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D. Basavaiah et al. / Tetrahedron: Asymmetry 18 (2007) 963–967
as it clearly indicates that enantioselectivities are better at
higher temperature (110 ꢁC) than at room temperature
probably due to better coordination of borane and ketone
with the catalyst at high temperature than at room temper-
ature. This result is, in fact, consistent with our earlier
result with a chiral guanidine, that is, (5S)-1,3-diaza-2-
imino-3-phenylbicyclo(3.3.0)octane 1.9
1H), 4.48 (dd, 1H, J = 5.6 Hz and 10.4 Hz), 5.12 (br s,
1H), 7.21–7.37 (m, 8H), 7.45–7.51 (m, 2H); 13C NMR
(50 MHz/CDCl3): d 25.35, 28.82, 48.52, 70.93, 87.26,
125.66, 126.07, 127.48, 128.06, 128.13, 128.40, 140.70,
143.61, 163.89; LC–MS (m/z): 279 (M+H)+; Anal. Calcd
for C18H18N2O: C, 77.67; H, 6.52; N, 10.06. Found: C,
77.89; H, 6.53; N, 10.05. Crystal data: Empirical formula,
C18H18N2O; formula weight, 278.34; colorless, rectangular
crystal; crystal dimensions, 0.35 · 0.30 · 0.28 mm3; ortho-
Since the level of reversal of stereoselectivity exhibited
by catalyst/catalytic source 2 at room temperature in
the borane-mediated reduction of phenacyl bromide 3a is
not impressive, we did not make any attempt towards
understanding the nature of catalyst generated in situ by
the reaction of 2 with BH3ÆSMe2 in refluxing toluene.
˚
rhombic, lattice type, primitive; a = 8.5608(5) A,
˚
˚
b = 10.1884(6) A, c = 16.9703(10) A; a = 90.00; b = 90.00;
3
˚
c = 90.00; V = 1480.16(15) A ; space group, P212121
(International Table No. 19); Z = 4; Dcalcd = 1.249 g/cm3;
˚
F0 0 0 = 592; k(MoKa) = 0.71073 A; R(I P 2r1) = 0.0549;
wR2 = 0.1275. Detailed X-ray crystallographic data is
available from the Cambridge Crystallographic Data Cen-
tre, 12 Union Road, Cambridge CB2 1EZ, UK (CCDC
No. 635393).
3. Conclusion
We have developed a novel chiral catalytic source (5S)-1-
aza-2-imino-3-oxa-4,4-diphenylbicyclo(3.3.0)octane 2, con-
taining an N–(C@NH)–O moiety for the borane-mediated
asymmetric reduction of prochiral ketones, which provides
the corresponding secondary alcohols with up to 93%
enantiomeric purity. Although this chiral source 2 provides
inferior (negligible) enantioselectivities at room tempera-
ture when compared to our earlier catalyst, chiral guani-
dine 1,9 with respect to the reversal of stereoselectivity, it
does give clear indication that an appropriate chiral cata-
lytic source containing the N–(C@NH)–O moiety might
provide high levels of temperature dependant stereodirec-
tionality thus leading to the production of both the enantio-
mers in high enantioselectivities in the borane-mediated
reduction of prochiral ketones. Work is currently in
progress towards the development of such a suitable chiral
catalytic source.
4.2. Asymmetric reduction of phenacyl bromide 3a: synthesis
of (S)-2-bromo-1-phenylethanol 4a: representative procedure
To a stirred solution of (5S)-1-aza-2-imino-3-oxa-4,4-di-
phenylbicyclo(3.3.0)octane 2 (0.02 mM, 0.4 mL, 0.05 M
solution in toluene) in toluene (4 mL) was added BH3ÆSMe2
(1 mM, 1 mL, 1 M solution in toluene) at room tempera-
ture and the reaction mixture heated at reflux for 15 min.
A solution of phenacyl bromide 3a (1 mM, 199 mg), in tolu-
ene (2 mL), was added slowly drop-wise and heated at
reflux for a further 15 min. The reaction mixture was
cooled to room temperature and quenched with MeOH.
The solvent was removed under a reduced pressure and
the residue thus obtained, purified by column chromato-
graphy (silica gel, 5% ethyl acetate in hexanes) to provide
the desired (S)-2-bromo-1-phenylethanol 4a in 85%
(171 mg) yield as a colorless oil.
4. Experimental
All alcohols 4a–j are known in the literature.12–20 In fact,
we have also prepared alcohols 4a–i and reported their
spectral data.12,13,15 The present spectral data (IR, 1H
and 13C NMR) of 4a–i are in agreement with the earlier
4.1. Synthesis of (5S)-1-aza-2-imino-3-oxa-4,4-diphenyl-
bicyclo(3.3.0)octane 2
1
This molecule was prepared following the literature proce-
dure for the preparation of guanidines via the reaction of
diamines with cyanogen bromide, with some modifica-
tion.21 To a stirred solution of (S)-2-(diphenylhydroxy-
methyl)pyrrolidine (8 mM, 2.02 g) in EtOH (18 mL) was
carefully added a solution of cyanogen bromide (16 mM,
1.694 g) in EtOH (2 mL) at 0 ꢁC. After stirring the reaction
mixture for 12 h at room temperature, it was heated at
100 ꢁC (about 2 h) to completely remove the boiling sol-
vents. The residue thus obtained was diluted with EtOH
(16 mL) and 1 M NaOH (16 mL) and was extracted with
CH2Cl2 (3 · 30 mL). The combined organic layer was dried
over anhydrous Na2SO4. The solvent was removed under
reduced pressure and the residue thus obtained, crystallized
(hexanes–EtOAc = 9:1) to provide the desired (5S)-1-aza-
data. The spectral data (IR, H and 13C NMR) of 4j is
reported in the literature20 and our data is in agreement
with the reported data.
Acknowledgments
We thank the CSIR (New Delhi) for funding this project.
We thank UGC (New Delhi) for recognizing our
University of Hyderabad as ‘University with Potential
for Excellence (UPE)’ and also recognizing the School
of Chemistry as a ‘Center for Advanced Studies in Chem-
istry’ and providing some instrumental facilities. K.V.R.
and B.S.R. thank the CSIR (New Delhi) for their research
fellowships. We also thank the National Single Crystal
X-ray Facility in our School of Chemistry funded by
the DST (New Delhi). We thank Professor Samudranil
Pal for helpful discussions regarding the X-ray crystal
structure.
2-imino-3-oxa-4,4-diphenylbicyclo(3.3.0)octane 2 in 70%
25
(1.56 g) yield. MP: 94–96 ꢁC; ½aꢀD ¼ ꢁ221:9 (c 1.14,
CHCl3); IR (KBr): 3341, 1676 cmꢁ1
;
1H NMR
(400 MHz/CDCl3): d 1.04–1.16 (m, 1H), 1.58–1.69 (m,
1H), 1.74–1.96 (m, 2H), 3.23–3.34 (m, 1H), 3.57–3.68 (m,
Basavaiah, Deevi
