Synthesis and structural characterization of novel camphor-derived amines

Article abstract of DOI:10.1002/chir.22069

Two novel 4-substituted camphidine derivatives 10a,b have been prepared from (+)-camphor (1) in five steps, the Beckmann rearrangement being the bottleneck of the synthesis. Isoborneol derivative 5b, formed as a side product during the hydrogenation of arylidene ketone 3b, under Beckmann rearrangement conditions yielded interesting novel rearrangement products 11 and 12. (1S)-(+)-Camphorquinone (13) was transformed into diamines 15 and 16 in two steps, the former being cyclized into an imidazoline salt 17, an N-heterocyclic carbene precursor. The structures of all novel compounds have been meticulously characterized using NMR techniques and/or single crystal X-ray analysis. Copyright

Full text of DOI:10.1002/chir.22069

CHIRALITY (2012)
Synthesis and Structural Characterization of Novel
Camphor-derived Amines
1
1
1
1
1,2
UROŠ GROŠELJ, ALEN SEVŠEK, SEBASTIJAN RIČKO, AMALIJA GOLOBIČ, JURIJ SVETE, AND BRANKO STANOVNIK1,2
*
1Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia
2EN-FIST Centre of Excellence, Ljubljana, Slovenia
ABSTRACT
Two novel 4-substituted camphidine derivatives 10a,b have been prepared from
(+)-camphor (1) in five steps, the Beckmann rearrangement being the bottleneck of the synthe-
sis. Isoborneol derivative 5b, formed as a side product during the hydrogenation of arylidene
ketone 3b, under Beckmann rearrangement conditions yielded interesting novel rearrangement
products 11 and 12. (1S)-(+)-Camphorquinone (13) was transformed into diamines 15 and 16
in two steps, the former being cyclized into an imidazoline salt 17, an N-heterocyclic carbene
precursor. The structures of all novel compounds have been meticulously characterized using
NMR techniques and/or single crystal X-ray analysis. Chirality 00:000–000, 2012. © 2012 Wiley
Periodicals, Inc.
KEY WORDS: camphor; enaminone methodology; Beckmann rearrangement; camphor-derived
amines; NHC ligand precursor
INTRODUCTION
novel cyclic and acyclic camphor-derived amines have been pre-
pared, accompanied by interesting rearrangement products.
Camphor is one of nature’s privileged scaffolds. It is readily
available in both enantiomeric forms. It undergoes a wide
variety of chemical transformations that, at first glance, func-
tionalize inactivated positions.1,2 All of the above makes
camphor a very desirable starting material for the preparation
of a wide variety of products ranging from natural products1,2
to chiral auxiliaries,3,4 ligands in asymmetric synthesis,5–10
organocatalysts,11–21 NMR shift reagents,22 and others.
Nevertheless, the literature search (SciFinder Scholar) for
4-substituted-1,8,8-trimethyl-3-azabicyclo[3.2.1]octanes of type
A (4-substituted camphidine derivatives) revealed only two
hits,23–26 whereas for 4-substituted-1,8,8-trimethyl-3-azabicyclo
[3.2.1]octan-2-ones of type B (4-substituted a-camphidone
derivatives) gave 11 hits. The latter could be regarded as
precursors of the former transformed via a reductive elabora-
tion. The parent a-camphidone24,27,28 (B; R = H) was prepared
in useful yields from camphor via the Beckmann rearrange-
ment29,30 or from camphoric imide26 (B; R = O). Parent camphi-
dine27 (A; R = H) was prepared in satisfactory yields from
camphene31 and from camphoric imide32 (B; R = O). Similarly,
several N-substituted camphidine derivatives have been
prepared from the corresponding camphor imides via
reduction with LiAlH433 (Fig. 1).
For the isomeric 4-substituted-1,8,8-trimethyl-2-azabicyclo
[3.2.1]octanes of type C and 4-substituted-1,8,8-trimethyl-2-
azabicyclo[3.2.1]octan-3-ones of type D, the literature search
gave no results except of one for the N-substituted derivative
of type D.34 The unsubstituted lactam35 (D; R = H) is prepara-
tively accessible36,37 and can be reductively converted to the
corresponding cyclic amine35,38 (C; R = H). The parent lactam
(D; R = H) can be easily functionalized in position 4, which is
not the case for the isomeric lactam (B; R = H). Compounds of
types A and C could potentially be used as catalysts in cova-
lent organocatalysis39 (Fig. 1).
EXPERIMENTAL
Materials and Methods
Melting points were determined on a Kofler micro hot stage and on SRS
OptiMelt MPA100—Automated Melting Point System (Stanford Research
Systems, Sunnyvale, CA, USA). The NMR spectra were obtained on a
Bruker Avance DPX 300 at 300 MHz for 1H and at 75.5 MHz for 13C nucleus,
and Bruker UltraShield 500 plus (Bruker, Billerica, MA, USA) at 500 MHz
for 1H and at 126MHz for 13C nucleus, using DMSO-d6 and CDCl3 with
TMS as the internal standard, as solvents. Mass spectra were recorded on
an AutoSpecQ spectrometer (Waters, Milford, MA, USA) and Agilent
6224 Accurate Mass TOF LC/MS (Agilent Technologies, Santa Clara,
CA, USA), and IR spectra on a Perkin-Elmer Spectrum BX FTIR
spectrophotometer (PerkinElmer, Waltham, MA, USA). Microanalyses
were performed on a Perkin-Elmer CHN Analyser 2400 II (PerkinElmer,
Waltham, MA, USA). Catalytic hydrogenations were performed in a Parr
Pressure Reaction Hydrogenation Apparatus (Moline, IL, USA). Column
chromatography was performed on silica gel (silica gel 60 (Sigma-Aldrich,
St. Louis, MO, USA), particle size: 0.035–0.070 mm). Medium-pressure
liquid chromatography (MPLC) was performed with Büchi Flash Chroma-
tography System (BUCHI Labortechnik AG, Flawil, Switzerland) (Büchi
Fraction Collector C-660, Büchi Pump Module C-605, Büchi Control Unit
C-620) on silica gel (LiChrosphereW Si 60 [12 mm] and/or LiChroprepW
Si 60 [12–15mm] (Merck, KGaA, Darmstadt, Germany)); column
dimensions (wet filled): 22Â 460 mm, 36 Â 460 mm, and 40Â 460 mm;
backpressure: 10–20Bar; detection: UV 254 nm.
Additional Supporting Information may be found in the online version of this
article.
Contract grant sponsor: Slovenian Research Agency (financial support);
Contract grant numbers: P1-0179, J1-0972,
Contract grant sponsor: Ministry of Science and Technology, Republic of
Slovenia (financial contribution for the purchase of Kappa CCD Nonius diffrac-
tometer); Contract grant numbers: Packet X-2000, PS-511-102,
*Correspondence to: Uroš Grošelj, Faculty of Chemistry and Chemical
Technology, University of Ljubljana, Aškerčeva cesta 5, PO Box 537, 1000
Ljubljana, Slovenia.
In this report, the results of a Beckmann rearrangement
study of 3-arylmethyl substituted camphor derivatives are
disclosed, together with the reductive transformation of a
camphorquinone-derived diimine. Along the way, several
© 2012 Wiley Periodicals, Inc.
E-mail: uros.groselj@fkkt.uni-lj.si
Received for publication 2 March 2012; Accepted 17 April 2012
DOI: 10.1002/chir.22069
Published online in Wiley Online Library
(wileyonlinelibrary.com).

GROŠELJ ET AL.
26.7, 30.7, 46.7, 49.3, 58.0, 122.7, 123.2, 125.2, 126.98, 127.01, 127.02, 127.3,
127.7, 129.0, 130.5, 130.6, 131.1, 131.3, 131.7, 144.9, 207.8.
General procedure for the hydrogenation of arylidene
compounds 3b–d
To a solution of arylidene compound 3 in anhydrous EtOH (150 ml) un-
der argon was added Pd–C, the reaction vessel was flushed with H2, and
the reaction mixture was hydrogenated in a Paar hydrogenator (P = 4
Bar) at room temperature for t1 min. The reaction mixture was filtered
through a plug of CeliteW and washed with CH2Cl2 (100 ml). Volatile com-
ponents were evaporated in vacuo, and the residue was purified by
MPLC. Fractions containing the separated products were combined,
and volatile components were evaporated in vacuo to give ketones 4/4′
and alcohol 5, respectively.
Fig. 1. SciFinder Scholar search (Substructure search, R = any atom except
H) as of January 2012 for systems A–D. Stereoisomers of the some compound
are regarded as a single hit.
(+)-Camphor (1), (1S)-(+)-camphorquinone (13), tert-butoxy bis
(dimethylamino)methane, anhydrous dimethylformamide, Grignard
reagents, hydroxylamine-O-sulfonic acid, and 10% palladium on charcoal
are commercially available (Sigma-Aldrich, St. Louis, MO, USA).
Compounds 2,14 3a,15 3b,15 and 4a/4a′14 were prepared following the
literature procedures.
Source of chirality: (+)-camphor (1) (Sigma-Aldrich), product
number 21300, purum, natural, 97.0% (GC, sum of enantiomers),
[a]2D0 = +42.5 Æ 2.5 (c = 10, EtOH), mp 176–180 ꢀC, ee not specified, and
(1S)-(+)-camphorquinone (13) (Aldrich), product number 272078, 99%,
[a]2D0 = + 100 (c = 1.9, PhMe); mp 197–201 ꢀC, ee not specified.
(1R,3R,4R)-3-(3,5-Bis(trifluoromethyl)benzyl)-1,7,7-trimethylbi-
cyclo[2.2.1]heptan-2-one (4b), (1R,3S,4R)-3-(3,5-bis(trifluoro-
methyl)benzyl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (4b′), and
(1R,2R,3R,4R)-3-(3,5-bis(trifluoromethyl)benzyl)-1,7,7-trimethylbi-
cyclo[2.2.1]heptan-2-ol (5b).
3b (3.78 g, 10.05mmol); Pd–C (10%,
80 mg); t1 = 10 min; crude products: 4b:4b′:5b = 55:18:27, 100% conversion;
MPLC (EtOAc/petroleum ether = 1:30).
4b: Elutes first from the column. Yield: 1.17 g (31%) of yellowish
solid; mp 70.2–74.6 ꢀC. [a]Dr.t. = +69.4 (c = 0.17, CH2Cl2). (C19H20F6O
requires: C, 60.32; H, 5.33. Found C, 60.35; H, 5.27.); EI-HRMS:
m/z = 379.1499 (MH+); C19H21F6O requires: m/z = 379.1497 (MH+); nmax
(KBr) 3453, 3050, 2959, 2892, 2877, 2359, 2342, 1735, 1625, 1470, 1449,
1380, 1354, 1326, 1313, 1279, 1173, 1125, 1099, 1019, 925, 896, 845, 727,
Syntheses
General procedure for the preparation of arylidene compounds
3c,d. To a solution of enaminone 2 in anhydrous tetrahydrofuran
(THF) under argon cooled to 0 ꢀC was added ArlMgBr, and the resulting
mixture was stirred at 0 ꢀC for 30 min and 4 h at room temperature. The
reaction mixture was quenched with NH4Cl (aq. sat.), volatile compo-
nents were evaporated in vacuo (the bulk of THF), and the residue was
extracted with CH2Cl2 (3 Â 70 ml). The combined organic phase was
dried over anhydrous Na2SO4 and filtered, and volatile components were
evaporated in vacuo. The residue was purified by column chromatogra-
phy. Fractions containing the product were combined, and volatile com-
ponents evaporated in vacuo to give the arylidene products 3c,d.
1
710, 682 cmÀ1. H-NMR (500 MHz, CDCl3): d 0.96 (s, Me); 0.97 (s, Me);
0.98 (s, Me); 1.26–1.33 (m, 1H of CH2); 1.50–1.57 (m, 1H of CH2);
1.65–1.72 (m, 1H of CH2); 1.95 (d, J = 4.0 Hz, H-C(4)); 1.96–2.04 (m, 1H
of CH2); 2.12 (dd, J = 4.2; 9.8 Hz, H-C(3)); 2.68 (dd, J = 9.8; 14.5 Hz, Ha-C
(3′)); 3.33 (dd, J = 4.2; 14.5 Hz, Hb-C(3′)); 7.66 (s, 2H of Arl); 7.74 (s, 1H
of Arl). 13C-NMR (CDCl3, 75.5 MHz): d 9.5, 20.5, 22.0, 29.2, 29.4, 37.3,
47.0, 47.2, 56.2, 57.8, 120.2–120.5 (m), 123.6 (q, J = 272.6 Hz), 129.0, 132.0
(q, J = 33.1 Hz), 144.2, 219.2.
4b′: Elutes second from the column. Yield: 490mg (13%) of yellowish
solid; mp 97.3–101.2 ꢀC. [a]Dr.t. = +45.4 (c = 0.12, CH2Cl2). (C19H20F6O
requires: C, 60.32; H, 5.33. Found C, 60.20; H, 5.37.); EI-HRMS:
m/z= 379.1482 (MH+); C19H21F6O requires: m/z= 379.1497 (MH+); nmax
(KBr) 3460, 3045, 2966, 2870, 1737, 1624, 1488, 1454, 1381, 1348, 1274,
(1R,4S,3E)-3-(3,5-Dimethylbenzylidene)-1,7,7-trimethylbicyclo
[2.2.1]heptan-2-one (3c). 2 (4.15 g, 20 mmol); THF (10 ml); (3,5-
dimethylphenyl) magnesium bromide (50 ml, 0.5 M, 25 mmol); column
chromatography (EtOAc/petroleum ether = 1:20). Yield: 4.63 g (86%) of
colorless oil. [a]rD.t. = +365.9 (c= 0.26, CHCl3). (C19H24O requires: C, 85.03;
H, 9.01. Found C, 84.38; H, 9.36.); EI-HRMS: m/z = 269.1908 (MH+);
1169, 1124, 1106, 1047, 1006, 928, 901, 844, 742, 732, 708, 682, 658 cmÀ1
.
1H-NMR (500 MHz, CDCl3): d 0.88 (s, Me); 0.95 (s, Me); 1.01 (s, Me);
1.35–1.42 (m, 1H of CH2); 1.65–1.72 (m, 1H of CH2); 1.73–1.80 (m, 1H of
CH2); 1.82–1.91 (m, 1H of CH2); 1.95 (t, J=3.9Hz, H-C(4)); 2.63–2.71
(m, Ha-C(3′), H-C(3)); 3.24 (q, J=9.9 Hz, Hb-C(3′)); 7.67 (s, 2H of Arl); 7.73
(s, 1H of Arl). 13C-NMR (CDCl3, 75.5MHz): d 9.7, 19.4, 19.8, 20.6, 31.2,
33.0, 46.1, 46.2, 51.5, 59.0, 120.4–120.7 (m), 123.6 (q, J= 272.6 Hz), 129.0,
132.0 (q, J= 33.1 Hz), 143.2, 219.0.
C
19H25O requires: m/z = 269.1905 (MH+); nmax (NaCl) 2960, 2924, 2871,
1727, 1642, 1600, 1474, 1450, 1389, 1371, 1325, 1268, 1252, 1152, 1106,
1065, 1038, 1014, 934, 866, 844 cmÀ1 1H-NMR (300 MHz, CDCl3): d 0.80
.
(s, Me); 1.00 (s, Me); 1.02 (s, Me); 1.46–1.65 (m, 3H); 1.72–1.83 (m, 1H);
2.12–2.24 (m, 1H); 2.34 (s, 6H, 2ÂMe); 3.10 (d, J = 4.2 Hz, H-C(4)); 6.98
(s, CH); 7.08 (s, 2H of Arl); 7.18 (s, 1H of Arl). 13C-NMR (75 MHz, CDCl3):
d 9.5, 18.5, 20.7, 21.5, 26.2, 30.9, 46.8, 49.4, 57.2, 127.8, 128.0, 130.7, 135.8,
138.3, 141.9, 208.4.
5b: Elutes third from the column. Yield: 983 mg (26%) of yellowish
oil. [a]rD.t. = +64.9 (c = 0.25, CH2Cl2). (C19H22F6O requires: C, 60.00; H,
5.83. Found C, 60.29; H, 6.00.); EI-HRMS: m/z = 379.1485 (M À 1)+;
C19H21F6O requires: m/z = 379.1497 (M À 1)+; nmax (NaCl) 3635, 3496,
2955, 2360, 1796, 1736, 1622, 1480, 1464, 1379, 1173, 1134, 1046, 926,
894, 842, 706, 682 cmÀ1 1H-NMR (500 MHz, CDCl3): d 0.82 (s, Me);
.
(1R,4S,4E)-1,7,7-Trimethyl-3-(phenanthren-9-ylmethylene)bicyclo
[2.2.1]heptan-2-one (3d). 2 (4.79 g, 23.11 mmol); THF (50 ml);
phenanthren-9-ylmagnesium bromide (50 ml, 0.5 M in THF, 25mmol);
column chromatography (EtOAc/petroleum ether = 1:30). Yield: 2.25 g
(28%) of yellowish solid; mp 128.3–132.2 ꢀC. [a]Dr.t. = +211.5 (c= 0.19, CH2Cl2).
(C25H24O requires: C, 88.20; H, 7.11. Found C, 88.28; H, 7.06.); EI-HRMS:
m/z = 341.1894 (MH+); C25H25O requires: m/z = 341.1905 (MH+); nmax
(KBr) 3479, 2958, 2923, 2869, 1720, 1638, 1493, 1449, 1389, 1370, 1322,
0.94 (s, Me); 0.96–1.01 (m, 1H of CH2); 1.02–1.08 (m, 1H of CH2); 1.23
(s, Me); 1.46–1.53 (m, 1H of CH2); 1.55 (d, J = 3.8 Hz, H-C(4)); 1.62
(d, J = 4.2 Hz, OH); 1.66–1.74 (m, 1H of CH2); 2.06 (q, J = 7.9 Hz, H-C
(3)); 2.83 (dd, J = 7.5; 14.4 Hz, Ha-C(3′)); 3.29 (dd, J = 8.1; 14.4 Hz, Hb-C
(3′)); 3.76 (dd, J = 4.2; 8.1 Hz, H-C(2)); 7.68 (s, 1H of Arl); 7.69 (s, 2H of
Arl). 1H-NMR (CDCl3 + D2O, 300 MHz): d 0.83 (s, Me); 0.94 (s, Me);
0.97–1.10 (m, 2H of CH2); 1.23 (s, Me); 1.45–1.54 (m, 1H of CH2); 1.55
(d, J = 4.2 Hz, H-C(4)); 1.64–1.75 (m, 1H of CH2); 2.06 (deg q, J = 7.7 Hz,
H-C(3)); 2.83 (dd, J = 7.5; 14.4 Hz, Ha-C(3′)); 3.30 (dd, J = 8.1; 14.4 Hz,
Hb-C(3′)); 3.75 (d, J = 8.2 Hz, H-C(2)); 7.69 (s, 3H of Arl). 13C-NMR
(CDCl3, 75.5 MHz): d 11.7, 21.7, 22.2, 30.0, 33.5, 36.3, 47.1, 50.1, 50.5,
52.1, 81.7, 119.6–119.9 (m), 123.9 (q, J = 272.5 Hz), 129.3, 131.6
(q, J = 32.9 Hz), 146.4.
1152, 1109, 1069, 914, 765, 743, 724cmÀ1 1H-NMR (CDCl3, 300MHz):
.
d 0.88 (s, Me); 0.98 (s, Me); 1.08 (s, Me); 1.57–1.89 (m, 3H of CH2);
2.14–2.26 (m, 1H of CH2); 2.98 (d, J = 4.2 Hz, H-C(4)); 7.58–7.73 (m, 5H of
Arl); 7.87–7.92 (m, H-C(3′), 1H of Arl); 8.10 (dd, J = 1.3; 8.1Hz, 1H of Arl);
8.66–8.76 (m, 2H of Arl). 13C-NMR (CDCl3, 75.5 MHz): d 9.5, 18.3, 20.8,
Chirality DOI 10.1002/chir

SYNTHESIS OF NOVEL CAMPHOR-DERIVED AMINES
(1R,3R,4R)-3-(3,5-Dimethylbenzyl)-1,7,7-trimethylbicyclo[2.2.1]
70mmol), and the resulting mixture was heated under reflux for 48h. Vola-
tile components were evaporated in vacuo, and to the residue, H2O was
added. The resulting precipitate was collected by filtration to give the prod-
uct as a mixture of epimers 6/6′. 6:6′ = 71:29. Yield: 1.37 g (96%) of white
solid; mp 132–146 ꢀC. [a]Dr.t. = +26.0 (c= 0.23, CHCl3). (C19H27NO requires:
C, 79.95; H, 9.53; N, 4.91. Found C, 80.17; H, 9.76; N, 4.88.);
EI-HRMS: m/z = 286.2180 (MH+); C19H28NO requires: m/z = 286.2171
(MH+); nmax (KBr) 3443, 3013, 2959, 2928, 1632, 1606, 1474, 1456, 1438,
1391, 1372, 1076, 930, 847, 738, 706, 673 cmÀ1 1H-NMR (500 MHz, CDCl3)
for 6: d 0.90 (s, Me); 1.03 (s, Me); 1.06 (s, Me); 1.11–1.17 (m, 1H of CH2);
1.40–1.47 (m, 1H of CH2); 1.61–1.70 (m, 1H of CH2); 1.74–1.79 (m, 1H
of CH2); 1.80 (d, J = 3.5 Hz, H-C(4)); 2.30 (s, 2ÂMe); 2.48 (dd, J = 10.0;
13.8 Hz, Ha-C(3′)); 2.67 (dd, J = 3.1; 9.9Hz, H-C(3)); 3.73 (dd, J = 2.9;
13.9 Hz, Hb-C(3′)); 6.84 (s, 1H of Arl); 6.89 (s, 2H of Arl); 7.59 (s, OH).
1H-NMR (500 MHz, CDCl3) for 6′: d 0.81 (s, Me); 0.89 (s, Me); 0.97
(s, Me); 1.47–1.53 (m, 1H of CH2); 2.29 (s, 2ÂMe); 2.42 (dd, J = 11.8;
14.3Hz, Ha-C(3′)); 3.17–3.24 (m, H-C(3)); 3.84 (dd, J= 4.2; 14.3Hz, Hb-C
(3′)); 6.82 (s, 1H of Arl); 6.86 (s, 2H of Arl). 13C-NMR (75 MHz, CDCl3)
for 6 and 6′: d 11.6, 12.1, 19.1, 19.3, 20.1, 21.0, 21.5, 22.6, 29.2, 32.1, 32.2,
33.5, 36.9, 43.1, 46.5, 47.5, 48.26, 48.33, 50.7, 53.1, 53.4, 126.8, 127.0,
127.57, 127.63, 137.8, 137.9, 141.0, 142.7, 170.1, 172.3.
heptan-2-one (4c), (1R,3S,4R)-3-(3,5-dimethylbenzyl)-1,7,7-
trimethylbicyclo[2.2.1]heptan-2-one (4c′), and (1R,2R,3R,4R)-3-(3,
5-dimethylbenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (5c).
3c (4.39 g, 16.35 mmol); Pd–C (10%, 500 mg); t1 =20min; crude products:
4c:4c′:5c = 68:24:8, 100% conversion; MPLC (EtOAc/petroleum ether = 1:30).
4c/4c′: Elute first from the column. 4c/4c′ = 75:25. Yield: 3.46 g
(78%) of colorless oil. [a]rD.t. = +31.8 (c = 0.33, CHCl3). (C19H26O requires:
C, 84.39; H, 9.69. Found C, 83.67; H, 9.97.); EI-HRMS: m/z = 271.2065
(MH+); C19H27O requires: m/z = 271.2062 (MH+); nmax (NaCl) 2960,
2873, 1741, 1605, 1447, 1392, 1374, 1323, 1265, 1104, 1040, 1019, 943,
851, 712 cmÀ1 1H-NMR (500 MHz, CDCl3) for 4c: d 0.93 (s, Me); 0.94
.
(s, Me); 0.95 (s, Me); 1.22–1.28 (m, 1H of CH2); 1.45–1.52 (m, 1H of
CH2); 1.59–1.66 (m, 1H of CH2); 1.89–1.96 (m, 1H of CH2); 1.98 (d,
J = 4.0 Hz, H-C(4)); 2.13 (dd, J = 3.7; 10.5 Hz, H-C(3)); 2.29 (s, 2ÂMe);
2.43 (dd, J = 10.5; 14.0 Hz, Ha-C(3′)); 3.16 (dd, J = 3.6; 14.1 Hz, Hb-C(3′));
6.81 (s, 2H of Arl); 6.83 (s, 1H of Arl). 1H-NMR (500 MHz, CDCl3) for
4c′: d 0.85 (s, Me); 0.92 (s, Me); 0.96 (s, Me); 1.31–1.38 (m, 1H of
CH2); 1.66–1.73 (m, 1H of CH2); 1.74–1.80 (m, 2H of CH2); 2.28
(s, 2ÂMe); 2.65–2.71 (m, H-C(3)); 3.09 (dd, J = 4.3; 14.3 Hz, Hb-C(3′)).
13C-NMR (75 MHz, CDCl3) for 4c: d 9.6, 20.6, 21.4, 22.1, 29.4, 29.5,
37.3, 46.7, 46.9, 57.0, 57.7, 126.6, 127.8, 138.0, 141.4, 220.6. 13C-NMR
(75 MHz, CDCl3) for 4c′: d 9.7, 19.4, 19.7, 20.5, 31.1, 32.7, 45.8, 45.9,
52.0, 58.8, 126.4, 127.8, 137.9, 140.4, 220.4.
5c: Elutes second from the column. Yield: 193 mg (4%) of colorless
oil. [a]rD.t. = +16.7 (c = 0.20, CHCl3). EI-HRMS: m/z = 295.2029 (MNa+);
C19H28ONa requires: m/z = 295.2038 (MNa+); nmax (NaCl) 3499, 2950,
(1R,3R,4R,2E)-3-(3,5-Dimethylbenzyl)-1,7,7-trimethylbicyclo
[2.2.1]heptan-2-one O-acetyl oxime (7) and (1R,3S,4R,2E)-3-(3,5-
dimethylbenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one O-acetyl
oxime (7′). A solution of 6 (57mg, 0.2mmol, d.e. =42%) in Ac2O (0.5ml)
was heated at 80 ꢀC for 20 h. Volatile components were evaporated in vacuo.
The residue was dissolved and evaporated four times with PhMe (2 ml) and
four times with CH2Cl2 (2 ml) to azeotropically remove all traces of Ac2O. The
crude product 7/7′ was characterized without further purification.
7:7′ = 71:29. Yield: full conversion; colorless oil. EI-HRMS: m/z= 328.2286
(MH+); C21H30NO2 requires: m/z= 328.2277 (MH+); nmax (NaCl) 2962,
2874, 1765, 1651, 1606, 1448, 1391, 1365, 1206, 1042, 1001, 954, 922, 877,
1735, 1605, 1477, 1460, 1388, 1370, 1280, 1095, 1048, 848, 698 cmÀ1 1H-
.
NMR (500 MHz, CDCl3): d 0.80 (s, Me); 0.92 (s, Me); 0.95–1.08 (m, 2H
of CH2); 1.24 (s, Me); 1.43–1.50 (m, 1H of CH2); 1.55 (d, J = 3.8 Hz, H-C
(4)); 1.58 (d, J = 3.9 Hz, OH); 1.63–1.70 (m, 1H of CH2); 2.10 (q,
J = 8.1 Hz, H-C(3)); 2.29 (s, 2ÂMe); 2.69 (dd, J = 8.1; 14.2 Hz, Ha-C(3′));
3.02 (dd, J = 8.1; 14.2 Hz, Hb-C(3′)); 3.76 (dd, J = 3.6; 8.0 Hz, H-C(2));
6.81 (s, 1H of Arl); 6.86 (s, 2H of Arl). 13C-NMR (75 MHz, CDCl3): d
11.9, 21.5, 21.9, 22.3, 30.1, 33.8, 36.1, 47.1, 49.97, 50.03, 52.0, 82.0, 126.8,
127.4, 137.9, 143.2.
1
851 cmÀ1. H-NMR (300 MHz, CDCl3) for 7: d 0.93 (s, Me); 1.06 (s, Me);
(1R,3R,4R)-1,7,7-Trimethyl-3-(phenanthren-9-ylmethyl)bicyclo
[2.2.1]heptan-2-one (4d) and (1R,3S,4R)-1,7,7-trimethyl-3-
(phenanthren-9-ylmethyl)bicyclo[2.2.1]heptan-2-one (4d′). 3d
(1.69 g, 4.93 mmol); Pd–C (10%, 150 mg); t1 = 60min; 100% conversion;
MPLC (EtOAc/petrol ether= 1:30). 4d:4d′ = 72:28. Yield: 1.48g (87%) of
1.15 (s, Me); 1.15–1.23 (m, 1H of CH2); 1.46–1.56 (m, 1H of CH2);
1.65–1.81 (m, 2H of CH2); 1.84 (d, J= 3.6 Hz, H-C(4)); 2.13 (s, OAc); 2.31
(s, 2ÂMe); 2.59 (dd, J=9.3; 13.9Hz, Ha-C(3′)); 2.72 (dd, J=3.2; 9.3Hz,
H-C(3)); 3.42 (dd, J=3.1; 13.9Hz, Hb-C(3′)); 6.82 (s, 1H of Arl); 6.85
(s, 2H of Arl). 1H-NMR (300 MHz, CDCl3) for 7′: d 0.84 (s, Me); 1.08
(s, Me); 2.13 (s, OAc); 2.30 (s, 2ÂMe); 2.49 (dd, J= 11.3; 14.3 Hz, Ha-C
(3′)); 3.21–3.30 (m, H-C(3)); 3.53 (dd, J=4.6; 14.4Hz, Hb-C(3′)). 13C-NMR
(75 MHz, CDCl3) for 7 and 7′: d 11.4, 11.9, 19.0, 19.2, 19.88, 19.94, 20.8,
21.5, 22.6, 28.9, 31.8, 33.0, 33.3, 38.2, 44.1, 46.5, 47.8, 48.5, 48.7, 51.5,
54.3, 54.6, 126.5, 126.6, 127.9, 128.0, 138.06, 138.15, 140.0, 141.8, 168.9,
169.0, 178.0, 180.3.
white solid; mp 49.2–62.0 ꢀC. [a]Dr.t. = +55.8 (c= 0.10, CH2Cl2). (C25H26
O
requires: C, 87.68; H, 7.65. Found C, 87.42; H, 7.84.); EI-HRMS:
m/z = 343.2061 (MH+); C25H27O requires: m/z = 343.2062 (MH+); nmax
(KBr) 3061, 2957, 2931, 2874, 2365, 2336, 1738, 1607, 1487, 1448, 1265,
1016, 887, 747, 668 cmÀ1 1H-NMR (CDCl3, 300MHz) for 4d: d 0.98
.
(s, Me); 0.99 (s, Me); 1.09 (s, Me); 1.10–1.19 (m, 1H of CH2); 1.42–1.52
(m, 1H of CH2); 1.59–1.70 (m, 1H of CH2); 1.84–1.96 (m, 1H of CH2);
2.10 (d, J = 4.0 Hz, H-C(4)); 2.32 (dd, J = 2.9; 9.9 Hz, H-C(3)); 2.90 (dd,
J= 10.0; 14.6 Hz, Ha-C(3′)); 3.85 (dd, J= 2.7; 14.4 Hz, Hb-C(3′)); 7.53–7.71
(m, 5H of Arl); 7.80–7.87 (m, 1H of Arl); 8.23–8.29 (m, 1H of Arl),
8.63–8.79 (m, 2H of Arl). 1H-NMR (CDCl3, 300MHz) for 4d′: d 0.81
(s, Me); 0.97 (s, 2ÂMe); 1.72–1.82 (m, 1H of CH2); 1.97–2.01 (m, H-C(4));
2.93–3.01 (m, H-C(3), Ha-C(3′)); 3.68–3.79 (m, Hb-C(3′)); 8.16–8.23 (m, 1H
of Arl). 13C-NMR (126 MHz, CDCl3) for 4d: d 9.7, 20.6, 22.3, 29.2, 29.4,
35.6, 47.2, 47.3, 55.2, 57.9, 122.6, 123.4, 124.7, 126.3, 126.5, 126.8, 126.9,
127.1, 128.2, 130.1, 130.8, 131.1, 131.8, 135.6, 221.0. 13C-NMR (126MHz,
CDCl3) for 4d′: d 9.8, 15.5, 19.5, 19.7, 20.6, 30.2, 31.3, 46.0, 46.3, 50.6, 59.0,
66.0, 122.6, 123.5, 124.4, 126.5, 126.7, 127.0, 129.9, 130.98, 131.01, 131.8,
134.6, 220.8.
3-(3,5-Dimethylphenyl)-2-(2,3,3-trimethylcyclopent-1-en-1-yl)
propanenitrile (8). To a solution of 6 (57 mg, 0.2 mmol, d.e. = 42%) in a
mixture of TFA (120 ml) and toluene (80 ml) was added 2,4,6-trichloro-1,3,
5-triazine (2.9 mg), and the resulting mixture was heated at 70 ꢀC for 1h.
Volatile components were evaporated in vacuo, and the residue was purified
by column chromatography (EtOAc/petroleum ether = 1:100). Fractions
containing the product were combined, and volatile components evaporated
in vacuo to give 8 in approximately 85% purity. Yield: 27 mg (43%, o ꢁ 0.85)
of colorless oil. EI-HRMS: m/z= 268.2065 (MH+); C19H26N requires:
m/z= 268.2065 (MH+); nmax (NaCl) 3015, 2955, 2934, 2863, 2238, 1767,
1660, 1607, 1459, 1379, 1361, 1207, 1163, 851, 704 cmÀ1 1H-NMR
.
(500 MHz, CDCl3): d 0.87 (s, Me); 0.96 (s, Me); 1.23 (t, J=2.0Hz, Me);
1.62–1.71 (m, H2-C(4)); 2.27 (s, 2ÂMe); 2.29–2.36 (m, Ha-C(5)); 2.36–2.44
(m, Hb-C(5)); 2.76 (dd, J=8.4; 13.3Hz, Ha-C(2′)); 3.00 (dd, J= 7.0; 13.3Hz,
Hb-C(2′)); 3.61 (dd, J=7.1; 8.2Hz, H-C(1′)); 6.77 (s, 2H of Arl); 6.87 (s, 1H
of Arl). 13C-NMR (126 MHz, CDCl3): d 9.6, 21.4, 26.26, 26.32, 30.1, 33.2,
37.9, 38.5, 47.5, 120.8, 125.9, 127.0, 128.8, 137.0, 138.1, 145.1.
(1R,3R,4R,2E)-3-(3,5-Dimethylbenzyl)-1,7,7-trimethylbicyclo
[2.2.1]heptan-2-one oxime (6) and (1R,3S,4R,2E)-3-(3,5-
dimethylbenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one
oxime (6′). To a solution of 4c (1.35g, 5 mmol; d.e. = 50%) in EtOH
(30ml) were added pyridine (4.04ml, 50mmol) and NH2OH–HCl (4.86g,
Chirality DOI 10.1002/chir

GROŠELJ ET AL.
General procedure for the Beckmann rearrangement of
of CH2); 2.89 (d, J = 7.3 Hz, H2C(4′)); 3.80 (td, J = 2.9; 7.2 Hz, H-C(4));
5.28 (s, NH); 7.64 (s, 2H of Arl); 7.80 (s, 1H of Arl). 13C-NMR
(126 MHz, CDCl3): d 13.5, 19.6, 20.7, 23.4, 37.2, 39.7, 43.9, 47.7, 52.1, 55.2,
121.3–121.4 (m), 123.4 (q, J= 272.7 Hz); 129.4–129.6 (m); 132.4 (q,
J= 33.4 Hz); 140.1, 179.1.
ketones 4/4′ with hydroxylamine-O-sulfonic acid
A mixture of ketones 4/4′ and NH2OSO3H in AcOH was heated under
reflux for t1 h. Volatile components were evaporated in vacuo. The
residue was dissolved/suspended in CH2Cl2 and carefully washed with
NaHCO3. Organic phase was dried over anhydrous Na2SO4 and filtered,
and volatile components were evaporated in vacuo. The residue was
purified by column chromatography (EtOAc/petroleum ether = 1:2).
Fractions containing the amide product 9/9′ were combined and volatile
components evaporated in vacuo. The residue was re-purified by MPLC.
Fractions containing the product were combined, and volatile
components evaporated in vacuo to give 9/9′.
(1R,4S,5S)-4-Benzyl-1,8,8-trimethyl-3-azabicyclo[3.2.1]octane
(10a). A solution of 9a (212 mg, 0.82 mmol) in LiAlH4 (9 ml, 1 M in
THF) under argon was heated at 56 ꢀC for 24 h. The reaction mixture
was cooled to room temperature and carefully quenched with NaOH
(1 M in H2O). The resulting mixture was extracted with Et2O
(3 Â 30 ml). The combined organic phase was dried over anhydrous
Na2SO4 and filtered, and volatile components were evaporated in vacuo.
The residue was purified by column chromatography (EtOAc/Et3N =
40:1). Fractions containing the product were combined, and volatile com-
ponents evaporated in vacuo to give 10a. Yield: 80 mg (40%) of colorless
oil. [a]rD.t. = +41.5 (c = 0.10, CH2Cl2). EI-HRMS: m/z = 244.2065 (MH+);
(1R,4S,5S)-4-Benzyl-1,8,8-trimethyl-3-azabicyclo[3.2.1]octan-
2-one (9a). 4a (2.18 g, 9 mmol, d.e. = 32%); NH2OSO3H (2.8 g,
24.76 mmol); AcOH (50 ml); t1 = 9 h; CH2Cl2 (300 ml); NaHCO3 (100 ml,
aq. sat.); column chromatography (EtOAc/petroleum ether = 1:2);
MPLC (EtOAc/petroleum ether = 1:2). Yield: 189 mg (8%) of dirty white
solid; mp 180.1–180.3 ꢀC (CH2Cl2/n-heptane). [a]rD.t. = À88.7 (c =0.13,
CH2Cl2). (C17H23NO requires: C, 79.33; H, 9.01; N, 5.44. Found C,
79.52; H, 9.30; N, 5.44.); EI-HRMS: m/z = 258.1846 (MH+); C17H24NO
requires: m/z = 258.1858 (MH+); nmax (KBr) 3198, 3080, 2974, 2961,
2943, 2866, 1655, 1602, 1495, 1476, 1454, 1403, 1368, 1345, 1276, 1114,
820, 739, 701 cmÀ1. 1H-NMR (CDCl3, 300 MHz): d 0.96 (s, Me); 1.01 (s,
Me); 1.08 (s, Me); 1.70–2.04 (m, 2ÂCH2, H-C(5)); 2.71 (d, J = 7.3 Hz,
H2-C(4′)); 3.73 (td, J = 2.7; 7.2 Hz, H-C(4)); 5.22 (br s, NH); 7.14–7.35
(m, Ph). 13C-NMR (CDCl3, 75.5 MHz): d 13.5, 19.5, 20.7, 23.4, 37.3,
39.9, 43.7, 48.1, 52.0, 55.3, 127.0, 129.0, 129.3, 137.5, 178.8.
C
17H26N requires: m/z = 244.2065 (MH+); nmax (NaCl) 3311, 3084, 3062,
3027, 2948, 2358, 1942, 1604, 1495, 1454, 1388, 1372, 1332, 1307, 1268,
1172, 1125, 1098, 1082, 1031, 1010, 935, 861, 818, 748, 700, 648,
618 cmÀ1. 1H-NMR (300 MHz, CDCl3): d 0.75 (s, Me); 0.84 (s, Me); 0.96
(s, Me); 1.37 (d, J = 3.8 Hz, H-C(5)); 1.49–1.77 (m, 4H of CH2); 1.91
(br s, NH); 2.20 (d, J = 12.1 Hz, Ha-C(2)); 2.46 (dd, J = 7.0; 13.2 Hz, Ha-C
(4′)); 2.61 (dd, J = 7.1; 13.2 Hz, Hb-C(4′)); 2.87 (d, J = 12.1 Hz, Hb-C(2));
3.36 (t, J = 7.0 Hz, H-C(4)); 7.12–7.31 (m, Ph). 13C-NMR (75 MHz, CDCl3):
d 17.3, 18.2, 20.8, 25.3, 35.0, 41.4, 42.8, 43.1, 49.1, 54.9, 55.6, 126.1, 128.5,
129.4, 139.8.
(1R,4S,5S)-4-Benzyl-1,8,8-trimethyl-3-azabicyclo[3.2.1]octan-
3-ium chloride (10a-HCl). 10a (50 mg, 0.2 mmol) was dissolved in
anhydrous Et2O (20 ml), followed by addition of HCl (2 M in EtOAc,
1 ml). After 5 min of stirring at room temperature, volatile components
were evaporated in vacuo to give 10a-HCl as a white solid. Mp
159.9–160.0 ꢀC. [a]Dr.t. = +53.0 (c = 0.12, CH2Cl2). (C17H26ClN requires:
C, 72.96; H, 9.36; N, 5.01. Found C, 72.90; H, 9.47; N, 4.95.); EI-HRMS:
m/z = 244.2072 (MH+); C17H26N requires: m/z = 244.2065 (MH+); nmax
(KBr) 3427, 3028, 2955, 2773, 1595, 1466, 1474, 1456, 1439, 1430,
(1R,4S,5S)-4-(3,5-Bis(trifluoromethyl)benzyl)-1,8,8-trimethyl-
3-azabicyclo[3.2.1]octan-2-one (9b) and (1R,4R,5S)-4-(3,5-bis
(trifluoromethyl)benzyl)-1,8,8-trimethyl-3-azabicyclo[3.2.1]octan-2-
one (9b′). 4b (1.12 g, 2.97mmol); NH2OSO3H (1.01g, 8.91 mmol); AcOH
(50ml); t1 = 12h; CH2Cl2 (100ml); NaHCO3 (50 ml, aq. sat.); column chro-
matography (EtOAc/petroleum ether = 1:2); MPLC (EtOAc/petroleum
ether/Et3N=80:160:1). 9a:9a′ = 77:23. Yield: 200 mg (17%) of pale yellow
solid; mp 104.9–124.7 ꢀC. [a]Dr.t. = À17.3 (c = 0.11, CH2Cl2). (C19H21F6NO
requires: C, 58.01; H, 5.38; N, 3.56. Found C, 58.15; H, 5.26; N, 3.60.);
EI-HRMS: m/z = 394.1623 (MH+); C19H22F6NO requires: m/z = 394.1606
(MH+); nmax (KBr) 2975, 1672, 1466, 1376, 1348, 1285, 1242, 1226, 1178,
1401, 1371, 1317, 1259, 740, 697 cmÀ1 1H-NMR (CDCl3, 300 MHz): d
.
0.85 (s, 2ÂMe); 0.95 (s, Me); 1.50 (d, J = 6.2 Hz, H-C(5)); 1.67–1.95
(m, 2H of CH2); 2.10–2.24 (m, 2H of CH2); 2.81 (d, J = 12.7 Hz, Ha-C
(2)); 3.01 (dd, J = 10.9; 13.2 Hz, Ha-C(4′)); 3.10 (d, J = 12.6 Hz, Hb-C
(2)); 3.28 (dd, J = 4.0; 13.3 Hz, Hb-C(4′)); 3.73 (dd, J = 3.7; 10.7 Hz, H-C
(4)); 7.15–7.32 (m, Ph); 8.78 (br s, NH+2). 13C-NMR (CDCl3,
75.5 MHz): d 16.8, 17.9, 20.0, 23.9, 33.3, 36.9, 41.8, 42.6, 44.9, 51.2,
56.7, 126.9, 128.7, 129.4, 136.3.
1142, 1054, 930, 915, 886, 842, 733, 708, 683 cmÀ1 1H-NMR (CDCl3,
.
300MHz) for 9b: d 0.97 (s, Me); 1.04 (s, Me); 1.08 (s, Me); 1.64–2.05
(m, 2ÂCH2, H-C(5)); 2.85–2.99 (m, H2-C(4′)); 3.81 (td, J = 3.0; 7.3 Hz, H-C
(4)); 5.97 (s, NH); 7.65 (s, 2H of Arl); 7.79 (s, 1H of Arl). 1H-NMR (CDCl3,
300 MHz) for 9b′: d 0.99 (s, Me); 1.10 (s, Me); 1.28 (s, Me); 1.43–1.54
(m, 1H); 2.11–2.25 (m, 1H); 3.00–3.17 (m, H2-C(4′)); 3.52 (t, J= 7.7 Hz,
H-C(4)); 6.20 (s, NH). 13C-NMR (CDCl3, 75.5 MHz) for 9b: d 13.3, 19.5,
20.6, 23.3, 37.2, 39.5, 43.8, 47.3, 52.0, 55.2, 121.0–121.3 (m), 123.4
(q, J = 272.3 Hz), 129.4–129.6 (m), 132.3 (q, J = 33.3Hz), 140.2, 179.3.
13C-NMR (CDCl3, 75.5MHz) for 9b′: d 13.6, 22.0, 24.3, 31.3, 36.8, 42.3,
42.8, 46.7, 52.3, 61.8, 132.3 (q, J= 33.2 Hz), 141.0, 178.5.
(1R,4S,5S)-4-(3,5-Bis(trifluoromethyl)benzyl)-1,8,8-trimethyl-
3-azabicyclo[3.2.1]octane (10b).
A
solution of 9b (30 mg,
0.076 mmol) in BH3 Â THF (4 ml, 1 M in THF) under argon was heated
under refluxed for 24h. The reaction mixture was cooled to room
temperature and carefully quenched with MeOH (2 ml), followed by
addition of KOH (200 mg) and H2O (1ml). The resulting mixture was
stirred at room temperature for 10min, then diluted with H2O (10ml), and
extracted twice with CH2Cl2 (50 ml). The combined organic phase was
dried over anhydrous Na2SO4 and filtered, and volatile components were
evaporated in vacuo. The oily residue was purified by column chromatogra-
phy ([1] EtOAc/petroleum ether = 1:1 to remove the nonpolar impurities/
starting material; [2] EtOAc/Et3N = 50:1 to elute the product). Fractions
containing the amine product were combined, and volatile components
evaporated in vacuo to give 10b. Yield: 10 mg (34%) of colorless oil. [a]Dr.
t. = +35.0 (c = 0.18, CH2Cl2). EI-HRMS: m/z = 380.1799 (MH+); C19H24F6N
requires: m/z = 380.1807 (MH+); nmax (NaCl) 2952, 2868, 1468, 1452, 1379,
1278, 1174, 1132, 923, 892, 843, 707, 683cmÀ1. 1H-NMR (500 MHz, CDCl3):
d 0.77 (s, Me); 0.87 (s, Me); 0.99 (s, Me); 1.35 (d, J= 4.6 Hz, H-C(5));
(1R,4S,5S)-4-(3,5-Bis(trifluoromethyl)benzyl)-1,8,8-trimethyl-
3-azabicyclo[3.2.1]octan-2-one (9b). 4b′ (300 mg, 0.79 mmol); NH2O-
SO3H (277 mg, 2.38 mmol); AcOH (15 ml); t1 =24 h; CH2Cl2 (150 ml);
(50 ml, aq. sat.); column chromatography (EtOAc/petroleum ether = 1:2);
MPLC (EtOAc/petroleum ether = 1:3). Yield: 51 mg (16%) of white solid;
mp 138–143 ꢀC. [a]Dr.t. =À34.4 (c = 0.09, CH2Cl2). (C19H21F6NO requires: C,
58.01; H, 5.38; N, 3.56. Found C, 57.97; H, 5.23; N, 3.52.); EI-HRMS:
m/z= 392.1458 (M À H)À; C19H20F6NO requires: m/z= 392.1455 (M À H)À;
nmax (KBr) 3228, 3097, 2976, 1675, 1621, 1465, 1375, 1348, 1283, 1242,
1226, 1179, 1128, 1054, 914, 887, 876, 843, 815, 733, 708, 682 cmÀ1
.
1H-NMR (500 MHz, CDCl3): d 0.98 (s, Me); 1.04 (s, Me); 1.09 (s, Me);
1.69–1.72 (m, H-C(5)); 1.77–1.83 (m, 1H of CH2); 1.86–2.03 (m, 3H
Chirality DOI 10.1002/chir

SYNTHESIS OF NOVEL CAMPHOR-DERIVED AMINES
1.54–1.75 (m, 4H of CH2, NH); 2.22 (d, J = 12.2Hz, Ha-C(2)); 2.62 (dd,
1340, 1310, 1284, 1193, 1136, 1062, 1046, 933, 898, 885, 846, 786, 714,
683 cmÀ1 1H-NMR (500 MHz, CDCl3): d 1.07 (dd, J = 0.9; 10.8 Hz, 1H of
J= 6.3; 13.5 Hz, Ha-C(4′)); 2.70 (dd, J= 7.7; 13.5 Hz, Hb-C(4′)); 2.88
(d, J= 12.2 Hz, Hb-C(2)); 3.39 (t, J= 6.8Hz, H-C(4)); 7.62 (s, 2H of Arl);
7.72 (s, 1H of Arl). 13C-NMR (126MHz, CDCl3): d 17.2, 18.3, 21.0,
25.3, 35.0, 41.4, 42.8, 43.3, 49.5, 54.9, 55.6, 120.4–120.6 (m), 123.6
(q, J = 272.7 Hz), 129.4–129.6 (m), 131.7 (q, J= 33.0 Hz), 142.4.
.
CH2); 1.25–1.39 (m, 3H of CH2); 1.36 (s, Me); 1.55 (s, Me); 1.57–1.63
(m, 1H of CH2); 1.99 (br d, J= 10.9 Hz, 1H of CH2); 2.03 (br s, CH); 2.80
(d, J= 13.6Hz, 1H of CH2); 3.17 (d, J = 12.4 Hz, 1H of CH2); 3.19 (s, CH2);
7.61 (s, 2H of Arl); 7.77 (s, 1H of Arl). 13C-NMR (126 MHz, CDCl3): d 15.3,
21.1, 23.2, 25.8, 35.2, 37.5, 47.4, 51.3, 56.4, 58.5, 98.7, 120.6–120.8 (m),
123.5 (q, J = 272.7Hz), 130.5–130.6 (m), 131.6 (q, J= 33.2 Hz), 141.0.
(1R,4S,5S)-4-(3,5-Bis(trifluoromethyl)benzyl)-1,8,8-trimethyl-
3-azabicyclo[3.2.1]octan-3-ium chloride (10b-HCl). To a solution
of 10b (8 mg, 0.021 mmol) in n-heptane (3 ml) were added two drops of
HCl (2 M in EtOAc). After 2 days in an open flask, the precipitated crys-
tals were collected by filtration to give 10b-HCl. Yield: 8 mg (91%) of
white solid; mp 231–242 ꢀC. [a]Dr.t. = +24.0 (c = 0.1, CH2Cl2).
(C19H24ClF6N requires: C, 54.88; H, 5.82; N, 3.37. Found C, 54.83; H,
5.80; N, 3.35.); EI-HRMS: m/z = 380.1805 (M+); C19H24F6N+ requires:
m/z = 380.1807 (M+); nmax (KBr) 3471, 2954, 1618, 1582, 1460, 1388,
(1S,2R,3S,4R)-1,7,7-Trimethyl-N2,N3-diphenylbicyclo[2.2.1]
heptane-2,3-diamine (15) and (1S,2S,3S,4R)-1,7,7-trimethyl-N2,
N3-diphenylbicyclo[2.2.1]heptane-2,3-diamine (16). NaCNBH3
(1.11 g, 17.7 mmol) was added to a solution of 14 (466 mg, 1.47 mmol) in
anhydrous MeOH (15 ml) under argon, followed by the addition of glacial
acetic acid (0.2 ml), and the reaction mixture was stirred at room temperature
for 5 h. Afterwards, water (30 ml) was added, and the reaction mixture was
stirred at room temperature for 1 h. MeOH was evaporated in vacuo from
the reaction mixture, water (70 ml) was added to the residue, and the
resulting mixture was extracted with EtOAc (2 Â 100 ml). The combined
organic phases were dried over anhydrous Na2SO4 and filtered, and volatile
components evaporated in vacuo. The residue (15:16 = 45:55) was purified
by column chromatography (EtOAc/hexanes = 1:30). Fractions containing
the separated products were combined and evaporated in vacuo to give
15 and 16, respectively.
1376, 1284, 1173, 1151, 1129, 892, 707, 684 cmÀ1 1H-NMR (500 MHz,
.
CDCl3): d 0.89 (s, 2ÂMe); 0.97 (s, Me); 1.39 (d, J = 6.8 Hz, H-C(5));
1.77–1.86 (m, 1H of CH2); 1.89–1.97 (m, 1H of CH2); 2.12–2.22 (m, 2H
of CH2); 2.84 (br d, J = 12.5 Hz, Ha-C(2)); 3.12 (be d, J = 9.6 Hz, Hb-C
(2)); 3.22 (br t, J = 12.2 Hz, Ha-C(4′)); 3.51 (br d, J = 11.4 Hz, Hb-C(4′));
3.75 (br s, H-C(4)); 7.65 (s, 2H of Arl); 7.78 (s, 1H of Arl); 9.13 (br s,
1H of NH+2);10.37 (br s, 1H of NH2+). 13C-NMR (126 MHz, CDCl3): d
16.8, 18.1, 20.1, 24.1, 33.4, 36.4, 41.9, 43.0, 45.0, 51.1, 56.4, 121.6, 123.3
(q, J = 272.8 Hz), 129.7, 132.4 (q, J = 33.4 Hz), 138.7.
15: Elutes first from the column. Yield: 192 mg (40%) of colorless oil.
[a]rD.t. = +73.6 (c = 0.33, CHCl3). EI-HRMS: m/z = 321.2330 (MH+);
rel-(1S,4R,2E)-2-(3,5-Bis(trifluoromethyl)benzylidene)-1,7,
7-trimethylbicyclo[2.2.1]heptane (11) and (3aR,4S,7R,7aS)-
7-(3,5-bis(trifluoromethyl)benzyl)-3a,7a-dimethylhexahydro-3H-4,7-
methanobenzo[d][1,2]oxathiole 2,2-dioxide (12). A mixture of 5b
(380 mg, 1 mmol) and NH2OSO3H (1.1 g, 9.73 mmol) in acetic acid
(15 ml) was heated under reflux for 24 h. The reaction mixture was
cooled to room temperature, and volatile components were evaporated
in vacuo. The residue was dissolved/suspended in CH2Cl2 (200 ml)
and carefully washed with NaHCO3 (50 ml, aq. sat.). The separated or-
ganic phase was dried over anhydrous Na2SO4 and filtered, and volatile
components were evaporated in vacuo. The residue was purified by col-
umn chromatography ([1] EtOAc/petroleum ether = 1:10 to elute 11; [2]
EtOAc/petroleum ether = 1:1 to elute 12). Fractions containing the
corresponding product were combined, and volatile components evapo-
rated in vacuo to give crude 11 and 12. 11 was re-purified by MPLC
(EtOAc/petroleum ether = 1:20). Fractions containing the product were
combined, and volatile components evaporated in vacuo to give 11.
Similarly, 12 was re-purified by MPLC (EtOAc/petroleum ether = 1:5).
Fractions containing the product were combined, and volatile compo-
nents evaporated in vacuo to give 12. 12 was additionally re-crystallized
from CH2Cl2/n-heptane.
C
22H29N2 requires: m/z = 321.2331 (MH+); nmax (NaCl) 3386, 3048,
3018, 2953, 2880, 1602, 1503, 1481, 1460, 1422, 1390, 1369, 1303, 1274,
1250, 1193, 1179, 1154, 1142, 1126, 1099, 1069, 1028, 992, 868, 747,
692 cmÀ1 1H-NMR (300 MHz, DMSO-d6): d 0.80 (s, Me); 0.92 (s, Me);
.
1.10 (s, Me); 1.22–1.44 (m, 2H of CH2); 1.53–1.64 (m, 1H of CH2);
1.68–1.80 (m, 1H of CH2); 1.87 (d, J = 4.3 Hz, H-C(4)); 3.38 (dd, J = 3.4;
8.2 Hz, CH); 3.45 (dd, J = 5.7; 8.1 Hz, CH); 4.77 (d, J = 5.5 Hz, NH);
5.13 (d, J = 3.3 Hz, NH); 6.40–6.45 (m, 2H of Ph); 6.48–6.58 (m, 4H of
Ph); 6.94–7.04 (m, 4H of Ph). 13C-NMR (75 MHz, CDCl3): d 12.3,
21.2, 21.9, 26.1, 36.3, 47.6, 49.5, 50.3, 62.5, 67.6, 113.2, 113.8, 117.0,
118.0, 129.2, 129.3, 148.3, 149.6.
16: Elutes second from the column. Yield: 256 mg (54%) of dirty white
solid; mp 75–86 ꢀC. [a]Dr.t. = À60.7 (c = 0.43, CHCl3). (C22H28N2 requires:
C, 82.45; H, 8.81; N, 8.74. Found C, 82.82; H, 9.22; N, 8.80.); EI-HRMS:
m/z = 321.2340 (MH+); C22H29N2 requires: m/z = 321.2331 (MH+); nmax
(NaCl) 3409, 3051, 2952, 2882, 1600, 1503, 1428, 1390, 1371, 1315, 1269,
1195, 1180, 1154, 1098, 1072, 1045, 1029, 992, 868, 747, 692 cmÀ1
.
1H-NMR (500 MHz, DMSO-d6): d 0.82 (s, Me); 0.83 (s, Me); 1.14
(s, Me); 1.17–1.25 (m, 1H of CH2); 1.30–1.38 (m, 1H of CH2); 1.68–1.78
(m, 1H of CH2, H-C(4)); 1.84–1.93 (m, 1H of CH2); 2.89 (t, J = 4.8 Hz, H-C
(3)); 3.79–3.85 (m, H-C(2)); 5.66 (d, J = 8.7 Hz, H-N(2′)); 5.81 (d,
J = 4.9 Hz, H-N(3′)); 6.41–6.50 (m, 4H of Ph); 6.72 (d, J = 7.9 Hz,
2H of Ph); 6.98–7.04 (m, 4H of Ph). 13C-NMR (126 MHz, DMSO-d6):
d 14.4, 19.1, 21.5, 26.4, 26.9, 47.1, 48.4, 50.5, 65.0, 65.7, 111.8, 112.1,
114.8, 114.9, 128.6, 128.8, 148.4, 149.6.
11: Elutes first from the column. Yield: 100 mg (27%) of white solid;
mp 91.0–95.1 ꢀC. [a]Dr.t. = 0.00 (c = 0.08, CH2Cl2). (C19H20F6 requires: C,
62.98; H, 5.56. Found C, 63.12; H, 5.43.); nmax (KBr) 3545, 3416, 2960,
1651, 1615, 1475, 1390, 1374, 1361, 1281, 1169, 1132, 1120, 938, 881,
844, 698, 682 cmÀ1 1H-NMR (500 MHz, CDCl3): d 0.77 (s, Me); 0.96
.
(s, Me); 1.06 (s, Me); 1.22–1.29 (m, 1H of CH2); 1.30–1.37 (m, 1H of
CH2); 1.75 (td, J = 3.8; 11.9 Hz, 1H of CH2); 1.82–1.90 (m, 1H of CH2);
1.95 (t, J = 4.3 Hz, H-C(4)); 2.25 (dd, J = 2.1; 16.7 Hz, Ha-C(3)); 2.68–2.75
(m, Hb-C(3)); 6.15 (br s, H-C(2′)); 7.63 (s, 1H of Arl); 7.75 (s, 2H
of Arl). 13C-NMR (126 MHz, CDCl3): d 13.3, 19.1, 19.9, 27.9, 34.9,
37.8, 45.2, 48.0, 53.6, 115.1, 118.9–119.1 (m), 123.8 (q,J = 272.6 Hz),
127.6–127.8 (m), 131.6 (q, J = 32.9 Hz), 140.9, 158.6.
12: Elutes second from the column. Yield: 40 mg (9%) of white solid
(CH2Cl2/n-heptane); mp 160–177 ꢀC. [a]Dr.t. = +12.5 (c = 0.14, CH2Cl2).
(C19H20F6O3S requires: C, 51.58; H, 4.56. Found C, 51.79; H, 4.59.); EI-HRMS:
m/z= 460.1378 (M + NH4)+; C19H24F6NO3S requires: m/z= 460.1376
(M + NH4)+; nmax (KBr) 3418, 2979, 1624, 1492, 1472, 1442, 1420, 1380,
(3aS,4S,7R,7aR)-4,8,8-Trimethyl-1,3-diphenyl-3a,4,5,6,7,7a-
hexahydro-1H-4,7-methanobenzo[d]imidazol-3-ium tetrafluorobo-
rate (17). One drop of formic acid was added to a mixture of 15
(171 mg, 0.534 mmol) and NH4BF4 (60 mg, 0.57 mmol) in HC(OEt)3
(1 ml) under argon. The reaction mixture was heated at 110 ꢀC for 4 h
under microwave irradiation (300 W). Upon cooling to room tempera-
ture, Et2O (20 ml) was added, and the resulting precipitate was collected
by filtration and washed with Et2O (10 ml). The resulting precipitate was
dissolved in CH2Cl2, filtered through a plug of CeliteW, and washed with
CH2Cl2. Volatile components were evaporated in vacuo, and to the
residue, Et2O (20 ml) was given to solidify the product. The
Chirality DOI 10.1002/chir

GROŠELJ ET AL.
Scheme 1. Preparation of 3-arylmethyl camphor derivatives 4/4′ and isoborneol derivatives 5.
the structures were produced using ORTEPIII.44 Structural and other
TABLE 1. Synthesis and catalytic hydrogenation of arylidene
crystallographic data have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication numbers
CCDC 864587–864595. A copy of the data can be obtained, free of charge,
by applying to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax:
+44(0)-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
compounds 3a–d
3
4
4′
5
4:4′:5
Arl
Yield (%)a
46
46
a
b
c
Ph
Ref.
Ref.
86
Ref. 45
31
Ref. 45
13
–
26
4
66:34:045
55:18:27
68:24:8
RESULTS AND DISCUSSION
3,5-CF3-C6H3
3,5-CH3-C6H3
Phenantren-9-yl
78b
87b
Syntheses
d
28
–
72:28:0
The precursors for the Beckmann rearrangement, 3-aryl-
methyl substituted camphor derivatives 4/4′, were prepared
in three steps from (+)-camphor (1). Following the literature
procedure,45 1 was transformed into 3-((dimethylamino)
methylene)camphor (2). Treatment of enaminone 2 with ex-
cess Grignard reagent(s) gave arylidene compounds 3a–d in
28–86% yield, in all cases with the (E)-configured exocyclic
C=C bond, exclusively. Next, catalytic hydrogenation of
arylidene compounds 3a–d in the presence of 10% Pd–C
furnished the expected 3-arylmethyl camphor derivatives as
mixtures of the major exo-epimers 4a–d and the minor endo-
epimers 4a′–d′ in 44–87% yield. Reduction of 3b and 3c
furnished along the desired ketones (4b/4b′ and 4c/4c′,
respectively) also the isoborneol derivatives 5b and 5c in
26% and 4% yield, respectively. The ketone products were
chromatographically separated from the corresponding iso-
borneol derivatives, whereas the ketone epimers could only
be separated in the case of 4b/4b′. The major exo-epimers
4 and 5 are the result of an attack of the reagent from the ste-
rically less hindered endo face of the C=C bond46 (Scheme 1,
Table 1).
Next, reaction of ketone 4c under conditions used by Page
et al.47 gave the corresponding oxime 6 in 96% yield and with
a slightly decreased diastereoisomer ratio. Various Beckmann
rearrangement attempts of 6 resulted in complex mixtures of
products. Only when 6 was treated with TFA in the presence
of catalytic amount of 2,4,6-trichloro-1,3,5-triazine (TCT) that
a Beckmann fragmentation product 8 was obtained in 43%
yield containing approximately 15% of unidentified co-prod-
uct. Formation of 8 could be explained via the initial
Beckmann fragmentation of 6, followed by 1,2-methyl migra-
tion and final proton elimination. Heating 6 in Ac2O yielded
O-acetylated product 7 in quantitative yields (Scheme 2).
Because of the failure to rearrange oxime 6, a direct
Beckmann rearrangement starting from ketones 4/4′ was
aYields after separation.
bKetone epimers 4/4′ could chromatographically not be separated.
precipitate was finely crushed, collected by filtration, and washed with
Et2O (20 ml) to give 17. Yield: 160 mg (71%) of dirty white solid; mp
222–225 ꢀC. [a]Dr.t. = +40.5 (c = 0.15, CHCl3). (C23H27BF4N2 requires: C,
66.04; H, 6.51; N, 6.70. Found C, 66.09; H, 6.72; N, 6.73.); EI-HRMS:
m/z = 331.2172 (M+); C23H27N2+ requires: m/z = 331.2169 (M+); nmax
(KBr) 3410, 2961, 1619, 1591, 1496, 1444, 1398, 1292, 1266, 1109, 1083,
1069, 1034, 762, 693 cmÀ1 1H-NMR (500 MHz, CDCl3): d 0.62 (s, Me);
.
0.80 (s, Me); 1.03 (s, Me); 1.30–1.37 (m, 1H of CH2); 1.38–1.44 (m, 1H
of CH2); 1.45–1.52 (m, H of CH2); 1.76–1.84 (m, 1H of CH2); 2.21 (d,
J = 4.8 Hz, H-C(4)); 5.02 (d, J = 10.9 Hz, CH); 5.05 (d, J = 10.9 Hz, CH);
7.16–7.21 (m, 1H of Ph); 7.23–7.27 (m, 1H of Ph); 7.31–7.39 (m, 6H of
Ph); 7.44–7.47 (m, 2H of Ph); 8.18 (s, CH). 13C-NMR (126 MHz, CDCl3):
d 12.8, 18.4, 23.2, 24.7, 33.6, 46.1, 49.1, 51.6, 70.0, 73.4, 120.1, 121.8,
128.4, 128.8, 130.2, 130.5, 134.7, 136.0, 154.2.
Single crystal X-ray structure analysis for compounds 4b,
4b′, 9a, 10a-HCl, 10b-HCl, 11, 12, 16, and 17
Single crystal diffraction data for compounds 4b, 4b′, 9a, 10a-HCl,
10b-HCl, 11, 12, 16, and 17 have been collected on a Nonius Kappa
CCD diffractometer (Bruker, Billerica, MA, USA) at room temperature
with MoKa radiation (0.71073 Å) and graphite monochromator using the
Nonius Collect Software.40 The data were processed using DENZO
software.41 Structures were solved with direct methods, using SIR97.42
A full-matrix least-squares refinement on F2 was employed with aniso-
tropic temperature displacement parameters for all non-hydrogen
atoms. H atoms bonded to N atoms were located using a difference
Fourier map. The remaining H atoms were placed at calculated posi-
tions and treated as riding, with C–H = 0.93, 0.98, 0.97, and 0.96 Å for
Csp2H, Csp3H, Csp3H2, and Csp3H3, respectively. SHELXL97 software43
was used for structure refinement and interpretation. Drawings of
Chirality DOI 10.1002/chir

SYNTHESIS OF NOVEL CAMPHOR-DERIVED AMINES
Scheme 2. Beckmann fragmentation of oxime 6.
Scheme 3. Synthesis of camphidine derivatives 10.
whereas rearrangement of 4b′ furnished 9b′ exclusively in
16% yield with retention of configuration. Ketones 4c/4c′
and 4d/4d′ failed to give detectable amounts of the
corresponding rearrangement products. Rearrangement of
4b into a mixture of 9b and 9b′ and of 4b′ exclusively into
9b′ clearly shows that the applied reaction conditions enable
epimerization48,49 at the chiral center bearing the arylmethyl
substituent, thus furnishing the thermodynamically more sta-
ble (less sterically hindered) endo-product (9b; e.g., 9a when
starting from 4a [d.e. = 32%]). In a complex reaction mixture,
no regioisomeric product of type D was detected and isolated, al-
though the tertiary carbon center (i.e., C(1)) has a preference
for the migration. Migration of C(1) frequently leads to Beck-
mann fragmentation products,50 which would explain the forma-
tion of a complex mixture of products. Finally, reduction of 9a
with LiAlH4 furnished the desired camphidine derivative 10a,
whereas reduction of 9b with BH3 Â THF furnished the
corresponding amine 10b. Reduction of 9b with LiAlH4 leads
Chirality DOI 10.1002/chir
Scheme 4. Rearrangement of isoborneol 5b.
attempted. Thus, upon treatment of 4a/4a′ with hydroxyl-
amine-O-sulfonic acid in AcOH at elevated temperature, the
endo-amide 9a was isolated in low yield (8%). Similarly,
ketone 4b yielded the corresponding rearrangement pro-
ducts as an inseparable mixture of the major endo-epimer
9b and minor exo-epimer 9b′ in 17% yield (9:9′ = 77:23),

GROŠELJ ET AL.
Scheme 5. Synthesis of NHC precursor 17.
to a mixture of amines because of a partial and unselective
the presence of NH4BF4 and catalytic amounts of formic acid
under microwave irradiation yielded the NHC precursor 17
in 71% yield. Attempts to cyclize the trans-diamine 16 failed
(Scheme 5).
hydrodefluorination of the CF3 group51,52 (Scheme 3).
Cyclic sec-amines 10a and 10b have been tested as cova-
lent organocatalysts in the Michael addition of 1-methylindole
to cinnamaldehyde53 and failed to give the expected product.
Interestingly, treatment of isoborneol 5b under conditions
used for the rearrangement of ketones 4/4′ (NH2OSO3H,
AcOH, elevated temperature) furnished two rearrangement
products, compounds 11 and 12 in 27% and 9%, respectively.
The letter was formed as a racemate ([a]rD.t. = 0, centrosym-
metric space group (P21/a) of the single crystal used for
X-ray analysis). Although mechanistic investigations of the
camphene sultone54,55 have been studied, we could, so far,
not explain the formation of the closely related sultone 12
(and of 11) (Scheme 4).
Structure Determination
The structures of novel compounds 3–12 and 15–17 were
determined by spectroscopic methods (IR, NMR spectros-
copy [1H-NMR and 13C-NMR, DEPT 90 and 135, COSY,
HSQC, HMBC, and NOESY experiments], and MS) and by
elemental analyses for C, H, and N. Compounds 4c, 4d, 6,
and 7 were characterized as mixtures of epimers. Com-
pounds 3c, 4c/4c′, 5c, 7/7′, 8, 10a, 10b, 15, and 16 were
not obtained in analytically pure form. Their identities were
confirmed by 13C-NMR and/or EI-HRMS.
Structures of compounds 4b, 4b′, 9a, 10a-HCl, 10b-HCl,
11, 12, 16, and 17 were determined by single crystal X-ray
analysis (Figs. 2–10).
The (2E)-configuration of oximes 6/6′ and 7/7′ was as-
cribed on the basis of the configuration of closely related
oximes.45 The (E)-configuration around the exocyclic C=C
bond in arylidene compounds 3c and 3d was determined
Finally, starting from (1S)-(+)-camphorquinone (13), fol-
lowing the literature procedure,56 camphordiimine 14 was
prepared. Reduction of 14 with NaCNBH3 afforded the major
trans-diamine 16 and the minor cis-diamine 15 in 54% and
40% yield, respectively. Cyclization of 15 with HC(OEt)3 in
Fig. 2. Ortep drawing of compound 4b.
Chirality DOI 10.1002/chir
Fig. 3. Ortep drawing of compound 4b′.

SYNTHESIS OF NOVEL CAMPHOR-DERIVED AMINES
Fig. 7. Ortep drawing of compound 11.
Fig. 4. Ortep drawing of compound 9a.
Fig. 8. Ortep drawing of compound 12.
Fig. 5. Ortep drawing of compound 10a-HCl.
Fig. 9. Ortep drawing of compound 16.
of the corresponding proton signals (if they do not overlap
Fig. 6. Ortep drawing of compound 10b-HCl.
on the basis of NOE between aromatic protons and H-C(4) in
the NOESY spectra. Similarly, the configuration(s) in position
(s) 2 and/or 3 and/or 4 of compounds 4b–d, 4b–d′, 5b,c, 9b,
10a,b-HCl, 11, 16, and 17 was/were determined on the ba-
sis of NOEs observed in the NOESY spectra between the
corresponding key proton signals (Fig. 11).
Alternatively, if NOESY measurements are not available,
the configuration at position 3 in camphor derivatives and at
position 4 in the corresponding ring expanded camphor deri-
vatives is easily determinable on the basis of the multiplicity
Fig. 10. Ortep drawing of compound 17.
Chirality DOI 10.1002/chir

GROŠELJ ET AL.
Fig. 11. Key NOEs observed in NOESY spectra of compounds 4b-d, 4b-d′, 5b,c, 9b, 10a,b-HCl, 11, 16, and 17 for the determination of configuration in
position 3 of camphor derivatives 6/6′ and 7/7′ based on the multiplicity of the corresponding protons.
with other signals). As has been demonstrated and rational-
ized previously, the proton signals with higher multiplicity
are positioned exo, whereas protons with lover multiplicity
are positioned endo, when comparing a pair of epimers; that
is, the exo-proton couples also with the adjacent bridgehead
proton and the exo-proton on the other side of the
bridge.46,57–59 For example, in the major exo-oxime 6 and
the corresponding OAc derivative 7, the endo-H proton
appears as a doublet of doublet at approximately 2.7 ppm,
whereas in the corresponding minor endo-epimers 6′ and 7′,
the corresponding exo-protons appear as multiplet at approxi-
mately 3.2 ppm (Fig. 11, bottom right).
the corresponding NHC precursors are the subject of further
studies.
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turned out to be the direct Beckmann rearrangement of
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SYNTHESIS OF NOVEL CAMPHOR-DERIVED AMINES
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Chirality DOI 10.1002/chir