Modular spiro bidentate nitrogen ligands - Synthesis, resolution and application in asymmetric catalysis

Article abstract of DOI:10.1002/ejoc.200800913

A family of new modular, chiral, bidentate, nitrogen-donor ligands containing the large spirobi(chroman) backbone 1 (SPAN) has been prepared. Enantiopure diamines containing the nitrogen donors at the 8,8′ positions of spirobi(chroman) 1 have been synthesized through the resolution of the 8,8′-diamino racemate 3. Accordingly, secondary and tertiary amines [(+)-6/(-)-6 and (+)-5/(-)-5, respectively] and imino derivatives [(+)-7/(-)-7] were obtained in both enantiomeric forms. A new SPAN derivative incorporating aldehyde groups at the 8,8′ positions of the spirobi(chroman) unit [(+)-9/(-)-9] has been synthesized with the aim to extend the ligand library by means of Schiff base chemistry. The derivatization of the isolated enantiomers of 9 obtained by diastereomer resolution gave derivatives containing the nitrogen atoms at the benzylic positions. The syntheses of ligands (+)-10/(-)-10, (+)-11 and (+)-12 illustrate the scope of this methodology. The coordination ability of ligand (-)-3 has been tested by the synthesis and characterization of complex [Pd(OAc)₂{(-)-3}] [(-)-13]. Some preliminary results related to the oxidative kinetic resolution of 1-phenylethanol with this Pd complex are reported. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800913

FULL PAPER
DOI: 10.1002/ejoc.200800913
Modular Spiro Bidentate Nitrogen Ligands – Synthesis, Resolution and
Application in Asymmetric Catalysis
Xavier Sala,[a] Eduardo J. García Suárez,[a] Zoraida Freixa,*[a] Jordi Benet-Buchholz,[a] and
Piet W. N. M. van Leeuwen[a]
Keywords: Diamines / Spiro compounds / Chiral ligands / Kinetic resolution / Asymmetric catalysis
A family of new modular, chiral, bidentate, nitrogen-donor
ligands containing the large spirobi(chroman) backbone 1
(SPAN) has been prepared. Enantiopure diamines containing
the nitrogen donors at the 8,8Ј positions of spirobi(chroman)
1 have been synthesized through the resolution of the 8,8Ј-
zation of the isolated enantiomers of 9 obtained by dia-
stereomer resolution gave derivatives containing the nitro-
gen atoms at the benzylic positions. The syntheses of ligands
(+)-10/(–)-10, (+)-11 and (+)-12 illustrate the scope of this
methodology. The coordination ability of ligand (–)-3 has
diamino racemate 3. Accordingly, secondary and tertiary been tested by the synthesis and characterization of complex
amines [(+)-6/(–)-6 and (+)-5/(–)-5, respectively] and imino
derivatives [(+)-7/(–)-7] were obtained in both enantiomeric
[Pd(OAc)2{(–)-3}] [(–)-13]. Some preliminary results related to
the oxidative kinetic resolution of 1-phenylethanol with this
Pd complex are reported.
forms.
A new SPAN derivative incorporating aldehyde
groups at the 8,8Ј positions of the spirobi(chroman) unit [(+)-
9/(–)-9] has been synthesized with the aim to extend the li-
gand library by means of Schiff base chemistry. The derivati-
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
metal center. The coordination geometries typical of cis-
coordinating ligands are not accessible, and catalysts with
new properties may be discovered.[7,8] Despite the large re-
search effort in this area, purely trans-coordinating ligands
are still elusive.[9] In recent years, our group has devoted a
considerable effort to develop a new series of preferentially
Introduction
Transition-metal complexes with ligands containing ni-
trogen-donor atoms constitute an important class of coor-
dination compounds able to perform a wide range of asym-
metric transformations.[1] Well-known advantages of nitro-
gen-based ligands are: (a) their chemical robustness (in
comparison to phosphanes), (b) their wide availability in
enantiomerically pure form (from the chiral pool or
through well-established racemate resolutions), (c) their rich
coordination chemistry in combination with inexpensive
first-row transition metals, and (d) their stabilization of
high-oxidation-state transition-metal species (useful for oxi-
dation catalysis). Not only simple amines and diamines,[2]
but also ligands containing sp2-hybridized, nitrogen donor
atoms (chiral oxazolines[3] and pyridines[4]) and one tertiary
diamine, (–)-sparteine,[5] have received much attention dur-
ing the past decades. Nitrogen-donor ligands possessing a
spiro chiral center, a frequently occurring theme in diphos-
phane-ligand chemistry, have been reported only recently.[6]
The development of wide-bite-angle ligands, especially
the trans-chelating ones, has been a worthwhile challenge
during recent decades. They provide access to scarcely ex-
plored catalysts with unusual ligand dispositions around the
trans-coordinating
spirobi(chroman)
diphosphanes
(SPANphos and its homologs), and their catalytic applica-
tions have been studied.[10,11] We found that the spiro-
bi(chroman) is flexible enough to allow for the formation
of cis complexes when trans sites are not available. While
the synthesis and catalytic application of trans-coordinating
phosphorus ligands has been intensively investigated by
us[10,11] and other groups,[7,12] nitrogen-containing analogs
remain largely unexplored.[13]
Herein, we report on the design and synthesis of a new
set of chiral, C2-symmetric, nitrogen-donor ligands contain-
ing the 4,4,4Ј,4Ј,6,6Ј-hexamethylspiro-2,2Ј-bi(chroman)
(SPAN) backbone. As for SPANphos, molecular modeling
shows a slight preference for the formation of trans com-
plexes in the absence of metal preferences. Small substitu-
ents at the nitrogen atoms diminish the destabilizing steric
interactions in the cis complexes. The preparation, resolu-
tion and complete characterization of ligands (+)-3/(–)-3,
(+)-5/(–)-5, (+)-6/(–)-6, (+)-7/(–)-7 bearing a wide variety of
nitrogen-containing functional groups is described
(Scheme 1). They can be prepared in a few steps from cheap
reagents and isolated in their enantiomerically pure forms.
In addition, the introduction of an extra carbon atom be-
[a] Catalan Institute of Chemical Research (ICIQ),
Avda Paisos Catalans 16, 43007 Tarragona, Spain
E-mail: zfreixa@iciq.es
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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tween the backbone structure and the nitrogen donor atoms of p-cresol with acetone[14]) was employed as the starting
has been investigated. These larger backbones have been material in the synthesis of ligands (+)-3/(–)-3, (+)-5/(–)-
obtained in enantiopure forms by the derivatization of 5, (+)-6/(–)-6, and (+)-7/(–)-7 (Scheme 1). The synthesis of
building block 9. By using these starting materials [(+)-9, dinitro compound 2 was initially attempted with metal ni-
(–)-9], a new group of modular, axially chiral ligands has trates[15] or NaNO2,[16] but no conversion was achieved. Ni-
been developed [(+)-10, (–)-10, (+)-11 and (+)-12, tric acid nitration was then employed (HNO3/CH3COOH,
Scheme 2]. Furthermore, the coordination behavior of some room temperature, 3 h), which afforded 2 in moderate yield
of these ligands towards Pd, as well as the catalytic activity (53%) due to partial backbone decomposition. The subse-
of the formed complexes in the oxidative kinetic resolution quent reduction of the nitro group (Sn powder, HCl, EtOH,
of secondary alcohols has been investigated.
80 °C, 1 h) rendered the racemic SPANamine 3 in good
yield (83%; for larger scale synthesis, more environmentally
friendly catalytic methods are available[17]). The optical res-
olution of 3 was first attempted unsuccessfully by means of
diastereomeric salt formation [-(+)-tartaric acid and
derivatives] and diastereomeric Pd complexation [di-µ-
chloridobis{(R)-2-[1-(dimethylamino)ethyl]phenyl-C,N}di-
palladium(II)].[18]
Results and Discussion
Synthesis of Axially Chiral, Spiro, Bidentate, Nitrogen Ligands
Racemic 4,4,4Ј,4Ј,6,6Ј-hexamethylspiro-2,2Ј-bi(chroman)
(1) (obtained on a 25 g scale by the acid-catalyzed reaction
Scheme 1.
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Modular Spiro Bidentate Nitrogen Ligands in Asymmetric Catalysis
The derivatization of 3 with carbamates was then at- AcOH, 2 h) led to SPANdimethylamines (+)-5 and (–)-5 in
tempted by means of (–)-menthyl chloroformate (DIPEA, moderate yields (61 and 58%, respectively) after chromato-
CH2Cl2, room temp., 16 h), and the expected dia- graphic purification. The N-arylation of (+)-3 and (–)-3 was
stereomeric mixture of the (–)-menthyl carbamate deriva- also attained by means of a transition-metal-free procedure
tives 4 were obtained in excellent yield (90%). The separa- recently published by Larock et al. (silylaryl triflate, CsF,
tion of the diastereomers was accomplished by semi-prepar- MeCN/CHCl3, room temp., overnight),[19] which yielded
ative LC (silica gel column, hexane/ethyl acetate, 50 mg/in- secondary SPANamines (+)-6 and (–)-6 in good yields (72
jection), affording carbamates (+)-4 and (–)-4 as enantio- and 71%, respectively). We envisaged that a wide set of im-
pure compounds. The subsequent carbamate cleavage was ines may be synthesized from (+)-3 and (–)-3 through Schiff
achieved by reaction with NaOMe in an autoclave (MeOH, base condensation reactions. This simple approach allows
145 °C, 15 h; then H2O, 145 °C, 3 h), leading to the desired, for a quick variation of the steric bulk around the coordi-
enantiopure, chiral SPANamines (+)-3 and (–)-3 (Scheme 1) nating nitrogen atom and a fine tuning of its electronic
in an almost quantitative yield (96 and 95%, respectively). properties just by modifying the aldehyde used in the con-
These chiral primary SPANamines were used as the starting densation reaction (and even to introduce additional chiral-
material to expand the ligand series to other nitrogen func- ity!). As an example, SPANimines (+)-7 and (–)-7 were
tional groups such as imines [(+)-7/(–)-7] and secondary synthesized by the condensation of (+)-3 and
[(+)-6/(–)-6] and tertiary [(+)-5]/[(–)-5] amines (Scheme 1), (–)-3 with benzaldehyde (PhCHO, toluene, Dean–Stark ap-
thus demonstrating the modularity of the synthetic ap- paratus, 20 h, 77% and 81%, respectively). The X-ray struc-
proach.
ture of the racemic form of this SPANimine has been
The reaction of SPANamines (+)-3 and (–)-3 with para- solved, and its ORTEP plot is presented as supporting in-
formaldehyde and a reducing agent (NaBH3CN, CH3CN, formation (Figure S1, Supporting Information). In ad-
Scheme 2.
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dition, SPANamines (+)-3/(–)-3 can be employed as chiral means of 3  HCl (THF, 30 min, room temp.) afforded the
building blocks for the synthesis of tetradentate ligands in axially enantiopure aldehydes (+)-9/(–)-9 in almost quanti-
combination with different chiral and achiral pyridinecar- tative yields (97% in both cases). Building block (+)-9 was
boxaldehydes.[20]
then employed for the synthesis of new nitrogen-donor li-
gands by means of Schiff base chemistry. Aniline was se-
lected, and SPANimine (+)-11 was obtained in excellent
yield (toluene, 4 Å molecular sieves, Dean–Stark apparatus,
12 h, 91%). The subsequent C=N bond reduction afforded
the secondary SPANamine (+)-12 (NaBH4, toluene, 12 h,
room temp., 98%). Ligands (+)-11 and (+)-12 are only se-
lected examples of the large number of compounds poten-
tially available from aldehydes (+)-9/(–)-9. The synthesis of
a variety of SPANamine and SPANimine derivatives is cur-
rently under development in our laboratory.
Synthesis of the SPANamine Homologs
Having developed synthetic routes for axially chiral
SPANamines and SPANimines, we envisaged modifying the
procedures to enlarge the ligand library. As mentioned
above, aldehydes (+)-9/(–)-9 (Scheme 2) were synthesized as
key building blocks for the preparation of this extended li-
brary. They allow the use of Schiff base chemistry to poten-
tially synthesize a large number of new ligand derivatives
(SPANimines) by condensation with different primary
amines. Also, the corresponding reduced species (secondary
SPANamines) will be accessible through simple procedures.
Along these lines, ligands (+)-11 and (+)-12 were synthe-
Coordination Chemistry and Catalysis
In a preliminary attempt to explore the coordinating abil-
sized to illustrate the potential of the synthetic methodol- ity of the synthesized ligands, chiral SPANamine (–)-3 was
ogy. treated with [Pd(COD)Cl2] (CH2Cl2, 6 h, room temp.). To
Racemic dibromo derivative 8 [obtained on a 10 g scale the orange-red suspension formed, Ag(OAc) was added, to
from 4,4,4Ј,4Ј,6,6Ј-hexamethylspiro-2,2Ј-bi(chroman) (1)] afford complex (–)-13 in good yield (75%) as an orange-
was employed as the starting material.[10] The lithiation of 8 brown solid. Structural characterization has been per-
through metal/halogen exchange with nBuLi (THF, –78 °C, formed in solution through NMR spectroscopy and in the
30 min), followed by the slow addition of DMF in THF solid state by means of the X-ray diffraction analysis of its
(–78 °C, 2 h; then –78 °C to room temperature) rendered racemic equivalent complex (Figure 2). In solution, a sym-
racemic aldehyde 9 in 74% yield (Scheme 2). Derivatization metric monomeric species containing ligand (–)-3 and two
through diastereomeric imine formation was the resolution acetate molecules coordinated to the Pd center was ob-
strategy selected in this case. (–)-Myrtanylamine was con- served (Figures S36 and S37, Supporting Information). In
densed with 9, and diastereomeric imines 10 were obtained the solid state, however, a dimeric species was formed, in
in excellent yield (absolute EtOH/CHCl3, 18 h, 25 °C, which one of the SPANamine groups was converted into
96%). The diastereomer separation was accomplished by
successive precipitation from methanol. Imine (+)-10 was
obtained in good yield and purity as a white solid (82%,
Ͼ99% de), and its diastereomeric counterpart, (–)-10, was
isolated in lower yield but similar purity from the mother
liquor (19%, Ͼ99% de). The X-ray structure of dia-
stereomeric imine (–)-10 was solved, and its ORTEP plot is
presented in Figure 1. Subsequent imine hydrolysis by
Figure 1. ORTEP view (ellipsoids are drawn at a 50% probability
level) of the molecular structure of (–)-10.
Figure 2. ORTEP view (ellipsoids are drawn at a 50% probability
level) of the molecular structure of complex 13.
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Modular Spiro Bidentate Nitrogen Ligands in Asymmetric Catalysis
an amido group bridging two Pd atoms. Apparently, upon
crystallization one molecule of acetic acid was eliminated.
Remarkably, this SPANamine coordinated in a cis fashion.
As a first test reaction for catalysis we chose the oxidative
kinetic resolution of 1-phenylethanol, as this reaction may
not necessarily need cis coordination of the diamine, al-
though previous studies all involved cis-diamines.[4] The
preliminary results for the catalytic activity of the (–)-3/
Pd(OAc)2 system are collected in Table 1.
Experimental Section
General: See Supporting Infoarmation.
Syntheses: 4,4,4Ј,4Ј,6,6Ј-Hexamethylspiro-2,2Ј-bi(chroman) (1)[14]
and 8,8Ј-dibromo-4,4,4Ј,4Ј,6,6Ј-hexamethylspiro-2,2Ј-bi(chroman)
(9) were obtained according to the methods previously described
by our group.[10]
8,8Ј-Dinitro-4,4,4Ј,4Ј,6,6Ј-hexamethylspiro-2,2Ј-bi(chroman) (2): To
a solution of 1 (4 g, 11.89 mmol) in AcOH (440 mL) was added
dropwise a solution of nitric acid (44 mL) in AcOH (44 mL) over
1 h, and the solution was stirred at room temperature for 3 h. The
volume was then reduced under reduced pressure (45 °C), and H2O
(100 mL) was added. The precipitates were collected, washed with
H2O and dried in vacuo to yield 2 as a white-yellow solid (2.7 g,
Table 1. Pd/(–)-3-catalyzed oxidative kinetic resolution of 1-phen-
ylethanol.[a]
Entry
Pd source
Temp. [°C] Time [h] Conv. [%] ee [%]
1
53%). M.p. 171–173 °C. H NMR (400 MHz, CDCl3): δ = 1.34 (s,
6 H), 1.55 (s, 6 H), 2.12 (d, J = 14.3 Hz, 2 H), 2.22 (d, J = 14.3 Hz,
2 H), 2.31 (s, 6 H), 7.25 (s, 2 H), 7.29 (s, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 20.6 (CH3), 30.9 (C), 31.9 (CH3), 33.1
(CH3), 46.2 (CH2), 98.8 (C), 122.8 (CH), 131.3 (CH), 131.6 (C),
134.9 (C), 140.0 (C), 141.1 (C) ppm. ESI-MS: m/z = 449.2 [M +
Na]+. C23H26N2O6 (426.46): calcd. C 64.78, H 6.15, N 6.57; found
C 64.55, H 6.42, N 6.33.
1
2
3
4
5
6
7
8
[PdCl2(COD)]
[Pd(allyl)Cl]2
[Pd(OAc)2]
[Pd(OAc)2]
[Pd(OAc)2]
[Pd(OAc)2]
[Pd(OAc)2]
[Pd(OAc)2]
80
80
80
80
65
42
42
42
95
42
42
42
42
22
32
40
61
36
30
20
20
12
7
22
21
33
41
23
23
55
35
50[b]
8,8Ј-Diamino-4,4,4Ј,4Ј,6,6Ј-hexamethylspiro-2,2Ј-bi(chroman) (3):
Sn powder (5.57 g, 46.9 mmol) was added portionwise to a solution
of 2 (2.5 g, 5.87 mmol) in EtOH (27 mL) and HCl (23.1 mL,
235 mmol). The resulting suspension was refluxed for 1 h. The re-
action was quenched with ice, and aqueous NaHCO3 (1 , 50 mL)
was added. The product was extracted with ethyl acetate
(3ϫ100 mL), the combined organic layers were washed with brine
(100 mL) and dried (MgSO4), and the solvent was evaporated in
vacuo. The crude product was then recrystallized from MeOH to
afford pure 3 as a white powder (1.750 g, 83%). M.p. 236–238 °C.
1H NMR (400 MHz, CDCl3): δ = 1.34 (s, 6 H), 1.55 (s, 6 H), 2.06
(d, J = 14.3 Hz, 2 H), 2.18 (d, J = 14.3 Hz, 2 H), 3.30 (s, 4 H),
6.32 (s, 2 H), 6.52 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 21.1 (CH3), 31.0 (C), 31.9 (CH3), 32.1 (CH3), 48.0 (CH2), 98.6
(C), 114.0 (CH), 115.9 (CH), 130.7 (C), 132.0 (C), 135.7 (C), 136.2
(C) ppm. HRMS (ESI): calcd. for C23H31N2O2 [M+] 367.2386;
found 367.2385. C23H30N2O2 (366.50): calcd. C 75.38, H 8.25, N
7.64; found C 75.30, H 8.23, N 7.55.
[a] Reactions were performed in toluene and with KOtBu. [b] 3 h
incubation at 80 °C.
These results clearly demonstrate the capacity of the
SPANamine (–)-3/Pd(OAc)2 system to enantiodifferentiate
in the oxidation of a racemic substrate such as 1-phenyl-
ethanol (up to 41% ee), and it is evident that SPANamine
3 is coordinated to the Pd atom during the catalysis. We are
currently investigating the coordination chemistry of
SPANamines under these reaction conditions. In addition,
we are developing the coordination chemistry of all the
SPAN nitrogen-donor ligands described in this paper with
other metals and studying their enantioselective reactivity
towards prochiral substrates.
Bis[(–)-menthyl] 4,4,4Ј,4Ј,6,6Ј-Hexamethylspiro-2,2Ј-bi(chroman)-
8,8Ј-bis(carbamate) (4): To a solution of 3 (2 g, 5.46 mmol) and
DIPEA (3.56 g, 27.3 mmol) in CH2Cl2 (86 mL) was added slowly
(–)-(1R,2S,5R)-menthyl chloroformate (5.78 mL, 27.3 mmol) at
0 °C. The mixture was stirred at room temperature for 16 h. After
the addition of aqueous NaHCO3 (50 mL), the organic layer was
Conclusions
A new, axially chiral, diamine ligand [(+)-3/(–)-3], con-
taining a spirobi(chroman) core, has been prepared in both
enantiomeric forms by the resolution of diastereoisomeric
intermediates. With this primary amine as the starting ma- separated, and the aqueous layer was extracted with CH2Cl2
(3ϫ60 mL). The combined organic layers were dried (MgSO4) and
concentrated, and the residue was purified by flash chromatog-
raphy with silica gel (40 g) and hexane/ethyl acetate (10:0.8) to af-
ford a diastereomeric mixture of 4 as a colorless oil that solidified
upon standing (3.5 g, 90%). 1H NMR (400 MHz, CDCl3): δ = 0.70
(d, J = 7.0 Hz, 6 H), δ = 0.74 (d, J = 7.0 Hz, 6 H), 0.80 (s, 6 H),
0.82 (s, 6 H), 0.90 (m, 8 H), 1.35 (s, 12 H), 1.55 (s, 6 H), 1.56 (s,
12 H), 1.57 (m, 6 H), 2.06 (m, 4 H), 2.07 (d, J = 14.4 Hz, 4 H),
2.20 (d, J = 14.4 Hz, 4 H), 2.27 (s, 6 H), 2.29 (s, 6 H), 4.47 (m, 2
H), 4, 73 (m, 2 H) 6.38 (s, 2 H), 6.50 (s, 2 H), 6.78 (s, 2 H), 6.80
terial, several new ligands containing diverse nitrogen func-
tional groups and substitution patterns around the nitrogen
atoms have been prepared. This asymmetric synthetic pro-
cedure was subsequently extended to a second modular
family of nitrogen donors through the synthesis and resolu-
tion of building block (+)-9/(–)-9. The potential of this chi-
ral dialdehyde for the synthesis of a wide range of SPANim-
ines and secondary SPANamines by means of simple Schiff
base chemistry was exemplified by the preparation of li-
gands (+)-11 and (+)-12. The coordination behavior of the (s, 2 H), 7.65 (s, 4 H) ppm. ESI-MS: m/z = 732 [M + H]+. HRMS
(ESI): calcd. for C45H66N2O6 [M+] 731.0212; found 731.0215.
new ligands was illustrated by the syntheses of Pd com-
plexes. The preliminary catalytic results for the (–)-3/
Pd(OAc)2 system showed moderate enantioselectivities in
the oxidative kinetic resolution of 1-phenylethanol.
Bis[(–)-menthyl] 4,4,4Ј,4Ј,6,6Ј-Hexamethylspiro-2,2Ј-bi(chroman)-
8,8Ј-bis(carbamates) [(+)-4 and (–)-4]: Carbamates 4 were separated
by semi-preparative LC with a silica gel column eluting with hex-
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ane/ethyl acetate (80:20) to give diastereomerically pure (+)-4 and
H2O (3 mL) and brine (3 mL) and dried with MgSO4. The organic
fraction was then concentrated in vacuo, and the yellow oil ob-
(–)-4 as colorless oils. (+)-4: Yield: 1.560 g, Ͼ99% de. [α]2D0 = +55
1
(c = 0.69, CHCl3). H NMR (400 MHz, CDCl3): δ = 0.72 (d, J = tained was recrystallized from MeOH to afford pure (+)-5 or (–)-5
7.0 Hz, 6 H), 0.89 (m, 12 H), 1.06 (m, 2 H), 1.22 (m, 2 H), 1.37 (s,
6 H), 1.59 (s, 6 H), 1.66 (m, 4 H), 1.81 (m, 2 H), 2.06 (m, 2 H),
2.07 (d, J = 14.4 Hz, 2 H), 2.20 (d, J = 14.4 Hz, 2 H), 2.29 (s, 6
H), 4.49 (m, 2 H), 6.51 (s, 2 H), 6.80 (s, 2 H), 7.65 (s, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 16.5 (CH3), 20.7 (C), 21.3
(CH3), 21.9 (CH3), 23.7 (CH2), 26.2 (CH3), 30.8 (C), 31.3 (CH3),
31.9 (CH), 32.3 (CH), 34.3 (CH2), 41.2 (CH2), 47.2 (CH3), 47.4
(CH2), 74.8 (CH), 98.9 (C), 117.4 (CH), 120.0 (CH), 127.3 (C),
131.2 (C), 131.2 (C), 136.4 (C), 153.1 (C) ppm. HRMS (ESI): calcd.
for C45H66N2O6Na [M+] 753.4819; found 753.4849. C45H66N2O6
(731.02): calcd. C 73.94, H 9.10, N 3.83; found C 73.10, H 9.32, N
3.75. (–)-4: Yield: 1.580 g, Ͼ99% de. [α]2D0 = –198 (c = 0.69, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 0.70 (d, J = 7.0 Hz, 6 H), 0.89
(m, 12 H), 1.04 (m, 2 H), 1.26 (m, 2 H), 1.35 (s, 6 H), 1.57 (s, 6
H), 1.64 (m, 4 H), 1.781 (m, 2 H), 2.06 (m, 2 H), 2.06 (d, J =
14.4 Hz, 2 H), 2.18 (d, J = 14.4 Hz, 2 H), 2.27 (s, 6 H), 4.47 (m, 2
as a white solid. (+)-5: Yield: 0.075 g, 65 %. M.p. 220–222 °C.
[α]2D0 = +156.3 (c = 0.36, CHCl3). H NMR (400 MHz, CDCl3): δ
1
= 1.33 (s, 6 H), 1.66 (s, 6 H), 2.02 (d, J = 14.4 Hz, 2 H), 2.19 (d, J
= 14.3 Hz, 2 H), 2.23 (s, 6 H), 2.33 (s, 12 H), 6.49 (s, 2 H), 6.77 (s,
2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.2 (CH3), 31.1 (C),
32.0 (CH3), 32.2 (CH3), 42.2 (CH3), 48.3 (CH2), 98.7 (C), 114.3
(CH), 115.9 (CH), 130.5 (C), 132.0 (C), 135.7 (C), 136.2 (C) ppm.
ESI-MS: m/z = 443.50 [M + H]+. C37H38N2O2 (442.60): calcd. C
76.74, H 9.01, N 6.63; found C 76.60; H 9.35; N 6.34. (–)-5: Yield:
0.072 g, 63%. M.p. 220–222 °C. [α]2D0 = –156.1 (c = 0.36, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 1.33 (s, 6 H), 1.66 (s, 6 H), 2.02
(d, J = 14.4 Hz, 2 H), 2.19 (d, J = 14.4 Hz, 2 H), 2.23 (s, 6 H),
2.33 (s, 12 H), 6.49 (s, 2 H), 6.77 (s, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 1.33 (s, 6 H), 1.66 (s, 6 H), 2.02 (d, J =
14.4 Hz, 2 H), 2.19 (d, J = 14.3 Hz, 2 H), 2.23 (s, 6 H), 2.33 (s, 12
H), 6.49 (s, 2 H), 6.77 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
H), 6.50 (s, 2 H), 6.78 (s, 2 H), 7.63 (s, 2 H) ppm. 13C NMR δ = 21.2 (CH3), 31.1 (C), 32.0 (CH3), 32.2 (CH3), 42.2 (CH3), 48.3
(100 MHz, CDCl3): δ = 16.6 (CH3), 20.7 (C), 21.4 (CH3), 22.0 (CH2), 98.7 (C), 114.3 (CH), 115.9 (CH), 130.5 (C), 132.0 (C),
(CH3), 23.7 (CH2), 26.2 (CH3), 30.9 (C), 31.3 (CH3), 31.9 (CH), 135.7 (C), 136.2 (C) ppm. ESI-MS: m/z = 443.62 [M + H]+.
32.4 (CH), 34.3 (CH2), 41.2 (CH2), 47.2 (CH3), 47.4 (CH2), 74.8 37H38N2O2 (442.60): calcd. C 76.74, H 9.01, N 6.63; found C
C
(CH), 98.9 (C), 117.4 (CH), 120.0 (CH), 127.2 (C), 131.2 (C), 131.3 76.62, H 9.56, N 6.50.
(C), 136.5 (C), 153.2 (C) ppm. HRMS (ESI): calcd. for
8,8Ј-Bis(phenylamino)-4,4,4Ј,4Ј,6,6Ј-hexamethylspiro-2,2Ј-bi-
C45H66N2O6Na [M+] 753.4819; found 753.4814. C45H66N2O6
(731.02): calcd. C 73.94, H 9.10, N 3.83; found C 73.11, H 9.21, N
3.56.
(chromans) [(+)-6 and (–)-6]: To a stirred solution of (+)-3 or (–)-
3 (0.1 g, 0.27 mmol) and silylaryl triflate (0.147 mL, 0.6 mmol) in
CH3CN/CHCl3 (4 mL) was added CsF (0.207 g, 1.36 mmol). The
reaction mixture was stirred at room temperature overnight and
8,8Ј-Diamino-4,4,4Ј,4Ј,6,6Ј-hexamethylspiro-2,2Ј-bi(chromans) [(+)-
3 and (–)-3]: To a stirred solution of (–)-4 or (+)-4 (1.5 g, monitored by TLC to establish completion. The resulting solution
2.05 mmol) in dry MeOH (30 mL) was added slowly NaOMe was washed with brine (5 mL) and extracted with Et2O (3ϫ7 mL).
(5.55 g, 102.7 mmol), and the resulting solution was stirred at
145 °C for 15 h in an autoclave. H2O (15 mL) was then added, and
the solution was refluxed for a further 3 h. The mixture was then
poured onto ice, partitioned between CH2Cl2 and H2O, and the
combined organic layers were washed with brine and dried with
anhydrous MgSO4. The solvent was evaporated under reduced
pressure to afford pure (+)-3 or (–)-3 as a pale yellow solid. (+)-3:
The combined Et2O fractions were dried with MgSO4 and concen-
trated in vacuo. The residue was then purified by flash chromatog-
raphy with silica gel (8 g) with hexane/ethyl acetate (10:1) to afford
pure (+)-6 or (–)-6 as a pale yellow solid. (+)-6: Yield: 0.184 g,
87%. [α]2D0 = +135.4 (c = 3.9, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 1.41 (s, 6 H), 1.60 (s, 6 H), 2.22 (d, J = 14.4 Hz, 2 H),
2.24 (d, J = 14.4 Hz, 2 H), 2.27 (s, 6 H), 5.28 (s, 2 H), 6.71 (m, 6
H), 6.83 (t, 3J = 7.3 Hz, 2 H), 6.85 (s, 2 H), 7.14 (t, J = 7.4 Hz)
Yield: 0.720 g, 96%. M.p. 236–238 °C. [α]2D0 = +187 (c = 1.0,
1
CHCl3). H NMR (400 MHz, CDCl3): δ = 1.34 (s, 6 H), 1.55 (s, 6 ppm. 13C NMR (100 MHz, CDCl3): δ = 21.4 (CH3), 31.4 (C), 32.1
H), 2.06 (d, J = 14.3 Hz, 2 H), 2.18 (d, J = 14.3 Hz, 2 H), 2.20 (s,
6 H), 3.30 (s, 4 H), 6.32 (s, 2 H), 6.52 (s, 2 H) ppm. 13C NMR 117.7 (CH), 118.3 (CH), 120.5 (CH), 128.9 (CH), 129.1 (CH),
(100 MHz, CDCl3): δ = 21.1 (CH3), 31.0 (C), 31.9 (CH3), 32.1 1131.3 (C), 133.1 (C), 133.4 (C), 136.8 (C), 142.6 (C) ppm. ESI-
(CH3), 48.0 (CH2), 98.6 (C), 114.0 (CH), 115.9 (CH), 130.7 (C), MS: m/z = 519.63 [M + H]+. C35H38N2O2 (518.69): calcd. C 81.05,
132.0 (C), 135.7 (C), 136.2 (C) ppm. HRMS (ESI): calcd. for H 7.38, N 5.40; found C 81.25, H 7.50, N 5.10. (–)-6: Yield: 0.170 g,
C23H30N2O2Na [M+] 389.2205; found 389.2221. C23H30N2O2 80%. [α]2D0 = +135.3 (c = 3.9, CHCl3). 1H NMR (400 MHz,
(CH3), 32.7 (CH3), 47.8 (CH2), 99.5 (C), 113.3 (CH), 117.3 (CH),
(366.50): calcd. C 75.38, H 8.25, N 7.64; found C 75.19, H 8.41, N
CDCl3): δ = 1.41 (s, 6 H), 1.60 (s, 6 H), 2.22 (d, J = 14.4 Hz, 2 H),
2.24 (d, J = 14.4 Hz, 2 H), 2.27 (s, 6 H), 5.28 (s, 2 H), 6.71 (m, 6
7.50. (–)-3: Yield: 0.712 g, 95%. M.p. 236–238 °C. [α]2D0 = –187 (c
= 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.34 (s, 6 H), H), 6.83 (t, 3J = 7.3 Hz, 2 H), 6.85 (s, 2 H), 7.14 (t, J = 7.4 Hz)
1.55 (s, 6 H), 2.06 (d, J = 14.3 Hz, 2 H), 2.18 (d, J = 14.3 Hz, 2
H), 2.20 (s, 6 H), 3.30 (s, 4 H), 6.32 (s, 2 H), 6.52 (s, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 21.1 (CH3), 31.0 (C), 31.9
(CH3), 32.1 (CH3), 48.0 (CH2), 98.6 (C), 114.0 (CH), 115.9 (CH),
130.7 (C), 132.0 (C), 135.7 (C), 136.2 (C) ppm. HRMS (ESI): calcd.
for C23H31N2O2Na [M+] 367.2386; found 367.2397. C23H30N2O2
(366.50): calcd. C 75.38, H 8.25, N 7.64; found C 75.30, H 8.23, N
7.55.
ppm. 13C NMR (100 MHz, CDCl3): δ = 21.4 (CH3), 31.4 (C), 32.1
(CH3), 32.7 (CH3), 47.8 (CH2), 99.5 (C), 113.3 (CH), 117.3 (CH),
117.7 (CH), 118.3 (CH), 120.5 (CH), 128.9 (CH), 129.1 (CH), 131.3
(C), 133.1 (C), 133.4 (C), 136.8 (C), 142.6 (C) ppm. ESI-MS: m/z
= 519.53 [M + H]+. C35H38N2O2 (518.69): calcd. C 81.05, H 7.38,
N 5.40; found C 81.15, H 7.70, N 5.22.
8,8Ј-Bis(benzylideneamino)-4,4,4Ј,4Ј,6,6Ј-hexamethylspiro-2,2Ј-bi-
(chromans) [(+)-7 and (–)-7]: To a stirred solution of (+)-3 or (–)-3
(0.3 g, 0.81 mmol) in toluene (30 mL) were added molecular sieves
8,8Ј-Bis(dimethylamino)-4,4,4Ј,4Ј,6,6Ј-hexamethylspiro-2,2Ј-bi(chro-
mans) [(+)-5 and (–)-5]: To a stirred solution of (+)-3 or (–)-3 (0.1 g, (4 Å, 4 g) and benzaldehyde (0.197 mL, 1.88 mmol). The mixture
0.27 mmol), NaBH3 CN (0.052 g, 0.82 mmol) and CH2O
(0.076 mL, 2.72 mmol) in CH3CN (1.5 mL) was added dropwise
AcOH (0.95 mL) at room temperature. After 2 h, the mixture was
diluted with Et2O (2 mL), washed with aqueous NaHCO3 (3 mL),
was then refluxed in a Dean–Stark apparatus, and completion was
observed after 20 h. The resulting solution was washed with H2O
(2ϫ20 mL), the organic layers were combined and dried (MgSO4),
and the solvent was evaporated in vacuo to provide pure (+)-7 or
6202
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Eur. J. Org. Chem. 2008, 6197–6205

Modular Spiro Bidentate Nitrogen Ligands in Asymmetric Catalysis
(–)-7 as a yellow solid. (+)-7: Yield: 0.340 g, 77%. M.p. 155–157 °C.
1.15 (s, 6 H), 1.22 (m, 2 H), 1.37 (s, 6 H), 1.58 (s, 6 H), 1.60 (s, 6
H), 1.75 (m, 2 H), 1.85 (d, J = 6.1 Hz, 4 H), 2.12 (d, J = 14.1 Hz,
1
[α]2D0 = +147.1 (c = 0.37, CHCl3). H NMR (400 MHz, CDCl3): δ
= 1.26 (s, 6 H), 1.36 (s, 6 H), 2.01 (d, J = 13.9 Hz, 2 H), 2.07 (d, J 2 H), 2.22 (d, J = 14.1 Hz, 2 H), 2.3 (m, 2 H), 3.23 (m, 2 H), 3.31
= 13.9 Hz, 2 H), 2.24 (s, 6 H), 6.52 (s, 2 H), 6.71 (s, 2 H), 7.39 (m,
(m, 2 H), 7.16 (s, 2 H), 7.42 (s, 2 H), 7.91 (s, 2 H) ppm. 13C NMR
7 H), 7.56 (m, 5 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.9 (100 MHz, CDCl3): δ = 20.23 (CH3), 20.76 (CH2), 23.26 (CH2),
(CH3), 31.0 (C), 32.0 (CH3), 33.1 (CH3), 46.5 (CH2), 97.4 (C), 118.4 26.23 (CH), 27.94 (CH2), 30.87 (CH), 31.96 (CH2), 32.72 (CH3),
(CH), 123.7 (CH), 128.0 (CH3), 128.4 (CH3), 128.7 (CH3), 130.2 33.54 (CH3), 38.62 (C), 41.48 (CH2), 42.11 (CH2), 44.52 (CH2),
(C), 130.8 (CH3), 132.9 (C), 136.0 (CH), 136.3 (C), 139.1 (C), 142.2
( C) , 1 61 . 9 ( C H ) p p m . E S I - M S : m/ z = 5 4 3 [ M + H ] +
37H38N2O2·2.8H2O (593.11): calcd. C 74.92, H 7.41, N 4.72;
found C 75.07, H 7.18, N 4.72. (–)-7: Yield: 0.360 g, 82%. M.p.
155–157 °C. [α]2D0 = –147.2 (c = 0.37, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 1.26 (s, 6 H), 1.36 (s, 6 H), 2.01 (d, J = 13.9 Hz, 2 H),
2.07 (d, J = 13.9 Hz, 2 H), 2.24 (s, 6 H), 6.52 (s, 2 H), 6.71 (s, 2 H),
47.51 (CH3), 68.47 (CH), 98.75 (C), 124.98 (C), 125.41 (CH),
128.90 (C), 131.0 (C), 147.85 (CH), 157.27 (C) ppm. ESI-MS: m/z =
663 [M + H]+. HRMS (ESI): calcd. for C45H63N2O2 [M+] 663.4811;
found 663.4819. (–)-10: Yield: 0.140 g, 12%, Ͼ99% de. M.p. 150–
152 °C. [α]2D0 = –171 (c = 0.69, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 0.87 (d, J = 9.6 Hz, 2 H), 0.91 (s, 6 H), 1.09 (s, 6 H),
1.22 (m, 2 H), 1.36 (s, 6 H), 1.60 (s, 6 H), 1.83 (m, 10 H), 2.11 (d,
.
C
7.39 (m, 7 H), 7.56 (m, 5 H) ppm. 13C NMR (100 MHz, CDCl3): δ J = 14.1 Hz, 2 H), 2.21 (d, J = 14.1 Hz, 2 H), 2.23 (s, 6 H), 2.30
= 20.9 (CH3), 31.0 (C), 32.0 (CH3), 33.1 (CH3), 46.5 (CH2), 97.4 (m, 4 H), 3.31 (m, 4 H), 7.16 (s, 2 H), 7.41 (s, 2 H), 7.96 (s, 2 H)
(C), 118.4 (CH), 123.7 (CH), 128.0 (CH3), 128.4 (CH3), 128.7 ppm. 13C NMR (100 MHz, CDCl3): δ = 20.23 (CH3), 20.76 (CH2),
(CH3), 130.2 (C), 130.8 (CH3), 132.9 (C), 136.0 (CH), 136.3 (C), 23.26 (CH2), 26.23 (CH), 27.94 (CH2), 30.87 (CH), 31.96 (CH2),
139.1 (C), 142.2 (C), 161.9 (CH) ppm. ESI-MS: m/z = 543
[M + H]+.C37H38N2O2·2.0H2O (578.71): calcd. C 76.79, H 7.31, N
4.84; found C 76.37, H 7.46, N 4.72.
32.72 (CH3), 33.54 (CH3), 38.62 (C), 41.48 (CH2), 42.11 (CH2),
44.52 (CH2), 47.51 (CH3), 68.47 (CH), 98.75 (C), 124.98 (C), 125.41
(CH), 128.90 (C), 131.0 (C), 147.85 (CH), 157.27 (C) ppm. ESI-
MS: m/z = 663 [M + H]+. HRMS (ESI): calcd. for C45H63N2O2
[M+] 663.4811; found 663.4813.
4,4,4Ј,4Ј,6,6Ј-Hexamethylspiro-2,2Ј-bi(chroman)-8,8Ј-dicarb-
aldehyde (9): Dibromo compound 8 (2 g, 4.1 mmol) was dissolved
in THF (90 mL), and the resulting solution was cooled to –78 °C.
nBuLi (8.54 mmol, 5.35 mL, 1.6  solution) in hexanes was added
dropwise to the cooled solution. After stirring the mixture for
40 min, DMF (0.342 mL, 4.41 mmol in 0.671 mL of THF) was
added to the solution of the lithium compound. After stirring the
mixture at –78 °C for 2 h, the mixture was warmed to ca. 0 °C and
the reaction quenched with HCl (6 ⁿ, 2 mL). The crude product
was partitioned between CHCl3 and H2O, and the organic layers
were combined and dried with anhydrous MgSO4. The solvent was
removed under reduced pressure. The crude product was purified
by flash chromatography with silica gel (40 g) with hexane/ethyl
acetate (10:3) to give pure 9 as a white solid. Yield: 1.180 g, 74%.
4,4,4Ј,4Ј,6,6Ј-Hexamethylspiro-2,2Ј-bi(chroman)-8,8Ј-dicarb-
aldehydes [(+)-9 and (–)-9]: To a stirred solution of (+)-10 or (–)-10
(0.120 g, 0.181 mmol) in THF (20 mL) was added HCl (0.661 mL,
18.2 mmol), and the mixture was stirred at room temperature for
30 min. H2O (30 mL) was then added, and a white precipitate ap-
peared, which was collected and dried under vacuum for 12 h to
afford pure aldehydes (+)-9 and (–)-9 as white solids. (+)-9: Yield:
0.065 g, 92%. M.p. 197–199 °C. [α]2D0 = –147.2 (c = 0.37, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 1.38 (s, 6 H), 1.59 (s, 6 H), 2.17
(d, J = 14.3 Hz, 2 H), 2.28 (d, J = 14.3 Hz, 2 H), 2.30 (s, 6 H),
7.36 (s, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.7 (CH3),
30.6 (C), 32.2 (CH3), 32.9 (CH3), 46.9 (CH2), 98.9 (C), 124.9 (C),
126.3 (CH), 131.6 (C), 133.3 (C), 133.8 (CH), 150.8 (C), 189.4 (CH)
ppm. HRMS (ESI): calcd. for C25H28O4Na [M+] 415.1885; found
415.1881. C25H28O4 (392.49): calcd. C 76.50, H 7.19; found C
1
M.p. 197–199 °C. H NMR (400 MHz, CDCl3): δ = 1.38 (s, 6 H),
1.59 (s, 6 H), 2.17 (d, J = 14.3 Hz, 2 H), 2.28 (d, J = 14.3 Hz, 2
H), 2.30 (s, 6 H), 7.36 (s, 4 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 20.7 (CH3), 30.6 (C), 32.2 (CH3), 32.9 (CH3), 46.9 (CH2), 98.9
(C), 124.9 (C), 126.3 (CH), 131.6 (C), 133.3 (C), 133.8 (CH), 150.8
(C), 189.4 (CH) ppm. HRMS (ESI): calcd. for C25H28O4Na [M+]
415.1885; found 415.1877. C25H28O4·0.4H2O (399.69): calcd. C
75.13, H 7.26; found C 74.83, H 7.16.
76.31, H 7.37. (–)-9: Yield: 0.066 g, 92%. M.p. 197–199 °C. [α]2D0
=
1
+147.2 (c = 0.37, CHCl3). H NMR (400 MHz, CDCl3): δ = 1.38
(s, 6 H), 1.59 (s, 6 H), 2.17 (d, J = 14.3 Hz, 2 H), 2.28 (d, J =
14.3 Hz, 2 H), 2.30 (s, 6 H), 7.36 (s, 4 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 20.7 (CH3), 30.6 (C), 32.2 (CH3), 32.9
(CH3), 46.9 (CH2), 98.9 (C), 124.9 (C), 126.3 (CH), 131.6 (C), 133.3
(C), 133.8 (CH), 150.8 (C), 189.4 (CH) ppm. ESI-MS: m/z (%) =
393 [M + H]+. C25H28O4 (392.49): calcd. C 76.50, H 7.19; found C
76.31, H 7.41.
4,4,4Ј,4Ј,6,6Ј-Hexamethyl-8,8Ј-bis{[(–)-cis-myrtanylimino]methyl}-
spiro-2,2Ј-bi(chroman) (10): To a stirred solution of 9 (1.3 g,
3.31 mmol) in EtOH/CHCl3 (1:1, 15 mL) was added (–)-cis-myrt-
anylamine (1.21 mL, 7.13 mmol), and the mixture was stirred at
room temperature for 18 h. The solvent was then removed under
reduced pressure to afford a pure diastereomeric mixture of 10 as
4,4,4Ј,4Ј,6,6Ј-Hexamethyl-8,8Ј-bis[(phenylimino)methyl]spiro-2,2Ј-
bi(chroman) [(+)-11]: To a stirred solution of (+)-9 or (–)-9 (0.560 g,
1.43 mmol) in toluene (40 mL) were added molecular sieves (5 g)
and aniline (0.3 mL, 3.28 mmol). The mixture was then refluxed in
a Dean–Stark apparatus, and completion was observed after 20 h.
The resulting solution was washed with H2O (2ϫ30 mL), and the
organic layers were combined and dried (MgSO4). The solvent was
evaporated in vacuo to provide pure (+)-11 or (–)-11 as a white
1
a colorless oil. Yield: 2.112 g, 96%. H NMR (200 MHz, CDCl3):
δ = 0.87 (m, 4 H), 0.93 (s, 6 H), 0.97 (s, 6 H), 1.08 (s, 6 H), 1.14
(s, 6 H), 1.18 (s, 12 H), 1.36 (s, 12 H), 1.60 (s, 12 H), 2.09 (m, 20
H), 3.30 (m, 8 H), 7.16 (s, 4 H), 7.41 (s, 4 H), 7.91 (s, 2 H), 7.96
(s, 2 H) ppm. HRMS (ESI): calcd. for C45H63N2O2 [M+] 663.4811;
found 663.4815.
solid. (+)-11: Yield: 0.702 g, 91%. M.p. 214–216 °C (dec.). [α]2D0
+234.7 (c = 0.37, CHCl3). H NMR (400 MHz, CDCl3): δ = 1.39
=
1
(4,4,4Ј,4Ј,6,6Ј-Hexamethyl-8,8Ј-bis{[(–)-cis-myrtanylimino]methyl}-
spiro-2,2Ј-bi(chromans) [(+)-10 and (–)-10]: The addition of MeOH
to the diastereomeric mixture 10 (1.720 g, 2.59 mmol) afforded 14.8 Hz, 2 H), 2.30 (s, 6 H), 6.82 (s, 2 H), 6.84 (s, 2 H), 7.17 (t, J
pure (–)-10 by selective precipitation. Pure (+)-10 was then isolated
from the mother liquor in lower yield. (+)-10: Yield: 0.720 g, 84%,
Ͼ99% de. M.p. 150–152 °C. [α]2D0 = + 65, (c 0.69, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 0.86 (d, J = 9.5 Hz, 2 H), 0.94 (s, 6 H),
(s, 6 H), 1.58 (s, 6 H), 2.19 (d, J = 14.8 Hz, 2 H), 2.26 (d, J =
3
= 7.4 Hz, 2 H), 7.28 (m, 6 H), 7.64 (s, 2 H), 8.11 (s, 2 H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 20.7 (CH3), 31.1 (C), 32.0 (CH3),
32.8 (CH3), 47.5 (CH2), 99.7 (C), 115.1 (CH), 121.0 (CH), 125.0
(C), 125.4 (CH), 125.5 (CH), 128.8 (CH), 130.2 (CH), 131.7 (C),
Eur. J. Org. Chem. 2008, 6197–6205
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6203

Z. Freixa, et al.
FULL PAPER
133.3 (C), 133.8 (C), 148.8 (C), 156.3 (CH) ppm. HRMS (ESI):
calcd. for C3 7 H3 9 N2 O2 [M+ ] 543.3012; found 543.3018.
C37H38N2O2 (542.71): calcd. C 81.88, H 7.06, N 5.16; found C
81.85, H 7.01, N 5.20.
Supporting Information (see footnote on the first page of this arti-
1
cle): ORTEP plot for the X-ray structure of ligand 11; H and 13C
NMR spectra of the final ligands and intermediates, 1D and 2D
NMR spectra of complex 14 and further experimental details.
4,4,4Ј,4Ј,6,6Ј-Hexamethyl-8,8Ј-bis[(phenylamino)methyl]spiro-2,2Ј-
Acknowledgments
bi(chroman) [(+)-12]: To
a stirred solution of (+)-11 (0.1 g,
0.184 mmol) in toluene (15 mL) was added portion-wise NaBH4
(0.056 g, 1.48 mmol), and the mixture was stirred overnight. The
resulting mixture was quenched with H2O (5 mL), and the solvent
was removed under reduced pressure. The crude product was then
partitioned between CH2Cl2 and H2O, and the organic layers were
combined and dried with anhydrous MgSO4. The solvent was re-
moved under reduced pressure to provide pure (+)-12 as a yellowish
solid. (+)-12: Yield: 0.98 g, 98%. M.p. 100–102 °C. [α]2D0 = +265.5
(c = 0.41, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.37 (s, 6 H),
1.54 (s, 6 H), 2.12 (d, J = 14.2 Hz, 2 H), 2.20 (d, J = 14.2 Hz, 2
The Spanish Ministerio de Educación y Ciencia is kindly acknowl-
edged for a “Ramon y Cajal” contract (Z. F.), Project CTQ2005-
03416/BQU and Consolider Ingenio 2010 (Grant No. CSD2006_
0003). We thank the European Union for a Marie Curie Chair
of Excellence Grant (P. W. N. M. v. L.) (MEXC-CT-2005-0023600,
http://europa.eu.int/mariecurieactions). Prof. Sergio Castillón and
Prof. Pablo Ballester are thanked for pleasant and helpful dis-
cussions. Susana Delgado, Enrique Cequier and Eduardo C. Escu-
dero-Adán are acknowledged for technical support.
3
4
H), 2.29 (s, 6 H), 3.40 (s, 2 H), 3.89 (s, 4 H), 6.23 (dd, J = 8.1, J
3
4
= 1.2 Hz, 4 H), 6.64 (dt, J = 8.1, J = 1.2 Hz, 2 H), 6.95 (s, 2 H),
7.04 (s, 2 H), 7.07 (t, 3J = 8.1 Hz, 4 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 20.9 (CH3), 30.7 (C), 32.0 (CH3), 33.3 (CH3), 43.6
(CH2), 47.1 (CH2), 97.7 (C), 112.9 (CH), 116.9 (CH), 126.5 (CH),
127.1 (C), 127.7 (CH), 128.7 (CH), 130.8 (C), 131.9 (C), 145.9 (C),
148.0 (C) ppm. HRMS (ESI): calcd. for C37H43N2O2 [M+]
547.3325; found 547.3318. C37H42N2O2 (546.74): calcd. C 81.28, H
7.74, N 5.12; found C 81.01, H 7.85, N 4.83.
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[PdII(OAc)2{(–)-3}] [(–)-13]: To
a sample of (–)-3 (0.154 g,
0.42 mmol) in CH2Cl2 (20 mL) was added [PdCl2(COD)] (0.120 g,
0.42 mmol), and the mixture was stirred at room temperature for
6 h. Ag(OAc)2 was then added, and the mixture was stirred over-
night. The dark brown solution was filtered through a frit contain-
ing Celite to remove the AgCl formed, and the volume was reduced
under vacuum to provide complex (–)-13 as an orange-brown solid.
Yield: 0.205 g, 83%. 1H NMR (400 MHz, CDCl3, 25 °C): δ = 1.28.
3
(s, 6 H), 1.42 (s, 6 H), 2.06 (s, 6 H), 2.14 (d, J = 14.4 Hz, 2 H),
3
2
2.41 (d, J = 14.4 Hz, 2 H), 2.42 (s, 6 H), 3.38 (d, J = 8.6 Hz, 2
H), 5.58 (d, 2J = 8.6 Hz, 2 H), 6.94 (s, 2 H), 7.57 (s, 2 H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 21.3 (CH3), 24.8 (CH3), 27.1 (CH3),
27.7 (CH3), 33.3 (C) 53.6 (CH2), 107.1 (C), 121.6 (CH), 122.2 (CH),
130.7 (C), 134.5 (C), 138.1 (C), 140.4 (C), 183.9 (C) ppm. ESI-MS:
m/z = 543 [M + H]+. C37H38N2O2 (542.72): calcd. C 81.88, N 5.16,
H 7.06; found C 81.62, N 5.01, H 7.41.
Oxidative Kinetic Resolution of 2-Propanol: A 10 mL Schlenk flask
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0.049 mmol), base (0.044 mmol) and a Pd source (0.0375 mmol)
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Received: September 17, 2008
Published Online: November 12, 2008
Eur. J. Org. Chem. 2008, 6197–6205
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6205