Stereoselective synthesis of new monoterpene β-amino alcohols

Article abstract of DOI:10.1016/j.tetasy.2009.06.007

The regio- and stereoselective osmium-catalysed aminohydroxylation of (+)-2-carene (99% ee), and (+)-3-carene (99% ee), (-)-β-pinene (99% ee) and (-)-camphene (75% ee) with chloramine-T is described. The products β-hydroxy-p-toluenesulfonamides were reduc

Full text of DOI:10.1016/j.tetasy.2009.06.007

Tetrahedron: Asymmetry 20 (2009) 1487–1492
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Tetrahedron: Asymmetry
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Stereoselective synthesis of new monoterpene b-amino alcohols
*
Krzysztof Z. Ła˛czkowski , Anna Kmieciak, Anna Kozakiewicz
´
Department of Chemistry, Nicolaus Copernicus University, 7 Gagarin Street, 87-100 Torun, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 April 2009
Accepted 8 June 2009
The regio- and stereoselective osmium-catalysed aminohydroxylation of (+)-2-carene (99% ee), and (+)-3-
carene (99% ee), (ꢀ)-b-pinene (99% ee) and (ꢀ)-camphene (75% ee) with chloramine-T is described. The
products b-hydroxy-p-toluenesulfonamides were reduced with sodium in liquid ammonia to give the
corresponding b-amino alcohols with 48–83% yields. The methylation-reduction of b-hydroxy-p-toluene-
sulfonamides gave b-methylamino alcohols with 33–55% yields.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
model reaction to determine the best reaction conditions. Chang-
ing the solvent, temperature, time and catalyst loading, we found
b-Amino alcohols are important physiologically active com-
pounds,1 for example, b-blockers,2 selective HIV protease inhibi-
tors3 and antibiotics.4 They are also used as chiral auxiliaries and
ligands in asymmetric synthesis.5–14 Several synthetic methods
leading to b-amino alcohols are known, for example, the reaction
of aziridines with oxygen nucleophiles,15 and epoxides with nitro-
gen nucleophiles,16 the reduction and addition of organometallics
that the reaction of 1-methylcyclohexene with chloramine-T in
tert-butanol–water, 5:1 in the presence of 0.4 mol % of osmium
tetroxide, after 18 h at reflux, gave the product in 78% yield. The
yield was slightly lower when compared to the reported 82% yield
obtained in tert-butanol after much longer time (96 h) and higher
catalyst loading.19 Considering our reaction conditions appropriate
for the aminohydroxylation of the selected terpenes, their
reactivity was examined and the following order was found: 2-car-
ene < 3-carene < 1-methylcyclohexene. Consequently, in the amin-
ohydroxylation reactions of carenes the catalyst loading was
increased to 1 mol %.
The aminohydroxylation of (+)-3-carene 1 with chloramine-T
under the conditions described above produced b-hydroxy-p-tolu-
enesulfonamide 5 in 68% yield. Its reduction with sodium in liquid
ammonia gave b-amino alcohol 6 in 72% yield. The reaction of 5
with methyl iodide in the presence of potassium carbonate in
N,N-dimethylformamide gave 7 in 89% yield. The N-methylated-
p-toluenesulfonamide group was reduced with sodium in liquid
ammonia and N-methyl-b-amino alcohol 8 was obtained in 67%
yield (Scheme 1). The b-hydroxy-p-toluenesulfonamides 5, 7 and
cis-b-amino alcohols 6, 8 were easily isolated by column chroma-
tography. Their structures were confirmed by 1H, 13C, HETCOR
and COSY NMR analysis. A monocrystal of 7 was obtained and its
X-ray analysis showed the cis-position of the hydroxyl and N-
methyl-p-toluenesulfonamido group (Fig. 1).30 The spectroscopic
data and specific rotation of 6 were identical with an authentic
sample, prepared by an independent much longer procedure.31
The same methodology was applied to (+)-2-carene 2 (99% ee),
which was transformed into the corresponding b-hydroxy-p-tolu-
enesulfonamide 9 in 48%. The lower yield when compared to the
reaction of (+)-3-carene is probably due to higher steric hindrance
of the double bond adjacent to the gem-dimethyl substituted
cyclopropane ring. b-Hydroxy-p-toluenesulfonamide 9 was trans-
formed into cis-b-amino alcohol 10, 48% yield, and its N-methyl
to
a
-amino acids,1 and aminohydroxylation of olefins.17–24
b-Amino alcohols derived from (ꢀ)- -pinene, and camphor-de-
rived DAIB are chiral auxiliaries and ligands.25 Recently, amino
a
alcohols prepared from (ꢀ)- -pinene and (ꢀ)-b-pinene were em-
a
ployed in a highly enantioselective reduction of ketones,5,26 and
the addition of diethylzinc to benzaldehyde.27 Herein we under-
took the synthesis of new b-amino alcohols and b-methylamino
alcohols from (+)-2- and (+)-3-carene, (ꢀ)-b-pinene, and (ꢀ)-
camphene by aminohydroxylation.
Recently, Pinheiro28 reported the reaction of (ꢀ)-camphene,
(ꢀ)- - and (ꢀ)-b-pinene with a stoichiometric amount of the imi-
a
do-osmium compound t-BuN@OsO3, and with chloramine-T trihy-
drate in the presence of osmium tetroxide. However, the products
b-hydroxy-p-toluenesulfonamides, obtained with high regio- and
stereoselectivity, were not transformed into the corresponding b-
amino alcohols.
2. Results and discussion
(+)-3-Carene 1, 99% ee; (+)-2-carene 2, 99% ee; (ꢀ)-b-pinene 3,
99% ee and (ꢀ)-camphene 4, 75% ee were used for the study. (ꢀ)-b-
Pinene, 99% ee, was prepared from commercial (ꢀ)-
a-pinene, 99%
ee, by a literature procedure.29 First, the aminohydroxylation of 1-
methylcyclohexene, reported earlier by Sharpless,19 was tested as a
* Corresponding author. Tel.: +48 56 6114531; fax: +48 56 6542477.
E-mail address: laczkows@chem.uni.torun.pl (K.Z. Ła˛czkowski).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.06.007

1488
K. Z. Ła˛czkowski et al. / Tetrahedron: Asymmetry 20 (2009) 1487–1492
OH
OH
NH2
NHTs
Chloramine-T, 1% mol OsO4
Na, NH3
Et2O, –78°C, 5 h
72%
t-BuOH / H2O (5 : 1), reflux, 18 h
68%
1
5
6
CH3I, K2CO3
DMF, rt, 20 h,
89%
H
N
OH
OH Ts
N
CH3
CH3
Na, NH3
Et2O, –78°C, 5 h
67%
7
8
Scheme 1. Stereoselective osmium-catalysed aminohydroxylation of (+)-3-carene.
b-amino alcohol 14 in 58% yield. Methylation of 13 produced the
N-methyl derivative 15 in a quantitative yield. Removal of the tosyl
group gave b-methylamino alcohol 16 in 37% yield. (Table 1) The
structure of 13, as established by X-ray analysis33 (Fig. 3), enables
the same structural assignment of its derivatives 14–16.
The aminohydroxylation of (ꢀ)-camphene 4 (75% ee), carried
out in the same manner as described above, produced the corre-
sponding b-hydroxy-p-toluenesulfonamide 17 in 60% yield. The
product was further transformed into the corresponding b-amino
alcohol 18 and its N-methyl derivative 20 (Table 1). Crystals of
17 could not be obtained, and its structure is based on 1H, 13C
and HETCOR NMR analysis. All b-hydroxy-p-toluenesulfonamides
and b-amino alcohols could be easily isolated by column
chromatography.
3. Conclusions
A convenient stereoselective synthesis of b-amino alcohols and
b-methylamino alcohols of high enantiomeric purity by osmium-
catalysed aminohydroxylation of (+)-3-carene, (+)-2-carene and
(ꢀ)-b-pinene has been developed. (ꢀ)-Camphene (75% ee) has also
been transformed into the corresponding b-amino alcohols. The fol-
lowing reactivity order of trisubstituted double bonds in this reac-
tion was observed: 2-carene < 3-carene < 1-methylcyclohexane.
Figure 1. X-ray crystal structure of 7.
derivative 12, 55% yield, by the reduction and methylation-reduc-
tion, respectively, following the same procedures as described for 6
and 8 (Table 1). The structure of b-hydroxy-N-methyl-p-toluene-
sulfonamide 11 was established by X-ray analysis (Fig. 2).32
Aminohydroxylation of (ꢀ)-b-pinene 3 produced the corre-
sponding b-hydroxy-p-toluenesulfonamide 13 in 73% yield, higher
compared to the carenes. The product was transformed with
4. Experimental
4.1. General
All experiments were carried out under an air atmosphere.
Reagents were generally of the best quality commercial grade
Table 1
Stereoselective osmium-catalysed aminohydroxylation of 2–4
Olefin
Product, yield (%)
Olefin
Product, yield (%)
Olefin
Product, yield (%)
R3R4N
R5R6N
HO
OH
OH
R1R2N
3
4
2
9: R1 = H, R2 = Ts,48%
10: R1 = H, R2 = H, 48%
11: R1 = Me, R2 = Ts, 42%
12: R1 = Me, R2 = H, 55%
13: R3 = H, R4 = Ts, 73%
14: R3 = H, R4 = H, 58%
15: R3 = Me, R4 = Ts, 99%
16: R3 = Me, R4 = H, 37%
17: R5 = H, R6 = Ts, 60%
18: R5 = H, R6 = H, 83%
19: R5 = Me, R6 = Ts, 99%
20: R5 = Me, R6 = H, 33%

K. Z. Ła˛czkowski et al. / Tetrahedron: Asymmetry 20 (2009) 1487–1492
1489
Figure 2. X-ray crystal structure of 11.
graphite monochromator, Mo K
a
radiation (k = 0.71073 Å). The
structure was solved by direct methods and refined with the full-
matrix least-squares on F2 with the use of SHELX-97.34 Non-hydro-
gen atoms were refined anisotropically, while hydrogen atoms
were constrained as riding atoms. The numerical absorption cor-
rection was applied.35 The absolute configuration was determined
by the Flack method.36
4.2. Materials
Silica Gel 60, E. Merck 230–400 mesh, was used for preparative
column chromatography. Analytical TLC was performed using
Macherey-Nagel Polygram Sil G/UV254 0.2 mm plates. (1S,6R)-(+)-
3-Carene (99% ee), (1S,6R)-(+)-2-carene (99% ee), (1S,5S)-(ꢀ)-
a-
pinene (99% ee), (1S,4S)-(ꢀ)-camphene (75% ee), chloramine-T
trihydrate, osmium tetroxide were commercial materials. (ꢀ)-b-
Pinene (99% ee) was prepared according to the literature.29
4.3. N-((1R,3R,4S,6S)-4-Hydroxy-4,7,7-trimethylbicyclo[4.1.0]
heptan-3-yl)-4-methylbenzene-sulfonamide 5. Typical
procedure
Chloramine-T trihydrate (8.50 g, 31.3 mmol) and osmium
tetroxide catalyst (2.5 ml, 0.25 mmol, 0.1 M solution in tert-butyl
alcohol) were added to a stirred solution of (+)-3-carene 2
(3.41 g, 25 mmol) in tert-butyl alcohol (25 ml) and water (5 ml),
and then the reaction mixture was stirred at reflux for 18 h. The
reaction mixture was cooled to room temperature and sodium
borohydride (0.40 g) was added, and the resulting solution was
stirred for 1 h at room temperature. Solvents were removed in
vacuo and the oily residue was extracted with ethyl acetate
(3 ꢁ 70 ml), washed with a 1% solution of sodium hydroxide in
brine (50 ml) and with brine (2 ꢁ 50 ml), dried over anhydrous
magnesium sulfate and concentrated. The crude product was puri-
fied on silica gel column chromatography (230–400 mesh) using
(n-hexan/ethyl acetate, 3:2): 5.47 g, 68%; mp 45–48 °C,
Figure 3. X-ray crystal structure of 13.
and used without further purification. 1H, 13C, HETCOR and COSY
NMR spectra were recorded on a Varian Gemini 200 multinuclear
instrument and on a Bruker AMX 300 MHz instrument. MS spectra
were recorded on an AMD 604 spectrometer. Optical rotations
were measured on a PolAAr 3000 automatic polarimeter. GC anal-
yses were performed on a Perkin-Elmer AutoSystem XL chromato-
graph. Melting points were determined in open glass capillaries
and are uncorrected. Elemental analyses and HRMS were per-
formed by Microanalysis Laboratory, Institute of Organic Chemis-
try, Polish Academy of Sciences, Warsaw. The X-ray data were
collected at 293(2) K with the Oxford Sapphire CCD diffractometer,
½
a 2D0
ꢂ
¼ þ34:5 (c 1.5, CHCl3). 1H NMR (200 MHz, CDCl3) d (ppm):
0.59 (td, J = 4.5 Hz, J = 9.0 Hz, 1H, CH), 0.68 (td, J = 1.2 Hz,
J = 9.0 Hz, 1H, CH), 0.85 (s, 3H, CH3), 0.94 (s, 3H, CH3), 1.09 (s, 3H,
CH3), 1.27 (dd, J = 4,5 Hz, J = 15.6 Hz, 1H, CH2), 1.50–1.69 (m, 2H,
CH2), 1.87 (s, 1H, OH), 2.05 (dd, J = 9.6 Hz, J = 15.6 Hz, 1H, CH2),

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K. Z. Ła˛czkowski et al. / Tetrahedron: Asymmetry 20 (2009) 1487–1492
2.42 (s, 3H, CH3), 2.82 (td, J = 7.8 Hz, J = 9.9 Hz, 1H, CH), 4.84 (d,
J = 9.6 Hz, 1H, NH), 7.28 (m, 2H, CH), 7.73 (m, 2H, CH); 13C NMR
(200 MHz, CDCl3) d (ppm): 14.91 (CH3), 15.84 (CH3), 21.46 (CH3),
28.44 (CH3), 25.61 (CH2), 34.14 (CH2), 20.46 (CH), 25.99 (CH),
56.95 (CH), 126.73 (2CH), 129.55 (2CH), 17.40 (C), 69.68 (C),
138.77 (C), 143.00 (C). Anal. Calcd for C17H25NO3S: C, 63.13; H,
7.79; N, 4.33; S, 9.91. Found: C, 63.05; H, 7.72; N, 4.41; S, 9.82.
64.06; H, 8.06; N, 4.15; S, 9.50. Found: C, 64.15; H, 8.01; N, 4.31;
S, 9.38.
4.6. (1S,3S,4R,6R)-3,7,7-Trimethyl-4-(methylamino)bicycl [4.1.0]
heptan-3-ol 8
This compound was prepared from 7 as described above: 1.37 g,
67%; mp 69–71 °C, ½a D20
ꢂ
¼ ꢀ29:9 (c 2.5, CHCl3). 1H, 1H ꢁ H COSY
1
4.4. (1S,3S,4R,6R)-4-Amino-3,7,7-trimethylbicyclo[4.1.0]heptan-
3-ol 6. Typical procedure
NMR (300 MHz, CDCl3) d (ppm) (subscript c or t means, that proton
is cis or trans to the dimethyl bridge): 0.63 (td, J = 4.5 Hz, J = 9.3 Hz,
1H, CH, H6t), 0.71 (td, J = 1.5 Hz, J = 9.3 Hz, 1H, CH, H1t), 0.88 (s, 3H,
CH3), 0.97 (s, 3H, CH3), 1.11 (dd, J = 4.5 Hz, J = 15.3 Hz, 1H, CH2,
H5c), 1.13 (s, 3H, CH3), 1.53 (ddd, J = 7.8 Hz, J = 9.6 Hz, J = 14.1 Hz,
1H, CH2, H2c), 1.84 (ddd, J = 1.5 Hz, J = 6.6 Hz, J = 14.1 Hz, 1H, CH2,
H2t), 1.96–2.04 (m, 4H, CH, CH2, NH, OH, H5t, H3c), 2.38 (s, 3H,
CH3); 13C NMR (300 MHz, CDCl3) d (ppm): 15.22 (CH3), 27.46
(CH3), 28.62 (CH3), 34.92 (CH3), 23.96 (CH2), 33.12 (CH2), 16.82
(CH), 19.93 (CH), 61.86 (CHN), 17.21 (C), 69.42 (C); HETCOR
1H ꢁ 13C NMR cross peaks: 0.63 (td)—16.82 (CH), 0.71 (td)—19.93
(CH), 0.88 (s)—15.22 (CH3), 0.97 (s)—28.62 (CH3), 1.11 (dd)—
33.12 (CH2), 1.13 (s)—27.46 (CH3), 1.53 (ddd)—23.96 (CH2), 1.84
(ddd)—23.96 (CH2), 1.96–2.04 (m)—33.12 (CH2), 61.86 (CHN),
2.38 (s)—34.92 (CH3); MS: EI 70 eV, m/z 138 (71.76), 125 (46.31),
124 (47.44), 110 (49.07), 87 (100.00), 57 (31.35), 44 (80.65), 43
(37.54), 41 (30.19). HRMS (EI) calcd for C11H21NO: 183.16231,
found 183.16298.
A solution of 5 (3.45 g, 10 mmol) in dry ethyl ether (50 ml) was
added to liquid ammonia (250 ml) at ꢀ78 °C after which sodium
(3.00 g) was added in portions. The reaction mixture was stirred
for 5 h at ꢀ78 °C and then was left overnight. The residue was
quenched with water (100 ml) and methanol (50 ml), extracted
with ethyl ether (4 ꢁ 100 ml), dried over anhydrous magnesium
sulfate and concentrated. The crude product was purified on silica
gel column chromatography (230–400 mesh) using (dichlorometh-
ane/methanol, 1:1, 2.5% triethylamine): 1.30 g, 72%; mp 65–69 °C,
1
½
a 2D0
ꢂ
¼ þ12:5 (c 3.2, CHCl3). 1H, 1H ꢁ H COSY NMR (300 MHz,
CDCl3) d (ppm) (subscript c or t means, that proton is cis or trans
to the dimethyl bridge): 0.56 (td, J = 4.5 Hz, J = 9.1 Hz, 1H, CH6t),
0.68 (t, J = 8.7 Hz, 1H, CH1t), 0.83 (s, 3H, CH3), 0.92 (s, 3H, CH3),
1.05 (s, 3H, CH3), 1.08 (dd, J = 4.5 Hz, J = 15.6 Hz, 1H, CH2, H5c),
1.45 (ddd, J = 8.7 Hz, J = 10.5 Hz, J = 14.7 Hz, 1H, CH2, H2c), 1.80
(dd, J = 6.9 Hz, J = 14.7 Hz, 1H, CH2, H2t), 1.99 (dd, J = 9.3 Hz,
J = 15.6 Hz, 1H, CH2, H5t), 2.08 (br s, 3H, OH, NH2), 2.24 (dd,
J = 6.9 Hz, J = 10.5 Hz, 1H, CH, H3c); 13C NMR (200 MHz, CDCl3) d
(ppm): 15.05 (CH3), 25.85 (CH3), 28.59 (CH3), 26.23 (CH2), 32.92
(CH2), 16.53 (CH), 20.39 (CH), 53.37 (CHN), 17.06 (C), 69.17 (C);
HETCOR 1H ꢁ 13C NMR cross peaks: 0.56 (td)—16.53 (CH), 0,68
(t)—20.39 (CH), 0.83 (s)—15.05 (CH3), 0.92 (s)—28.59 (CH3), 1.05
(s)—25.85 (CH3), 1.08 (dd)—32.92 (CH2), 1.45 (ddd)—26.23 (CH2),
1.80 (dd)—26.23 (CH2), 1.99 (dd)—32.92 (CH2), 2.24 (dd)—53.37
(CHN). MS: EI 70 eV, m/z 124 (52.89), 111 (37.34), 96 (38.72), 84
(30.90), 73 (100.00), 44 (48.36), 41 (39.91); HRMS (EI) calcd for
C10H19NO: 169.14666, found 169.14640.
4.7. N-((1S,2S,3R,6R)-3-Hydroxy-3,7,7-trimethylbicyclo[4.1.0]
heptan-2-yl)-4-methylbenzene-sulfonamide 9
This compound was prepared from 2 as described above: 48%;
mp 157–160 °C, ½a D20
ꢂ
¼ þ48:7 (c 1.5, CHCl3). 1H NMR (300 MHz,
CDCl3) d (ppm): 0.10 (dd, J = 3.6 Hz, J = 9.3 Hz, 1H, CH), 0.56 (s,
3H, CH3), 0.59 (t, J = 8.1 Hz, 1H, CH), 0.80 (s, 3H, CH3), 1.11 (ddd,
J = 7.8 Hz, J = 12.3 Hz, J = 14.7 Hz, 1H, CH2), 1.26 (s, 3H, CH3),
1.50–1.64 (m, 2H, CH2), 1.74 (s, 1H, OH), 1.78–1.92 (m, 1H, CH2),
2.40 (s, 3H, CH3), 2.80 (dd, J = 3.6 Hz, J = 10.2 Hz, 1H, CH), 5.13 (d,
J = 11,1 Hz, 1H, NH), 7.30 (m, 2H, CH), 7.77 (m, 2H, CH); 13C NMR
(200 MHz, CDCl3) d (ppm): 14.61 (CH3), 21.38 (CH3), 26.18 (CH3),
28.17 (CH3), 14.72 (CH2), 35.23 (CH2), 19.66 (CH), 26.08 (CH),
54.70 (CH), 127.10 (2CH), 129.52 (2CH), 17.15 (C), 70.03 (C),
138.86 (C), 142.97 (C). Anal. Calcd for C17H25NO3S: C, 63.13; H,
7.79; N, 4.33; S, 9.91. Found: C, 63.02; H, 7.74; N, 4.45; S, 9.87.
4.5. N-((1R,3R,4S,6S)-4-Hydroxy-4,7,7-trimethylbicyclo[4.1.0]
heptan-3-yl)-N-4-dimethylbenzene-sulfonamide 7. Typical
procedure
Methyl iodide (1.60 g, 1.2 mmol) and potassium carbonate
(2.20 g, 13.9 mmol) were added to the solution of 5 (3.00 g,
9.3 mmol) in dry N,N-dimethylformamide (30 ml). The reaction
mixture was stirred for 20 h at room temperature and then filtered
through Celite pad and concentrated to dryness. To the crude prod-
uct water (50 ml) was added. Then the product was extracted with
ethyl acetate (2 ꢁ 50 ml), dried over anhydrous magnesium sulfate
and concentrated. The crude product was purified on silica gel col-
umn chromatography (230–400 mesh) using (n-hexane/ethyl ace-
4.8. (1S,2S,3R,6R)-2-Amino-3,7,7-trimethylbicyclo[4.1.0]heptan-
3-ol 10
This compound was prepared from 9 as described above:
48%; mp 58–60 °C, ½a D20
ꢂ
¼ ꢀ8:4 (c 2.7, CHCl3). 1H, 1H ꢁ H COSY
1
NMR (300 MHz, CDCl3) d (ppm) (subscript c or t means, that pro-
ton is cis or trans to the dimethyl bridge): 0.24 (dd, J = 9.3 Hz,
J = 3.6 Hz, 1H, CH, H1t), 0.69 (t, J = 9.0 Hz, 1H, CH, H6t), 0.92 (s,
3H, CH3), 1.01 (s, 3H, CH3), 0.95–1.07 (m, 1H, CH2, H4c), 1.10
(s, 3H, CH3), 1.51 (ddt, J = 1.2 Hz, J = 7.5 Hz, J = 14.7 Hz, 1H, CH2,
H5c), 1.58 (ddd, J = 1.5 Hz, J = 8.1 Hz, J = 14.1 Hz, 1H, CH2, H4t),
1.83–1.98 (m, 1H, CH2, H5t), 2.12 (br s, 3H, OH, NH2), 2.35 (d,
J = 3.6 Hz, 1H, CH); 13C NMR (300 MHz, CDCl3) d (ppm): 15.11
(CH3), 26.29 (CH3), 29.16 (CH3), 15.09 (CH2), 34.38 (CH2), 19.88
(CH), 26.57 (CH), 51.69 (CHN), 16.83 (C), 68.88 (C); HETCOR
1H ꢁ 13C NMR cross peaks: 0.24 (dd)—26.57 (CH), 0.69 (t)—
19.88 (CH), 0.92 (s)—15.11 (CH3), 1.01 (s)—29.16 (CH3), 0.95–
1.07 (m)—34.38 (CH2), 1.10 (s)—26.29 (CH3), 1.51 (ddt)—15.09
(CH2), 1.58 (ddd)—34.38 (CH2), 1.83–1.98 (m)—15.09 (CH2),
2.35 (d)—51.69 (CHN); MS: EI 70 eV, m/z 96 (100.00), 84
(32.73), 83 (31.20); HRMS (EI) calcd for C10H19NO (M+H+)
170.15394, found 170.15473.
tate, 3:2): 2.77 g, 89%; mp 153–155 °C, ½a D20
¼ þ64:5 (c 2.0, CHCl3).
ꢂ
Crystals of this product could be obtained by slow evaporation of
n-pentane/diethyl ether solution. 1H NMR (200 MHz, CDCl3) d
(ppm): 0.58 (td, J = 4.4 Hz, J = 9.2 Hz, 1H, CH), 0.72 (t, J = 8.8 Hz,
1H, CH), 0.96 (s, 3H, CH3), 0.98 (s, 3H, CH3), 1.19 (s, 3H, CH3),
1.20 (dd, J = 7.0 Hz, J = 14.2 Hz, 1H, CH2), 1.35 (dd, J = 4.6 Hz,
J = 15.2 Hz, 1H, CH2), 1.82 (s, 1H, OH), 1.84 (ddd, J = 7.6 Hz,
J = 12.0 Hz, J = 14.2 Hz, 1H, CH2), 1.98 (dd, J = 9.4 Hz, J = 15.6 Hz,
1H, CH2), 2.41 (s, 3H, CH3), 2.89 (s, 3H, CH3), 3.48 (dd, J = 7.0 Hz,
J = 12.2 Hz, 1H, CH), 7.27 (m, 2H, CH), 7.33 (m, 2H, CH); 13C NMR
(200 MHz, CDCl3) d (ppm): 14.85 (CH3), 21.44 (CH3), 25.67 (CH3),
28.85 (CH3), 29.72 (CH3), 18.54 (CH2), 36.28 (CH2), 16.56 (CH),
20.64 (CH), 59.18 (CH), 126.91 (2CH), 129.52 (2CH), 17.98 (C),
71.08 (C), 137.25 (C), 142.90 (C). Anal. Calcd for C18H27NO3S: C,

K. Z. Ła˛czkowski et al. / Tetrahedron: Asymmetry 20 (2009) 1487–1492
1491
4.9. N-((1S,2S,3R,6R)-3-Hydroxy-3,7,7-trimethylbicyclo[4.1.0]
heptan-2-yl)-N,4-dimethylbenzene-sulfonamide 11
(300 MHz, CDCl3) d (ppm): 0.89 (s, 3H, CH3), 1.20 (s, 3H, CH3), 1.50
(d, J = 9.9 Hz, 1H, CH2), 1.66–1.81 (m, 3H, CH2), 1.87–2.20 (m, 6H,
2CH, 0.5CH2, OH, NH2), 2.16–2.23 (m, 1H, CH2), 2.60 (d, J = 12.6 Hz,
1H, CH2, H10), 2.72 (d, J = 12.6 Hz, 1H, CH2, H10); 13C NMR
(300 MHz, CDCl3) d (ppm): 23.49 (CH3), 27.58 (CH3), 24.86 (CH2),
27.13 (CH2), 28.68 (CH2), 51.31 (CH2), 41.00 (CH), 49.48 (CH),
38.11 (C), 75.46 (C); HETCOR 1H ꢁ 13C NMR cross peaks: 0.89 (s)—
23.49 (CH3), 1.20 (s)—27.58 (CH3), 1.50 (d)—27.13 (CH2), 1.66–1.81
(m)—28.68 (CH2), 1.87–2.20 (m)—24.86 (CH2), 41.00 (CH), 49.48
(CH), 2.16–2.23 (m)—27.13 (CH2), 2.60 (d)—51.31 (CH2), 2.72 (d)—
51.31 (CH2); MS: EI 70 eV, m/z 139 (92.50), 121 (36.83), 83 (78.78),
69 (100.00), 41 (57.27); HRMS (EI) calcd for C10H19NO (M+H+)
170.15394, found 170.15323. Anal. Calcd for C10H19NO: C, 70.86;
H, 11.35; N, 8.15. Found: C, 70.96; H, 11.31; N, 8.28.
Thiscompoundwasprepared from9as describedabove:42%;mp
140–142 °C, ½a 2D0
¼ ꢀ51:0 (c 1.45, CHCl3). Crystals of this product
ꢂ
could be obtained by slow evaporation of n-pentane/diethyl ether
solution. 1H NMR (300 MHz, CDCl3) d (ppm): 0.34 (dd, J = 4.8 Hz,
J = 9.0 Hz, 1H, CH), 0.70 (t, J = 8.4 Hz, 1H, CH), 0.74 (s, 3H, CH3),
0.98 (s, 3H, CH3), 1.14 (ddd, J = 7.8 Hz, J = 12.3 Hz, J = 13.2 Hz, 1H,
CH2), 1.32 (s, 3H, CH3), 1.53–1.63 (m, 3H, CH2, OH), 1.79–1.94 (m,
1H, CH2), 2.41 (s, 3H, CH3), 3.05 (s, 3H, CH3), 3.46 (d, J = 4.8 Hz, 1H,
CH), 7.30 (m, 2H, CH), 7.68 (m, 2H, CH); 13C NMR (300 MHz, CDCl3)
d (ppm): 14.80 (CH3), 21.44 (CH3), 25.92 (CH3), 28.32 (CH3), 31.39
(CH3), 14.78 (CH2), 36.89 (CH2), 19.41 (CH), 20.05 (CH), 57.60 (CH),
127.11 (2CH), 129.42 (2CH), 17.22 (C), 71.91 (C), 137.00 (C), 142.78
(C). Anal. Calcd for C18H27NO3S: C, 64.06; H, 8.06; N, 4.15; S, 9.50.
Found: C, 64.21; H, 8.10; N, 4.27; S, 9.32.
4.13. N-(((1R,2S,5S)-2-Hydroxy-6,6-dimethylbicyclo[3.1.1]
heptan-2-yl)methyl)-N-4-dimethylbenzene-sulfonamide 15
4.10. (1S,2S,3R,6R)-3,7,7-Trimethyl-2-(methylamino)bicyclo[4.1.0]
heptan-3-ol 12
This compound was prepared from 13 as described above: 99%;
½
a 2D0
ꢂ
¼ ꢀ16:5 (c 3.5, CHCl3). 1H NMR (300 MHz, CDCl3) d (ppm):
1.00 (s, 3H, CH3), 1.26 (s, 3H, CH3), 1.48 (d, J = 7.2 Hz, 1H, CH2),
1.70–2.04 (m, 5H, CH, 1.5CH2, OH), 2.12 (t, J = 5.5 Hz, 1H, CH),
2.18–2.25 (m, 2H, CH2), 2.43 (s, 3H, CH3), 2.85 (d, J = 15.9 Hz, 1H,
CH2), 2.87 (s, 3H, CH3), 3.16 (d, J = 14.4 Hz, 1H, CH2), 7.32 (m, 2H,
CH), 7.66 (m, 2H, CH); 13C NMR (300 MHz, CDCl3) d (ppm): 21.48
(CH3), 23.18 (CH3), 27.28 (CH3), 39.18 (CH3), 24.83 (CH2), 27.02
(CH2), 28.19 (CH2), 59.79 (CH2), 40.98 (CH), 50.09 (CH), 127.52
(2CH), 129.69 (2CH), 38.28 (C), 76.89 (C), 134.17 (C), 143.45 (C).
Anal. Calcd for C18H27NO3S: C, 64.06; H, 8.06; N, 4.15; S, 9.50.
Found: C, 64.02; H, 8.12; N, 4.38; S, 9.53.
This compound was prepared from 11 as described above: 55%;
ꢂ
oil, ½a 2D0
¼ þ36:4 (c 2.15, CHCl3). 1H, 1H ꢁ H COSY NMR (300 MHz,
1
CDCl3) d (ppm) (subscript c or t means, that proton is cis or trans to
the dimethyl bridge): 0.35 (dd, J = 3.9 Hz, J = 9.3 Hz, 1H, CH, H1t),
0.69 (td, J = 1.8 Hz, J = 8.7 Hz, 1H, CH, H6t), 0.93 (s, 3H, CH3), 1.05
(s, 3H, CH3), 1.12 (ddd, J = 7.5 Hz, J = 11.1 Hz, J = 14.4 Hz, 1H, CH2,
H4c), 1.22 (s, 3H, CH3), 1.47 (ddt, J = 2.2 Hz, J = 7.5 Hz, J = 14.7 Hz,
1H, CH2, H5c), 1.60 (ddd, J = 2.5 Hz, J = 8.1 Hz, J = 14.4 Hz, 1H, CH2,
H4t), 1.85–1.96 (m, 1H, CH2, H5c), 1.97 (d, J = 4.2 Hz, 1H, CH, H2c),
2.20–2.40 (br s, 2H, OH, NH), 2.49 (s, 3H, CH3); 13C NMR
(300 MHz, CDCl3) d (ppm): 15.31 (CH3), 26.93 (CH3), 28.59 (CH3),
34.32 (CH3), 15.11 (CH2), 35.73 (CH2), 19.94 (CH), 24.88 (CH),
60.72 (CHN), 16.85 (C), 69.58 (C); HETCOR 1H ꢁ 13C NMR cross
peaks: 0.35 (dd)—24.88 (CH), 0.69 (td)—19.94 (CH), 0.93 (s)—
15.31 (CH3), 1.05 (s)—28.59 (CH3), 1.12 (ddd)—35.73 (CH2), 1.22
(s)—26.93 (CH3), 1.47 (ddt)—15.11 (CH2), 1.60 (ddd)—35.73 (CH2),
1.85–1.96 (m)—15.11 (CH2), 1.97 (d)—60.72 (CHN), 2.49 (s)—
34.32 (CH3); MS: EI 70 eV, m/z 110 (100.00), 98 (30.23), 97
(35.22), 57 (49.93), 36 (31.46); HRMS (EI) calcd for C11H21NO:
183.16231, found 183.16184.
4.14. (1R,2S,5S)-6,6-Dimethyl-2-((methylamino)methyl)bicyclo
[3.1.1]heptan-2-ol 16
This compound was prepared from 15 as described above: 37%;
mp 38–40 °C, ½a 2D0
ꢂ
¼ ꢀ60:0 (c 1.15, CHCl3). 1H, 1H ꢁ H COSY NMR
1
(300 MHz, CDCl3) d (ppm): 0.92 (s, 3H, CH3), 1.21 (s, 3H, CH3), 1.51
(d, J = 9.9 Hz, 1H, CH2), 1.71–1.84 (m, 3H, CH2), 1.87–1.99 (m, 3H,
2CH, 0.5CH2), 2.13–2.21 (m, 1H, CH2), 2.44 (s, 3H, CH3), 2.53 (d,
J = 12.0 Hz, 1H, CH2, H10), 2.67 (d, J = 12.0 Hz, 1H, CH2, H10), 2.61–
2.83 (br s, 2H, OH, NH); 13C NMR (300 MHz, CDCl3) d (ppm): 23.57
(CH3), 27.56 (CH3), 37.16 (CH3), 24.91 (CH2), 27.15 (CH2), 29.15
(CH2), 61.93 (CH2), 40.91 (CH), 50.35 (CH), 38.11 (C), 75.00 (C); HET-
COR1H ꢁ 13C NMR cross peaks: 0.92 (s)—23.57(CH3), 1.21 (s)—27.56
(CH3), 1.51 (d)—27.15 (CH2), 1.71–1.84 (m)—24.91 (CH2), 29.15
(CH2), 1.87–1.99 (m)—24.91 (CH2), 40.91 (CH), 50.35 (CH), 2.13–
2.21 (m)—27.15 (CH2), 2.44 (s)—37.16 (CH3), 2.53 (d)—61.93 (CH2),
2.67 (d)—61.93 (CH2); MS: EI 70 eV, m/z 45 (67.17), 44 (100.00);
HRMS (EI) calcd for C11H21NO: 183.16231, found 183.16291.
4.11. N-(((1R,2S,5S)-2-Hydroxy-6,6-dimethylbicyclo[3.1.1]
heptan-2-yl)methyl)-4-methylbenzene-sulfonamide 13
This compound was prepared from 3 as described above: 73%;
mp 130–133 °C, ½a D20
ꢂ
¼ ꢀ19:0 (c 1.5, CHCl3), lit.28 t.t. 123–125 °C,
½
a 2D0
ꢂ
¼ ꢀ3:0 (c 1.3, CHCl3). Crystals of this product could be ob-
tained by slow evaporation of diethyl ether solution. 1H NMR
(300 MHz, CDCl3) d (ppm): 0.88 (s, 3H, CH3), 1.19 (s, 3H, CH3),
1.33 (d, J = 10.2 Hz, 1H, CH2), 1.64–1.96 (m, 6H, CH, 2CH2, OH),
2.01 (t, J = 5.0 Hz, 1H, CH), 2.22 (m, 1H, CH2), 2.43 (s, 3H, CH3),
2.91 (dd, J = 12.3 Hz, J = 6.3 Hz, 1H, CH2), 3.03 (dd, J = 12.3 Hz,
J = 6.3 Hz, 1H, CH2), 4.83 (t, J = 6.3 Hz, 1H, NH), 7.31 (m, 2H, CH),
7.73 (m, 2H, CH); 13C NMR (300 MHz, CDCl3) d (ppm): 21.45
(CH3), 23.02 (CH3), 27.17 (CH3), 24.53 (CH2), 26.70 (CH2), 28.64
(CH2), 52.56 (CH2), 40.90 (CH), 49.56 (CH), 127.01 (2CH), 129.64
(2CH), 38.15 (C), 76.08 (C), 136.93 (C), 143.26 (C). Anal. Calcd for
C17H25NO3S: C, 63.13; H, 7.79; N, 4.33; S, 9.91. Found: C, 63.22;
H, 7.81; N, 4.40; S, 9.75.
4.15. N-(((1R,2R,4S)-2-Hydroxy-3,3-dimethylbicyclo[2.2.1]
heptan-2-yl)methyl)-4-methylbenzene-sulfonamide 17
Thiscompoundwasprepared from4 as describedabove:60%; mp
116–118 °C, ½a 2D0
ꢂ
¼ þ14:2 (c 1.25, CHCl3), lit.28 mp 126–128 °C,
½
a 2D0
ꢂ
¼ þ14:1 (c 1.84, CHCl3). 1H NMR (200 MHz, CDCl3) d (ppm):
0.89 (s, 3H, CH3), 0.95 (s, 3H, CH3), 1.00–1.20 (m, 1H, CH2), 1.20–
1.60 (m, 3H, CH2, OH), 1.60–1.80 (m, 3H, CH2), 1.80–1.90 (m, 1H,
CH), 2.10 (m, 1H, CH), 2.43 (s, 3H, CH3), 2.83 (dd, J = 4.4 Hz,
J = 12.2 Hz, 1H, CH2), 3.13 (dd, J = 7.8 Hz, J = 12.0 Hz, 1H, CH2), 4.86
(m, 1H, NH), 7.33 (m, 2H, CH), 7.74 (m, 2H, CH); 13C NMR
(200 MHz, CDCl3) d (ppm): 21.51 (CH3), 21.89 (CH3), 24.88 (CH3),
22.78 (CH2), 23.40 (CH2), 34.19 (CH2), 46.17 (CH2), 47.85 (CH),
49.65 (CH), 127.11 (2CH), 129.71 (2CH), 44.03 (C), 81.37 (C),
136.55 (C), 143.33 (C). Anal. Calcd for C17H25NO3S: C, 63.13; H,
7.79; N, 4.33; S, 9.91. Found: C, 63.01; H, 7.84; N, 4.55; S 9.82.
4.12. (1R,2S,5S)-2-(Aminomethyl)-6,6-dimethylbicyclo[3.1.1]
heptan-2-ol 14
This compound was prepared from 13 as described above: 58%;
mp 45–47 °C, ½a 2D0
ꢂ
¼ ꢀ51:3 (c 2.6, CHCl3). 1H, 1H ꢁ H COSY NMR
1

1492
K. Z. Ła˛czkowski et al. / Tetrahedron: Asymmetry 20 (2009) 1487–1492
4.16. (1R,2R,4S)-2-(Aminomethyl)-3,3-dimethylbicyclo[2.2.1]
heptan-2-ol 18
thank Professor Marek Zaidlewicz for his comments on the
manuscript.
This compound was prepared from 17 as described above: 83%;
References
mp 89–91 °C, ½a 2D0
ꢂ
¼ þ18:7 (c 1.1, DMSO). 1H, 1H ꢁ H COSY NMR
1
1. Bergmeier, S. C. Tetrahedron 2000, 56, 2561–2576.
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(300 MHz, C5D5N) d (ppm): 0.90 (s, 3H, CH3), 1.07 (m, 1H, CH2),
1.20 (s, 3H, CH3), 1.20–1.44 (m, 2H, CH2), 1.47–1.57 (m, 1H, CH2),
1.70 (m, 2H, CH), 2.33 (m, 2H, CH2), 2.89 (d, J = 12.9 Hz, 1H, CH2,
H10), 3.07 (d, J = 12.9 Hz, 1H, CH2, H10), 4.42 (br s, 3H, OH, NH2); 13
C
´
5. Krzeminski, M. P.; Wojtczak, A. Tetrahedron Lett. 2005, 46, 8299–8302.
NMR (300 MHz, C5D5N) d (ppm): 22.19 (CH3), 26.30 (CH3), 23.15
(CH2), 24.29 (CH2), 34.93 (CH2), 44.36 (CH2), 47.88 (CH), 50.20
(CH), 43.20 (C), 80.54 (C); HETCOR 1H ꢁ 13C NMR cross peaks: 0.90
(s)—22.19 (CH3), 1.07 (m)—34.93 (CH2), 1.20 (s)—26.30 (CH3),
1.20–1.44 (m)—23.15 (CH2), 24.29 (CH2), 1.47–1.57 (m)—24.29
(CH2), 1.70 (m)—50.20 (CH), 2.33 (m)—34.93 (CH2), 47.88 (CH),
2.89 (d)—44.36 (CH2), 3.07 (d)—44.36 (CH2); MS: EI 70 eV, m/z 169
(32.30), 139 (64.58), 138 (36.21), 109 (36.16), 100 (62.86), 95
(54.35), 72 (37.11), 69 (54.64), 67 (58.78), 43 (100.00), 41 (63.63);
HRMS (EI) calcd for C10H19NO: 169.14666, found 169.14583.
6. Cho, B. T.; Ryu, M. H.; Chun, Y. S.; Dauelsberg, C.; Wallbaum, S.; Martens, J. Bull.
Korean Chem. Soc. 1994, 15, 53–57.
´
7. Krzeminski, M. P.; Zaidlewicz, M. Tetrahedron: Asymmetry 2003, 14, 1463–1466.
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Trans. 1 1985, 2039–2044.
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12. Masui, M.; Shiori, T. Tetrahedron Lett. 1998, 39, 5195–5198.
13. Ła˛czkowski, K. Z.; Pakulski, M. M.; Krzemin´ ski, M. P.; Jaisankar, P.; Zaidlewicz,
M. Tetrahedron: Asymmetry 2008, 19, 788–795.
14. Jaworska, M.; Ła˛czkowski, K. Z.; Wełniak, M.; Welke, M.; Wojtczak, A. Appl.
Catal. A: Gen. 2009, 357, 150–158.
15. Hu, X. E. Tetrahedron 2004, 60, 2701–2743.
4.17. N-(((1R,2R,4S)-2-Hydroxy-3,3-dimethylbicyclo[2.2.1]
heptan-2-yl)methyl)-N-4-dimethylbenzene-sulfonamide 19
16. Sabitha, G.; Babu, S. R.; Reddy, M. S. K.; Yadav, J. S. Synthesis 2002, 2254–2258.
17. Morgan, A. J.; Masse, C. E.; Panek, J. S. Org. Lett. 1999, 1, 1949–1952.
18. Sharpless, K. B.; Patrick, D. W.; Truesdale, L. K.; Biller, S. A. J. Am. Chem. Soc.
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19. Sharpless, K. B.; Chong, A. O.; Oshima, K. J. Org. Chem. 1976, 41, 177–179.
20. Herranz, E.; Sharpless, K. B. J. Org. Chem. 1978, 43, 2544–2548.
21. Rudolph, J.; Sennhenn, P. C.; Vlaar, C. P.; Sharpless, K. B. Angew. Chem., Int. Ed.
1996, 35, 2810–2813.
22. Herranz, E.; Biller, S. A.; Sharpless, K. B. J. Am. Chem. Soc. 1978, 100, 3596–3598.
23. Demko, Z. P.; Bartach, M.; Sharpless, K. B. Org. Lett. 2000, 2, 2221–2223.
24. Reddy, K. L.; Sharpless, K. B. J. Am. Chem. Soc. 1998, 120, 1207–1217.
25. Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991, 30, 49–69.
26. Hobuss, D.; Baro, A.; Laschat, S.; Frey, W. Tetrahedron 2008, 64, 1635–1640.
This compound was prepared from 17 as described above: 99%;
mp >200 °C, ½a 2D0
ꢂ
¼ þ1:4 (c 2.2, DMSO). 1H NMR (200 MHz, DMSO-
d6) d (ppm): 0.80 (s, 3H, CH3), 0.85 (s, 3H, CH3), 0.97 (d, J = 9.6 Hz,
1H, CH), 1.10–1.50 (m, 3H, CH2, OH), 1.62 (m, 2H, CH2), 1.97 (d,
J = 11.4 Hz, 1H, CH2), 2.07 (d, J = 3.0 Hz, 1H, CH), 2.38 (s, 3H, CH3),
2.41 (m, 1H, CH2), 2.73 (s, 3H, CH3), 3.13 (br s, 1H, CH2), 3.54 (d,
J = 13.6 Hz, 1H, CH2), 7.43 (m, 2H, CH), 7.61 (m, 2H, CH); 13C
NMR (200 MHz, DMSO-d6) d (ppm): 20.94 (CH3), 21.98 (CH3),
25.54 (CH3), 37.23 (CH3), 22.19 (CH2), 23.47 (CH2), 33.89 (CH2),
52.31 (CH2), 46.80 (CH), 49.07 (CH), 127.22 (2CH), 129.76 (2CH),
44.44 (C), 80.69 (C), 133.25 (C), 143.12 (C). Anal. Calcd for
C18H27NO3S: C, 64.06; H, 8.06; N, 4.15; S, 9.50. Found: C, 63.98;
H, 7.96; N, 4.46; S, 9.64.
´
27. Binder, C. M.; Bautista, A.; Zaidlewicz, M.; Krzeminski, M. P.; Oliver, A.;
Singaram, B. J. Org. Chem. 2009, 74, 2337–2343.
28. Pinheiro, S.; Pedraza, S. F.; Farias, F. M. C.; Goncalves, A. S.; Costa, P. R. R.
Tetrahedron: Asymmetry 2000, 11, 3845–3848.
29. Brown, H. C.; Zaidlewicz, M.; Bhat, K. S. J. Org. Chem. 1989, 54, 1764–1766.
30. Crystallographic data for the structures in this letter have been deposited with
the Cambridge Crystallographic Data Centre as supplementary publication.
Copies of the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (fax: +44(0) 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk). Colourless 0.36 ꢁ 0.27 ꢁ 0.22 mm crystals of 7 were
obtained from n-pentane/diethyl ether solution. The compound crystallised in
the orthorhombic space group P212121. Cell parameters a = 7.9054(4),
b = 13.0108(7), c = 17.472(1) Å, V = 1797.1(2) Å3, Dcalcd 1.247 Mg/m3, Z = 4,
4.18. (1R,2R,4S)-3,3-Dimethyl-2-((methylamino)methyl)bicyclo
[2.2.1]heptan-2-ol 20
This compound was prepared from 19 as described above: 33%;
F(0 0 0) = 728,
l
= 0.194 mmꢀ1. The maximum and minimum transmissions
(I).
1
½
a 2D0
ꢂ
¼ þ18:2 (c 1.35, MeOH). 1H, 1H ꢁ H COSY NMR (300 MHz,
of 0.9576 and 0.9330. R1 = 0.0527, wR2 = 0.0898 for reflections I > 2
r
C5D5N) d (ppm): 0.93 (s, 3H, CH3), 1.06 (d, J = 11.1 Hz, 1H, CH2),
1.20 (s, 3H, CH3), 1.19–1.22 (m, 1H, CH2), 1.30–1.44 (m, 2H, CH2),
1.47–1.58 (m, 1H, CH2), 1.69 (m, 1H, CH), 2.30–2.37 (m, 2H, CH,
CH2), 2.48 (s, 3H, CH3), 2.69 (d, J = 12.0 Hz, 1H, CH2, H10), 2.94 (d,
J = 12.0 Hz, 1H, CH2, H10), 4.80 (br s, 2H, OH, NH); 13C NMR
(300 MHz, C5D5N) d (ppm): 22.25 (CH3), 26.18 (CH3), 36.83 (CH3),
23.38 (CH2), 24.37 (CH2), 35.05 (CH2), 54.71 (CH2), 48.68 (CH),
50.02 (CH), 44.06 (C), 80.11 (C); HETCOR 1H ꢁ 13C NMR cross peaks:
0.93 (s)—22.25 (CH3), 1.06 (d)—35.05 (CH2), 1.20 (s)—26.18 (CH3),
1.19–1.22 (m)—24.37 (CH2), 1.30–1.44 (m)—23.38 (CH2), 1.47–
1.58 (m)—24.37 (CH2), 1.69 (m)—50.02 (CH), 2.30–2.37 (m)—35.05
(CH2), 48.68 (CH), 2.48 (s)—36.83 (CH3), 2.69 (d)—54.71 (CH2), 2.94
(d)—54.71 (CH2); MS: EI 70 eV, m/z 45 (64.93), 44 (100.00); HRMS
(EI) calcd for C11H21NO: 183.16231, found 183.16196.
Absolute structure was determined by the Flack method, x = 0.05(7). The
structural data for 7 have been deposited at the Cambridge Crystallographic
Data Centre: (CCDC No. 719487).
31. Krzemin´ ski M. P.; PL Pat. Appl. 383483, 10.04, 2007.
32. Colourless 0.36 ꢁ 0.19 ꢁ 0.12 mm crystals of 11 were obtained from n-
pentane/diethyl ether solution. The compound crystallised in the
orthorhombic space group P212121. Cell parameters a = 6.1766(4),
b = 11.3964(7), c = 25.951(2) Å, V = 1826.7(2) Å3, Dcalcd 1.227 Mg/m3, Z = 4,
F(0 0 0) = 728,
of 0.9774 and 0.9347. R1 = 0.0659, wR2 = 0.1069 for reflections I > 2
l
= 0.191 mmꢀ1. The maximum and minimum transmissions
r
(I). The
absolute structure was determined by the Flack method, x = ꢀ0.01(8). Non-
hydrogen atoms were refined anisotropically, hydrogen atoms were
constrained as riding atoms. The structural data for 11 have been deposited
at the Cambridge Crystallographic Data Centre: (CCDC No. 719488).
33. Colourless 0.54 ꢁ 0.24 ꢁ 0.1 mm crystals of 13 were obtained from diethyl
ether solution. The compound crystallised in the monoclinic space group P21.
Cell parameters a = 11.8432(8), b = 6.6168(4), c = 21.884(1) Å, b = 96.386(5)°,
V = 1704.3(2) Å3, Dcalcd 1.261 Mg/m3, Z = 4, F(0 0 0) = 696,
l
= 0.202 mmꢀ1. The
maximum and minimum transmissions of 0.9673 and 0.9316. R1 = 0.0514,
wR2 = 0.1063 for reflections I > 2 (I). Absolute structure was determined by the
r
Acknowledgements
Flack method, x = 0.08(7). The structural data for 13 have been deposited at the
Cambridge Crystallographic Data Centre: (CCDC No. 719486).
34. Sheldrick, G. M. SHELXS97 and SHELXL97. University of Göttingen: Germany, 1997.
35. CRYSALIS CCD171 and RED171 package of programs, Oxford Diffraction, 2000.
36. Flack, H. D., Acta Crystallogr., Sect. A 1983, 39, 876–881.
Financial support from the Committee for Scientific Research,
Warsaw, Grant PBZ-KBN-126/T09/2004, is acknowledged. We also