Synthesis of enantiomerically pure cis- and trans-1,2- diaminoindanes

Article abstract of DOI:10.1016/S0957-4166(98)00330-9

The four isomers of cis- and trans-1,2-diaminoindanes 5 and 11 were prepared in three steps and high enantiomeric excess by a key lipase- catalyzed selective transesterification of racemic cis-2-azido-1-indanol and trans-1-azido-2-indanol, respectively.

Full text of DOI:10.1016/S0957-4166(98)00330-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 3263–3273
Synthesis of enantiomerically pure cis- and trans-1,2-
diaminoindanes
Christelle Bit, Anton A. Mitrochkine, Gérard Gil, Marcel Pierrot and Marius Réglier∗
Chimie, Biologie et Radicaux Libres, UMR-CNRS 6517, Universités d-Aix-Marseille 1 et 3, Faculté des Sciences et Techniques
de St. Jérôme, case 432, av. Escadrille Normandie-Niemen, F-13397 Marseille Cedex 20, France
Received 21 July 1998; accepted 11 August 1998
Abstract
The four isomers of cis- and trans-1,2-diaminoindanes 5 and 11 were prepared in three steps and high
enantiomeric excess by a key lipase-catalyzed selective transesterification of racemic cis-2-azido-1-indanol and
trans-1-azido-2-indanol, respectively. © 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
Recently, we reported on indano-[1,2-b]aziridine derivatives as mechanism-based inhibitors1 and 2-
aminoindanes as substrates2 of dopamine β-hydroxylase (DBH; EC 1.14.17.1),3 a copper-containing
monooxygenase which catalyses the transformation of dopamine into noradrenaline. In the course of
this study designed to investigate the topology of the DBH active site, the need for preparing useful
quantities of enantiomerically pure cis- and trans- 1,2-diaminoindanes 5 and 11 became apparent. Despite
the importance of this functionality, the synthesis of cis-1,2-diaminoindane 11 is only described in the
literature.4 A simple retrosynthetic analysis suggested that the target molecules 5 and 11 might be easily
accessible from azidoindanols 1 and 7, respectively, by an SN2 type substitution of the OH group by an
azido anion followed by reduction (Scheme 1).
2. Results and discussion
Using this strategy, the transformation of (ꢀ)-cis-2-azido-1-indanol 1 into (ꢀ)-trans-1,2-
diaminoindane 5 was realized in three steps as depicted in Scheme 2. Reaction of (ꢀ)-1 with
NaH in THF gave quantitatively the corresponding alcoholate which reacted in situ with tosylchloride
∗
Corresponding author. E-mail: marius.reglier@lbs.u-3mrs.fr
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00330-9

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Scheme 1. Retrosynthetic analysis for the synthesis of 1,2-diaminoindane compounds 5 and 11
to give tosylate derivative (ꢀ)-3. SN2 type substitution of the tosyl group with NaN3 in DMF afforded
(ꢀ)-trans-1,2-diazidoindane 4. Catalytic reduction with H2 in the presence of palladium on charcoal in
absolute ethanol gave (ꢀ)-trans-1,2-diaminoindane 5, quantitatively.
Scheme 2. Preparation of trans-1,2-diaminoindane 5 and its bis-imine derivative 6: (i) NaH in THF at rt, then TsCl; (ii) NaN3
in DMF at 60°C; (iii) H2, Pd/C in EtOH at rt; (iv) in EtOH at 70°C
Encouraged by the simplicity and the efficiency (61% in three steps) of this preparation, we decided
to apply this sequence to the synthesis of chiral trans-1,2-diaminoindanes 5. Recently, we described the
preparation of cis-2-azido-1-indanol 1 in both enantiomerically pure forms by enantioselective lipase

C. Bit et al. / Tetrahedron: Asymmetry 9 (1998) 3263–3273
3265
catalyzed transesterification.5,6 We found that lipase 237.87† was able to transform 75% of (ꢀ)-1 to
(1R,2S)-cis-1-acetoxy-2-azidoindane 2 with low enantiomeric excess (21% ee) after 4 days at room
temperature. On the contrary, the 25% of remaining (1S,2R)-cis-2-azido-1-indanol 1 showed an excellent
enantiomeric excess (95% ee, 99% after recrystallization in CCl4). Since it was not possible to obtain
(1R,2S)-cis-1-acetoxy-2-azidoindane 2 in higher enantiomeric excess than 20% with lipase 237.87, we
looked for more efficient lipases. We found that lipase Candida antarctica A catalyzed the transformation
of 66% of (ꢀ)-1 to (1S,2R)-2 with 35% ee, and the 34% of remaining (1R,2S)-1 was obtained with 93%
ee (99% after recrystallization in CCl4) (Scheme 3).
Scheme 3. Lipase catalyzed enzymatic resolution of (ꢀ)-cis-2-azido-1-indanol 1
By the same method used for racemic 1, optically active aminoindanols (1R,2S)-1 (93% ee) and
(1S,2R)-1 (95% ee) were converted into the trans-diazido compounds (1S,2S)-4 (90% ee), [α]25=+30.5
D
(c 0.1, CHCl3) and (1R,2R)-4 (90% ee), [α]25=−28 (c 0.3, CHCl3), respectively, without significant
D
loss of enantiomeric purity as determined by HPLC. Finally, hydrogenation led to the trans-diamino
compounds (1S,2S)-5, [α]25=+12.3 (c 3, CHCl3) and (1R,2R)-5, [α]25=−20.4 (c 0.7, CHCl3) in
D
D
quantitative yields. Determination of the enantiomeric excesses of diamines 5 is more problematic
because the two enantiomers were not resolved by HPLC. In order to determine their enantiomeric
excesses, we chose to derivatize compounds 5 into bis-imine compounds 6 by reaction with 2 equiv.
of 3,5-di-tert-butyl-2-hydroxy-benzaldehyde. After this operation, the two enantiomers (1S,2S)-6 (99%
ee), [α]25=+262.5 (c 0.7, CHCl3) and (1R,2R)-6 (99% ee), [α]25=−292.5 (c 0.5, CHCl3) can be
D
D
resolved by HPLC (Chiralcel column OD-H, Daicel; hexane:iPrOH=99.75:0.25), and the enantiomeric
excesses measured indicate that both diamino compounds (1S,2S)-5 and (1R,2R)-5 were obtained in high
enantiomeric purity. Another advantage of the derivatization into bis-imine derivatives is that compounds
6 are crystalline. Thus crystallization of (ꢀ)-6 in CH2Cl2/MeOH gave crystals suitable for an X-ray
analysis (Table 1).
As an alternative to the methodology above described, it was envisaged that the cis-1-amino-2-indanol
13 which is commercially available in both enantiomeric forms could serve as precursors for trans-1,2-
diaminoindane 5 via a three-step sequence involving the SN2 type substitution of the hydroxyl group by
the azido anion and a reduction step. In order to avoid the formation of the undesired N-Tos derivative
during the tosylation reaction, introduction of the tBoc amino protective group on (1S,2R)-13 was realized
by the classical method.7 With the protected substrate, O-tosylation using NaH and TsCl in THF at room
temperature afforded 13% of the expected tosylate (1S,2R)-15, in addition to 58% of the oxazolidinone
†
We thank Rohm GmbH company for the gift of this lipase.

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Table 1
Crystallographic data for compounds 6, 12 and 16
1
(1S,2R)-16. The structure of (1S,2R)-16 was established by H NMR and 13C NMR spectroscopy and
confirmed by X-ray analysis (Table 1). The formation of compound (1S,2R)-16 can be easily explained
by an intramolecular attack of alcoholate anion A to the tBoc group followed by the displacement of
tBuO− anion and tosylation of the N–H group of B. Finally, when performing the reaction at 0°C, tosylate
(1S,2R)-15 was obtained in 60% yield as the unique product. Substitution of tosyl group with NaN3 in

C. Bit et al. / Tetrahedron: Asymmetry 9 (1998) 3263–3273
3267
DMF followed by catalytic hydrogenation afforded (1S,2S)-5 which was transformed into the bis-imine
derivative (1S,2S)-6 99% ee. In the same way, optically active aminoindanol (1R,2S)-13 was converted
into (1R,2R)-5 and (1R,2R)-6 99% ee (Scheme 4).
Scheme 4. Alternative preparation of trans-1,2-diaminoindane 5: (i) (Boc)2O in MeOH at rt; (ii) NaH in THF; (iii) NaN3 in
DMF at 60°C; (iv) H2, Pd/C in EtOH at rt
cis-1,2-Diazidoindane 10 can be considered as a precursor of cis-1,2-diaminoindane 11. cis-1,2-
Diazidoindane 10 can be obtained from epoxyindane via the trans-1-azido-2-indanol 7 (NaN3).8 Thus,
when realizing the preparative kinetic resolution of (ꢀ)-trans-1-azido-2-indanol 7,8,9 we found that lipase
237.87 converts racemic trans-1-azido-2-indanol 7 to 44% of (1R,2R)-trans-2-acetoxy-1-azidoindane 8,
[α]25=−81.6 (c 46, CHCl3), lit.8 [α]25=−85.5 (c 1.5, CHCl3) with 97% ee. The remaining (1S,2S)-7,
D
D
[α]25=+74.2 (c 41, CHCl3), lit.8 [α]25=+64 (c 18, CHCl3) was obtained in 37% yield and 98% ee. The
D
D
corresponding trans alcohol (1R,2R)-7 (97% ee), [α]25=−60 (c 11, CHCl3) was obtained in high yields
D
by transesterification of the acetoxy group in (1R,2R)-8 with MeONa in MeOH (Scheme 5).
Transformations of 1-azido-2-indanols 7 to cis-1,2-diaminoindanes 11 were realized once more by
the three classical steps already used for the synthesis of compounds 5 (Scheme 6). Crystallization of
compound 12 in CH2Cl2 gave crystals suitable for an X-ray analysis (Table 1). Optically active cis-
azidoindanols (1S,2S)-7 (98% ee) and (1R,2R)-7 (97% ee) were converted into cis-diamino compounds
(1S,2R)-11, [α]25=−42.5 (c 0.8, CHCl3) and (1R,2S)-11, [α]25=+38.6 (c 1.2, CHCl3), respectively,
D
D
and their bis-imine derivatives (1S,2R)-12 (99% ee), [α]25=+45.9 (c 0.6, CHCl3) and (1R,2S)-12
D
(99% ee), [α]25=−45.1 (c 0.5, CHCl3) were separated by HPLC (Chiralcel column OD-H, Daicel;
D
hexane:iPrOH=95:5.

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Scheme 5. Lipase catalyzed enzymatic resolution of (ꢀ)-trans-1-azido-2-indanol 7
3. Conclusion
In summary, enantioselective lipase catalyzed transesterification of (ꢀ)-cis-2-azido-1-indanol 1 and
(ꢀ)-trans-1-azido-2-indanol 7 followed by simple chemical transformations (O-tosylation, stereospecific
azidation and hydrogenation) provides a simple and rapid access to the four isomers of cis- and trans-
1,2-diaminoindane 5 and 11 in good yields and very high enantiomeric excess.
4. Experimental
All the reagents were purchased from Sigma–Aldrich and used without purification. Lipase 237.87
was obtained from Rohm GmbH. Solvents were freshly distilled under Ar: MeOH/Mg, THF/sodium
benzophenone ketyl, DMF/CaH2 and CCl4/P2O5. Elemental analyses: CHN Technicon microanalyser.
1
NMR: Bruker AC-200 (200 MHz and 50.32 MHz, for H and 13C, respectively), CDCl3 as solvent and
TMS as internal standard. HPLC: Chiralcel OD-H column (250×4.6 mm), 20°C, UV detection at 214

C. Bit et al. / Tetrahedron: Asymmetry 9 (1998) 3263–3273
3269
Scheme 6. Preparation of cis-1,2-diaminoindane 7 and its bis-imine derivative 12: (i) NaH in THF at rt, then TsCl; (ii) NaN3 in
DMF at 60°C; (iii) H2, Pd/C in EtOH at rt; (iv) in EtOH at 70°C
nm. Each enantiomer was identified by spiking with an authentic sample. Specific rotation: Perkin–Elmer
341, concentrations c are given in g 100 mL−1
.
4.1. cis-2-Azido-1-tosyloxyindane 3
A solution of 1 (2 g, 11.4 mmol) in anhydrous THF (10 mL) was slowly added to NaH/THF suspension
(300 mg, 12.5 mmol in 30 mL) placed under Ar and maintained at rt. The mixture was stirred for 30 min
and TsCl (500 mg, 2.5 mmol) in anhydrous THF (10 mL) was slowly added. The mixture was stirred at
rt for 3 h, washed with brine and water and dried over Na2SO4. Evaporation of the solvent under reduced
pressure and flash chromatography (SiO2, CH2Cl2) gave 3 (2.8 g, 75%). 1H NMR, δ: 7.90 (d, J 8.2 Hz;
2H), 7.50–7.10 (m; 6H), 5.85 (d, J 5.2 Hz; 1H), 4.10 (dt, J 6.7 and 5.2 Hz; 1H), 3.15 (m; 2H), 2.50
(s; 3H). 13C NMR, δ: 145.1 (C), 140.1 (C), 136.1 (C), 133.7 (C), 130.0 (CH), 129.8 (CH), 127.7 (CH),
127.6 (CH), 125.8 (CH), 125.0 (CH), 83.1 (CH), 62.2 (CH), 34.8 (CH2), 21.6 (CH3).
4.2. trans-1,2-Diazidoindane 4
A solution of 3 (460 mg, 1.4 mmol) in DMF (20 mL) was treated with NaN3 (100 mg, 1.5 mmol) at
60°C for 3 h. The mixture was then cooled to room temperature, diluted with water (40 mL) and extracted
with CH2Cl2 (4×20 mL). The combined extracts were washed with brine and dried over Na2SO4.
Concentration under reduced pressure followed by flash chromatography (SiO2, pentane:Et2O=1:1) gave
4 (230 mg, 82%). C9H8N6 (200.08): calcd C 53.98, H 4.03, N 41.99; found: C 54.36, H 4.12, N 41.35.

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1H NMR, δ: 7.50–7.10 (m; 4H), 4.80 (d, J 5.5 Hz; 1H), 4.15 (ddd, J 7.6, 6.6 and 5.5 Hz; 1H), 3.35
(dd, J 16.3 and 7.6 Hz; 1H), 2.95 (dd, J 16.3 and 6.6 Hz; 1H). 13C NMR, δ: 140.0 (C), 139 (C), 129.4
(CH), 127.6 (CH), 125.0 (CH), 124.4 (CH), 70.1 (CH), 67.5 (CH), 36 (CH2). HPLC: hexane:isopropanol
(99.75:0.25), 1 mL/min; retention time: 7 min for (1S,2S)-4 and 16 min for (1R,2R)-4.
4.3. trans-1,2-Diaminoindane 5
A solution of 4 (500 mg, 2.5 mmol) in absolute EtOH (40 mL) was hydrogenated with H2 in the
presence of 10% Pd/C (50 mg) at rt for 12 h. The mixture was centrifuged and concentrated under
reduced pressure to give 5 (370 mg, 99%) as the crude product. 1H NMR, δ: 7.40–7.20 (m; 4H), 3.75 (d,
J 7.2 Hz; 1H), 3.20 (m; 2H), 2.60 (dd, J 13 and 6.5 Hz; 1H), 1.80 (br. s; 4H). 13C NMR, δ: 144.6 (C),
139.5 (C), 127.2 (CH), 126.5 (CH), 124.2 (CH), 122.8 (CH), 64.3 (CH), 63.4 (CH), 38.8 (CH2).
4.4. trans-[N,N0-Di(3,5-di-tert-butyl-2-hydroxy-benzylideneamino)-indane] 6
3,5-di-tert-Butyl-2-hydroxy-benzaldehyde (0.47 g, 2 mmol) was added as a solid to a solution of 5
(0.2 g, 1 mmol) in absolute EtOH (10 mL). The mixture was heated to reflux for 1 h and then water was
added (3 mL). The resulting yellow solid was collected by filtration to give 6 (0.55 g, 95%). C39H52N2O2
(580.4): calcd C 80.63, H 9.03, N 4.83; found C 79.39, H 8.50, N 4.18. 1H NMR, δ: 13.55 (s; 1H), 13.50
(s; 1H), 8.50 (s; 1H), 8.45 (s; 1H), 7.40–7.00 (m; 8H), 4.90 (d, J 7.3 Hz; 1H), 4.30 (dt, J 8.6 and 7.3
Hz; 1H), 3.35 (d, J 8.6 Hz; 2H), 1.45 (s; 9H), 1.25 (s; 9H). 13C NMR, δ 168.0 (CH), 167.2 (CH), 158.1
(C), 142.2 (C), 140.4 (C), 140.3 (C), 136.7 (C), 128.3 (CH), 127.9 (CH), 127.3 (CH), 127.2 (CH), 126.6
(CH), 126.5 (CH), 124.8 (CH), 124.2 (CH), 117.8 (C), 79.7 (CH), 78.0 (CH), 39.1 (CH2), 35.1 (C), 34.2
(C), 31.5 (CH3), 29.5 (CH3). HPLC: hexane:isopropanol (99.75:0.25), 1 mL/min; retention time: 2.9 min
for (1S,2S)-6 and 3.7 min for (1R,2R)-6.
4.5. Lipase catalyzed transesterification of (ꢀ)-trans-1-azido-2-indanol 7
A suspension of (ꢀ)-7 (4.28 g, 24 mmol), vinyl acetate (11 g, 123 mmol) and lipase 237.87 (1.73
g) in hexane:ether (120:80 mL) was stirred at 40°C for 3 h. The suspension was filtered and dried over
Na2SO4. Concentration under reduced pressure followed by flash chromatography (SiO2, CH2Cl2) gave
(1R,2R)-8 (2.33 g, 44%, 97% ee) and (1S,2S)-7 (1.59 g, 37%, 98% ee).
(+)-(1S,2S)-trans-1-Azido-2-indanol (1S,2S)-7: Clear yellow oil. [α]25=+74.2 (c 41, CHCl3).
D
1
C9H9N3O (175.07): calcd C 61.69, H 5.18, N 23.0; found C 60.58, H 5.12, N 23.96. H NMR, δ:
7.40–7.10 (m; 4H), 4.65 (d, J 5.1 Hz; 1H), 4.45 (ddd, J 6.6, 5.8 and 5.1 Hz; 1H), 3.25 (dd, J 16.2
and 6.6 Hz; 1H), 2.86 (dd, J 16.2 and 5.8 Hz; 1H), 2.08 (br. s; 1H). 13C NMR, δ: 139.8 (C), 137.9
(C), 129.2 (CH), 127.5 (CH), 125.4 (CH), 124.7 (CH), 78.7 (CH), 71.9 (CH), 39.0 (CH2). HPLC:
hexane:isopropanol (98:2), 1 mL/min; retention time: 19 min for (1S,2S)-7 and 24 min for (1R,2R)-7.
(−)-(1R,2R)-trans-1-Azido-2-acetoxyindane (1R,2R)-8: Clear yellow oil. [α]25=−81.6 (c 46, CHCl3).
D
1
C11H11N3O2 (217.08): calcd C 60.81, H 5.11, N 19.35; found C 60.69, H 5.06, N 20.12. H NMR, δ:
7.40–7.10 (m; 4H), 5.32 (ddd, J 6.9, 4.6 and 4.1 Hz; 1H), 4.85 (d, J 4.1 Hz; 1H), 3.50 (dd, J 16.8 and 6.9
Hz; 1H), 2.85 (dd, J 16.8 and 4.8 Hz; 1H), 2.05 (s; 3H). 13C NMR, δ: 170.7 (C), 139.8 (C), 137.4 (C),
129.4 (CH), 127.5 (CH), 125.2 (CH), 124.7 (CH), 79.4 (CH), 69.4 (CH), 36.8 (CH2), 21.0 (CH3). HPLC:
hexane:isopropanol (98:2), 1 mL/min; retention times: 5 min for (1S,2S)-8 and 7 min for (1R,2R)-8.

C. Bit et al. / Tetrahedron: Asymmetry 9 (1998) 3263–3273
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4.6. (−)-(1R,2R)-trans-1-Azido-2-indanol (1R,2R)-7
A mixture of (1R,2R)-8 (0.3 g, 1.4 mmol) and MeONa (0.11 g, 1.7 mmol) in MeOH (10 mL) was
stirred for 30 min. The solution was filtered and washed with brine. The product was then dried with
Na2SO4 and the solvent was removed in vacuo. (1R,2R)-7 (0.245 g, 100%, 99% ee) was isolated as a
yellow oil.
4.7. trans-1-Azido-2-tosyloxyindane 9
Under the same conditions used for the preparation 3, treatment of compound 7 (175 mg, 1 mmol)
with NaH (30 mg, 1.2 mmol) and TsCl (210 mg, 1.1 mmol) in THF (10 mL) gave compound 9 (193
mg, 60%) which was used without further purification. C16H15O3N3S (329.08): calcd C 58.34, H 4.59,
1
N 12.77; found C 57.17, H 4.73, N 13.04. H NMR, δ: 7.85 (d, J 8.2 Hz; 2H), 7.40 (d, J 8.6 Hz; 2H),
7.30–7.10 (m; 4H), 4.90 (m; 2H), 3.35 (dd, J 15.9 and 6.5 Hz; 1H), 3.05 (dd, J 15.9 and 5.1 Hz; 1H),
2.50 (s; 3H). 13C NMR, δ: 145.4 (C), 138.6 (C), 136.6 (C), 133.2 (C), 130.1 (CH), 128.0 (CH), 129.7
(CH), 127.8 (CH), 125.3 (CH), 124.6 (CH), 85.3 (CH), 69.4 (CH), 36.9 (CH2), 21.6 (CH3).
4.8. cis-1,2-Diazidoindane 10
Under the same conditions used for the preparation of 4, treatment of 9 (330 mg, 1 mmol) in DMF
(15 mL) with NaN3 (70 mg, 1.1 mmol) at 60°C for 3 h gave 10 (106 mg, 53%). C9H8N6 (200.08):
1
calcd C 53.98, H 4.03, N 41.99; found C 53.93, H 3.78, N 42.31. H NMR, δ: 7.40–7.10 (m; 4H),
4.80 (t, J 5.5 Hz; 1H), 4.25 (dt, J 6.5 and 5.5 Hz; 1H), 3.15 (d, J 6.5 Hz; 2H). 13C NMR, δ: 139.5
(C), 137.3 (C), 129.5 (CH), 127.5 (CH), 125.2 (CH), 124.7 (CH), 66.8 (CH), 63.9 (CH), 35.4 (CH2).
HPLC: hexane:isopropanol (99.75:0.25), 1 mL/min; retention time: 14 min for (1S,2R)-10 and 31 min
for (1R,2S)-10.
4.9. cis-1,2-Diaminoindane 11
Under the same conditions used for the preparation of 5, hydrogenation of 10 (0.5 g, 2.5 mmol) in
1
MeOH (40 mL) gave 11 (370 mg, 99%). H NMR, δ: 7.60–7.10 (m; 4H), 4.23 (d, J 5.5 Hz; 1H), 3.73
(ddd, J 16.2, 5.5 and 4.1 Hz; 1H), 3.11 (dd J 15.8 and 6.2 Hz; 1H), 2.75 (dd J 15.8 and 4.1 Hz; 1H), 1.80
(br. s; 4H). 13C NMR, δ: 144.6 (C), 140.4 (C), 127.2 (CH), 126.5 (CH), 124.2 (CH), 122.8 (CH), 64.3
(CH), 63.4 (CH), 38.8 (CH2).
4.10. cis-[N,N0-Di(3,5-di-tert-butyl-2-hydroxy-benzylideneamino)-indane] 12
Under the same conditions used for the preparation of 6, diamine 11 (0.2 g, 1.3 mmol) was transformed
into 12 (0.5 g, 90%). C39H52N2O2 (580.40): calcd C 80.63, H 9.03, N 4.83; found C 80.06, H 9.20, N
4.84. 1H NMR, δ: 13.45 (s; 1H), 13.3 (s; 1H), 8.45 (s; 1H), 8.4 (s; 1H), 7.0–7.5 (m; 8H), 4.95 (d, J 5.9
Hz; 1H), 4.4 (ddd, J 5.9, 6.8 and 6.6 Hz; 1H), 3.4 (dd, J 15.6 and 6.6 Hz; 1H), 3.25 (dd, J 15.6 and 6.8
Hz; 1H), 1.35 (s; 9H), 1.25 (s; 9H). 13C NMR, δ: 166.1 (CH), 165.9 (CH), 158.2 (C), 141.8 (C), 141.4
(C), 139.6 (C), 136.7 (C), 128.5 (CH), 127.0 (CH), 126.0 (CH), 125.8 (CH), 125.2 (CH), 124.9 (CH),
(CH) 117.7 (C), 76.2 (CH), 73.3 (CH), 38.6 (CH2), 34.9 (C), 34.0 (C), 31.5 (CH3), 29.3 (CH3). HPLC:
hexane:isopropanol (95:5), 1 mL/min; retention time: 3.4 min for (1S,2R)-12 and 4.3 min for (1R,2S)-12.

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4.11. cis-1-(tert-Butoxycarbonylamino)-2-indanol 14
A mixture of 13 (0.15 g, 1 mmol) and (Boc)2O (0.3 g, 1.4 mmol) in MeOH (30 mL) was stirred for 1
h at reflux and 1 h at rt. Concentration under reduced pressure followed by flash chromatography (SiO2,
1
CH2Cl2:MeOH=90:10) gave 14 (200 mg, 98%) as a white solid. H NMR, δ: 7.20–7.00 (m; 4H), 5.20
(d, J 5.2 Hz; 1H), 4.90 (dd, J 5.1 and 5.2 Hz; 1H), 4.45 (tdd, J 5.1, 4.8 and 2 Hz; 1H), 3.00 (dd, J 16.5
and 4.8 Hz; 1H), 2.80 (dd, J 2 and 16.5 Hz; 1H), 2.65 (d, J 5.1 Hz; NH), 1.40 (s; 9H).
4.12. cis-1-(tert-Butoxycarbonylamino)-2-tosyloxy-indane 15
Under the same conditions used for the preparation of 3, treatment of 14 (300 mg, 1.2 mmol)
with NaH (30 mg, 1.3 mmol) and TsCl (340 mg, 1.8 mmol) in THF (20 mL) gave a mixture of
compounds 15 (60 mg, 13%) and 16 (230 mg, 58%) which were separated by flash chromatography
(SiO2, CH2Cl2:MeOH=90:10).
cis-1-(tert-Butoxycarbonylamino)-2-tosyloxy-indane 15. 1H NMR, δ: 7.80 (d, J 8.2 Hz; 2H),
7.10–7.40 (m; 6H), 5.20–5.30 (m; 2H), 5.00 (d, J 9.3 Hz; NH), 3.08 (bs; 2H), 2.40 (s; 3H), 1.4 (s; 9H).
13C NMR, δ: 155.7 (C_O), 145 (C), 139 (C), 138.1 (C), 133.7 (C), 130.0 (CH), 128.5 (CH), 127.9
(CH), 127.4 (CH), 125.1 (CH), 123.6 (CH), 83.7 (CH), 57.6 (CH), 37.5 (CH2), 29.7 (C), 29.4 (3 CH3),
21.7 (CH3).
1
N-Tosyl-indano[1,2-d]oxazolidin-2-one 16. H NMR, δ: 7.90 (d, J 8.2 Hz; 2H), 7.40–7.20 (m; 6H),
5.90 (d, J 7.2 Hz; 1H), 5.28 (ddd, J 7.2, 4.9 and 2.7 Hz; 1H), 3.30 (m; 2H), 2.41 (s; 3H). 13C NMR,
δ: 151.7 (C_O), 145.5 (C), 139.6 (C), 137.6 (C), 135 (C), 130.26 (CH), 129.7 (CH), 128.5 (CH), 128.2
(CH), 127.1 (CH), 125.4 (CH), 78.9 (CH), 65.2 (CH), 38 (CH), 21.7 (CH3).
4.13. trans-2-Azido-1-(tert-butoxycarbonylamino)-indane 17
Under the same conditions used for the preparation of 4, treatment of 15 (100 mg, 0.25 mmol) in DMF
1
(5 mL) with NaN3 (20 mg, 0.28 mmol) at 60°C for 3 h gave 17 (50 mg, 72%). H NMR, δ: 7.40–7.10
(m; 4H), 5.10 (t, J 7.2 Hz; 1H), 4.75 (d, J 7.2 Hz; NH), 4.00 (dt, J 7.5 and 7.2 Hz; 1H), 3.25 (dd, J 15.9
and 7.5 Hz; 1H), 2.85 (dd, J 15.9 and 7.2 Hz; 1H), 1.40 (s; 9H). 13C NMR, δ: 162.5 (C_O), 141.5 (C),
137.6 (C), 129.6 (CH), 127 (CH), 126.8 (CH), 125.1 (CH), 78.8 (CH), 65.1 (CH), 38 (CH2), 31.1 (C),
28.3 (3CH3).
4.14. X-Ray structure analysis
Crystals of suitable quality and size were obtained by slow evaporation of CH2Cl2/MeOH 6 and 12
and CH2Cl2/Et2O 16 solutions, mounted on a glass fibre and used for measurements. For compounds
6 and 12, the data were measured at room temperature on an Enraf–Nonius CAD4 diffractometer [Mo-
Kα radiation, λ(Mo-Kα)=0.71073 Å]. During data collection, three standard reflections were measured
periodically as a general check of crystal and instrument stability. The data reduction was performed
with Begin in SDP-Plus.10 The structures were solved by direct methods with MULTAN8011 and were
refined with LSFM-Plus. The scattering factors were taken from the International Tables for X-Ray
Crystallography.12 For compound 16, the data were measured at room temperature on an Enraf–Nonius
Kappa CCD diffractometer [Mo-Kα radiation, λ(Mo-Kα)=0.71073 Å] and a 180° φ scan was performed
with 2° steps. The structure was solved by direct methods using SIR.13 All non-hydrogen atoms were

C. Bit et al. / Tetrahedron: Asymmetry 9 (1998) 3263–3273
3273
refined anisotropically with Maxus14 through cycles of full-matrix least squares. Hydrogen atoms were
introduced at idealized positions, included in the calculations but not refined.
Acknowledgements
We are grateful to Drs. Shroot and Charpentier (CIRD Galderma), C.N.R.S. and Provence-Alpes-Côte
d’Azur country for the scholarship to one of us (C.B.).
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