Evaluation of (+)-sparteine-like diamines for asymmetric synthesis

Article abstract of DOI:10.1021/jo049182w

Three new (+)-sparteine-like diamines were prepared from (-)-cytisine and evaluated as sparteine surrogates in the α-lithiation rearrangement of cyclooctene oxide and the palladium(II)/diamine catalyzed oxidative kinetic resolution of 1-indanol. The new diamines exhibited opposite enantioselectivity to that observed with (-)-sparteine but increasing the steric hindrance of the N-alkyl group beyond N-Et had a detrimental effect on enantioselectivity. The optimal N-Me diamine was evaluated with much success in five other (-)-sparteine-mediated processes involving different metals (lithium, magnesium, and copper) and different types of reaction mechanisms.

Full text of DOI:10.1021/jo049182w

cinnamyl alcohol;8 (ii) desymmetrization of a meso
anhydride using phenylmagnesium chloride;9 (iii) asym-
metric substitution of N-pivaloyl-o-ethylaniline;10 (iv)
dynamic resolution of tert-butylphenylphosphine-bo-
rane,11 and (v) copper(II)-mediated resolution of BINOL.12
This study includes a variety of metals (lithium, mag-
nesium, and copper) and, importantly, a range of different
reaction mechanisms (i.e. not simply asymmetric depro-
tonation). Herein we describe the results of these studies.
Eva lu a tion of (+)-Sp a r tein e-lik e Dia m in es
for Asym m etr ic Syn th esis
Michael J . Dearden, Matthew J . McGrath, and
Peter O’Brien*
Department of Chemistry, University of York,
Heslington, York YO10 5DD, United Kingdom
paob1@york.ac.uk
Received May 14, 2004
Abstr a ct: Three new (+)-sparteine-like diamines were
prepared from (-)-cytisine and evaluated as sparteine
surrogates in the R-lithiation rearrangement of cyclooctene
oxide and the palladium(II)/diamine catalyzed oxidative
kinetic resolution of 1-indanol. The new diamines exhibit-
ed opposite enantioselectivity to that observed with
(-)-sparteine but increasing the steric hindrance of the
N-alkyl group beyond N-Et had a detrimental effect on
enantioselectivity. The optimal N-Me diamine was evaluated
with much success in five other (-)-sparteine-mediated
processes involving different metals (lithium, magnesium,
and copper) and different types of reaction mechanisms.
Our previously described route to diamine 1 from
extracted3 (-)-cytisine was easily modified for the prepa-
ration of diamines 2a -c (Scheme 1). Standard acylation
of (-)-cytisine with aqueous sodium hydroxide and the
appropriate acid chloride furnished N-acylated cytisines
3a -c in 65-84% yield. Then, pyridone hydrogenation
gave crude lactams 4a -c (isolated but not purified) which
were directly subjected to reduction with excess lithium
aluminum hydride in refluxing THF to give diamines
2a -c. After purification by Kugelrohr distillation, di-
amines 2a -c were isolated as colorless oils in 81-89%
As part of our ongoing program of research into the
development of new sparteine-like ligands for asymmetric
synthesis, we recently described the synthesis of diamine
1 and its evaluation as a (+)-sparteine surrogate.1,2
Diamine 1 can be readily prepared in three steps from
(-)-cytisine (extracted from Laburnum anagyroides seeds3)
and was shown to have good “(+)-sparteine-like” proper-
ties: essentially equal and opposite enantioselectivity
was achieved with (-)-sparteine and diamine 1 in four
different test reactions.1 With these initial results in
hand, we wanted to determine whether the N-Me sub-
stituent in diamine 1 was optimal for high enantioselec-
tivity. Thus, three new diamines 2a -c with N-alkyl
groups of different steric demands (N-Et, N-nBu and
1
yield over the two steps. As far as can be judged by H
NMR spectroscopy, diamines 2a -c (and lactams 4a -c,
isolated and characterized in separate experiments) were
obtained as single diastereoisomers and we have assigned
their relative stereochemistry to be that shown in Scheme
1 based on preferential pyridone hydrogenation on the
less hindered exo face of 3a -c and by analogy with the
synthesis of diamine 1 (the stereochemistry of which was
secured by X-ray crystallography of an intermediate
lactam2).
Over the past few years, the Hodgson group have
extensively studied enantioselective epoxide desymme-
trization using alkyllithiums/diamines (e.g. (-)-sparteine)
and they have reported several pioneering contribu-
tions.5,13-16 For the R-lithiation -rearrangement of medium-
ring cycloalkene oxides with alkyllithiums,5,15 the opti-
mized reaction conditions (85:15-95:5 er) are 2.4 equiv
t
N-CH2 Bu) were synthesized and have been evaluated in
comparison with diamine 1 and (-)-sparteine in the
R-lithiation rearrangement of cyclooctene oxide5 and the
palladium(II)/diamine catalyzed oxidative kinetic resolu-
tion of 1-indanol.6,7 Recently, Kann et al. have reported
a comparison between (-)-sparteine, diamine 1, and a
N-iPr-substituted analogue of 1 in the asymmetric lithia-
tion of phosphine-borane complexes.4 Furthermore, we
have also evaluated the efficacy of diamine 1 as a (+)-
sparteine surrogate in a wider range of (-)-sparteine-
mediated asymmetric reactions: (i) carbolithiation of (E)-
(1) Dearden, M. J .; Firkin, C. R.; Hermet, J .-P. R.; O’Brien, P. J .
Am. Chem. Soc. 2002, 124, 11870.
(2) Hermet, J .-P. R.; Porter, D. W.; Dearden, M. J .; Harrison, J . R.;
Koplin, T.; O’Brien, P.; Parmene, J .; Tyurin, V.; Whitwood, A. C.;
Gilday, J .; Smith, N. M. Org. Biomol. Chem. 2003, 1, 3977.
(3) Marrie`re, D. E.; Rouden, J .; Tadino, V.; Lasne, M.-C. Org. Lett.
2000, 2, 1121.
(4) J ohansson, M.; Schwartz, L. O.; Amedjkouh, M.; Kann, N. C.
Eur. J . Org. Chem. 2004, 1894.
(5) Hodgson, D. M.; Lee, G. P.; Marriott, R. E.; Thompson, A. J .;
Wisedale, R.; Witherington, J . J . Chem. Soc., Perkin Trans. 1 1998,
2151.
(6) J ensen, D. R.; Pugsley, J . S.; Sigman, M. S. J . Am. Chem. Soc.
2001, 123, 7475.
(8) Norsikian, S.; Marek, I.; Klein, S.; Poisson, J .-F.; Normant, J .
F. Chem. Eur. J . 1999, 5, 2055.
(9) Shintani, R.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 1057.
(10) (a) Basu, A.; Beak, P. J . Am. Chem. Soc. 1996, 118, 1575. (b)
Basu, A.; Gallagher, D. J .; Beak, P. J . Org. Chem. 1996, 61, 5718. (c)
Thayumanavan, S.; Basu, A.; Beak, P. J . Am. Chem. Soc. 1997, 119,
8209.
(11) Wolfe, B.; Livinghouse, T. J . Am. Chem. Soc. 1998, 120, 5116.
See also: Williams, B. S.; Dani, P.; Lutz, M.; Spek, A. L.; van Koten,
G. Helv. Chim. Acta 2001, 84, 3519.
(12) Zhang, Y.; Yeung, S.-M.; Wu, H.; Heller, D. P.; Wu, C.; Wulff,
W. D. Org. Lett. 2003, 5, 1813.
(7) Ferraira, E. M.; Stolz, B. M. J . Am. Chem. Soc. 2001, 123, 7725.
10.1021/jo049182w CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/29/2004
J . Org. Chem. 2004, 69, 5789-5792
5789

SCHEME 1. Syn th esis of Dia m in es 2a -c fr om
(-)-Cytisin e
at -78 °C for 5 h followed by warming to room temper-
ature, cyclooctene oxide 5 gave bicyclic alcohol (-)-6 in
84% yield and with 83:17 er (entry 1), virtually identical
with that reported by Hodgson et al. (81% yield, 85:15
er5) under comparable conditions. When the reactions
were carried out with diamines 1 and 2a -c (entries 2-5),
bicyclic alcohol (+)-6 was the major product (opposite
enantioselectivity to (-)-sparteine) and enantioselectivity
comparable to that obtained with (-)-sparteine (entry 1)
was observed with diamines 1 (81:19 er) and 2a (82:18
er) (entries 2 and 3), i.e., ligands that have the least
sterically demanding N-alkyl substituents. In contrast,
as the steric size of the N-alkyl group increased, the
enantioselectivity was compromised (entries 4-5): di-
amine 2c with the most sterically hindered N-alkyl group
t
(N-CH2 Bu) gave bicyclic alcohol (+)-6 in 53% yield and
with 66:34 er (entry 5). From this, we conclude that
sterically undemanding N-alkyl groups (e.g. N-Me in
1 and N-Et in 2a ) in (-)-cytisine-derived diamines
or conformationally constrained bispidines such as
(-)-sparteine are optimal for high enantioselectivity in
the R-lithiation rearrangement of cyclooctene oxide 5.
Next, the palladium(II)/diamine catalyzed oxidative
kinetic resolution of 1-indanol was used to evaluate the
enantioselectivity with the different diamines. The use
of palladium(II)/(-)-sparteine/oxygen as reagents for the
kinetic resolution of secondary alcohols (by oxidation to
the corresponding ketones) was independently reported
by the groups of Sigman6 and Stolz7 in 2001. Since then,
extensive efforts from both groups have resulted in
additional mechanistic insight17 (e.g., the role of excess
(-)-sparteine) and the development of new reagent
systems18 (e.g., the use of carbonate bases, tert-butyl
alcohol, as solvent or additive). In particular, these efforts
culminated in Bagdanoff and Stolz’s report of an opti-
mized room-temperature system that utilizes palladium-
(II)/(-)-sparteine/cesium carbonate in chloroform and
air.19 Surprisingly, despite all of the developments to
reaction conditions and significant efforts in addressing
substrate scope, there has been only one example of
ligand variation ((-)-R-isosparteine17d) since those in the
original disclosures6,7 (where (-)-sparteine was identified
as the optimum chiral ligand).
We limited the initial study described here to the
conditions originally reported by Ferraira and Stolz7 and
selected the resolution of 1-indanol rac-7 (actually one
of the worst substrates) as representative. Thus, 1-in-
danol rac-7 was subjected to reaction with palladium-
(II)/diamine/oxygen in toluene at 60 °C for 54 h and the
selectivity factor (s) was calculated by using the percent
conversion (C) to ketone 8 and the percent ee of the
unreacted 1-indanol 7.20 The results obtained with
the different diamines are shown in Table 2. With
(-)-sparteine, indanol (R)-7 was obtained as the major
TABLE 1. Eva lu a tion of Dia m in es in th e r-Lith ia tion
r ea r r a n gem en t of Cycloocten e Oxid e
entry
diaminea
major product yield (%)b
erc
1
2
3
4
5
(-)-sparteine (-)-6
84
70
72
53
53
83:17 (85:15)
19:81
18:82
27:73
34:66
1
(+)-6
(+)-6
(+)-6
(+)-6
2a
2b
2c
a
Reaction conditions: 2.4 equiv of sBuLi, 2.4 equiv of diamine,
b
Et2O, -78 °C, 5 h. Isolated yield of (-)- or (+)-6 after purification
by column chromatography. c Enantiomer ratio determined by
chiral HPLC (Daicel Chiralpak AD) of the 2,4-dinitrobenzoate (the
value in parentheses is the literature er under essentially the same
reaction conditions5).
of sec-butyllithium (or isopropyllithium) and 2.5 equiv of
(-)-sparteine (or (-)-R-isosparteine) in Et2O at -90 °C
(or -98 °C). For the R-lithiation rearrangement of cy-
clooctene oxide 5 into bicyclic alcohol 6, we carried out
our comparative study using commercially available sec-
butyllithium at the more convenient reaction tempera-
ture of -78 °C. The results are presented in Table 1. With
use of 2.4 equiv of sec-butyllithium/(-)-sparteine in Et2O
(13) For some representative examples, see: (a) Hodgson, D. M.;
Buxton, T. J .; Cameron, I. D.; Gras, E.; Kirton, E. H. M. Org. Biomol.
Chem. 2003, 1, 4293. (b) Hodgson, D. M.; Gras, E. Angew. Chem., Int.
Ed. 2002, 41, 2376. (c) Hodgson, D. M.; Stent, M. A. H.; Stefane, B.;
Wilson, F. X. Org. Biomol. Chem. 2003, 1, 1139. (d) Hodgson, D. M.;
Maxwell, C. R.; Miles, T. J .; Paruch, E.; Stent, M. A. H.; Matthews, I.
R.; Wilson, F. X.; Witherington, J . Angew. Chem., Int. Ed. 2002, 41,
4313. (e) Hodgson, D. M.; Maxwell, C. R.; Matthews, I. Tetrahedron:
Asymmetry 1999, 10, 1847. (f) Hodgson, D. M.; Robinson, L. A. Chem.
Commun. 1999, 309. (g) Hodgson, D. M.; Robinson, L. A.; J ones, M. L.
Tetrahedron Lett. 1999, 40, 8637.
(14) For a review, see: Hodgson, D. M.; Gras, E. Synthesis 2002,
1625.
(15) Hodgson, D. M.; Cameron, I. D.; Christlieb, M.; Green, R.; Lee,
G. P.; Robinson, L. A. J . Chem. Soc., Perkin Trans. 1 2001, 2161.
(16) (a) Hodgson, D. M.; Galano, J .-M.; Christlieb, M. Chem.
Commun. 2002, 2436. (b) Hodgson, D. M.; Galano, J .-M.; Christlieb,
M. Tetrahedron 2003, 59, 9719.
(17) (a) Mueller, J . A.; J ensen, D. R.; Sigman, M. S. J . Am. Chem.
Soc. 2002, 124, 8202. (b) J ensen, D. R.; Sigman, M. S. Org. Lett. 2003,
5, 63. (c) Mueller, J . A.; Sigman, M. S. J . Am. Chem. Soc. 2003, 125,
7005. (d) Trend, R. K.; Stolz, B. M. J . Am. Chem. Soc. 2004, 126, 4482.
(18) (a) Bagdanoff, J . T.; Ferreira, E. M.; Stolz, B. M. Org. Lett. 2003,
5, 835. (b) Mandal, S. K.; J ensen, D. R.; Pugsley, J . S.; Sigman, M. S.
J . Org. Chem. 2003, 68, 4600. (c) Mandal, S. K.; Sigman, M. S. J . Org.
Chem. 2003, 68, 7535. (d) Caspi, D. D.; Ebner, D. C.; Bagdanoff, J . T.;
Stolz, B. M. Adv. Synth. Catal. 2004, 346, 185.
(19) Bagdanoff, J . T.; Stolz, B. M. Angew. Chem., Int. Ed. 2004, 43,
353.
5790 J . Org. Chem., Vol. 69, No. 17, 2004

TABLE 2. Eva lu a tion of Dia m in es in th e Oxid a tive
Kin etic Resolu tion of 1-In d a n ol
SCHEME 2. Eva lu a tion of Dia m in e 1 in
Ca r bolith ia tion a n d Desym m etr iza tion of a m eso
An h yd r id e
major
but opposite enantioselectivity to (-)-sparteine in a
mechanistically diverse set of reactions. Two examples
are shown in Scheme 2. Normant, Marek, and co-workers
have demonstrated that highly enantioselective carbo-
lithiation of cinnamyl derivateives (e.g. 9 f 10) can be
achieved using alkyllithiums in the presence of
(-)-sparteine.8 In our hands, carbolithiation of
(E)-cinnamyl alcohol 9 using n-butyllithium/diamine 1
in cumene at 0 °C for 1 h gave alcohol (R)-10 in 71% yield
with 87:13 er. This is essentially opposite to the enanti-
oselectivity obtained by Normant with (-)-sparteine (82%
yield, 91.5:8.5 er in favor of (S)-10).8 It should be noted
in passing that Normant has also described a comple-
mentary route to alcohol (R)-10 (85:15 er) via carbolithia-
tion of (Z)-cinnamyl alcohol using (-)-sparteine.8 More
recently, Shintani and Fu reported the combination of
Grignard reagents and (-)-sparteine as a way of desym-
metrizing meso anhydrides to the corresponding keto
acids (e.g. 11 f 12).9 Indeed, this was the first highly
selective example of asymmetric synthesis with Grignard
reagents and (-)-sparteine. Following Fu’s protocol,
reaction of phenylmagnesium chloride/diamine 1 with
meso anhydride 11 in toluene at -78 °C for 20 h
generated a 78% yield of keto acid (1R,3S)-12 with 89:
11 er (Fu reported a 77% yield of (1S,3R)-12 with 91:9
er using (-)-sparteine9). These results clearly indicate
that diamine 1 is a good surrogate for (+)-sparteine in
these two reactions.
For completeness, we felt it important to demonstrate
that diamine 1 was able to match (-)-sparteine in
reactions where thermodynamic equilibration at some
stage in the reaction profile was the driving force for the
observed enantioselectivity.21 Three very different ex-
amples were selected and the results are presented in
Scheme 3. Following detailed mechanistic work, Beak
and co-workers demonstrated that the lithiation-elec-
trophilic trapping of N-pivaloyl-o-ethylaniline 13 (e.g. 13
f 14) proceeded via a dynamic thermodynamic resolution
of the intermediate lithiated species.10,21 With Beak’s
protocol, N-pivaloyl-o-ethylaniline 13 was treated with
2.4 equiv of s-butyllithium in Et2O at -25 °C for 2 h to
generate the dianion. Subsequently, diamine 1 (2.9 equiv)
was added and the organolithium species were allowed
to equilibrate over 45 min. The predominant organo-
lithium at -25 °C was then “trapped” by rapid cooling
to -78 °C (a temperature where it is presumed to be
entry
diaminea
product C (%)b er of 7 (%)c
sd
1
2
3
4
5
(-)-sparteine
(R)-7
(S)-7
(S)-7
(S)-7
-
67
41
68
64
0
96:4
28:72
9:91
8.0 (8.3)
6.8
1
2a
2b
2c
5.3
3.4
21:79
a
Reaction conditions: 20 mol % of diamine, 5 mol % of
b
Pd(nbd)Cl2, toluene, O2, 3 Å molecular sieves, 60 °C, 54 h. C )
1
% conversion to ketone 8, determined from the H NMR spectrum
of the crude product. c Enantiomer of 7 determined by chiral HPLC
d
(Daicel Chiralpak OJ -R) of the crude product. s ) selectivity
factor, calculated from the % conversion (C) and the % ee of 720
(the value in parentheses is the literature selectivity factor under
essentially the same reaction conditions7).
product with s ) 8.0 (entry 1) and this was satisfyingly
comparable to the literature value (s ) 8.3).7 With
diamines 1 and 2a ,b, the kinetic resolution proceeded in
the opposite sense and indanol (S)-7 was the major
product, but with reduced selectivity factors (entries
2-4). The least sterically hindered diamine 1 (N-Me)
gave the most selective kinetic resolution (s ) 6.8; entry
2) and this is the largest selectivity factor reported for a
reaction that proceeds with the opposite sense of induc-
tion compared to (-)-sparteine. In contrast, increasing
the steric size of the N-alkyl group in diamines 2a -c had
a detrimental effect on the selectivity factor. Indeed, with
the most sterically hindered diamine 2c, there was no
conversion into ketone 8 (entry 5). Similarly poor selec-
tivity and low reactivity were noted by Stolz when
(-)-sparteine was replaced with (-)-R-isosparteine and
were rationalized by an experimentally derived model.17d
This process is clearly very sensitive to seemingly small
changes in diamine structure and it appears that
(-)-sparteine is an optimal ligand for this process.
The results presented thus far indicate that the orig-
inally introduced diamine 1 (N-Me substituent) is the
best (+)-sparteine mimic, a conclusion that Kann et al.
independently reached using a N-iPr-substituted ana-
logue of diamine 1 in phosphine-borane lithiations.4
Thus, we went on to evaluate the scope and limitations
of diamine 1 in five other reactions. Since three out of
four of our originally reported “test reactions” were in
fact asymmetric deprotonations,1 it was particularly
important to show that diamine 1 could induce similar
(20) The selectivity factor (s) is a measure of the relative rate of
reaction of the two enantiomers (krel(fast/slow)) and can be calculated from
the following equation: s ) ln[(1 - C)(1 - ee)]/ln[(1 - C)(1 + ee)],
where C is the % conversion and ee is the % enantiomeric excess. See:
Kagan, H. B.; Fiaud, J . C. In Topics in Stereochemistry; Eliel, E. L.,
Ed.; Wiley & Sons: New York, 1988; Vol. 18, pp 249-330.
(21) (a) Beak, P.; Anderson, D. R.; Curtis, M. D.; Laumer, J . M.;
Pippel, D. J .; Weisenburger, G. A. Acc. Chem. Res. 2000, 33, 715. (b)
Beak, P.; Basu, A.; Gallagher, D. J .; Park, Y. S.; Thayumanavan, S.
Acc. Chem. Res. 1996, 29, 552.
J . Org. Chem, Vol. 69, No. 17, 2004 5791

(II).12 Mechanistically, it is presumed that the resolution
proceeds via dynamic thermodynamic resolution of the
BINOL-copper(II)-sparteine complex. In our hands,
Wulff’s protocol gave a good yield and excellent er using
diamine 1 (Scheme 3). Thus, copper(I) chloride was
sonicated in MeOH/air for 30 min before degassing with
argon/sonication for 1 h. Complexation with BINOL rac-
17 (in CH2Cl2) followed by equilibration for 8 h at room
temperature and then “trapping” at -25 °C for 16 h
before low temperature (-25 °C) quench and workup
afforded an 86% yield of BINOL (R)-17 with 99:1 er.
Using (-)-sparteine, Wulff reported a 96% yield of
BINOL (S)-17 with 96:4 er.12
SCHEME 3. Eva lu a tion of Dia m in e 1 in Dyn a m ic
Th er m od yn a m ic Resolu tion s.
In summary, three new (+)-sparteine-like diamines
were prepared and evaluated in two different reactions.
From this, together with Kann’s recent report using a
N-iPr-substituted analogue of 1 and other results from
our laboratory,23 we conclude that diamine 1 is the most
useful (+)-sparteine surrogate to date. Increasing the
steric size of the N-alkyl substituent from N-Me (as in
diamine 1) has an adverse effect on the enantioselectivity
of the R-lithiation rearrangement of cyclooctene oxide and
the palladium(II)/diamine catalyzed oxidative kinetic
resolution of 1-indanol. The epoxide rearrangement reac-
tion was somewhat more tolerant and both diamines 1
(N-Me) and 2a (N-Et) gave good enantioselectivity. In
contrast, the oxidative kinetic resolution of 1-indanol was
very sensitive to the steric hindrance of the diamine
ligand: diamine 1 (N-Me) gave the highest selectivity
factor (s ) 6.8) with the opposite sense to (-)-sparteine
configurationally stable). Electrophilic quenching at -78
°C followed by workup then gave a 58% yield of silyl
adduct (S)-14 (93:7 er). This should be compared to the
72% yield of (R)-14 (95:5 er) obtained by Basu and Beak
using (-)-sparteine.10a It is worth noting in passing that
Beak has also reported two routes (involving either a
transmetalation protocol or a sacrificial electrophile) to
silyl adduct (S)-14 using (-)-sparteine but neither pro-
ceed with very high enantioselectivity.
t
whereas diamine 2c (N-CH2 Bu) did not oxidize any
1-indanol to the corresponding ketone. Significantly, we
have also demonstrated the usefulness of diamine 1 in a
wide range of asymmetric transformations that utilize
different metals (lithium, palladium, magnesium, and
copper) and proceed via diverse mechanistic pathways.
Further optimization of the ligand and/or reaction condi-
tions will be required to obtain satisfactory results in
Livinghouse’s dynamic thermodynamic resolution of tert-
butylphenylphosphine-borane 15. Nonetheless, in six out
of the seven processes presented here (and two others4,23),
diamine 1 is the best way of accessing the opposite
enantiomers of the products obtained from the
(-)-sparteine-mediated reactions.
In contrast to the success observed with the asym-
metric substitution of N-pivaloyl-o-ethylaniline 13, the
attempted dynamic thermodynamic resolution of lithi-
ated tert-butylphenylphosphine-borane rac-15 returned
only racemic 16. As reported by Wolfe and Livinghouse,11
lithiation of rac-15 with n-butyllithium/diamine 1 fol-
lowed by equilibration at room temperature for 1 h and
then trapping with 2-(chloromethyl)anisole at -78 °C
gave a 38% yield of phosphine-borane rac-16 (Scheme
3). Crucial to the success of the Livinghouse procedure
is the formation of a “voluminous precipitate” during the
1 h at room temperature, a process that presumably
drives the dynamic resolution under these conditions.11
Using diamine 1, we did not observe a precipitate with
the solution remaining homogeneous throughout.
For comparison, we repeated the reaction with
(-)-sparteine: a precipitate did indeed form and the
enantioselectivity (96:4 er) was essentially the same as
that reported by Livinghouse.11
Ack n ow led gm en t. This work was supported by the
BBSRC (M.J .D.) and the EPSRC (M.J .M.).
Su p p or tin g In for m a tion Ava ila ble: Full experimental
procedures and characterization data, derivatization proce-
dures for determining er of 6, 10, and 12, characterization data
As a final example, we were attracted to the recent
work of Wulff et al. on the use of copper(II) and
(-)-sparteine to resolve racemic BINOL 17. Following
Kocovsky and co-worker’s original report,22 Wulff opti-
mized a procedure for the efficient resolution of BINOL
rac-17 using (-)-sparteine and in situ-generated copper-
1
for lactams 4a -c, and H/13C NMR spectra of new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O049182W
(22) (a) Smircina, M.; Lorenc, M.; Hanus, V.; Sedmera, P.; Kocovsky,
P. J . Org. Chem. 1992, 57, 1917. (b) Smircina, M.; Polakova, J .;
Vyskocil, S.; Kocovsky, P. J . Org. Chem. 1993, 5, 4534.
(23) We have also found that diamine 1 is optimal for the asym-
metric lithiation-trapping of N-Boc pyrrolidine. These results will be
reported elsewhere, together with a detailed computational study.
5792 J . Org. Chem., Vol. 69, No. 17, 2004