; which
were synthesized by N,N-dibenzylation of the correspond-
ing commercially available 2-aminoalkanols 9 or ent-9.14
If R is a stereogenic moiety, the pro-R- and the pro-S-pro-
tons in 1 are in a diastereotopic relationship and a selec-
tion between HR and HS is already accomplished by
achiral bases;6 in the presence of (-)-sparteine (4) double
stereoselection occurs.7 Different reactivity of the diaste-
reotopic protons can be caused solely by the steric situa-
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

1574
J. Schwerdtfeger et al.
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Reagents and conditions: a) i. NaOH/K2CO3 (1:1), MeOH/H2O
(1:1), reflux; ii. BnBr (3 equiv), b) LiAlH4/THF or Et2O, reflux,
c) i. NaOH/K2CO3 (1:1), MeOH/H2O (1:1), reflux; ii. BnBr (2
equiv) (for 7a and ent-7g:2 equiv BnCl); d) i. NaH/THF or Et2O; ii.
8.
Scheme 2
Substrate- and Reagent-Directed Deprotonations
For deprotonation, the carbamates 10b–h were stirred in
diethyl ether solution with approximately 2 equivalents
sec-butyllithium in the presence of TMEDA (Method A)
or (-)-sparteine (4) (Method B), usually for 1–6 hours;
subsequently, the electrophile was added in an amount ex-
ceeding the amount of sec-butyllithium (Scheme 3, Table
2). Usual aqueous work-up and chromatographic purifica-
tion gave the products 16 and 17. When TMEDA was
used as ligand, usually analytically pure mixtures of 16
Scheme 3
Table 1 2-(N,N-Dibenzylamino)alkyl Carbamates 10 and ent-10 Prepared from the Corresponding Alcohols 7 and ent-7
Producta
R
Yield (%)
mp (°C)
[a]2D0 (c, solvent)
Purificationb
10a
10b
10c
ent-10c
10d
10e
10f
10g
ent-10g
10h
H
CH3
C2H5
C2H5
(CH3)2CHCH2
(CH3)2CH
C6H5CH2
C6H5
C6H5
(C6H5 )2N-(CH2)3
91
83
79
79
95
83
81
84
94e
83
32c
45–47d
oil
oil
oil
oil
oil
oil
oil
–
E/P, 1:2
E/P, 1:5→1:2
E/P, 1:4
E/P, 1:4
E/P, 1:4
E/P, 1:4
E/P, 1:4
E/P, 1:6
E/P, 1:4
E/P, 1:5
+ 2.1 (1, acetone)
–41.8 (2, acetone)
+44.2 (1, acetone)
–38.9 (1, CHCl3)
–62.6 (1, CH2Cl2)
– 6.4 (1, CHCl3)
+54.5 (1, CHCl3)
–54.3 (2, CHCl3)
– 1.8 (1, acetone)
oil
a All new compounds gave correct C,H-analyses (C 0.4, H 0.4).
b CC on silica gel; E = Et2O, P = pentane.
c From the melt.
d From E/P.
e 1 equiv of DMPU was added to the reaction mixture.
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Deprotonation of Chiral and Achiral 2-Aminoalkyl Carbamates
1575
Table 2 Prepared Compounds 16 and 17 or ent-16 and ent-17 by Lithiation of 10 or ent-10 and Reaction with Electrophiles [Method A:
TMEDA; Method B: (–)-Sparteine]
Entry Sub-
strate
Electrophile
Me- Productsa
thod
R
El
Yield Ratio
(%) (ee or dr) (°C)
mp
[a]2D0 b,c,d
e
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
10a
CO2
B
A
B
A
B
A
B
A
B
A
A
B
A
B
A
B
A
17ab
rac-17ac
17ac
rac-17ad
17ad
rac-17af
17af
H
H
H
H
H
H
H
H
CO2Me
Me3Si
Me3Si
Bu3Sn
Bu3Sn
Me
56
80
70
68
70
75
73
51
44
92
76
48
45
64
49
59
82
>95%
–
>95%
–
>95%
–
>95%
–
50%
39:61
39:61
<5:>95
35:65
<5:>95
36:64
<5:>95
37:63
oil
oil
oil
oil
oil
oil
117f
oil
oil
–7.8b
Me3SiCl
Bu3SnCl
MeI
+6.2b
+28.4b
–35.7b
–6.3b
Me
PhCH2Br
DOMe
rac-17ag
17ag
PhCH2
PhCH2
D
CO2Me
CO2Me
CO2Me
CO2Me
Bu3Sn
Bu3Sn
Me
H
10b
16ba+17bag
16bb+17bbg
17bb
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
e
CO2
e
CO2
99f
–8.6c
MeOCOCl
MeOCOCl
Bu3SnCl
16bb+17bbg
17bb
16bd+17bdg
17bd
+0.9c
16bf:
+22.8c
17bf:
+6.6c
MeI
16bf+17bf
oil
oil
18
B
17bf
CH3
Me
56
<5:>95
19
20
Me2C=O
PhCOCl
A
B
16bh+17bhg
17bi
CH3
CH3
Me2C(OH)
PhC(=O)
33h
64
26:74
<5:>95
94–95f
oil
17bi::
–19.6c
16bj:
–4.9c
21
Me2CHCOCl
A
16bj+17bj
CH3
Me2CHC(=O) 54
36:64
oil
17bj:
–55.2c
22
23
24
25
26
27
28
29
30
31
32
33
34
10c
PhCOCl
A
B
A
B
A
B
A
B
A
B
A
B
A
16ci+17cig
–
CH3CH2
CH3CH2
PhC=O
68
91:9
i
ent-10c CO2
ent-16cb+ent-17cb CH3CH2
ent-16cb CH3CH2
ent-16cd+ent-17cdg CH3CH2
ent-16cd CH3CH2
ent-16cf+ent-17cfg CH3CH2
ent-16cf CH3CH2
ent-16ci+ent-17cig CH3CH2
ent-16ci CH3CH2
ent-16cj+ent-17cjg CH3CH2
ent-16cj CH3CH2
ent-16ck+ent-17ck CH3CH2
CO2Me
CO2Me
Bu3Sn
Bu3Sn
Me
65
57
70
59
72
56
74
64
56
85
34
>95:<5
>95:<5
89:11
>95:<5
88:12
>95:<5
88:12
>95:<5
86:14
oil
+17.4c
+53.6c
e
Bu3SnCl
oil
oil
MeI
j
Me
–
PhCOCl
Me2CHCOCl
EtCOClk
DOMe
PhC=O
PhC=O
Me2CHC=O
Me2CHC=O
EtC=O
120–121f –76.9c
>95:<5
90:10
oil
oil
–31.6c
ent-16ck:
–10.9c
35
36
37
38
39
40
41
42
10d
A
B
A
A
A
B
A
A
16da+17dag
(CH3)2CHCH2
(CH3)2CHCH2
(CH3)2CHCH2 CO2H
(CH3)2CHCH2 Me
(CH3)2CH
(CH3)2CH
(CH3)2CH
C6H5CH2
D
86
82:18
i
–
CO2
MeI
MeOCOCl
16dbl
84
86
55
>95:<5
81:19
37:63
174f
+2.2b
16df+17dfg
16eb+17ebg
10e
10f
CO2Me
i
–
CH3I
DOMe
16ef+17efg
16fa+17fag
Me
D
57
98
41:59
94:6
43
44
45
46
47
B
A
B
A
B
16fa+17fag
16fb+17fbg
16fb+17fbg
16fb+17fbg
16fb+17fbg
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
D
68
43
33
75
70
9:91
e
CO2
CO2Me
CO2Me
CO2Me
CO2Me
89:11
9:91
MeOCOCl
95:5
11:89
>85:<15m
86:14
48
49
MeI
A
A
16ff+17ffg
C6H5CH2
C6H5CH2
Me
PhC=O
68
75
PhCO2Me
16fin +17fi
134–135f 16fi:
+74.9d
50
51
52
53
54
B
A
B
A
B
16fi+17fig
16fj+17fjg
16fj+17fjg
16ga+17gag
16ga+17gag
C6H5CH2
C6H5CH2
C6H5CH2
C6H5
PhC=O
Me 2CHC=O
Me 2CHC=O
D
D
55
42
11
93
17
7:93
Me2CHCO2Me
DOAc
90:10
16:84
42:58
13:87
10g
C6H5
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

1576
J. Schwerdtfeger et al.
PAPER
Table 2 (continued)
Entry Sub-
strate
Electrophile
Me- Productsa
thod
R
El
Yield Ratio
(%) (ee or dr) (°C)
mp
[a]2D0 b,c,d
55
56
MeOCOCl
A
B
B
B
B
B
A
A
A
16gb+17gb
16gb+17gb
ent-16gb+ent-17gb C6H5
ent-16ge+ent-17ge C6H5
C6H5
C6H5
CO2Me
CO2Me
CO2Me
Me3Sn
Me
85
38:62
oil
oil
16gb: +82.6b
17gb: +45.7b
–82.3b
46o
38p
10q
71
<2:>98
>98:<2
>98:<2
>98:<2
57
58
59
60
61
62
63
ent-10g CO2
53f
136f
182
e
Me3SnCl
MeJ
DOMe
MeOCOCl
Bu3SnCl
PhCOCl
–33.4b
ent-16gf+ent-17gf
C6H5
(C6H5)2N-(CH2)3
(C6H5)2N-(CH2)3 CO2Me
(C6H5)2N-(CH2)3 Bu3Sn
(C6H5)2N-(CH2)3 PhC=O
-47.9b
i
10h
–
16hb+17hbg
16hd+17hdg
16hi+17hig
78
66
60
84:16
82:18
86:14
a All new compounds gave correct C,H-analyses (C 0.4, H 0.4).
b c = 1, CHCl3.
c c = 1, acetone.
d c = 1, CH2Cl2.
e Subsequent methylation with diazomethane.
f From E/P.
g Not separated.
h 56% of 10b reisolated. The reaction with (CD3)2C=O gave [D]6-16bh/[D]6-17bh in 40% yield (ratio 28:72) and 16ba/17ba, 42%, ratio 40:60.
i No deprotonation achieved under standard conditions.
j Not recorded.
k With methyl propionate; yield 17%, ratio 91:9.
l Free acid.
m After chromatographic purification.
n Pure 16fi after recrystallization from E/P.
o Deprotonation time 24 h; after 2 h only 8%, after 6 h 19% yield of 17gb.
p Deprotonation at –45°C for 5 h.
q Deprotonation at –45°C for 1 h; 80% ent-10g were recovered.
and 17 were isolated, which were separable at this stage. they bear non- or slightly acidic hydrogen atoms.
Since the deprotonation is a kinetically controlled process Consequently, n-alkanoylations are less rewarding than
and the intermediate lithium compounds react with com- isobutanoylations or aroylations (Table 2, Entries 30, 32,
plete retention of configuration,4,5 the product ratios 16/17 34). Compound 17gb is a protected derivative of (2R,3S)-
directly reflect the ratios 12/14 (see below and Table 3). 3-phenylisoserine15 which forms the side chain in taxol
When the base sec-butyllithium/(-)-sparteine is used, due antibiotics.
to its strong preference for abstraction of the pro-S-proton
The achiral glycinol carbamate 10a is deprotonated
in alkyl carbamates, usually one of the following situa-
smoothly both under conditions A and B (Table 2, Entries
tions occurs: Either the intermediate 15, resulting from re-
1–9). The racemate is produced in the presence of
moval of the pro-S-proton, is formed with high
TMEDA whereas (-)-sparteine (4) gives rise to highly
diastereoselectivity (starting from 10b, 10f and 10g), or
enantioenriched products. The benzylation, however, ap-
plying Method B (Entry 9), yields a partially racemized
no deprotonation occurs in several mismatched7 cases
(10c, 10d, 10h) and - surprisingly also - in the (S)-valinol
product 17ag, presumably caused by a single-electron
derivative 10e, were a slightly matched situation is ex-
transfer (SET)16 during the alkylation step. The deblock-
ing and the stereochemical assignments of typical prod-
ucts are described below.
pected. In the (R)-configured educt ent-10c, both the sub-
strate-directed and the reagent-directed preference in the
presence of (-)-sparteine (4) favour the pro-S-H, and,
consequently, diastereomerically pure substitution prod-
The reaction of the lithiated TMEDA intermediates 12
and 14 or the (-)-sparteine complexes 13 and 15 with
prochiral aldehydes is expected to form up to four diaste-
ucts ent-16c were formed via the (-)-sparteine complex
ent-13c (Table 2, Entries 25, 27, 29, 31, 33). On the other
reomers 18, 19, 20, and 21, since an outstanding facial se-
hand, the (S)-enantiomer 10c with its internal preference
lectivity at the carbonyl group is not expected to operate
(Scheme 4).
for the abstraction of the pro-R-H could not be deproto-
nated under conditions B (Entry 23). This again demon-
strates that the sparteine-reagent is much more sensitive
against steric overcrowding than sec-butyllithium/
TMEDA.
Starting from carbamate ent-10c, by (-)-sparteine-medi-
ated deprotonation, the diastereomer ent-13c is produced
almost exclusively. Its addition to benzaldehyde afforded
two epimers ent-18cl (anti,anti) and ent-19cl (anti,syn),
which differ in the configuration at the benzylic stereo-
center (for stereochemical assignment see below); the ra-
tio is 30:70 (Table 3). To our surprise, the diastereomeric
complexes 12d/14d (ratio ~ 5:1) and 12f/14f (ratio ~ 9:1)
From the large number of experiments can be concluded
that methyl iodide, silyl- and stannyl chlorides, carbon di-
oxide, alkoxycarbonyl chlorides, acid chlorides, esters, al-
dehydes, and ketones are suitable electrophiles as long as
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Deprotonation of Chiral and Achiral 2-Aminoalkyl Carbamates
1577
also yielded only two adducts 18dm/19dm and 18fl/19fl,
respectively, arising form the major Li•TMEDA interme-
diate 12 with the relative configuration u17 (1R,2S). The
minor l-diastereomer 14 (1S,2S) obviously has a lower re-
activity towards carbonyl addition; the reasons are still
unknown. Unlike to the results, outlined in Table 2, the di-
astereomeric aldehyde adducts 18 and 19 are easily sepa-
rated by liquid chromatography on silica gel.
Scheme 4
Deblocking and Stereochemical Correlations
For the removal of the 2,2,4,4-tetramethyl-1,3-oxazoli-
dine-3-carbonyl group, three methods have been devel-
oped (Scheme 5). Method C: cleavage of the aminoacetal
moiety in the oxazolidine ring and subsequent alkaline hy-
drolysis of the intermediate N-(b-hydroxyalkyl)carbamic
acid ester 22;4 Method D: refluxing in 5 N aqueous hydro-
chloric acid in THF;4 and Method E: reductive cleavage
with lithium alanate4 which proceeds smoothly if an adja-
cent hydroxy group for "anchoring" the hydride is present
or is formed during the reduction.
Reagents and Conditions: a) MeSO3H (4–7 equiv)/MeOH, 4–20 h,
reflux; b) Ba(OH)2•8H2O or KOH/MeOH, 4–24 h, reflux; c) i. 5 N aq
HCl/THF, 4–12 h, reflux ii. aq. KOH. d) LiAlH4, THF or Et2O, re-
flux.
Scheme 5
yields the major diastereomers 23 in accordance to the
prediction by the Felkin–Anh model18 (Scheme 6).
Further examples were mainly selected with a view to pre-
pare amino alcohols either of known relative configura-
tion or useful for structure elucidation (Table 4). As
known from the work of Reetz et al.,13b,c the addition of
Grignard reagents to 2-(N,N-dibenzylamino)alkanals
The samples of 23bf, df, ef, and ff prepared by this meth-
od, proved to be identical with the appropriate amino al-
cohols, obtained by decarbamoylation of 16bf, df, ef, and
ff. The hydrolytic removal of the carbamate group in 17af
Table 3 Addition of Intermediates 12/14 or 13/15 to Aldehydes
Entry Substrate Aldehyde
Me- Productsa
thod
R
R1
Yield
(%)
Ratio
mp
(°C)
[a]2D0 (c, solvent)
1
2
3
ent-10c C6H5CH=O
B
A
A
ent-18clb+
ent-19cl
18flb+
CH3CH2
C6H5CH2
C6H5
C6H5
70
75
53
30:70
19:81
30:70
56c
46c
+55.9 (1, acetone)
+ 7.6 (1, acetone)
+ 3.6 (1, CH2Cl2)
+11.7 (1, CH2Cl2)
– 4.7 (1, CHCl3)
–16.5 (1, CHCl3)
10f
C6H5CH=O
169c
74c
19fl
10d
CH3CH2CH=O
18dmb+
19dm
(CH3)2CHCH2 CH3CH2
119d
71d
a All new compounds gave correct C,H-analyses (C 0.4, H 0.4).
b Less polar diastereomer on silica gel.
c From Et2O/pentane.
d From pentane.
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

1578
J. Schwerdtfeger et al.
PAPER
Table 4 Selected Data of Compounds, Prepared for Confirming the Relative or Absolute Configuration of Precursors
En-
try
Substrate
(Method,
Scheme)
R
El
Producta
Yield
(%)
mpb
(°C)
[α]2D0
(c, solvent)
Confi-
gurationc
1
2
17ab
(E, 7)
17af
(C, 5)
17ag
(C, 5)
17bf
(D, 5)
ent-16cf
(D, 5)
16df
(C, 5)
17df
(C, 5)
16ef
(C, 5)
17ef
(C, 5)
16ff
(D, 5)
17ff
(D, 5)
ent-16gf
(D, 5)
ent-16gf
(8)
ent-23cf
(9)
ent-33
(9)
ent-18cl
(C, 5 and 10)
ent-19cl
(Cg, 5 and 10)
18fl
H
–
30
55
71
67
33
31
83
81
71
65
69
59
60
13
87
92
68
75
94
86
70
28
61
75
55
oil
oil
oil
oil
oil
oil
oil
oil
112
oil
oil
oil
oil
oil
oil
+ 45.6 (1, CHCl3)d
+ 99.4 (2, CHCl3)d
+ 26.1 (1, CHCl3)f
+ 84.5 (1, CHCl3)
+ 22.6 (1, acetone)
+ 31.9 (1, CHCl3)
+ 60.4 (1, CHCl3)
2R
H
CH3
24afe
24age
24bf
2S
3
H
C6H5CH2
2S
4
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
–
2S,3S
5
CH3CH2
(CH3)2CHCH2
(CH3)2CHCH2
(CH3)2CH
(CH3)2CH
C6H5CH2
C6H5CH2
C6H5
ent-23cf
23df
2S,3R
6
2R,3S
7
24df
2S,3S
8
23ef
+
9.6 (2, CH2Cl2)
2R,3S
9
24ef
+ 43.2 (2, CH2Cl2)
+ 26.8 (1, CHCl3)
+ 44.9 (1, CHCl3)
–119.1 (2, CHCl3)
– 97.2 (2, CHCl3)
+ 19.2 (1, acetone)
– 26.8 (0.4, acetone)
+ 93.0 (1, acetone)
+ 34.0 (1, acetone)
2S,3S
10
11
12
13
14
15
16
17
18
19
20
21
22
23
23ff
2R,3S
24ff
2S,3S
ent-23gfe
ent-32
ent-33
ent-34
ent-25cl
ent-26cl
25fl
2S,3R
–
4R,5S
–
–
2S,3R
–
–
4R,5S
CH3CH2
CH3CH2
C6H5CH2
C6H5CH2
CH3CH2
CH3CH2
C6H5CH2
C6H5CH2
–
1S,2R,3R
1R,2R,3R
1R,2S,3S
1S,2S,3S
4R(1R),5S
4R(1R),5R
4S(1S),5R
4S(1S),5S
–
38–39
–
54–55
50–51
–
1.68 (1, CH2Cl2)
5.5 (1, CH2Cl2)
(E, 5 and 10)
19fl
(E, 5 and 10)
ent-25cl
(10)
ent-26cl
(10)
25fl
–
26fl
+
–
ent-35cl
ent-36cl
35fl
141–142
89–90
+ 46.8 (1, acetone)
+105.0 (1, acetone)
–
–
57–58
+
9.64 (1, CH2Cl2)
(10)
26fl
–
36fl
114–115
– 63.9 (1, CH2Cl2)
(10)
a All new compounds gave correct C,H-analyses (C ± 0.4, H ± 0.4).
b From E/P.
c Positions correspond to the IUPAC name.
d >95%ee.
e Molecular weight confirmed by high resolution mass spectrometry.
f 50%ee.
g NaOH instead of Ba(OH)2
8H2O was used.
•
by method C provided the amino alcohol (+)-(S)-24af ium(III) [Pr(hfc)3] showed two sets of signals. No line
(Table 4) which was also obtained by N,N-dibenzylation doubling was observed with a sample of (+)-(S)-24af, thus
1
of (S)-2-aminopropan-1-ol. The H NMR spectrum of the enantiomeric purity is better than >95%ee. The treat-
rac-24af in the presence of tris-[3-(heptafluoro- ment of the methyl ester 17ab with LiAlH4 (Method E,
propylhydroxymethylene)-(+)-camphorato]praesodym-
Scheme 7) produced (+)-(R)-3-(N,N-dibenzylamino)pro-
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Deprotonation of Chiral and Achiral 2-Aminoalkyl Carbamates
1579
Scheme 6
Scheme 9
During these and the subsequent studies we experienced
that there is no need in securing the relative configuration
of each compound by individual chemical correlations
due to the following observed regularities:
1. The ratio of diastereomers in the product remains
roughly constant for each carbamate 10.
2. The a,b-syn-amino alcohols24 23 are less polar than the
anti-diastereomers 24 on silica gel due to their greater
ability to form intramolecular hydrogen bridges and, thus,
have the higher Rf-values.
Scheme 7
3. If the addition of (-)-sparteine (4) supports the forma-
tion of a particular diastereomer, it results from the substi-
tution of the pro-S-proton.
pane-1,2-diol (30); for comparison the (-)-(S)-enantiomer
ent-30 was prepared by conventional means from the to-
sylate 31;19 17ab is a derivative of D-isoserine. According
to the general rule,4,5 sec-butyllithium/(-)-sparteine ab-
stracts with very high selectivity the pro-S-proton in the
substrate 10a.
Reduction of the diastereomerically pure phenyl ketone
16fi with NaBH4 afforded two epimeric alcohols 18fl and
19fl (Scheme 10). These are identical with the products
isolated from the reaction of the corresponding Li•TME-
DA complexes 12f and 14f with benzaldehyde. These ex-
periments demonstrate, that each of both epimeric
alcohols has the same configuration at the carbamoyloxy-
substituted carbon atom and the minor diastereomer 14f
does not undergo carbonyl addition under the applied re-
action conditions. The second hydroxy group was liberat-
ed by method C and the diols were converted to the
corresponding 1,3-dioxolan-2-ones.25 The trans-configu-
The relative configuration of ent-16gf [prepared by the
(-)-sparteine method, Table 2] was confirmed by convert-
ing ent-16gf into the oxazolidine ent-32 by partial hydro-
genolytic debenzylation and condensation with
formaldehyde (Scheme 8).20 A strong nuclear Overhauser
effect (NOE) between H-4 and H-5 and, as well, between
the methyl- and the 4-phenyl protons gives evidence for
the cis-configuration of the oxazolidine.
The amino alcohol ent-23cf (prepared from ent-16cf) was
converted via transfer-hydrogenolysis,21 formation of the
N-Cbz-derivative ent-33 and its base-mediated
cyclization22 into the cis-2-oxazolidinone ent-34 (Scheme
9). The coupling constant J4,5 of 7 Hz is in accordance to
data in the literature23 for the cis-relationship, NOE
experiments also support this assignment.
Scheme 8 Reagents and conditions: a) Method C; b) Pd/MeOH/
Figure X-ray structure of 36fl27
HCO2H; c) (CH2 = O)n
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

1580
J. Schwerdtfeger et al.
PAPER
corresponding lithium complexes ent-13c and ent-15c to
benzaldehyde. After deprotection by method C the diols
ent-25cl and ent-26cl were transformed to the 1,3-diox-
olan-2-ones ent-35cl and ent-36cl. NOE-experiments per-
formed on ent-36cl (J4,5 = 7.2 Hz) also give strong
evidence for trans-relationship of the 4-H and 5-H.
Attempts to replace the N,N-dibenzyl protection of the
amino group by the N-diphenylmethylene group28 were
only partially successful.29
Stereochemical Course of the Deprotonation
The product ratio 16/17 reflects the rate of formation of
the diastereomeric lithium/TMEDA or lithium/(-)-
sparteine complexes 12/14 or 13/15 which arise from the
removal of the diastereotopic pro-R- and the pro-S-pro-
ton, respectively, with different rate. The deprotonation is
irreversible, no equilibration occurs under the reaction
conditions, and the substitution usually proceeds with
strict stereoretention. Further, as previously demonstrat-
ed,11a the bulky dibenzylamino group is a very poor ligand
to lithium. From this one must conclude that intra- and in-
termolecular participation of the amino substituent as a
lithium-complexing ligand in the deprotonation step does
not play a significant role. This assumption is supported
by the observation that deprotonation of 10 does not pro-
ceed when a bidentate diamine is not present in the reac-
tion mixture.
Reagents and conditions: a) NaBH4, from ent-16ci: ent-18cl (53%) +
ent-19cl (23%); ratio 70:30; Zn(BH4)2, from ent-16ci: ent-18cl (87%)
+ ent-19cl (11%); ratio 88:12; NaBH4, from 16fi: 18fl (63%) + 19fl
(27%); ratio 70:30; NaBH4/MnCl2, from 16fi: 18fl (76%) + 19fl
(18%); ratio 82:18; b) See Scheme 5; Method C, yields see Table 4;
c) (EtO)2C = O, K2CO3, D, yields see Table 4
Scheme 10
ration of 36fl (J4,5 = 7.6 Hz),26 obtained from the diol of
26fl, clearly demonstrates its syn-configuration. On the
other hand, the diol 25fl yielded the cis-substituted hetero-
cycle 35fl (J4,5 = 8.9 Hz).
Further support for the correct stereochemical assignment
comes from the observation, that the 1,3-syn-relationship
in 18fl causes a stronger low-field shift of the OH-proton
(CDCl3, d = 4.69) when compared to 19fl (CDCl3,
d = 2.11).24 From 36fl a single crystal X-ray analysis27
was obtained (Figure), which shows the assigned relative
configuration.
The reduction of the enantiomeric ketone ent-16ci with
Zn(BH4)2 led to the alcohols ent-18cl and ent-19cl, which
are identical with those obtained from the reaction of the
Scheme 11
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Deprotonation of Chiral and Achiral 2-Aminoalkyl Carbamates
1581
Table 5 Substrate-Induced Diastereoselectivity in the Deprotona-
tion of Carbamates 10 by s-BuLi/TMEDA
Conclusion
The reaction sequence, consisting of the activation of the
a-position in 2-(N,N-dibenzylamino)alkanols by a steri-
cally demanding carbamoyl residue, deprotonation, and
introduction of an electrophile permits for the diastereose-
lective, general synthesis of more complex, optically ac-
tive b-amino-a-hydroxy derivatives. From the many
examples collected in this work, the means for approach-
ing a particular stereoisomer can be easily estimated. The
application of the method for the preparation of 1,4-di-
amino-2,3-diols is reported in the subsequent paper.32a
Some differences are observed in the stereoselective lithi-
ation of cyclic aminoalkyl carbamates derived from N-
benzyl-(S)-prolinol.6,32b
10
R
Ratioa
12•
TMEDA/14 TMEDA
•
b
c
d
e
f
CH3
38:62
88:12
82:18
40:60
90:10
40:60
83:17
CH3CH2
(CH3)2CHCH2
(CH3)2CH
C6H5CH2
C6H5
g
h
Bn2N(CH2)3
a Concluded from the average ratio of products 16 and 17.
As we assume the transition states (TS) D and E (Scheme
11) compete in the transposition of HR and HS, respective-
ly, onto the sec-butyl residue of the intramolecularly at-
tached base, to form either 12 or 14. In the carbamates 10
bearing a primary alkyl residue R (10c, d, f, h) a substrate-
directed ul-stereoselectivity of at least 80:20 in favour to
the TS D is observed. In TS D, the electronegative groups
OCby and NBn2, both bearing lone pairs, occupy an anti-
periplanar relationship. TS E is expected to become more
favourable when R is a bulky group. This may be the rea-
son for the slight internal lk-preference in the valinol and
phenylglycinol carbamates 10e and 10g. As Table 5 dem-
onstrates, no such simple general relationship between the
diastereomer ratio and the size of R is given, since the
alaninol derivative 10b (R = CH3) exhibits also slight lk-
selectivity. Semiempirical calculations are in progress in
order to find out the reasons.
All reactions which are sensitive to moisture were carried out under
argon. All solvents were purified by distillation and dried, if neces-
sary, prior to use. 1H and 13C NMR spectra were recorded on Bruker
WM300 spectrometer. Optical rotations were recorded on a Perkin-
Elmer polarimeter 241 at 20°C. Mps were obtained on Gallenkamp
melting point apparatus MFB-595 and are uncorrected. Products
were purified by flash column chromatography on silica gel (40–63
mm).
N,N-Dibenzylation of 9a, 9c, ent-9c, and ent-9g; Preparation of
Alcohols 7a, 7c, ent-7c, and ent-7g; General Procedure14
A suspension of the aminoalcohol 9 or ent-9 (56 mmol), K2CO3
(12.3 g, 89 mmol), and NaOH (3.6 g, 89 mmol) in H2O/MeOH
(60 mL, 1:1) was refluxed for 30 min. BnBr [19.7 g, 13.7 mL, 115
mmol; for 9a and ent-9g: BnCl (14.6 g, 13.2 mL, 115 mmol)] was
added dropwise and stirring under reflux was continued for 6 h. The
cooled mixture was extracted with Et2O (4 î 80 mL) and the col-
lected extracts were dried (MgSO4). The solvents were evaporated
in vacuo and the crude products were purified by flash chromato-
graphy (Et2O/pentane, 1:4) to yield the pure alcohols 7a33 (5.8 g,
43%), 7c (14.6 g, 97%), ent-7c (14.8 g, 98%) and ent-7g34 (8.18 g,
46%).
The sec-butyllithium/(-)-sparteine reagent with its pref-
erence for pro-S-protons enforces the substrate-controlled
stereoselectivity only in the (S)-alaninol and (S)-phenylg-
lycinol derivatives 10b and 10g, and even overrides it in
the (S)-phenylalaninol carbamate 10f. The latter is an ex-
ception, since the (S)-enantiomer 10c (R = ethyl), 10d
(R = isobutyl), 10e (R = isopropyl) and 10h [R = 2-(N,N-
dibenzylamino)ethyl] do not react under (-)-sparteine
conditions B. Presumably in 10f, the formation of a p-
complex, bearing the phenyl residue in a favourable posi-
tion, facilitates the approach of the lithium cation (TS
F).30
(R)-2-(N,N-Dibenzylamino)butanol (ent-7c)
Colorless oil; Rf 0.48 (Et2O/pentane, 1:1); [a]D +6.5 (c = 1, aceto-
ne).
IR (film): n = 3410 cm–1 (OH).
1H NMR (CDCl3, 300 MHz): d = 0.90 (t, 3J3,4 = 7.4 Hz, 4-H3), 1.10–
1.30, 1.78 (m, ddq, 2J3,3 = 13.6 Hz, 3J2,3 = 3.8 Hz, 3-H2), 2.70 (dddd,
3J1,2 = 4.9 Hz, 2-H), 3.11 (br s, OH), 3.42, 3.81 (2 d, 2JBn = 13.4 Hz,
NCH2Ph), 3.35–3.54 (m, 1-H2), 7.20–7.32 (m, 10H, C6H5).
13C NMR (CDCl3, 75 MHz): d = 12.0 (C-4), 18.2 (C-3), 53.5
(NCH2Ph), 60.8 (C-1), 61.1 (C-2), 127.4, 128.7, 129.3, 139.6
(C6H5).
However, when creating a matched pair situation by ap-
plying the enantiomer (R)-10, a rapid and selective depro-
tonation takes place (see for ent-10c, Table 2, Entries 25,
27, 29, 31, 33). We have already utilized the diminished
reactivity in the mismatched pair for the efficient kinetic
resolution of a cyclopropyl-substituted aminoalcohol.9
Obviously, the lk-TS E, TMEDA replaced by (-)-
sparteine (4), is sterically overcrowded due to the bulky
ligand. It is predictable, that a smaller chiral ligand, such
as (R,R)- or (S,S)-1,2-bis(dimethylamino)cyclohexane
will serve better in these situations.31 On the other hand,
the use of bulkier achiral diamines than TMEDA, should
increase the substrate-directed stereoselectivity.
Anal. Calcd. for C18H23NO (269.4): C, 80.26; H, 8.61. Found C,
80.28; H, 8.66.
(S)-2-(N,N-Dibenzylamino)butanol (7c)
[a]D -5.9 (c = 1, acetone).
N,N,O-Tribenzylation of Amino Acids 5b, d-h and Subsequent
Reduction of the Benzyl Ester with LiAlH4; Preparation of Al-
cohols 7b, d–h; General Procedure13
To a refluxing suspension of the amino acid 5 (100 mmol) was ad-
ded a solution of K2CO3 (23.3 g, 168 mmol) and NaOH (6.7 g, 168
mmol) in H2O/MeOH (120 mL, 1:1) followed by BnBr (51.3 g, 35.6
mL, 300 mmol) added. Stirring under reflux was continued for 1 h.
The cooled mixture was extracted with Et2O (3 î 120 mL). The
combined Et2O extracts were dried (MgSO4) and concentrated in
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

1582
J. Schwerdtfeger et al.
PAPER
vacuo. The crude product was dissolved in anhyd THF or Et2O and
added dropwise to a suspension of LiAlH4 (2.4 g, 63 mmol) at 0°C.
The mixture was refluxed until the benzyl ester 6 could not be de-
tected by TLC any longer (1–12 h). The slurry was cooled down to
0°C and cautiously treated with H2O (2.4 mL), aq NaOH (2.4 mL,
15%), and H2O (7.2 mL) in that order. The mixture was refluxed for
1 h. The precipitate was filtered and washed with THF or Et2O
(100 mL). The filtrate was dried (MgSO4) and the solvent was eva-
porated under reduced pressure. Flash chromatography (Et2O/ pen-
tane 1:4 to 1:2) of the residues afforded the pure alcohols 7b, d–h.
cyclohexane/hexane (1.50 mL, 2.00 mmol) at -78 °C. Stirring was
continued for 3–6 h before the electrophile was introduced.
Time for deprotonation: 10a Æ 3 h; 10b, 10c, ent-10c, 10h Æ 4 h;
10d, 10e, 10f, 10g, ent-10g Æ 6 h.
Carboxylation: After stirring at -78°C for 3–6 h, a stream of dry
CO2 was introduced to the solution of the deprotonated carbamate
via a syringe for 30 min. After warming to r.t. and hydrolysis with
H2O (10 mL), 2 N HCl was added until pH 5. The organic layer was
separated and the aqueous phase was extracted with Et2O (3 î 10
mL). The collected extracts were dried (MgSO4) and the solvents
were evaporated in vacuo. The crude product was dissolved in Et2O
(10 mL) and treated with ethereal CH2N2 solution until remaining
yellow. After stirring for 1 h, silica gel (50 mg) was added and the
mixture was stirred for 15 min in order to destroy the excess of
CH2N2. The subsequent flash chromatographic purification (Et2O/
pentane, 1:1 to 1:8) yielded the methyl esters 16xb and 17xb ( or
ent-16xb and ent-17xb).
7b35
Yield: 15.6 g (56%), [a]D +45.9 (c = 1, acetone).
7d35,13c
Yield: 14.0 g (47%), [a]D +75.5 (c = 1, CHCl3).
7e35,13c
Yield: 21.3 g (75%), [a]D +17.0 (c = 1, CH2Cl2).
Other electrophiles: After stirring at -78°C for 3–6 h, the electro-
phile was slowly introduced with a syringe. The mixture was allo-
wed to warm up to r. t. for 12 h and H2O (10 mL) was added. The
Et2O layer was separated and the aqueous phase was extracted with
Et2O (3 î 10 mL). The combined Et2O were dried (MgSO4) and
evaporated in vacuo. The residue was purified by flash chromato-
graphy (Et2O/pentane, 1:1 to 1:8) to afford the substituted carbama-
tes. For yields and physical data of substituted carbamates 16, ent-
16, 17, or ent-17, see Tables 2 and 6. For yields and physical data of
substituted carbamates 18, ent-18, 19, and ent-19, see Tables 3, 7,
and 8.
7f36,13c
Yield: 23.5 g (71%), [a]D +42.5 (c = 1, CHCl3).
7g34
Yield: 25.1 g (79%), [a]D +148.6 (c = 1, CHCl3).
(S)-2,5-Bis(N,N-dibenzylamino)-1-pentanol (7h)
Yield: 27.3 g (57%) from L-ornithin•HCl and BnBr (88.9 g, 61.8
mL, 520 mmol); colorless crystals; mp 87–88°C (pentane); Rf 0.42
(Et2O/pentane, 1:1); [a]D +35.1 (c = 1, acetone).
IR (KBr): n = 3100–3500 cm–1 (OH).
1H NMR (CDCl3, 300 MHz): d = 1.59–1.70 (m, 3-H2, 4-H2), 2.41
Deprotection of Substituted Carbamates 16, ent-16, 17, ent-17,
18, ent-18, 19, and ent-19; Preparation of Alcohols 23, ent-23,
24, ent-24, 25, ent-25, 26, and ent-26; General Procedures4
Method C: A solution of the substituted carbamate (1.00 mmol) and
MeSO3H (324 mL, 480 mg, 5.00 mmol) in MeOH (10 mL) was re-
fluxed for 4 h. After the addition of Ba(OH)2•8H2O (3.79 g,
12 mmol) the suspension was heated under reflux for 4 h. The inor-
ganic salts were removed by filtration over silica gel (1 g) and
washed with MeOH (30 mL). The solvent was evaporated in vacuo
and the residue was purified by flash chromatography (Et2O/penta-
ne, 1:4 to 1:8) to give the pure alcohol.
(dd, 3J4,5 = 6.7–7.1 Hz, 5-H2), 2.65–2.72 (m, 2-H), 3.30–3.34 (m, 1-
2
H2), 3.34, 3.52, 3.57, 3.74 (4 d, JBn = 13.4, 13.6 Hz, NCH2Ph),
7.17–7.40 (m, 20H, C6H5).
13C NMR (CDCl3, 75 MHz): d = 23.4, 25.4 (C-3, C-4), 53.8 (C-5),
54.4, 59.1, 59.7, 61.4 (NCH2Ph), 65.6 (C-2), 77.5 (C-1), 127.4,
127.7, 128.7, 129.0, 129.3, 129.5, 139.9, 140.3 (C6H5).
Anal. Calcd. for C33H38N2O (478.68): C, 82.52; H, 8.08. Found C,
82.80; H, 8.00.
Carbamoylation of the Alcohols 7a–h, ent-7c, and ent-7g; Prep-
aration of the Carbamates 10a-h, ent-10c, and ent-10g; General
Procedure4
Method D: The substituted carbamate (1.00 mmol) was dissolved in
THF (1 mL) and 5 N HCl (5 mL). After heating the solution under
reflux for 12 h 5 N NaOH was added until pH 10. The mixture was
extracted with Et2O (3 î 10 mL) and the collected extracts were
dried (MgSO4) and concentrated in vacuo. The crude product was
purified by flash chromatography (Et2O/pentane, 1:4 to 1:8) to give
the pure alcohol.
A solution of the alcohol 7 or ent-7 (40 mmol) in anhyd THF (40
mL) was added dropwise to a suspension of NaH (2.0 g, 50 mmol,
60% in mineral oil) in THF (50 mL). The mixture was refluxed for
1 h, before 2,2,4,4-tetramethyloxazolidine-3-carbonyl chloride4
(CbyCl, 8; 8.6 g, 44 mmol) in THF (20 mL) was added. After ref-
luxing for 6 h and cooling to r.t., H2O (50 mL) and Et2O (50 mL)
were added carefully to the mixture. The organic layer was separa-
ted and the solution was extracted with Et2O (3 î 50 mL). The col-
lected extracts were dried (MgSO4). The solvents were evaporated
in vacuo and the crude products were purified by flash chromato-
graphy (silica gel, eluents see Table 1) to yield pure carbamates
10a–h, ent-10c, and ent-10g.
Method E: To a suspension of LiAlH4 (38 mg, 1.00 mmol) in anhyd
THF (7 mL) was added dropwise the substituted carbamate
(0.50 mmol) in THF (8 mL) at 0°C. After refluxing the mixture for
6 h, it was hydrolyzed with H2O (38 mL), 15% NaOH solution (38
mL), and H2O (114 mL) at 0°C. After heating under reflux for further
30 min the precipitate was filtered and washed with THF (15 mL).
The filtrate was dried (MgSO4) and concentrated in vacuo. Flash
chromatography of the residue (Et2O/pentane 1:4 to 1:8) afforded
the free alcohol. For yields and physical data of alcohols 23, ent-23,
24, ent-24, 25, ent-25, 26, and ent-26 see Tables 4, 7, and 8.
Deprotonation of Carbamates 10 and ent-10 with s-BuLi and
Preparation of Substituted Products 16, ent-16, 17, ent-17, 18,
ent-18, 19, and ent-19; General Procedures
M e t h o d A : Carbamate 10 or ent-10 (1.00 mmol) and TMEDA
(232 mg, 2.00 mmol) were dissolved in anhyd Et2O (15 mL) under
argon in a dry ice/acetone bath and s-BuLi (1.3 M) in cyclohexane/
hexane (1.50 mL, 2.00 mmol) was added to the solution dropwise.
After stirring for 3–6 h the electrophile was introduced.
(S)-3-(N,N-Dibenzylamino)propane-1,2-diol (ent-30)
A solution of 31 (858 mg, 3.00 mmol), dibenzylamine (1.19 g, 1.15
mL, 6.00 mmol) and DMPU (768 mg, 723 mL, 6.00 mmol) in tolue-
ne (15 mL) was refluxed for 12 h.37 H2O (6 mL) was added and the
two layers were separated. The organic solvent was evaporated in
vacuo and the residue was purified by flash chromatography on alu-
minium oxide (Et2O/pentane, 1:5) to give the acetonide of ent-30
(315 mg, 34%). The acetonide (311 mg, 1.00 mmol) and MeSO3H
(192 mg, 130 mL, 2.00 mmol) were dissolved in MeOH (5 mL) and
M e t h o d B : To a stirred solution of carbamate 10 (or ent-10)
(1.00 mmol) and (-)-sparteine (4) (469 mg, 2.00 mmol) in anhyd
Et2O (15 mL) under argon was added dropwise s-BuLi (1.3 M) in
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Deprotonation of Chiral and Achiral 2-Aminoalkyl Carbamates
Table 6 Selected Data of C-1 Substituted Carbamates 16, ent-16, 17, and ent-17a
Prod- IR (KBr/
1583
1H NMR (300 MHz, CDCl3), d, J (Hz)
13C NMR (75 MHz, CDCl3), d
C-1 C-2 N-CH2Ph R and El in Scheme 3
uct
film)
1-H
2-H
N-CH2Ph
(2JBn
R and El in
ν (cm-1
)
)
Scheme 3
17ab 1755,
5.32 (dd,
2.87/2.90, 3.02/
3.48, 3.79
3.69 (s,
COOCH3)
71.2 54.6 58.4
65.3 54.7 57.7
67.6 57.9 57.7
68.3 58.7 58.7
72.3 39.2 57.0*
51.9 (COOCH3),
170.4 (COOCH3)
1700
3J1,2 = 4.3, 7.3) 3.05 (2 dd, 2J2,2
=
=
=
=
(2 d, 2JBn
=
13.7)
13.6)
17ac 1685, 840 5.20 (dd,
2.60/2.61, 2.84/
3.44, 3.76
0.00 [s,
Si(CH3)3]
–3.9 [Si(CH3)3]
3J1,2 = 3.5, 9.8) 2.86 (2 dd, 2J2,2
(2 d, 2JBn
=
14.0)
13.6)
17ad 1685,
5.16/5.20 (dd, 2.56/2.59, 3.16/
3.37, 3.80
0.78–1.59b [m,
Sn(C4H9)3]
9.8, 13.7, 27.5, 29.4
[Sn(C4H9)3]
1675
3J1,2 = 2.9,
3.18 (2 dd, 2J2,2
14.0)
(2 d, 2JBn
=
11.0)
13.6)
17af 1685
17ag 1690
16bbc
5.15 (ddq, 3J1,2 2.41/2.47, 2.65/
3.60, 3.62
(2 s)
1.21 (d,
1-CH3)
18.9 (C-1)
= 6.3, 6.4,
2.72 (2 dd, 2J2,2
2.57–2.78b (m)
3J1,1-
= 6.3) 13.0)
CH
3
3.03 (dd,
3.57, 3.65
2.57–2.78b (m,
1-CH2Ph)
58.6* (1-CH2Ph)
3J1,2 = 6.0, 7.8)
(2 d, 2JBn
=
13.7)
5.46 (d,
3J1,2 = 5.0)
17bb 1755,
5.21 (d,
3.47 (dq, 3J2,3
7.2)
=
3.35, 3.95
1.18 (d, 3-H3),
3.61 (s,
COOCH3)
68.8 51.9 54.1
8.6 (C-3), 54.9
(COOCH3), 170.3
(COOCH3)
1695
3J1,2 = 5.3)
(2 d, 2JBn
=
13.6)
16bd
5.46-5.52 (m)
17bd 1685
5.14 (d,
3.45–3.52 (m)
3.38/3.39,
3.86
0.80–0.92,
1.20–1.59b
[2 m,
71.8 56.5 53.8
8.7 (C-3), 10.7, 14.0,
27.9, 29.4 [Sn(C4H9)3]
3J1,2 = 11.0)
(2 d, 2JBn
=
13.6)
Sn(C4H9)3],
0.95 (d, 3J2,3
=
=
6.7, 3-H3)
16bf 1690
17bf 1695
5.17 (dq, 3J1,2
=
=
2.17–2.73 (m)
2.59–2.71 (m)
3.48, 3.76
1.12 (d, 3J2,3
6.7, 3-H3),
1.24 (d,
70.8 56.2 53.0
72.4 57.2 54.5
8.3 (C-3), 18.0
(1-CH3)
7.6, 3J1,1- CH
(2 d, 2JBn
=
3
6.2)
13.8)
1-CH3)
5.10 (dq, 3J1,2
=
=
3.41, 3.69
1.05 (d, 3J2,3
6.0, 3-H3),
1.17 (d,
=
9.9 (C-3), 18.4
(1-CH3)
6.8, 3J1,1- CH
(2 d, 2JBn
=
3
6.4)
13.8)
1-CH3)
16bhc
5.16 (d,
3J1,2 = 10.7)
17bh 1675d
4.76 (d,
3.48–3.58 (m)
3.21–3.32b,
3.95–4.20b
(2 m)
0.49–0.57b (m,
3-H3), 1.03–
1.22b [m,
80.3 53.6/ 54.9
53.9
8.01, 8.45 (C-3), 23.6–
28.5 [C(OH)(CH3)2],
72.1/73.9
3J1,2 = 3.3)
C(OH)(CH3)2]
[C(OH)(CH3)2]
17bi 1685
16bj 1680
6.12 (d,
3.57 (dq, 3J2,3
6.8)
=
=
3.17, 3.86
1.10 (d, 3-H3)
79.1 54.3 54.6
70.9 53.9 54.2
8.3 (C-3), 196.0
(PhC=O)
3J1,2 = 6.0)
(2 d, 2JBn
=
13.2)
5.94 (d,
2.39 (dq, 3J2,3
6.7)
3.35, 3.87
0.99, 1.04 [2 d,
8.9 (C-3), 19.1, 19.4
[CH(CH3)2], 34.6
[CH(CH3)2], 210.1
(C=O)
3J1,2 = 10.3)
(2 d, 2JBn
=
3JCH,
= 6.7,
CH
3
13.1)
6.9,
CH(CH3)2];
1.14 (d, 3-H3);
3.10 [m,
CH(CH3)2]
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

1584
J. Schwerdtfeger et al.
PAPER
Table 6 (continued)
Prod- IR (KBr/
1H NMR (300 MHz, CDCl3), d, J (Hz)
13C NMR (75 MHz, CDCl3), d
C-1 C-2 N-CH2Ph R and El in Scheme 3
uct
film)
1-H
2-H
N-CH2Ph
(2JBn
R and El in
n (cm-1)
)
Scheme 3
17bj 1690
5.54 (d,
2.16 (dq, 3J2,3
6.7)
=
3.26, 3.92
1.00, 1.03[2 d,
80.6 54.6 54.7
8.0 (C-3), 17.5, 19.9
[CH(CH3)2], 37.1
[CH(CH3)2], 209.4
(C=O)
3J1,2 = 5.7)
(2 d, 2JBn
=
3JCH, CH = 6.4,
3
12.9)
7.1,
CH(CH3)2],
1.20 (d, 3-H3),
3.10 [q,
CH(CH3)2]
ent-
16cb 1700
1750,
5.69 (s)
2.98–3.05 (m)
3.34/3.36,
3.83/3.85
0.84 (dd, 3J3,4
= 7.2, 7.5, 4-
H3), 1.60–1.81
(m, 3-H2), 3.38
(s, COOCH3)
69.3 59.3 52.8
10.5 (C-4), 19.9 (C-3),
50.9 (COOCH3),
170.2 (COOCH3)
(2 d, 2JBn
=
13.6)
ent-
16cd
1670
5.67 (d,
2.76 (dd, 3J2,3
2.8)
=
3.43, 3.97
0.73, 1.17–
1.40 [2 m,
Sn(C4H9)3],
1.05 (dd, 3J3,4
= 7.4, 4-H2),
1.95 (m, 3-H2)
70.2 61.8 54.2
10.1, 12.4, 28.1, 29.3
[Sn(C4H9)3], 12.4
(C-4), 23.6 (C-3)
3J1,2 = 9.0)
(2 d, 2JBn
=
13.4)
ent-
4.87 (m)
17cdc
ent-
1690
5.52 (dq, 3J1,2
=
2.44–2.51 (m)
3.54
1.01 (dd, 3J3,4
= 7.4, 4-H3),
1.14 (d,
1-CH3), 1.60–
1.80 (m, 3-H2)
68.8 62.8 54.0
12.7 (C-4), 19.6 (C-3),
19.9 (1-CH3)
16cfc
2.6,3J1,1-
=
(d, 2JBn
=
=
CH
3
6.8)
13.9)
ent-
5.25-5.33 (m) 2.53–2.60 (m)
3.56
1.28 (d,
17cfc
(d, 2JBn
13.6)
3J1,1- CH = 6.8,
1-CH3)3
(ent-) 1690
16ci
6.62 (s)
3.08–3.17 (m)
3.67, 3.98/
4.00
0.92 (dd, 3J3,4
= 7.2, 7.5,
4-H3), 1.81–
1.95 (m, 3-H2)
75.5 59.5 54.4
12.3 (C-4), 20.0 (C-3),
197.8 (C=O)
(2 d, 2JBn
=
13.9)
(ent-)
6.35 (d,
17cid
3J1,2 = 5.3)
ent-
16cj 1685
1750,
5.89 (s)
2.35–2.48 (m)
3.47, 3.99/
4.01
0.80 [d,
76.2 58.7 54.2
12.1 (C-4), 17.9, 19.7
[CH(CH3)2], 20.5
(C-3), 36.5
3JCH, CH = 6.4,
3
(2 d, 2JBn
=
6.8,
13.9)
CH(CH3)2],
0.96 (dd, 3J3,4
= 7.2, 7.5, 4-
H3), 1.61–1.89
(m, 3-H2),
[CH(CH3)2], 211.4
(C=O)
2.97–3.08 [m,
CH(CH3)2]
ent-
5.70 (d,
17cjc
3J1,2 = 5.3)
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Deprotonation of Chiral and Achiral 2-Aminoalkyl Carbamates
1585
Table 6 (continued)
Prod- IR (KBr/
1H NMR (300 MHz, CDCl3), d, J (Hz)
13C NMR (75 MHz, CDCl3), d
C-1 C-2 N-CH2Ph R and El in Scheme 3
uct
film)
1-H
2-H
N-CH2Ph
(2JBn
R and El in
n (cm-1
)
)
Scheme 3
ent-
16ck
1690
5.75 (s)
3.04–3.10 (m)
3.45, 3.97/
3.99
0.95+ (dd,
59.2* 58.9* 53.9
7.4 (COCH2CH3),
11.8 (C-4), 20.6 (C-3),
31.9 (COCH2CH3),
207.71 (C=O)
3JCH
=
, CH
2
(2 d, 2JBn
=
7.2, 7.4, 3
13.8)
COCH2CH3),
0.96+ (dd,
3J3,4 = 7.4, 4-
H3), 1.36–1.84
(m, 3-H2),
2.13, 2.29
(2 dq, 2JCH
=
2
17.8,
COCH2CH3)
ent-
5.46 (d,
3.20–3.27 (m)
3.28–3.36 (m)
3.34
17ckc
3J1,2 = 5.0)
(d, 2JBn
=
12.9)
16dbe 1755,
1700,
5.76 (d,
3.64, 3.80/
3.82
0.58, 0.89 [2 d,
70.5 58.5 53.9
21.4, 23.6
3J1,2 = 4.9)
3JCH, CH = 6.4,
[CH(CH3)2], 24.4
[CH(CH3)2], 37.1/37.3
(C-3), 174.7 (COOH)
3
1685
(2 d, 2JBn
=
CH(CH3)2],
1.27–1.67b (m,
3-H2), 1.70–
1.91 [m,
13.5)
CH(CH3)2]
16df 1700,
5.59 (dq,
2.58 (ddd, 3J2,3
5.5, 10.0)
=
3.50, 3.84/
3.86
0.51, 0.91[2 d,
68.6 58.4 53.8
19.5 (1-CH3), 21.4,
24.1 [CH(CH3)2], 24.5
[CH(CH3)2], 36.3
(C-3)
1690d
3J1,2 = 2.6,
3JCH, CH = 6.5,
3
3J1,1- CH = 6.6,)
(2 d, 2JBn
=
6.7,
CH(CH3)2],
1.14 (d,
3
13.6)
1-CH3), 1.79–
2.01 [m,
CH(CH3)2]
17dfc
5.32 (dq, 3J1,2
=
3.4,
3J1,1- CH = 6.7)
3
16ebc 1750,
5.97 (s)
1690d
17ebc
5.50 (d,
3J1,2 = 2.6)
16efc 1690d
5.59 (dq, 3J1,2
=
2.6,
3J1,1- CH = 6.9)
3
17efc
5.48 (dq, 3J1,2
=
2.6,
3J1,1- CH = 6.7)
3
16fb 1750,
1700,
5.85 (d,
3.48–3.61 (m)
3.50, 3.90/
3.92
2.76–2.91,
74.4 61.0 55.1
34.4 (C-3), 51.7
(COOCH3), 170.1
(COOCH3)
3J1,2 = 2.2)
3.06 (m + dd,
2J3,3 = 14.3,
3J2,3 = 9.8,
1690d
(2 d, 2JBn
=
13.8)
3-H2), 3.58 (s,
COOCH3)
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

1586
J. Schwerdtfeger et al.
PAPER
Table 6 (continued)
Prod- IR (KBr/
1H NMR (300 MHz, CDCl3), d, J (Hz)
13C NMR (75 MHz, CDCl3), d
C-1 C-2 N-CH2Ph R and El in Scheme 3
uct
film)
1-H
2-H
N-CH2Ph
(2JBn
R and El in
n (cm-1
)
)
Scheme 3
17fbc
5.04 (d,
3.48–3.61b (m)
3.52, 4.01–
4.17
2.76–2.91,
74.4 60.9 55.0
29.7 (C-3), 51.6
(COOCH3); 170.1
(COOCH3)
3J1,2 = 4.3)
3.16 (m + dd,
2J3,3 = 12.7,
3J2,3 = 4.4,
(d + m, 2JBn
13.1)
=
3-H2), 3.52 (s,
COOCH3)
16ff 1690d
5.41-5.62 (m) 2.89–3.10b (m)
3.63, 3.74
2.89–3.10b (m,
3-H2)
69.6 62.8 53.8
19.7 (1-CH3), 33.1
(C-3)
(2 d, 2JBn
=
13.8)
17ffc
5.07 (dq, 3J1,2
=
=
3.7, 3J1,1- CH
3
6.6)
16fi 1675
6.65 (d, 3J1,2
1.4)
=
3.53–363 (m)
3.63–3.82 (m)
3.70, 2.92/
2.89, 3.07
75.6 59.5 54.2
33.1/33.3 (C-3), 197.3
(C=O)
3.95 (2 d, 2JBn (2 dd, 2J3,3
=
= 14.3)
14.3, 3J2,3
5.3, 10.0,
3-H2)
=
17fic
5.90 (d, 3J1,2
4.8)
=
3.41, 4.07/
2.83–3.04,
76.7 61.2 54.8
28.8 (C-3), 195.6
(C=O)
4.11 (2 d, 2JBn 3.21 (m + dd,
= 14.3)
2J3,3 = 12.9,
3J2,3 = 3.8, 3-
H2)
16fjc
17fjc
5.95 (d, 3J1,2
0.5)
=
=
3.51, 4.01/
0.79, 1.09[1 d,
75.9
54.8
17.5, 19.4
3
4.02 (2 d, 2JBn JCH,
= 6.8,
[CH(CH3)2], 36.5
[CH(CH3)2], 210.8
CC=O)
CH
3
= 13.0)
CH(CH3)2]
5.26 (d, 3J1,2
5.0)
0.76, 0.94[2 d,
16.9, 19.3
[CH(CH3)2], 28.5
(C-3), 36.2
3JCH, CH = 6.4,
3
CH(CH3)2]
[CH(CH3)2]
(ent-) 1750,
16gb 1700,
1690
5.70/5.73 (d,
4.23/4.26 (d)
4.30 (d)
3.12, 3.93
3.83 (s.
COOCH3)
72.3 63.4 54.2
52.0 (COOCH3),
170.3 (COOCH3)
3J1,2 = 10.2)
(2 d, 2JBn
=
13.6)
17gb 1740,
1695,
5.81 (d, 3J1,2
8.0)
=
3.25, 4.30
3.38 (s,
COOCH3)
73.6 63.5 54.5/54.6 51.6/51.7 (COOCH3),
(2 d, 2JBn
=
169.9 (COOCH3)
1685
13.5)
ent-
16ge
1685
5.79/5.81 (d,
4.08–4.46 (m)
3.83 (d)
3.04, 4.11
–0.30 [s,
Sn(CH3)3]
68.8 64.7 53.5
68.4* 67.5* 54.0
–8.87 [Sn(CH3)3]
3J1,2 = 12.6)
(2 d, 2JBn
=
13.4)
ent- 1685,
16gf 1675
5.85 (dq, 3J1,2
10.3, 3J1,1-CH3
6.3)
=
=
3.03, 4.06 (2 0.94 (d, CH3)
19.4 (CH3)
x d, 2J = 13.4)
16hbc 1740,
5.79 (d, 3J1,2
1.2)
=
3.10–3.21b (m)
3.38–3.94b
(m)
1.36–1.50*
70.3 58.7 53.8, 58.2 24.4, 25.7 (C-3, C-4),
51.8 (COOCH3), 53.4
(C-5), 170.2
1680
(4-H2), 1.73–
1.84* (3-H2),
2.28 (dd, 3J4,5
= 6.7, 5-H2),
3.38–3.94b (m,
COOCH3)
(COOCH3)
17hbc
5.36 (d, 3J1,2
=
3.10–3.21b (m)
4.3)
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Deprotonation of Chiral and Achiral 2-Aminoalkyl Carbamates
1587
Table 6 (continued)
Prod- IR (KBr/
1H NMR (300 MHz, CDCl3), d, J (Hz)
13C NMR (75 MHz, CDCl3), d
C-1 C-2 N-CH2Ph R and El in Scheme 3
uct
film)
1-H
2-H
N-CH2Ph
(2JBn
R and El in
n (cm-1)
)
Scheme 3
16hdc 1660
5.69 (d, 3J1,2
10.3)
=
2.79 (dd, 3J2,3
8.6)
=
3.39–3.96
(m)
0.68–0.75,
0.83–0.98,
1.13–1.65b
[3 m,
69.8 60.1 53.9, 57.9 9.91, 13.6 27.5, 28.9
[Sn(C4H9)3], 25.1,
25.9 (C-3, C-4), 53.4
(C-5)
Sn(C4H9)3],
1.13–1.65b (m,
3-H2, 4-H2),
2.41 (ddd, 2J5,5
= 13.6, 3J4,5
=
6.9, 5-H2)
17hdc
4.73–4.82 (m)
16hic 1685
6.69 (d, 3J1,2
1.7)
=
3.16–3.20b (m)
3.16–3.20b (m)
3.38–3.97b
(m)
1.40–1.83 (m,
3-H2, 4-H2),
2.26 (dd, 3J4,5
= 6.9, 5-H2)
75.4 57.7 54.1, 58.2 25.1, 25.2 (C-3, C-4),
53.6 (C-5), 197.8
(C=O)
17hic
6.29 (d, 3J1,2
=
2.44 (m, 5-H2)
5.0)
a NMR data of the Cby group and the aromatic rings are omitted.*or +NMR data, signed by these symbols, are interchangeable.
b As part of a multiplet.
c Data, which could be determined form the 1H and 13C NMR spectra of the diastereomeric mixture of 16/17.
d From the diastereomeric mixture 16/17.
e Free acid.
the mixture was stirred for 12 h at r.t. After addition of solid K2CO3
(500 mg, 3.62 mmol) the inorganic salts were filtered off and the fil-
trate was concentrated in vacuo. Purification of the crude product by
flash chromatography (EtOAc/pentane, 2:1) gave ent-30 (176 mg,
65%) as colorless crystals.
ded dropwise and the slurry was stirred for 12 h at r.t. The solids
were filtered, washed with MeOH (2 î 10 mL) and the solvent was
evaporated in vacuo. The residue was dissolved in MeOH (3 mL)
and aq formaldehyde (6 mL, 37%) was added. After stirring for 3 h
at r.t. the pH of the solution was adjusted with K2CO3 to 11. The
aqueous phase was extracted with Et2O (3 î 10 mL). The combi-
ned Et2O were dried (MgSO4) and concentrated in vacuo. Flash
chromatography (Et2O/pentane, 1:4Æ2:1) of the crude product
gave ent-32 (130 mg, 22%) as a pale yellow oil; Rf 0.71 (Et2O/pen-
tane, 1:1).
ent-30
[a]D -48.8 (c = 1 in CHCl3).
The enantiomer 30 was obtained as colorless crystals (55%) by
treatment of 17ab with LiAlH4 according to general Method E.
IR (film): n = 745, 695 cm–1 (C6H5).
30
1H NMR (CDCl3, 300 MHz): d = 0.83 [d, 3J5,5-1 = 6.6 Hz, 5-(1-H3)],
3.34, 3.40 (2 d, 2JBn = 13.5 Hz, NCH2Ph), 3.89 (d, 3J4,5 = 7.7 Hz, 4-
H), 4.04, 4.70 (2 d, 2J2,2 = 2.6 Hz, 2-H2), 4.43 (dq, 5-H), 7.20–7.43
(m, 10 H, C6H5).
13C NMR (CDCl3, 75 MHz): d = 17.7 [5-(C-1)], 55.8 (NCH2Ph),
69.8 (C-4), 77.4 (C-5), 85.9 (C-2), 127.0, 127.3, 128.2, 128.3,
138.3, 138.6 (C6H5).
Rf 0.08 (Et2O/pentane, 1:1); mp 55°C (Et2O/pentane); [a]D +45.6
(c = 1 in CHCl3).
IR (KBr): n = 3410 cm–1 (OH).
1H NMR (CDCl3, 300 MHz): d = 2.46, 2.66 (2 dd, 2J3,3 = 12.8 Hz,
3J2,3 = 4.4, 9.0 Hz, 3-H2), 3.37, 3.61 (2 dd,2J1,1 = 11.4 Hz,3J1,2 = 3.6,
4.7 Hz, 1-H2), 3.48, 3.76 (2 d, 2JBn = 13.4 Hz, NCH2Ph), 3.78 (dddd,
2-H), 6.95–7.25 (m, 10 H, C6H5).
Anal. Calcd. for C17H19NO (254.4): C, 80.27; H, 7.53. Found C,
80.11; H, 7.43.
13C NMR (CDCl3, 75 MHz): d = 55.9 (C-3), 58.8 (NCH2Ph), 64.8
(C-1), 67.9 (C-2), 127.3, 128.5, 129.1, 138.4 (C6H5).
(For the remaining data see Table 4.)
Anal. Calcd. for C17H21NO2 (271.4): C, 75.25; H, 7.80. Found C,
75.23; H, 7.74.
(2S,3R)-3-[N-Benzyl-N-(benzyloxycarbonyl)amino]-2-pentanol
(ent-33)
(For remaining data see Table 4.)
Freshly prepared Pd, obtained from PdCl2 (342 mg, 1.90 mmol, 30
mol%), was suspended in MeOH/HCOOH (10 mL, 95:5) and a so-
lution of alcohol ent-23cf (1.8 g, 6.30 mmol) in MeOH/HCO2H (10
mL, 95:5) was added dropwise. Stirring was continued for 2 h at r.t.
and the Pd was filtered. After removing the solvent in vacuo the re-
sidue was recrystallized from Et2O/pentane to give the mono-de-
benzylated amino alcohol as colorless needles (363 mg, 31%). A
(4R,5S)-3-Benzyl-5-methyl-4-phenyl-1,3-oxazolidine (ent-32)20
A suspension of PdCl2 (163 mg, 0.92 mmol, 40 mol%) in MeOH
(20 mL) was hydrogenated with 1 atm of H2 for 30 min. The sol-
vent was decanted, the Pd was washed with MeOH (2 î 10 mL),
and suspended in MeOH/HCO2H (10 mL, 95:5). A solution of ent-
23gf (773 mg, 2.30 mmol) in MeOH/HCO2H (5 mL, 95:5) was ad-
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

1588
J. Schwerdtfeger et al.
PAPER
Table 7 Selected Data of Methyl-Substituted Amino Alcohols 23 and 24a
1H NMR (300 MHz, CDCl3), δ, J (Hz)
Prod- IR (KBr/
13C NMR (75 MHz, CDCl3), δ
C-2 N-CH2Ph R and 1-CH3 in
uct
film)
1-H
2-H
N-CH2Ph
R and 1-CH3 in Scheme 6
C-1
ν (cm-1)
Scheme 6
24af 3430
3.85 (tq,
2.41 (d)
3.40, 3.84 1.05 (d, 1-CH3)
63.2 61.5 58.6
20.0 (1-CH3)
3J1,2 = 6.1,
(2 d,
3J1,1-CH
=
2JBn = 13.5)
3
6.6)
24agb 3453
24bf 3400
3.89–3.98 2.58, 2.73 3.34, 3.80 2.39–2.51 (m, CH2Ph)
68.4 61.3 58.5
66.0 59.3 52.4
65.8 62.7 54.4
59.3 (CH2Ph)
(m)
(2 dd, 3J1,2 (2 d,
2
= 5.7, 7.2) JBn = 13.3)
3.53 (dq,
2.40 (dq,
3.23, 3.74 0.92 (d, 3-H3), 0.98 (d, 1-CH3)
6.78 (C-3), 18.4
(1-CH3)
3J1,1-CH
=
3J2,3 = 6.8) (2 d,
3
6.0)
2JBn = 13.2)
ent-
3400
3.83 (dq,
2.48 (ddd, 3.56, 3.66 0.91 (dd, 4-H3) 1.09 (d, 1-CH3),
1.42, 1.66 (2 ddq, 3J3,4 = 7.2, 7.9,
2JBn = 13.9) 3-H2)
11.4 (C-4), 17.4
(C-3), 19.7 (1-
CH3)
23cf
3J1,2 = 6.4, 3J2,3 = 6.8) (2 d,
3J1,1-CH
=
3
6.8)
23df 3400
24df 3600
3.92 (dq,
2.70 (ddd, 3.61, 3.71 0.78, 0.91 [2 d, 3JCH, CH = 6.4,
66.8 59.4 55.3
20.9, 22.9, 23.0
[1-CH3,
CH(CH3)2], 25.0
(CH(CH3)2], 34.7
(C-3)
3
3J1,2 = 4.2, 3J2,3 = 6.6, (2 d,
6.5, CH(CH3)2], 1.18 (d, 1-CH3),
3J1,1-CH
=
7.0)
2JBn = 13.5) 1.27, 1.57 (2 ddd, 2J3,3 = 13.7,
3J3,4 = 6.6, 6.8, 3-H2), 1.72 [ddq,
3
6.6)
CH(CH3)2], 2.21–2.40 (m, OH)
3.60 (dq,
2.40 (ddd, 3.40, 3.83 0.95 [d, 3JCH, CH = 6.5,
67.5 63.0 53.9
19.9, 23.0, 23.4
[1-CH3,
CH(CH3)2]; 26.7
[CH(CH3)2]; 35.6
(C-3)
3
3J1,2 = 9.1, 3J2,3 = 4.2, (2 d,
CH(CH3)2], 1.09 (d, 1-CH3),
3J1,1-CH
=
6.8)
2JBn = 13.4) 1.09–1.32, 1.50–1.79 [2 m, 3-H,
CH(CH3)2], 4.30–4.54 (m, OH)
3
6.1)
23ef 3400
24ef 3360
3.84 (dq,
2.48 (dd,
3.75, 3.88 0.95 (d, 1-CH3), 1.20 [2 d,
67.6 66.1 56.5
68.1 63.4 54.0
67.9 64.3 55.2
66.7 66.2 54.0
69.4* 66.9* 54.6
19.8, 20.8, 23.2
[1-CH3,
CH(CH3)2], 28.2
[CH(CH3)2]
3J1,2 = 5.0, 3J2,3 = 9.1) (2 d,
3JCH, CH = 6.7, CH(CH3)2], 2.15
3J1,1-CH
=
2JBn = 13.4) [dqq, C3H(CH3)2], 2.80 (br s,
3
6.4)
OH)
3.88 (dq,
2.25 (dd,
3.45, 3.92 1.11 (d, 1-CH3); 1.04, 1.07 [2 d,
19.1, 21.1, 23.9
[1-CH3,
CH(CH3)2], 24.7
[CH(CH3)2]
3J1,2 = 9.3, 3J2,3 = 2.0) (2 d,
3JCH, CH = 7.2, CH(CH3)2], 2.25
3J1,1-CH
=
2JBn = 13.1) [dqq, C3H(CH3)2] 4.31 (br s, OH)
3
6.0)
23ff
24ff
3450
3360
3.86 (dq,
2.99 (ddd, 3.61, 3.80 1.24 (d, 1-CH3), 1.86-2.15 (m,
21.2 (1-CH3), 32.2
(C-3)
3J1,2 = 4.7, 3J2,3 = 6.7, (2 d,
OH), 2.79, 3.09 (2 dd, 2J3,3
=
3J1,1-CH
=
6.8)
2JBn = 13.7) 13.3, 3-H2)
3
6.6)
3.74 (dq,
2.79 (ddd, 3.36, 3.88 0.97 (d, 1-CH3), 2.64, 3.08
(2 dd, 2J3,3 = 13.9, 3-H2), 4.35 (s,
2JBn = 13.2) OH)
20.4 (1-CH3), 32.3
(C-3)
3J1,2 = 8.8, 3J2,3 = 6.1, (2 d,
3J1,1-CH
=
6.2)
3
6.0)
ent-
23gf
4.49 (dq,
3.50 (d)
3.06, 3.85 1.31–1.51 (m, OH), 1.43 (d, 1-
20.8 (1-CH3)
3J1,2 = 8.9,
(2 d,
CH3)
3J1,1-CH
=
2JBn = 13.8)
3
6.1)
a NMR data of the Cby group and the aromatic rings are omitted. * NMR data, signed by this symbol, are interchangeable.
b 1-Benzyl instead of 1-methyl substituted amino alcohol.
part of the mono-debenzylated amino alcohol (75 mg, 0.39 mmol)
was dissolved in anhyd THF (10 mL) and added to a suspension of
NaH (80 mg, 2.00 mmol, 60% in mineral oil) in anhyd THF (5 mL).
Benzyloxycarbonyl chloride (0.66 mL, 2.00 mmol, 25% in toluene)
was added dropwise and the mixture was stirred for 16 h at r.t. After
addition of H2O (3 mL) the mixture was extracted with EtOAc
(3 î 10 mL) and the combined organic layers were dried (MgSO4)
and concentrated in vacuo. Flash chromatography of the crude pro-
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Deprotonation of Chiral and Achiral 2-Aminoalkyl Carbamates
1589
Table 8 Selected Data from Substituted Monocarbamates 18, 19 and Their Deprotected Derivatives 25, 26a
Product IR (KBr/film)
1H NMR (300 MHz, CDCl3), d, J (Hz)
2-H N-CH2Ph R in Scheme 10
4.60(d,3J1,2 5.54 (dd, 3J2,3 3.52–3.64, 1.04 (dd,3J4,5 = 7.2, 7.5,
13C NMR (75 MHz, CDCl3), d
C-2 N-CH2Ph R in Scheme 10
13.3 (C-5), 20.4
n (cm-1)
1-H
C-1
ent-18cl 3300–3600,
74.6* 76.9* 54.2
75.2* 76.0* 53.9
74.1* 74.6* 53.8
1675
= 6.8)
= 6.4)
3.69 (m + s) 5-H3), 1.62–1.88 (m,
4-H2); 2.98–3.08 (m,
(C-4), 60.5 (C-3)
3-H), 4.42 (s, OH)
ent-19cl 3300–3600,
4.76 (d,
5.60 (dd, 3J2,3 3.44, 3.75
0.93 (t, 3J4,5 = 7.2,
5-H3); 1.74–1.84 (m,
4-H2); 2.35 (s, OH),
2.56–2.62 (m, 3-H)
12.7 (C-5), 20.7
(C-4), 58.4 (C-3)
1675
3J1,2 = 7.2) = <1.5)
(2 d, 2JBn
=
13.6)
18dmc
19dmc
3480, 1675,
1660
3.48–3.76b 5.28 (dd, 3J1,2 3.48–3.76b 0.64, 0.92 [2 d,
22.3, 23.7
[CH(CH3)2],
24.9
[CH(CH3)2],
37.1 (C-4), 54.8
(C-3)
(m)
= 7.0, 3J2,3
4.6)
=
(m)
3JCH,CH = 6.6, 6.7,
3
CH(CH3)2], 1.21–1.70b
(m, 4-H2), 1.78–2.02
[m, CH(CH3)2], 3.01–
3.10 (m, 3-H, OH)
3480, 1675,
1660
3.60–3.76b 5.26 (dd, 3J1,2 3.60–3.76b 0.68 [d, 3JCH,CH = 6.4,
73.9* 75.2* 54.0
21.9, 23.8
[CH(CH3)2],
24.9
(m)
=
3J2,3 = 5.3) (m)
CH(CH3)2], 0.838–2.11b
[m, CH(CH3)2,
CH(CH3)2, 4-H2, OH]
2.91 (ddd, 3J3,4 = 8.0,
10.3, 3-H)
[CH(CH3)2],
36.9 (C-4), 55.6
(C-3)
18fl
19fl
3300–3600,
1675
4.67(d,3J1,2 5.64 (dd,3J2,3 3.08–3.75b 3.08–3.75b (m, 3-H,
74.1* 76.9* 53.8
73.9* 75.9* 53.7
33.6 (C-4), 60.6
(C-3)
= 6.1)
= 6.2)
(m)
4-H2), 4.69 (s, OH)
3410, 1675
4.98(d,3J1,2 5.69 (dd,3J2,3 3.58, 3.62
2.11 (s, OH), 2.91–3.27
(m, 3-H, 4-H2)
33.6 (C-4), 58.2
(C-3)
= 6.0)
= 5.0)
(2 d, 2JBn
=
13.8)
ent-25cl 3200–3600
ent-26cl 3200–3550
4.17 (d,
3.74 (dd,3J2,3 3.56, 3.93
1.10 (t, 3J4,5 = 7.5,
5-H3), 1.69, 1.88
(2 ddq, 3J3,4 = 7.2, 4-
H2), 2.92 (m, 3-H)
73.5 79.8
74.4 75.4
55.0
54.8
14.1 (C-5), 19.4
(C-4), 64.1 (C-3)
3J1,2 = 7.9) = 8.3)
(2 d, 2JBn
=
13.0)
4.83 (d,
3J1,2 = 5.3) = 5.3)
3.93 (dd,3J2,3 3.55, 3.73
0.99 (t, 3J4,5 = 7.5,
5-H3); 1.61, 1.84
(2ddq, 3J3,4 = 4.9 Hz,
4-H2), 2.23 (s, OH),
2.51 (ddd, 3-H)
13.1 (C-5), 19.5
(C-4), 59.8 (C-3)
(2 d, 2JBn
=
13.6)
25fl
26fl
3370
3380
4.22(d,3J1,2 3.84 (dd,3J2,3 3.58, 3.87
3.08, 3.10 (2 dt, 2J4,4
14.3, 3J3,4 = 5.7, 7.0,
4-H2), 3.36 (ddd, 3-H)
=
73.3 78.8
73.9 75.7
54.7
54.4
32.6 (C-4), 63.8
(C-3)
= 7.6)
= 7.6)
(2 d, 2JBn
=
13.2)
4.77(d,3J1,2 4.01 (dd,3J2,3 3.61, 3.68
2.92–3.14 (m, 3-H,
4-H2)
33.5 (C-4), 59.5
(C-3)
= 5.5)
= 4.5)
(2 d, 2JBn
=
13.7)
a NMR data of the Cby group and the aromatic rings are omitted. * NMR data, signed by this symbol, are interchangeable.
b As part of a multiplett.
c The phenyl group in scheme 10 adjacent to C-1 is replaced by an ethyl residue. NMR data of the ethyl group are omitted.
duct (Et2O/pentane, 1:1) gave ent-33 (111 mg, 87%) as a colorless
oil.
(m, 3-H), 3.92 (m, 2-H), 4.23, 4.72 (2 d, 2JBn = 15.5 Hz, NCH2Ph),
5.19 (s, OCH2Ph), 7.13–7.39 (m, 10 H, C6H5).
Rf 0.21 (Et2O/pentane 1:1).
13C NMR (CDCl3, 75 MHz): d = 11.7 (C-5), 18.8 (C-4), 21.5 (C-1),
53.0 (NCH2Ph), 67.7 (OCH2Ph), 67.9 (C-3), 71.1 (C-2), 127.7,
128.1, 128.2, 128.3, 128.8, 136.6, 138.2 (C6H5), 157.6 (C = O).
IR (film): n = 3200-3600 (OH), 1675 cm–1 (NC = O).
1H NMR (CDCl3, 300 MHz): d = 0.87 (t, 3J4,5 = 7.2 Hz, 5-H3), 1.02
Anal. Calcd. for C20H25NO3 (327.4): C, 73.37; H, 7.70. Found C,
73.34; H, 7.96.
3
(d, J1,2 = 6.4 Hz, 1-H3), 1.58–1.80, 1.87–2.05 (2 ¥ m, 4-H2), 3.14
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

1590
J. Schwerdtfeger et al.
PAPER
(For the remaining data see Table 4.)
suspension was stirred for 1 h and subsequently treated with NaBH4
(39 mg, 1.00 mmol) at 0°C. The suspension was heated under reflux
for 24 h, and excess of NaBH4 was hydrolyzed with H2O (3 mL) and
the organic solvent was evaporated in vacuo. The aqueous phase
was extracted with Et2O (3 î10 mL). The combined ethereal phases
were dried (MgSO4) and concentrated in vacuo. Purification of the
crude product by flash chromatography (Et2O/pentane, 1:8) gave
18fl (78 mg, 76%) and 19fl (17 mg, 18%); diastereomeric ratio
82:18. For physical data of 18fl and 19fl see Tables 3 and 8.
(4R,5S)-3-Benzyl-4-ethyl-5-methyl-2-oxazolidinone (ent-34)22
A solution of ent-33 in THF (10 mL) and MeOH (5 mL) was stirred
with aq KOH (2.5 mL, 7.5 N) for 5 h at r.t. After neutralization with
HCl (10%) the mixture was extracted with EtOAc (3 î 10 mL). The
combined extracts were dried (MgSO4) and concentrated in vacuo.
Purification of the residue by flash chromatography (Et2O/pentane,
1:2Æ2:1) yielded ent-34 (58 mg, 92%) as a colorless liquid; Rf 0.20
(Et2O/pentane 1:1).
Cyclic Carbonates ent-35cl, ent-36cl, 35fl, and 36fl; General
Procedure25
IR (film): n = 1740 (NC = O), 1075, 1045 cm–1 (COC).
1H NMR (CDCl3, 300 MHz): d = 0.88 [t, J4-1,4-2 = 7.4 Hz, 4-(2-
3
A suspension of diol 25 or 26 (0.20 mmol) in excess dimethyl or
diethyl carbonate (5 mL) and solid K2CO3 (100 mg, 0.72 mmol) was
heated at 80°C, until the substrate could not longer be detected by
TLC (approx. 3–6 d). The solids were filtered and washed with
Et2O (30 mL). The filtrate was concentrated in vacuo and the resi-
due was purified by flash chromatography (Et2O/pentane, 1:4 to
1:7) to give the cyclic carbonate as pure compound.
3
H3)], 1.35 [d, J5,5-1 = 6.4 Hz, 5-(1-H3)], 1.50–1.71 [m, 4-(1-H2)],
3
2
3.49 (ddd, J4,5 = 7.0 Hz, 4-H), 4.06, 4.81 (2 d, JBn = 15.3 Hz,
NCH2Ph), 4.62 (dq, 5-H), 7.26–7.37 (m, 5 H, C6H5).
13C NMR (CDCl3, 75 MHz): d = 8.7 [4-(C-2)], 13.6 [5-(C-1)], 19.0
[4-(C-1)], 45.1 (NCH2Ph), 57.5 (C-4), 72.9 (C-5), 126.8, 126.9,
127.7, 135.4 (C6H5), 157.5 (C = O).
[4R(1R),5S]-4-[1-(N,N-Dibenzylamino)propyl]-5-phenyl-1,3-di-
oxolan-2-one (ent-35cl)
C13H17NO2 (219.3; EI, 70 eV) calculated:219.12593,
found:219.12651.
Yield: 56 mg (70%); transparent colorless crystals; mp 141–142°C
(Et2O/pentane); Rf 0.40 (Et2O/pentane, 1:1); [a]D +46.8 (c = 1, ace-
tone).
(For remaining data see Table 4.)
IR (KBr): n = 1785 cm–1 (C = O).
(1S,2R,3R)- and (1R,2R,3R)-3-(N,N-Dibenzylamino)-1-phenyl-
2-O-(2,2,4,4-tetramethyl-1,3-oxazolidine-3-carbonyl)-1,2-pen-
tanediol (ent-18cl and ent-19cl)
1H NMR (CDCl3, 300 MHz): d = 0.56 [dd, 3J4-2, 4-3 = 7.2 Hz, 4-(3-
3
H3)], 0.95–1.03, 1.49–1.61 [2 m, 4-(2-H2)], 2.47 [ddd, J4,4-1 = 2.3
3
2
Hz, J4-1,4-2 = 3.4 and 9.6 Hz, 4-(1-H)], 3.38, 3.84 (2 d, JBn = 13.9
Reduction of ent-16ci with NaBH4
3
Hz, NCH2Ph), 5.20 (dd, J4,5 = 8.7 Hz, 4-H), 5.73 (d, 5-H), 7.01–
NaBH4 (106 mg, 2.8 mmol) was added to a solution of ketone ent-
16ci (529 mg, 1.00 mmol) in MeOH (14 mL), H2O (2 mL) and Et2O
(6 mL). After stirring for 2 d at r.t. H2O (3 mL) was added and the
aqueous solution was extracted with Et2O (3 î 15 mL). The combi-
ned organic layers were dried (MgSO4) and the solvents were remo-
ved in vacuo. Flash chromatography on silica gel (Et2O/pentane,
1:4Æ1:1) afforded ent-18cl (282 mg, 53%) and ent-19cl (123 mg,
23%) in a diastereomeric ratio of 70:30.
7.36 (m, 15 H, C6H5).
13C NMR (CDCl3, 75 MHz): d = 11.4 [4-(C-3)], 19.2 [4-(C-2)], 54.6
(NCH2Ph), 58.5 [4-(C-1)], 79.5* (C-4), 80.5* (C-5), 125.8, 127.4,
128.6, 128.8, 129.1, 139.4 (C6H5), 155.0 (C = O).
Anal. Calcd. for C26H27NO3 (401.5): C, 77.78; H, 6.78. Found C,
77.75; H, 6.75.
[4R(1R),5R]-4-[1-(N,N-Dibenzylamino)propyl]-5-phenyl-1,3-
dioxolan-2-one (ent-36cl)
Yield: 20.9 mg (26%); colorless solid; mp 89–90°C (Et2O/pentane);
Rf 0.57 (Et2O/pentane, 1:1); [a]D +105.0 (c = 1, acetone).
38
Reduction of ent-16ci with Zn(BH4)2
Ketone ent-16ci (529 mg, 1.00 mmol) was dissolved in anhyd Et2O
(20 mL) and treated with freshly prepared Zn(BH4)2 (16.5 mL, 5.00
mmol, ~0.3 mol/L in Et2O) at r.t. After stirring for 3 h, the mixture
was hydrolyzed with H2O (5 mL). The Et2O layer was separated and
the aqueous phase was extracted with Et2O (3 î 15 mL). The com-
bined Et2O extracts were dried (MgSO4) and concentrated in vacuo.
Flash chromatography of the residue (Et2O/pentane, 1:4) gave ent-
18cl (460 mg, 87%) and ent-19cl (64 mg, 12%) in a diastereomeric
ratio of 88:12. For physical data of ent-18cl and ent-19cl see Tables
3 and 8.
IR (KBr): n = 1800 cm–1 (C = O).
1H NMR (CDCl3, 300 MHz): d = 1.11 [dd, 3J4-2, 4-3 = 7.4 Hz, 4-(3-
2
H3)], 1.62, 1.91 [2 ddq, J4-2,4-2 = 14.3 Hz, 3J4-1,4-2 = 7.5 Hz, 4-(2-
H2)], 2.75 [ddd, 3J4,4-1 = 4.5 Hz, 4-(1-H)], 3.38, 3.75 (2 d, 2JBn = 13.6
3
Hz, NCH2Ph), 4.75 (dd, J4,5 = 7.2 Hz, 4-H), 4.98 (d, 5-H), 7.06–
7.48 (m, 15 H, C6H5).
13C NMR (CDCl3, 75 MHz): d = 11.2 [4-(C-3)], 17.4 [4-(C-2)], 53.2
(NCH2Ph), 59.5 [4-(C-1)], 80.8* (C-4), 81.3* (C-5), 125.5, 126.2,
127.3, 128.0, 128.2, 128.7, 135.1, 137.8 (C6H5), 153.5 (C = O).
(1R,2S,3S)- and (1S,2S,3S)-3-(N,N-Dibenzylamino)-1,4-diphe-
nyl-2-O-(2,2,4,4-tetramethyl-1,3-oxazolidine-3-carbonyl)-1,2-
butanediol (18fl and 19fl)
Anal. Calcd. for C26H27NO3 (401.50): C, 77.78; H, 6.78. Found C,
77.58; H, 6.80.
Reduction of 16fi with NaBH4
[4S(1S),5R]-4-[1-(N,N-Dibenzylamino)-2-phenylethyl]-5-phe-
nyl-1,3-dioxolan-2-one (35fl)
Yield: 56.6 mg (61%); colorless solid; mp 57–58°C (Et2O/pentane);
Rf 0.23 (Et2O/pentane, 1:2); [a]D +9.6 (c = 1, CH2Cl2).
NaBH4 (57 mg, 1.50 mmol) was added to a solution of ketone 16fi
(177 mg, 0.30 mmol) in MeOH (5 mL) and Et2O (3 mL) at 0°C. Stir-
ring was continued for 24 h and the mixture was allowed to warm
up to r.t. Hydrolysis with H2O (5 mL) was followed by extraction of
the aqueous phase with Et2O (3 î 10 mL). The combined Et2O ex-
tracts were dried (MgSO4) and concentrated in vacuo. Purification
of the residue by flash chromatography (Et2O/pentane, 1:6) affor-
ded 18fl (111 mg, 63%) and 19fl (48 mg, 27%); diastereomeric ra-
tio 70:30.
IR (KBr): n = 1785 cm–1 (C = O).
1H NMR (CDCl3, 300 MHz): d = 2.28, 2.84 [2 dd, 2J4-2,4-2 = 13.9 Hz,
3
3J4-1,4-2 = 2.8, 11.1 Hz, 4-(2-H2)], 3.25 [ddd, J4,4-1 = 1.0 Hz, 4-(1-
H)], 3.47, 3.74 (2 ¥ d, 2JBn = 13.6 Hz, NCH2Ph), 5.36 (dd, 3J4,5 = 8.9
Hz, 4-H), 5.81 (d, 5-H), 6.90–7.34 (m, 20 H, C6H5).
13C NMR (CDCl3, 75 MHz): d = 31.3 [4-(C-2)], 54.1 (NCH2Ph),
57.5 [4-(C-1)], 79.7* (C-4), 79.9* (C-5), 125.4, 126.1, 127.0, 127.9,
128.2, 128.5, 128.8, 129.3, 132.7, 138.2, 138.9 (C6H5), 154.5
(C = O).
39
Reduction of 16fi with NaBH4/MnCl2
To a solution of the ketone 16fi (100 mg, 0.17 mmol) in MeOH (10
mL) and Et2O (3 mL) was added MnCl2 (43 mg, 0.34 mmol) and the
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Deprotonation of Chiral and Achiral 2-Aminoalkyl Carbamates
1591
Anal. Calcd. for C31H29NO3 (463.6): C, 80.32; H, 6.31. Found C,
80.31; H, 6.33.
(11) (a) Sommerfeld, P.; Hoppe, D. Synlett 1992, 764.
(b) Guarnieri, W.; Grehl, M.; Hoppe, D. Angew. Chem. 1994,
106, 1815; Angew. Chem. Int. Ed. Engl. 1994, 33, 1734.
(c) Guarnieri, W.; Sendzik, M.; Fröhlich, R.; Hoppe, D.
Synthesis 1998, 1274.
(d) Sendzik, M.; Guarnieri, W.; Hoppe, D. Synthesis 1998,
1287.
[4S(1S),5S]-4-[1-(N,N-Dibenzylamino)-2-phenylethyl]-5-phe-
nyl-1,3-dioxolan-2-one (36fl)
Yield: 69.5 mg (75%); transparent colorless crystals; mp 114–
115°C (Et2O/pentane); Rf 0.47 (Et2O/pentane, 1:2); [a]D -63.9
(c = 1, CH2Cl2).
(12) (a) Schwerdtfeger, J. Dissertation, University of Kiel, 1993.
(b) Kolczewski, S. Dissertation, University of Münster, 1995.
(c) Weber, B. Diploma Thesis, University of Münster,
1995.(d) Weber, B. Dissertation, University of Münster,
1998.
IR (KBr): n = 1800 cm–1 (C = O).
1H NMR (CDCl3, 300 MHz): d = 3.07, 3.18 [2 dd,2J4-2,4-2 = 13.8 Hz,
3J4-1,4-2 = 6.4, 7.2 Hz, 4-(2-H2)], 3.22–3.30 [m, 4-(1-H)], 3.53, 3.69
(2 d, 2JBn = 13.6 Hz, NCH2Ph), 4.72 (d, 3J4,5 = 7.6 Hz, 5-H), 4.80 (br
d, 4-H), 6.93–7.45 (m, 20 H, C6H5).
13C NMR (CDCl3, 75 MHz): d = 31.5 [4-(C-2)], 54.2 (NCH2Ph),
60.4 [4-(C-1)], 81.5* (C-4), 83.9* (C-5), 126.2, 126.7, 127.2, 128.3,
128.8, 129.2, 129.4, 129.6, 135.7, 138.5, 138.8 (C6H5), 154.2
(C = O).
(13) (a) Velluz, L.; Amiard, G.; Heymes, R. Bull. Soc. Chim. Fr.
1954, 1012.
(b) Reetz, M. T.; Drewes, M. W.; Schmitz, A. Angew. Chem.
1987, 99, 1186; Angew. Chem., Int. Ed. Engl. 1987, 26, 1141.
(c) Drewes, M. W. Dissertation, University of Marburg, 1990.
(14) Govindachari, T. R.; Rajagopalan, T. G.; Viswanathan, N. J.
Chem. Soc., Perkin Trans. 1 1974, 1161.
Anal. Calcd. for C31H29NO3 (463.6): C, 80.32; H, 6.31. Found C,
80.26; H, 6.48.
(15) For selected examples see:
Ojima, I.; Habus, I.; Zhao, M. J. Org. Chem. 1991, 56, 1681.
(b) Farina, V.; Hauck, S. I.; Walker, D. G. Synlett 1992, 761.
(c) Gou, D.-M.; Liu, Y.-C.; Chen, C.-S. J. Org. Chem. 1993,
58, 1287.
d) Brieva, R.; Crich, J. Z.; Sih, C. J. J. Org. Chem. 1993, 58,
1068.
Acknowledgement
Generous support by the Deutsche Forschungsgemeinschaft and the
Fonds der Chemischen Industrie is gratefully acknowledged.
(e) Mukai, C.; Kim, I. J.; Hanaoka, M. Tetrahedron 1993, 49,
8323.
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Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York

1592
J. Schwerdtfeger et al.
PAPER
(26) For further carbonates and their cis,trans-coupling constants
see: Iida, T.; Itaya, T. Tetrahedron 1993, 49, 10511.
(27) X-ray crystal structure analysis of 36fl: formula C31H29NO3,
M = 463.55, colourless crystal, 0.45 ¥ 0.40 ¥ 0.20 mm,
a = 12.478(1), b = 12.481(1), c = 16.610(1) Å,
(28) O’Donnell, M. J.; Polt, R. L. J. Org. Chem. 1982, 47, 2663.
(29) Boie, C.; Hoppe, D. Synthesis 1997, 176.
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(31) Behrens, K. Dissertation, University of Münster, 1997.
(32) (a) Weber, B.; Kolczewski, S.; Fröhlich, R.; Hoppe, D.
Synthesis 1999, subsequent paper.(b) Weber, B.;
Schwerdtfeger, J.; Fröhlich, R.; Göhrt, A.; Hoppe, D.
Synthesis 1999, in print.
(33) Enders, D.; Schiffers, R. Synthesis 1996, 53.
(34) (a) For NMR data see: Meguro, M.; Asao, N.; Yamamoto, Y.
J. Chem. Soc., Perkin Trans. I 1994, 2597.
(b) For the specific rotation of (R)-7g , see: de Sousa, S. E.;
O’Brien, P. Tetrahedron Lett. 1997, 38, 4885.
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(36) O’Brien, P.; Powell, H. R.; Raithby, P. R.; Warren, S. J.
Chem. Soc., Perkin Trans. I 1997, 1031.
b = 105.24(1)∞, V = 2495.8(3) Å3, rcalc = 1.234 g cm–3,
F(000) = 984 e, m = 0.79 cm–1, empirical absorption
correction via j scan data (0.965 £ C £ 0.984), Z = 4,
monoclinic, space group P21 (No. 4), l = 0.71073 Å, T = 198
K, 23124 reflections collected ( h, k, l), [(sinq)/l] = 0.72
Å–1, 11564 independent and 8998 observed reflections [I ≥ 2
s(I)], 631 refined parameters, R = 0.050, wR2 = 0.100, max.
residual electron density 0.15 (–0.17) e Å–3, Flack parameter
–0.2(8), hydrogens calculated and refined as riding
atoms.Data set was collected with an Enraf Nonius
KappaCCD diffractometer. Programs used: data collection
COLLECT, data reduction DENZO-SMN and SORTAV,
structure solution SHELXS-97, structure refinement
SHELXL-97, graphics SCHAKAL-92.
Crystallographic data (excluding structure factors) for the
structures reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC-111959. Copies of the data can be
obtained free of charge on application to The Director, CCDC,
12 Union Road, CambridgeCB2 1EZ, UK [fax: int.
code+44(1223)336-033, e-mail: deposit@ccdc.cam.ac.uk].
(37) DeKoening, H.; Springer-Fidder, A.; Moolenar, M. J.;
Huisman, H. O. Recl. Trav. Chim. Pays-Bas 1973, 92, 237.
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1960, 82, 6074.
(39)Taniguchi, M.; Fujii, H.; Oshima, K.; Utimo, K. Tetrahedron
1993, 49, 11169.
Article Identifier:
1437-210X,E;1999,0,09,1573,1592,ftx,en;Z01999SS.pdf
Synthesis 1999, No. 9, 1573–1592 ISSN 0039-7881 © Thieme Stuttgart · New York