Synthesis of iridium complexes with novel planar chiral chelating imidazolylidene ligands

TETRAHEDRON:

ASYMMETRY

Pergamon

Tetrahedron: Asymmetry 14 (2003) 1733–1746

Synthesis of iridium complexes with novel planar chiral chelating

imidazolylidene ligands

Carsten Bolm,* Thilo Focken and Gerhard Raabe

Institut fu¨r Organische Chemie der RWTH Aachen, Professor-Pirlet-Straße 1, D-52056 Aachen, Germany

Received 11 March 2003; accepted 23 April 2003

Abstract—New planar chiral imidazolium salts such as (S_p)-1-[4-(4,4-dimethyl-4,5-dihydrooxazolyl)[2.2]paracyclophane-12-

ylmethyl]-3-methyl imidazolium bromide (S_p)-8a have been synthesized starting from enantiopure 4,12-

dibromo[2.2]paracyclophane (S_p)-4. Deprotonation of these salts followed by reaction with [Ir(COD)Cl]₂yielded chelating iridium

imidazolylidene complexes 9a–c, which were applied in asymmetric hydrogenations of alkenes. The solid state structure of (S_p)-9c

1. Introduction

catalyst.⁶The synthesis and application of complexes of

type 2 bearing chelating biscarbene ligands has been

reported by Crabtree, Faller and Peris.⁷

Since the early reports on metal complexes bearing

N-heterocyclic carbene (NHC) ligands by Ofele and

1a

8

Wanzlick^1bin 1968 and the ﬁrst isolation of free NHCs

by Arduengo in 1991,²much progress has been made

with respect to the synthesis and the catalytic applica-

tions of NHCs and their metal complexes.^3,4Hence,

they now represent a signiﬁcant alternative to phos-

phine ligands in homogenous catalysis. In particular,

NHC complexes of ruthenium have become very popu-

lar in oleﬁn metathesis and exhibit superior properties

to the analogous phosphine ligands.⁵

However, only a few examples are known to date

directly relating to the application of chiral NHC lig-

ands in asymmetric catalysis. First, Herrmann and,

shortly after, Enders reported enantioselective hydro-

silylations using rhodium NHC complexes.⁸The appli-

cation of chiral ruthenium NHC complexes in asym-

metric oleﬁn metathesis was demonstrated by Grubbs

and Hoveyda.⁹Other examples include the use of silver

NHC complexes in the conjugate addition of diethyl-

zinc to unsaturated ketones,¹⁰and the application of

chiral triazonium salts as catalysts in the enantioselec-

tive benzoin condensation and Stetter reaction.¹¹Asym-

metric hydrogenations were reported by Burgess et al.¹²

They successfully applied iridium complex 3 bearing a

chiral chelating imidazolylidene ligand in catalyzed

hydrogenations of unfunctionalized alkenes giving

products with up to 99% ee in 98% yield.

Only recently have transition metal NHC complexes

been applied in the catalytic hydrogenations of alkenes

and transfer hydrogenations of ketones. Nolan et al.

have prepared saturated and unsaturated iridium NHC

complexes such as 1, which are similar to Crabtree’s

Recently, we reported on the synthesis of the ﬁrst

planar chiral carbene and metal complexes thereof.¹³In

this case, the planar chirality of the molecules origi-

nated from a ferrocene backbone. We have now

extended those studies and focused our attention on

syntheses of planar chiral pseudo-ortho-disubstituted

[2.2]paracyclophanes¹⁴with imidazolylidenyl and oxa-

zolinyl substituents. Furthermore, we have investigated

applications of the corresponding iridium carbene com-

plexes in catalyzed asymmetric oleﬁn hydrogenations.

* Corresponding author. Tel.: +49 241-8094675; fax: +49 241-

8092391; e-mail: carsten.bolm@oc.rwth-aachen.de

doi:10.1016/S0957-4166(03)00353-7

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C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

2. Results and discussion

treated with KOt-Bu in THF, and subsequent reactions

of the in situ formed carbenes with [Ir(COD)Cl)]₂fol-

lowed by anion exchange with NaBARF¹⁸afforded

complexes 9a–c in yields of 48–74%. The BARF coun-

terion was chosen, since it had previously been shown

to be superior over other bulky counterions such as

The syntheses of the desired compounds started from

enantiopure 4,12-dibromo[2.2]paracyclophane (S_p)-

4.^14,15Following a standard protocol for the synthesis

of oxazolines as described by Pelter,¹⁶(S_p)-4 was

treated with 1 equiv. of n-BuLi, and the resulting

carbanion was trapped with carbon dioxide affording

carboxylic acid (S_p)-5 in 87% yield (Scheme 1).

[2.2]Paracyclophanes (S_p)-6a and (S,S_p)-6b bearing a

bromo and an oxazolinyl substituent in the 4 and 12

positions, respectively, were then obtained from (S_p)-5

by sequential formation of the acid chloride, its treat-

ment with the appropriate amino alcohol and subse-

quent oxazoline formation by ring closure (80–87%

overall yields). Metallation of (S_p)-6a and (S,S_p)-6b

with t-BuLi followed by reaction with CO₂gave the

corresponding lithium carboxylates which were reduced

with LiAlH₄. The resulting alcohols were then reacted

with pyridine/PBr₃to afford methyl bromides (S_p)-7a

and (S,S_p)-7b, respectively (for details see Scheme 1).

Upon heating of mixtures of (S_p)-7a or (S,S_p)-7b and

imidazoles¹⁷in DMF, the desired imidazolium salts

(S_p)-8a,c and (S,S_p)-8b,d were obtained in yields rang-

ing from 50 to 97%. The diastereomeric products

(S,R_p)-6b, (S,R_p)-7b, (S,R_p)-8b and (S,R_p)-8d were pre-

pared by the same reaction sequence starting from the

R_p-enantiomer of 4.

−

PF₆. Interestingly, only (S_p)-8a, (S,S_p)-8b, (S_p)-8c, and

(S,R_p)-8b reacted well (to give (S_p)-9a, (S,S_p)-9b, (S_p)-

9c, and (S,R_p)-9b, respectively), whereas no products

were obtained from (S,S_p)-8d and (S,R_p)-8d. Pre-

sumably, the combination of the two bulky substituents

at both donor sites of the latter [2.2]paracyclophanes

(at the carbene a mesityl and at the oxazoline group a

tert-butyl substituent) inhibited complex formation due

to steric crowding.

Complexes 9a–c are bright yellow, air-stable solids. The

NMR spectra are consistent with the proposed chelat-

ing structures. The proton NMR spectra exhibit pro-

nounced chemical shifts for the two ortho protons (5-H

and 13-H) of the [2.2]paracyclophane rings, which show

low- and high-ﬁeld absorptions at l=9.4–9.6 and 4.6–

5.4 ppm, respectively. In the ¹³C NMR spectra the

signals for the coordinated carbenes appear at l=176–

178 ppm. Final structural proof was obtained by single-

crystal X-ray analysis of complex (S_p)-9c (Fig. 1).

Suitable crystals were obtained from a solvent mixture

Scheme 1. Reagents and conditions: (a) n-BuLi, THF, −78°C,

CO₂, 87% yield. (b) i. SOCl₂; ii. NEt₃, amino alcohol, CH₂Cl₂;

iii. SOCl₂, NaOH, 80–87% yield. (c) i. t-BuLi, THF, −78°C,

CO₂; ii. LiAlH₄, 52–73% yield; iii. PBr₃, pyridine, THF,

69–93% yield. (d) Imidazoles, DMF, 80°C, 50–97% yield.

Figure 1. The structure of (S_p)-9c in the solid state. The anion

has been omitted for clarity. The ellipsoids have been plotted

at the 30% probability level. [Ir1ꢀC43: 2.05(1), Ir1ꢀC1:

2.12(2), Ir1ꢀC2: 2.14(2), Ir1ꢀC5: 2.23(1), Ir1ꢀC6: 2.17(2),

Next, we focused on the preparation of iridium com-

plexes 9. For their syntheses imidazolium salts 8 were

,

Ir1ꢀN3: 2.137(9), C1ꢁC2: 1.34(2), C5ꢁC6: 1.37(2) A].

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

1735

of EtOH, CH₂Cl₂and Et₂O. The solid state structure

showed a signiﬁcant steric crowding around the metal

core, which might be the reason for the unavailability

of deﬁned structures of (S,S_p)-9b and (S,R_p)-9b.

matched combinations played only a minor role as

indicated by the insigniﬁcant variation in conversion

and ee in catalyses with those complexes (Table 1, entry

2 versus entry 3). At 50°C the conversion of 10a

increased up to 76%, however, now the enantioselectiv-

ity was lower as compared to the room temperature

experiments. The same trend was observed in the

hydrogenation of allylic alcohol 10b (Table 1, entry 5).

The best result was achieved in the hydrogenation of

dimethyl itaconate 10c using (S_p)-9c as catalyst. In this

case, full conversion was even observed at room tem-

perature applying the relatively low hydrogen pressure

of 10 bar. Reducing the latter further to 1 bar resulted

in a lower conversion of the substrate, but at the same

time, the ee of the product increased to 46% (Table 1,

entry 8). At 25°C and under 50 bar of hydrogen

monoesters 10d and 10e afforded the corresponding

saturated products with 38 and 21% ee, respectively

(Table 1, entries 9 and 10).

The iridium complexes were then tested as chiral cata-

lysts in the asymmetric hydrogenation of alkenes.^19,20

Although at room temperature their activities were

rather low (at a catalyst loading of 1 mol%), all com-

plexes except one, (S_p)-9a, led to optically active prod-

ucts 11 (Table 1). Interestingly, the most promising

results with respect to enantioselectivity were achieved

with planar chiral (S_p)-9c, which proved superior to its

analoges (S,S_p)-9b and (S,R_p)-9b having additional

stereogenic centers at the oxazolinyl groups. At 25°C

(and 50 bar of hydrogen pressure), the conversions in

the hydrogenation of trans-a-methyl stilbene 10a did

not exceed 35% affording the product with 28% ee at

best using (S_p)-9c as catalyst. The performance of

diastereomeric complexes (S,S_p)-9b and (S,R_p)-9b was

almost equal, leading to lower yields and reduced enan-

tioselectivities (12 and 11% ee, respectively) under com-

parable conditions (Table 1, entries 2 and 3). In all

cases, the (R)-enantiomer of the product was predomi-

nantly formed. Apparently, cooperative effects between

the stereogenic elements²¹in the diastereomeric com-

plexes (S,S_p)-9b and (S,R_p)-9b leading to matched/mis-

On the basis of these results, we conclude that the steric

properties of the substituents on both the imidazole as

well as the oxazoline ring play an important role in the

activity of the catalyst. For example, in contrast to its

N-mesityl analogue (S_p)-9c, the N-methyl complex (S_p)-

9a showed no activity at all in the room temperature

hydrogenation of 10a (Table 1, entries 1 and 4). When

Table 1. Asymmetric hydrogenations with various Ir complexes 9 as catalysts^a

Entry

Substrate

Catalyst

p(H₂) (bar)

T (°C)

Conversion (%)^b

Ee (%)^c

1

2

3

4

5

6

7

8

10a

10b

10c

10d

10e

(S_p)-9a

(S,S_p)-9b

(S,R_p)-9b

(S_p)-9c

50^d

50^f

10^d

1^g

25/50

25

−/40

17/61

15/59

35/76

25/100

100

46

99

100

−/0

12/4 (R)

11/10 (R)

28/15 (R)

11/4^e

9 (R)

13 (R)

46 (R)

38 (R)

21 (R)

9

10

50^d

^aSee Section 3 for reaction details.

^bDetermined by ¹H NMR; conversions at 25°C/50°C.

^cDetermined by HPLC using a chiral column; the absolute conﬁgurations were assigned by comparison of the HPLC retention times with

literature values; ee’s at 25°C/50°C.

^dReaction time: 6–24 h.

^eAbsolute conﬁguration not determined.

^fReaction time: 2 h.

^gReaction time: 48 h.

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C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

3.2. Synthesis of (S_p)-4-bromo-12-(4,4-dimethyl-4,5-

dihydrooxazolyl)[2.2]paracyclophane (S_p)-6a

complexes (S,S_p)-9b and (S,R_p)-9b were used as cata-

lysts, product formation was observed, and in these

cases we attribute the catalytic activity to the presence

of the sterically bulky tert-butyl groups on the oxa-

zolinyl substituents. Unfortunately, complexes bearing

a combination of an N-mesityl on the imidazole and a

tert-butyl group on the oxazoline moiety could not be

prepared. However, since we expect promising cata-

lytic activities from those complexes, attempts to syn-

thesize these compounds will be pursued further.

3.2.1.

(S_p)-4-Bromo-12-carboxy[2.2]paracyclophane

(S_p)-5.

In summary, we have synthesized new iridium imida-

zolylidine complexes with planar chiral [2.2]paracyclo-

phanes as ligands. They have been applied as catalysts

in the asymmetric hydrogenations of alkenes giving

enantiomerically enriched products with up to 46% ee.

Studies towards improvements of activity and stereose-

lectivity are currently on-going in our laboratories.

(S_p)-pseudo-ortho-Dibromo[2.2]paracyclophane (S_p)-4

(10.0 g, 27.3 mmol) was placed in a Schlenk ﬂask

under an argon atmosphere and dissolved in anhy-

drous THF (120 mL). After cooling to −78°C in a dry

ice/acetone bath, a solution of n-BuLi in pentane (20.0

mL, 32.0 mmol) was added slowly. The reaction mix-

ture was stirred at −78°C for 1 h, and subsequently

carbon dioxide was bubbled through it for 30 min.

The solution was then allowed to slowly warm to

room temperature, acidiﬁed with 5 M HCl to pH 1–2,

and extracted with dichloromethane (3×100 mL). The

combined organic extracts were washed with 10 M

NaOH (4×100 mL). After acidiﬁcation of the aqueous

layers to pH 1–2 with concentrated HCl and extrac-

tion with dichloromethane (3×100 mL), the combined

organic phase was dried (MgSO₄) and concentrated to

3. Experimental

3.1. General information

pseudo-ortho-Dibromo[2.2]paracyclophane¹⁵and 1-

mesitylimidazole¹⁷were prepared according to pub-

lished procedures. (S)-t-Leucinol was prepared from

(S)-t-leucine (obtained as a gift from Degussa). The

following reagents and solvents are commercially

available and were used as received: 2-amino-2-methyl-

propan-1-ol (Aldrich), n-BuLi (1.6 M in n-hexane,

give

7.90

g

of

(S_p)-4-bromo-12-car-

boxy[2.2]paracyclophane (S_p)-5 as a white solid (87%

yield). The product can be recrystallized from glacial

acetic acid. Mp 228–229°C; [h]²_D⁵=+141 (c 1.1,

1

CHCl₃); H NMR (400 MHz, DMSO-d₆) l 2.74–2.89

Merck-Schuchardt), t-BuLi (1.48

M in pentane,

(m, 3H, CH₂), 2.98–3.08 (m, 3H, CH₂), 3.23 (ddd, 1H,

J=13.0, 8.7, 2.9 Hz, CH₂), 3.91–3.97 (m, 1H, CH₂),

6.44 (d, 1H, J=1.6 Hz, 5-H), 6.54 (d, 1H, J=7.7 Hz,

Aryl-CH), 6.62–6.65 (m, 2H, Aryl-CH), 6.68 (dd, 1H,

J=8.0, 2.0 Hz, 15-H), 7.58 (d, 1H, J=1.9 Hz, 13-H),

12.51 Hz (bs, 1H, COOH); ¹³C NMR (100 MHz,

DMSO-d₆) l 32.8, 34.3, 35.7, 36.1 (CH₂), 126.6 (qC),

131.3 (C-13), 131.5 (qC), 132.2 (CH), 135.4 (C-5),

136.0, 136.6, 137.3 (CH), 139.1, 139.6, 142.2, 142.6

(qC), 168.6 (CꢁO); IR (KBr) w˜ 1679, 1297, 1273 cm⁻¹;

MS (EI, 70 eV) m/z (%) 332 (31), 330 (34, M⁺), 185

(100), 184 (44), 183 (99), 182 (35), 148 (57), 103 (24),

91 (19), 77 (25). Anal. calcd for C₁₇H₁₅BrO₂: C, 61.65;

H, 4.56. Found: C, 61.85; H, 4.75.

Merck-Schuchardt), KOt-Bu (1 M, Aldrich), 1-

methylimidazole (Aldrich), anhydrous DMF (Aldrich).

[Ir(COD)Cl]₂was obtained as a gift from OMG. THF

was distilled under nitrogen from sodium benzophe-

none ketyl and CH₂Cl₂from calcium hydride prior to

use. All reactions were performed under an inert

atmosphere of argon using standard Schlenk tech-

niques. The NMR spectra were recorded on a Varian

Mercury 300 (¹H NMR at 300 MHz; ¹³C NMR at 75

MHz), a Varian Inova 400 (¹H NMR at 400 MHz;

¹³C NMR at 100 MHz; ¹⁹F NMR at 376 MHz), or

Varian Unity 500 (¹H NMR at 500 MHz; ¹³C NMR

at 125 MHz; ¹¹B NMR at 160 MHz) spectrometer.

Chemical shifts are given in ppm with internal refer-

encing to TMS (¹H NMR), external CFCl₃(¹⁹F

NMR), external BF₃·OEt₂(¹¹B NMR) or the solvent

peaks (¹H, ¹³C NMR). Assignments are based on 2D

NMR experiments. IR spectra were measured on a

Perkin–Elmer 1760 FT spectrometer, mass spectra

were obtained by using a Varian MAT 212 (EI, ESI,

APCI) and a Finnigan MAT 95 (SIMS-FAB) spec-

trometer. Only fragments containing the isotopes of

the highest abundance are listed. Elemental analyses

were carried out at the Institut fu¨r Organische Chemie

der RWTH Aachen on a Heraeus CHNO-Rapid

apparatus. Melting points were measured with a Bu¨chi

B-540 melting point determination apparatus. Optical

rotations were measured on a Perkin–Elmer 241 polar-

meter.

3.2.2. (S_p)-4-Bromo-N-(1-hydroxy-2-methyl-2-propyl)-

[2.2]paracyclophane-12-carboxamide.

(S_p)-4-Bromo-12-carboxy[2.2]paracyclophane

(S_p)-5

(7.4 g, 22.3 mmol) was stirred in thionyl chloride at

60°C for 4 h. After evaporation of SOCl₂in vacuo,

remaining traces of it were removed by destillation

with small portions of toluene (3×5 mL). The residue

was dissolved in anhydrous CH₂Cl₂(20 mL) and

cooled to 0°C.

A solution of 2-amino-2-methyl-

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

1737

propan-1-ol (4.2 mL, 44.0 mmol) and NEt₃(6.1 mL,

44.1 mmol) in CH₂Cl₂(30 mL) was added over 1 h

while maintaining the temperature at 0°C. The reaction

mixture was allowed to warm to room temperature and

stirred over night. The solution was diluted with

dichloromethane (50 mL) and washed with aqueous

NaHCO₃(2×80 mL) and brine (80 mL). The organic

phase was concentrated and the residue puriﬁed by

column chromatography on silica gel (hexane:ethyl ace-

tate, 7:3) to give 7.88 g (88% yield) of (S_p)-4-bromo-N-

(1-hydroxy-2-methyl-2-propyl)[2.2]paracyclophane-12-ca

rboxamide as a white, crystalline solid. Mp 152–154°C;

13-H); ¹³C NMR (100 MHz, CDCl₃) l 28.8, 28.9

(CH₃), 33.0, 34.2, 36.1, 36.4 (CH₂), 68.1 (C(CH₃)₂),

78.6 (OCH₂), 126.8, 128.6 (qC), 130.6 (C-13), 131.5,

135.1, 135.2, 135.3, 135.9 (CH), 139.0, 139.4, 140.7,

142.3 (qC), 161.9 (C=N); IR (KBr) w˜ 2961, 2929, 2898,

1627, 1303, 1192 cm⁻¹; MS (EI, 70 eV) m/z (%) 385

(22), 383 (26, M⁺), 202 (15), 201 (100), 146 (11), 103

(10). Anal. calcd for C₂₁H₂₂BrNO: C, 65.63; H, 5.77; N,

3.64. Found: C, 65.81; H, 5.84; N, 3.58.

3.3. Synthesis of (S,S_p)-4-bromo-12-(4-tert-butyl-4,5-

dihydrooxazolyl)[2.2]paracyclophane (S,S_p)-6b

1

[h]²_D⁵=+63 (c 1.0, CHCl₃); H NMR (400 MHz, CDCl₃)

l 1.41 (s, 3H, CH₃), 1.48 (s, 3H, CH₃), 2.77–2.87 (m,

2H, CH₂), 2.96–3.06 (m, 2H, CH₂), 3.07–3.18 (m, 2H,

CH₂), 3.44 (ddd, 1H, J=9.3, 2.6 Hz, CH₂), 3.68–3.79

(m, 3H, CH₂OH, CH₂), 4.85 (bs, 1H, OH), 6.08 (bs,

1H, NH), 6.52 (d, 1H, J=7.7 Hz, Aryl-CH), 6.56–6.61

(m, 3H, Aryl-CH), 6.80 (d, 1H, J=1.6 Hz, 5-H), 7.17

(d, 1H, J=1.7 Hz, 13-H); ¹³C NMR (100 MHz,

CDCl₃) l 25.2, 25.2 (CH₃), 32.9, 34.8, 34.9, 36.0 (CH₂),

57.0 (C(CH₃)₂), 71.3 (CH₂OH), 126.6 (qC), 126.9 (C-

13), 131.8 (CH), 135.0 (C-5), 135.2 (CH), 135.4 (qC),

135.6, 136.3 (CH), 138.8, 139.8, 139.8, 142.4 (qC),

170.0 (CꢁO); IR (KBr) w˜ 3254, 3162, 3068, 2981, 2964,

2934, 2858, 1630, 1568, 1548, 1348, 1067 cm⁻¹; MS (EI,

70 eV) m/z (%) 403 (20), 401 (20, M⁺), 332 (18), 330

(20), 219 (29), 148 (10), 147 (100), 146 (12), 131 (32),

103 (22), 77 (16). Anal. calcd for C₂₁H₂₄BrNO₂: C,

62.69; H, 6.01; N, 3.48. Found: C, 62.39; H, 5.79; N,

3.22.

3.3.1. (S,S_p)-4-Bromo-N-(1-hydroxy-3-dimethyl-2-butyl)-

[2.2]paracyclophane-12-carboxamide.

This compound was prepared by the method described

for

(S_p)-4-bromo-N-(1-hydroxy-2-methyl-2-propyl)-

using (S_p)-4-

[2.2]paracyclophane-12-carboxamide

bromo-12-carboxy-[2.2]paracyclophane (S_p)-5 (5.0 g,

15.1 mmol), SOCl₂(10 mL), CH₂Cl₂(30 mL), NEt₃(4.2

mL, 30.1 mmol), and (S)-t-leucinol (3.5 g, 29.9 mmol).

Puriﬁcation by column chromatography on silica gel

(EtOAc:hexane, 1:2 to 2:1) yielded 5.26 g (81%) of the

title compound as a white solid. Mp 150–152°C; [h]²_D⁵=

+70 (c 1.0, CHCl₃); ¹H NMR (300 MHz, CDCl₃) l 1.09

(s, 9H, CH₃), 2.64 (bs, 1H, OH), 2.74–2.88 (m, 2H,

CH₂), 2.97–3.20 (m, 4H, CH₂), 3.45 (ddd, 1H, J=13.2,

9.2, 2.3 Hz, CH₂), 3.59 (dd, 1H, J=11.1, 7.8 Hz,

CH₂OH), 3.72 (ddd, 1H, J=12.2, 10.2, 2.0 Hz, CH₂),

3.90 (dd, 1H, J=11.2, 3.3 Hz, CH₂OH), 4.04 (ddd, 1H,

J=9.3, 7.8, 3.5 Hz, CHtBu), 5.99 (bd, 1H, J=9.2 Hz,

NH), 6.51 (d, 1H, J=7.7 Hz, Aryl-CH), 6.56–6.60 (m,

3H, Aryl-CH), 6.79 (d, 1H, J=1.8 Hz, 5-H), 7.28 (d,

1H, J=1.3 Hz, 13-H); ¹³C NMR (75 MHz, CDCl₃) l

27.7 (3C, C(CH₃)₃), 32.9, 34.4, 34.9, 35.1, 36.1

(C(CH₃)₃, CH₂), 60.0 (CHtBu), 63.6 (CH₂OH), 127.0

(C-13), 131.5 (CH), 134.8 (qC), 134.9 (C-5), 135.6,

135.7, 136.1 (CH), 138.8, 139.8, 140.0, 142.5 (qC),

170.2 (CꢁO); IR (KBr) w˜ 3424, 3329, 2962, 2929, 2866,

1659, 1623, 1513, 1477, 1085 cm⁻¹; MS (EI, 70 eV) m/z

(%): 432 (11), 431 (48), 430 (12), 429 (M⁺, 47), 374 (11),

372 (11), 355 (11), 332 (46), 330 (45), 315 (18), 313 (16),

248 (16), 247 (100), 147 (87), 146 (12), 132 (14), 131

(87), 104 (11), 103 (44). Anal. calcd for C₂₃H₂₈BrNO₂:

C, 64.19; H, 6.56; N, 3.25. Found: C, 64.30; H, 6.24; N,

3.15.

3.2.3.

(S_p)-4-Bromo-12-(4,4-dimethyl-4,5-dihydrooxa-

zolyl)[2.2]paracyclophane (S_p)-6a.

(S_p)-4-Bromo-N-(1-hydroxy-2-methyl-2-propyl)[2.2]-

paracyclophane-12-carboxamide (7.65 g, 19.0 mmol)

was stirred in thionyl chloride at room temperature for

4 h. After concentration of the reaction mixture in

vacuo at 40°C, the residue was dissolved in CH₂Cl₂

(200 mL) and stirred with a solution of sodium hydrox-

ide (10%, 200 mL) over night. After phase separation,

the organic layer was washed with brine (50 mL), dried

(MgSO₄) and evaporated to yield 7.26 g (99% yield) of

(S_p)-4-bromo-12-(4,4-dimethyl-4,5-dihydrooxazolyl)-

[2.2]paracyclophane (S_p)-6a as a pale orange solid. No

by-product was detectable by NMR spectroscopy. An

analytical pure sample of (S_p)-6a was obtained by

recrystallization from methanol. Mp 104–106°C; [h]²_D⁵=

+81 (c 1.2, CHCl₃); ¹H NMR (400 MHz, CDCl₃) l 1.40

(s, 3H, CH₃), 1.46 (s, 3H, CH₃), 2.74–2.82 (m, 2H,

CH₂), 2.94–3.10 (m, 3H, CH₂), 3.15–3.23 (m, 1H, CH₂),

3.45 (ddd, 1H, J=13.2, 10.1 Hz, 1.7 Hz, CH₂), 4.03 (d,

1H, J=7.9 Hz, OCH₂), 4.12 (d, 1H, J=8.0 Hz, OCH₂),

4.24 (ddd, 1H, J=12.3, 9.9, 1.3 Hz, CH₂), 6.46 (d, 1H,

J=7.7 Hz, Aryl-CH), 6.53–6.60 (m, 3H, Aryl-CH),

6.62 (d, 1H, J=1.4 Hz, 5-H), 7.65 (d, 1H, J=1.3 Hz,

3.3.2. (S,S_p)-4-Bromo-12-(4-tert-butyl-4,5-dihydrooxa-

zolyl)[2.2]paracyclophane (S,S_p)-6b.

1738

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

This compound was prepared by the same procedure as

described for (S_p)-6a using (S,S_p)-4-bromo-N-(1-

hydroxy-3-dimethyl-2-butyl)-[2.2]paracyclophane-12-

carboxamide (5.0 g, 11.6 mmol) and SOCl₂(40 mL).

The product was obtained as a pale yellow solid (4.76 g,

99% yield). No by-product was detectable by NMR

spectroscopy. The compound can be recrystallized from

MS (EI, 70 eV) m/z (%) 431 (40), 429 (M⁺, 44), 374

(15), 372 (16), 332 (52), 330 (50), 315 (15), 313 (13), 248

(14), 247 (99), 147 (99), 146 (10), 132 (13), 131 (100),

103 (50). Anal. calcd for C₂₃H₂₈BrNO₂: C, 64.19; H,

6.56; N, 3.25. Found: C, 64.44; H, 6.53; N, 3.11.

3.4.2. (S,R_p)-4-Bromo-12-(4-tert-4,5-dihydrooxazolyl)-

[2.2]paracyclophane (S,R_p)-6b.

1

methanol. Mp 103–105°C; [h]²_D⁵=+7 (c 1.0, CHCl₃); H

NMR (400 MHz, CDCl₃) l 1.08 (s, 9H, CH₃), 2.75–

2.87 (m, 2H, CH₂), 3.02–3.12 (m, 3H, CH₂), 3.14–3.22

(m, 1H, CH₂), 3.46 (ddd, 1H, J=13.2, 9.9, 1.4 Hz,

CH₂), 4.07 (dd, 1H, J=10.0, 9.0 Hz, OCH₂), 4.19 (t,

1H, J=8.6 Hz, CHtBu), 4.28 (dd, 1H, J=10.3, 8.3 Hz,

OCH₂), 4.31–4.37 (m, 1H, CH₂), 6.49 (d, 1H, J=8.0

Hz, Aryl-CH), 6.54–6.62 (m, 4H, Aryl-CH), 7.61 (bs,

1H, 13-H); ¹³C NMR (100 MHz, CDCl₃) l 26.8 (3C,

C(CH₃)₃), 32.9, 34.0 (CH₂), 34.6 (C(CH₃)₃), 35.9, 36.1

(CH₂), 67.9 (OCH₂), 77.4 (CHtBu), 126.9, 128.2 (qC),

130.0 (C-13), 131.5, 135.1, 135.3, 135.5, 135.8 (CH),

139.0, 139.3, 140.8, 142.3 (qC), 162.9 (CꢁN). IR (KBr)

w˜ 2956, 2928, 2866, 1638, 1047, 1031, 984 cm⁻¹; MS (EI,

70 eV) m/z (%) 413 (38), 411 (M⁺, 36), 230 (17), 229

(100), 147 (11). Anal. calcd for C₂₃H₂₆BrNO: C, 66.99;

H, 6.36; N, 3.40. Found: C, 66.77; H, 6.49; N, 3.29.

This compound was prepared by the same procedure as

described for (S_p)-6a using (S,R_p)-4-bromo-N-(1-

hydroxy-3-dimethyl-2-butyl)-[2.2]paracyclophane-12-

carboxamide (6.2 g, 14.4 mmol) and SOCl₂(50 mL).

The product was obtained as a pale yellow solid (5.86 g,

99% yield). No by-product was detectable by NMR

spectroscopy. The compound can be recrystallized from

1

methanol. Mp 60–62°C; [h]²_D⁵=−110 (c 1.0, CHCl₃); H

NMR (300 MHz, CDCl₃) l 1.02 (s, 9H, C(CH₃)₃),

2.72–2.84 (m, 2H, CH₂), 2.93–3.10 (m, 3H, CH₂), 3.14–

3.24 (m, 1H, CH₂), 3.45 (ddd, 1H, J=13.1, 9.9, 1.6 Hz,

CH₂), 4.05–4.20 (m, 3H, CH₂, OCH₂, CHtBu), 4.33

(dd, 1H, J=9.7, 7.9 Hz, OCH₂), 6.47 (d, 1H, J=7.7

Hz, Aryl-CH), 6.53–6.60 (m, 3H, Aryl-CH), 6.66 (d,

1H, J=1.4 Hz, 5-H), 7.66 (bs, 1H, 13-H); ¹³C NMR

(100 MHz, CDCl₃) l 26.5 (3C, C(CH₃)₃), 32.9, 34.3

(CH₂), 34.4 (C(CH₃)₃), 36.2, 36.4 (CH₂), 68.4 (OCH₂),

76.9 (CHtBu), 126.9, 128.3 (qC), 130.5 (C-13), 131.4,

135.1, 135.2 (CH), 135.3 (C-5), 135.8 (CH), 139.0,

139.4, 140.5, 142.3 (qC), 163.4 (CꢁN); IR (KBr) w˜ 2932,

2866, 1645, 1477, 1048, 1031, 980 cm⁻¹; MS (EI, 70 eV)

m/z (%) 413 (26), 411 (M⁺, 26), 230 (15), 229 (100), 147

(12). Anal. calcd for C₂₃H₂₆BrNO: C, 66.99; H, 6.36; N,

3.40. Found: C, 66.79; H, 6.20; N, 3.29.

3.4. Synthesis of (S,R_p)-4-bromo-12-(4-tert-4,5-dihy-

drooxazolyl)[2.2]paracyclophane (S,R_p)-6b

3.4.1. (S,R_p)-4-Bromo-N-(1-hydroxy-3-dimethyl-2-butyl)-

[2.2]paracyclophane-12-carboxamide.

This compound was prepared by the method described

for

(S_p)-4-bromo-N-(1-hydroxy-2-methyl-2-propyl)-

using (R_p)-4-

[2.2]paracyclophane-12-carboxamide

3.5. Synthesis of (S_p)-4-bromomethyl-12-(4,4-dimethyl-

4,5-dihydrooxazolyl)[2.2]paracyclophane (S_p)-7a

bromo-12-carboxy-[2.2]paracyclophane (R_p)-5 (5.6 g,

16.9 mmol), SOCl₂(12 mL), CH₂Cl₂(40 mL), NEt₃(4.8

mL, 34.4 mmol), and (S)-t-leucinol (4.0 g, 34.1 mmol).

The title compound was obtained as a white solid in

88% yield (6.44 g) after puriﬁcation on silica gel

(EtOAc:hexane, 1:1). Mp 146°C; [h]²_D⁵=−53 (c 1.0,

3.5.1.

(S_p)-4-(4,4-Dimethyl-4,5-dihydrooxazolyl)-12-

hydroxymethyl[2.2]paracyclophane.

1

CHCl₃); H NMR (400 MHz, CDCl₃) l 1.05 (s, 9H,

CH₃), 2.78–2.89 (m, 3H, CH₂, OH), 3.00–3.04 (m, 2H,

CH₂), 3.11–3.20 (m, 2H, CH₂), 3.45 (ddd, 1H, J=13.2,

9.1, 2.5 Hz, CH₂), 3.82–3.89 (m, 1H, CH₂OH), 3.85

(ddd, 1H, J=12.5, 8.7, 3.9 Hz, CH₂), 4.07–4.15 (m, 2H,

CH₂OH, CHtBu), 6.32 (bd, 1H, J=9.4 Hz, NH), 6.53

(d, 1H, J=7.9 Hz, Aryl-CH), 6.57–6.61 (m, 2H, Aryl-

CH), 6.64 (d, 1H, J=8.0 Hz, Aryl-CH) 6.94 (d, 1H,

J=1.3 Hz, 5-H), 7.24 (d, 1H, J=1.6 Hz, 13-H). ¹³C

NMR (100 MHz, CDCl₃) l 27.5 (3C, C(CH₃)₃), 32.9

(CH₂), 34.1 (C(CH₃)₃), 34.6 (CH₂), 34.9 (CH₂), 36.0

(CH₂), 60.3 (CHtBu), 63.7 (CH₂OH), 126.3 (C-13),

126.4 (qC), 131.9 (CH), 135.2 (C-5), 135.3, 135.4 (CH),

136.1 (qC), 136.5 (CH), 138.7, 139.7, 140.1, 142.8 (qC),

170.1 (CꢁO). IR (KBr) w˜ 3305, 2935, 1638, 1536 cm⁻¹;

At −78°C a solution of oxazoline (S_p)-6a (5.2 g, mmol)

in THF (100 mL) was treated slowly with a solution of

t-BuLi in pentane (20.0 mL, 29.6 mmol). After stirring

for 1 h at this temperature, carbon dioxide was bubbled

through the reaction mixture for 30 min (at −78°C). After

warming slowly to room temperature, the reaction mix-

ture was carefully degassed by means of a super sonic

bath, and then LiAlH₄(1.0 g, 27.1 mmol) was added at

0°C. The mixture was stirred at room temperature over

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

1739

J=7.9 Hz, OCH₂), 4.14 (d, 1H, J=7.9 Hz, OCH₂),

4.18 (ddd, 1H, J=12.1, 10.1, 1.5 Hz, CH₂), 4.32 (d,

1H, J=10.1 Hz, CH₂Br), 4.51 (d, 1H J=10.4 Hz,

CH₂Br), 6.42 (d, 1H, J=1.2 Hz, 5-H), 6.48 (d, 1H,

J=7.9 Hz, 8-H), 6.52 (dd, 1H J=7.8, 1.7 Hz, 7-H),

6.56 (d, 1H, J=7.9 Hz, 16-H), 6.60 (dd, 1H, J=8.0,

1.9 Hz, 15-H), 7.11 (bs, 1H, 13-H), ¹³C NMR (125

MHz, CDCl₃) l 28.3, 28.4 (CH₃), 32.9 (CH₂), 33.2

(CH₂Br), 33.8, 34.1 (CH₂), 35.6 (CH₂), 67.5

(C(CH₃)₂), 78.6 (OCH₂), 128.4 (qC), 131.3 (C-13),

133.1 (C-5), 133.2 (C-7), 135.0 (C-15), 135.4 (C-8),

136.2 (C-16), 136.9, 137.8, 139.2, 140.6, 140.8 (qC),

162.1 (CꢁN); IR (KBr) w˜ 2957, 2930, 2859, 1630, 1587,

1300, 1195, 1039, 986, 622 cm⁻¹; MS (EI, 70 eV) m/z

(%) 399 (36), 397 (34, M⁺), 318 (29), 202 (17), 201

(100), 200 (13), 146 (12), 117 (13), 115 (15). Anal.

calcd for C₂₂H₂₄BrNO: C, 66.33; H, 6.07; N, 3.52.

Found: C, 66.17; H, 6.26; N, 3.38.

night. Then, it was treated with aqueous HCl (5 M)

until a pH of ꢀ4 was reached. After phase separation,

the aqueous layer was extracted with dichloromethane

(3×40 mL). The combined organic phase was dried

(MgSO₄), concentrated, and the remaining residue was

puriﬁed by column chromatography on silica gel (hex-

ane:ethyl acetate, 2:1) to give 3.33 g of (S_p)-4-(4,4-

dimethyl-4,5-dihydrooxazolyl)-12-hydroxymethyl[2.2]-

paracyclophane (73% yield) as a white solid. Mp 121–

122°C; [h]²_D⁵=+107 (c 1.0, CHCl₃); ¹H NMR (500

MHz, CDCl₃) l 1.38 (s, 3H, CH₃), 1.57 (s, 3H, CH₃),

2.78–2.91 (m, 3H, CH₂), 3.06–3.16 (m, 3H, CH₂), 3.27

(ddd, 1H, J=12.8, 9.8, 3.1 Hz, CH₂), 3.63–3.68 (m,

1H, CH₂), 4.14 (d, 1H, J=8.2 Hz, OCH₂), 4.19 (d,

1H, J=7.9 Hz, OCH₂), 4.54 (d, 1H, J=15.3 Hz,

CH₂OH), 4.68 (d, 1H J=15.0 Hz, CH₂OH), 5.90 (bs,

1H, OH), 6.42 (d, 1H, J=7.6 Hz, 16-H), 6.46 (dd, 1H

J=7.7, 1.6 Hz, 15-H), 6.56 (d, 1H, J=7.6 Hz, 7-H),

6.61 (dd, 1H, J=7.9, 1.8 Hz, 8-H), 6.80 (bs, 1H,

13-H), 7.19 (d, 1H, J=1.9 Hz, 5-H); ¹³C NMR (125

MHz, CDCl₃) l 28.2, 28.3 (CH₃), 32.2, 33.3, 34.4,

34.7 (CH₂), 63.0 (CH₂OH), 66.8 (C(CH₃)₂), 79.9

(OCH₂), 127.3 (C-13), 128.8 (qC), 130.5 (C-5), 131.2

(C-15), 134.1 (C-16), 135.3 (C-8), 135.5 (C-7), 135.8,

139.5, 139.7, 139.7, 140.5 (qC), 165.4 (CꢁN); IR (KBr)

w˜ 3254, 2963, 2925, 2898, 2852, 1642, 1420, 1307, 1188,

1070, 1046, 966, 652 cm⁻¹; MS (70 eV) m/z (%) 336

(12), 335 (56, M⁺), 202 (23), 201 (100). Anal. calcd for

C₂₂H₂₅NO₂: C, 78.77; H, 7.51; N, 4.18. Found: C,

78.80; H, 7.56; N, 4.13.

3.6. Synthesis of (S,S_p)-4-bromomethyl-12-(4-tert-butyl-

4,5-dihydrooxazolyl)[2.2]paracyclophane (S,S_p)-7b

3.6.1.

(S,S_p)-4-(4-tert-Butyl-4,5-dihydrooxazolyl)-12-

hydroxymethyl[2.2]paracyclophane.

3.5.2. (S_p)-4-Bromomethyl-12-(4,4-dimethyl-4,5-dihydro-

oxazolyl)[2.2]paracyclophane (S_p)-7a.

This compound was prepared by the method described

for

(S_p)-4-(4,4-dimethyl-4,5-dihydrooxazolyl)-12-

hydroxymethyl[2.2]paracyclophane using (S,S_p)-6b

(4.12 g, 10.0 mmol), t-BuLi (15 mL, 22.5 mmol), THF

(220 mL) and LiAlH₄(0.8 g, 21.3 mmol). Puriﬁcation

by column chromatography (pentane:ethyl acetate,

4:1) gave 2.42 g (66%) of the title compound as a

white solid. Mp 89–90°C; [h]²_D⁵=+74 (c 1.0, CHCl₃);

¹H NMR (300 MHz, CDCl₃) l 0.97 (s, 9H, CH₃),

2.76–2.95 (m, 3H, CH₂), 3.04–3.19 (m, 3H, CH₂), 3.28

(ddd, 1H, J=12.5, 9.2, 3.3 Hz, CH₂), 3.56–3.66 (m,

1H, CH₂), 4.16 (dd, 1H, J=10.2, 7.3 Hz, CHtBu),

4.27 (dd, 1H, J=8.6, 7.3 Hz, OCH₂), 4.43 (dd, 1H,

J=10.1, 8.8 Hz, OCH₂), 4.53 (bd, 1H, J=15.6 Hz,

CH₂OH), 4.68 (bd, 1H, J=15.1 Hz, CH₂OH), 5.99

(bs, 1H, CH₂OH), 6.41 (d, 1H, J=7.9 Hz, 16-H), 6.46

(dd, 1H, J=7.7, 1.8 Hz, 15-H), 6.56 (d, 1H, J=7.6

Hz, 8-H), 6.60 (dd, 1H, J=7.9, 1.9 Hz, 7-H), 6.75 (s,

1H, 13-H), 7.23 (d, 1H, J=2.0 Hz, 5-H); ¹³C NMR

(75 MHz, CDCl₃) l 26.2 (3C, C(CH₃)₃), 32.6, 33.7

(CH₂), 34.6 (C(CH₃)₃), 34.7, 35.0 (CH₂), 63.4

(CH₂OH), 69.9 (OCH₂), 75.1 (CHtBu), 127.7 (CH),

129.1 (qC), 130.5, 131.4, 134.2, 135.7, 135.8 (CH),

136.1, 139.8, 140.0, 140.1, 140.9 (qC), 167.0 (CꢁN); IR

(KBr) w˜ 2949, 2864, 1637, 1480, 1044 cm⁻¹; MS (EI,

70 eV) m/z (%) 364 (18), 363 (M⁺, 68), 306 (11), 230

(32), 229 (100), 228 (12), 147 (13), 131 (11), 105 (10).

Anal. calcd for C₂₄H₂₉NO₂: C, 79.30; H, 8.04; N, 3.85.

Found: C, 79.36; H, 8.11; N, 3.76.

A

solution of (S_p)-4-(4,4-dimethyl-4,5-dihydrooxa-

zolyl)-12-hydroxymethyl[2.2]paracyclophane (2.69 g,

8.0 mmol) and pyridine (0.32 mL, 4.0 mmol) in THF

(120 mL) was treated with PBr₃(0.76 mL, 8.0 mmol)

at 0°C.

A white, cloudy precipitate immediately

formed. The reaction mixture was stirred at room tem-

perature over night and then washed with an ice-cold,

saturated NaHCO₃(60 mL) solution. The aqueous

phase was extracted with dichloromethane (3×50 mL).

The combined organic phases were dried (MgSO₄),

concentrated and the residue was puriﬁed using a

short silica gel column and hexane:ethyl acetate (4:1)

as the eluent. Thus, 2.98 g (93% yield) of (S_p)-7a was

obtained as a white solid. Mp 70–72°C; [h]²_D⁵=+14 (c

1

1.1, CHCl₃); H NMR (500 MHz, CDCl₃) l 1.44 (s,

3H, CH₃), 1.45 (s, 3H, CH₃), 2.76–2.82 (m, 1H, CH₂),

2.86–2.93 (m, 2H, CH₂), 2.97–3.03 (m, 1H, CH₂),

3.08–3.13 (m, 1H, CH₂), 3.15–3.20 (m, 1H, CH₂), 3.47

(ddd, 1H, J=13.8, 10.3, 1.6 Hz, CH₂), 4.06 (d, 1H,

1740

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

3.40–3.47 (m, 1H, CH₂), 4.06 (t, 1H, J=10.2 Hz,

3.6.2.

(S,S_p)-4-Bromomethyl-12-(4-tert-butyl-4,5-dihy-

CHtBu), 4.24 (t, 1H, J=9.4 Hz, OCH₂), 4.40 (t, 1H,

J=9.5 Hz, OCH₂), 4.55 (d, 1H, J=15.4 Hz, CH₂OH),

4.68 (d, 1H, J=15.4 Hz, CH₂OH), 5.84 (bs, 1H,

CH₂OH), 6.45 (d, 1H, J=7.7 Hz, 16-H), 6.50 (d, 1H,

J=7.7 Hz, 15-H), 6.55 (d, 1H, J=7.7 Hz, 8-H), 6.58

(dd, 1H, J=7.7, 1.3 Hz, 7-H), 6.80 (s, 1H, 13-H), 7.15

(s, 1H, 5-H); ¹³C NMR (100 MHz, CDCl₃) l 26.7 (3C,

C(CH₃)₃), 32.6, 33.6 (CH₂), 34.0 (C(CH₃)₃), 34.2, 35.0

(CH₂), 63.7 (CH₂OH), 69.8 (OCH₂), 76.5 (CHtBu),

128.1 (C-13), 129.2 (qC), 130.1 (C-5), 131.4 (C-16),

134.1 (C-15), 135.5 (C-8), 135.9 (C-7), 136.2, 139.5,

139.8, 139.9, 141.0 (qC), 167.5 (CꢁN); IR (KBr) w˜ 2942,

2866, 1638, 964 cm⁻¹; MS (EI, 70 eV) m/z (%) 364 (17),

363 (M⁺, 68), 306 (11), 230 (24), 229 (100), 228 (11), 147

(10). Anal. calcd for C₂₄H₂₉NO₂: C, 79.30; H, 8.04; N,

3.85. Found: C, 78.98; H, 8.31; N, 3.65.

drooxazolyl)[2.2]paracyclophane (S,S_p)-7b.

This compound was prepared by the same procedure as

described for (S_p)-7a using (S,S_p)-4-(4-tert-butyl-4,5-

dihydrooxazolyl) - 12 - hydroxymethyl[2.2]paracyclo-

phane (2.17 g, 6.0 mmol), THF (100 mL), PBr₃(0.57

mL, 6.0 mmol), and pyridine (0.24 mL, 3.0 mmol). The

product was puriﬁed by chromatography using a short

column (silica gel; pentane:Et₂O, 9:1) to give 7b as a

white solid (1.76 g, 69% yield). Mp 164–166°C; [h]²_D⁵=−

3.7.2. (S,R_p)-4-Bromomethyl-12-(4-tert-butyl-4,5-dihy-

drooxazolyl)[2.2]paracyclophane (S,R_p)-7b.

1

26 (c 1.0, CHCl₃); H NMR (400 MHz, CDCl₃) l 1.07

(s, 9H, CH₃), 2.83–2.92 (m, 3H, CH₂), 2.94–3.10 (m,

2H, CH₂), 3.16–3.22 (m, 1H, CH₂), 3.47 (ddd, 1H,

J=13.1, 10.2, 1.7 Hz, CH₂), 4.09 (dd, 1H, J=10.2, 8.3

Hz, CHtBu), 4.19–4.26 (m, 2H, CH₂, OCH₂), 4.26 (d,

1H, J=10.2 Hz, CH₂Br), 4.31 (dd, 1H, J=10.2, 8.5 Hz,

OCH₂), 4.48 (d, 1H, J=10.1 Hz, CH₂Br), 6.40 (bs, 1H,

5-H), 6.50 (d, 1H, J=7.7 Hz, 8-H), 6.52–6.54 (m, 1H,

7-H), 6.55 (d, 1H, J=7.7 Hz, 16-H), 6.58 (dd, 1H,

J=7.7, 1.7 Hz, 15-H), 7.08 (bs, 1H, 13-H); ¹³C NMR

(100 MHz, CDCl₃) l 26.7 (3C, C(CH₃)₃), 33.3 (CH₂),

33.6 (CH₂Br), 34.2, 34.3 (CH₂), 34.7 (C(CH₃)₃), 35.3

(CH₂), 68.3 (OCH₂), 76.8 (CHtBu), 128.5 (qC), 131.1

(C-13), 133.5 (CH), 133.6 (C-5), 135.4, 135.5, 136.4

(CH), 137.2, 138.2, 139.4, 140.8, 141.0 (qC), 163.3

(CꢁN). IR (KBr) w˜ 2957, 2929, 2895, 2864, 1638 cm⁻¹;

MS (EI, 70 eV) m/z (%) 428 (12), 427 (49), 426 (12), 425

(M⁺, 48), 347 (10), 346 (42), 229 (100), 228 (13), 117

(14), 115 (13).

This compound was prepared by the same procedure as

described for (S_p)-7a using (S,R_p)-4-(4-tert-butyl-4,5-

dihydrooxazolyl)-12-hydroxymethyl[2.2]paracyclophane

(1.95 g, 5.4 mmol), CH₂Cl₂(60 mL), PBr₃(0.51 mL, 5.4

mmol), and pyridine (0.43 mL, 5.3 mmol). The product

was obtained as a white solid (1.59 g, 70% yield) after

puriﬁcation using a short column (silica gel; pen-

tane:Et₂O, 4:1). Mp 75–76°C; [h]²_D⁵=−52 (c 1.0, CHCl₃);

¹H NMR (300 MHz, CDCl₃) l 1.04 (s, 9H, CH₃),

2.77–3.10 (m, 5H, CH₂), 3.12–3.23 (m, 1H, CH₂), 3.43–

3.51 (m, 1H, CH₂), 3.99 (ddd, 1H, J=12.0, 9.8, 2.3 Hz,

CH₂), 4.08 (dd, 1H, J=9.9, 8.7 Hz, CHtBu), 4.16 (t, 1H,

J=8.4 Hz, OCH₂), 4.36 (d, 1H, J=10.1 Hz, CH₂Br), 4.33

(dd, 1H, J=9.8, 8.0 Hz, OCH₂), 4.47 (d, 1H, J=10.2 Hz,

CH₂Br), 6.47–6.53 (m, 4H, Aryl-CH) 6.58 (dd, 1H,

3.7. Synthesis of (S,R_p)-4-bromomethyl-12-(4-tert-butyl-

4,5-dihydrooxazolyl)[2.2]paracyclophane (S,R_p)-7b

3.7.1.

(S,R_p)-4-(4-tert-Butyl-4,5-dihydrooxazolyl)-12-

J=7.9, 1.8 Hz, 15-H), 7.06 (d, 1H, J=2.0 Hz, 13-H); ¹³

C

hydroxymethyl[2.2]paracyclophane.

NMR (75 MHz, CDCl₃) l 26.6 (3C, C(CH₃)₃), 33.3

(CH₂), 33.4 (CH₂Br), 34.2 (CH₂), 34.3 (C(CH₃)₃), 34.4,

35.7 (CH₂), 68.6 (OCH₂), 76.9 (CHtBu), 128.9 (qC),

131.2 (C-13), 133.4, 133.5 (CH), 135.1 (C-15), 135.5,

136.2 (CH), 137.2, 138.0. 139.4, 140.7, 140.9 (qC), 163.8

(CꢁN); IR (KBr) w˜ 2950, 2900, 2862, 1648, 1071, 977

cm⁻¹; MS (EI, 70 eV) m/z (%) 427 (38), 425 (M⁺, 40), 346

(35), 230 (16), 229 (100), 228 (12), 117 (12), 115 (10).

Anal. calcd for C₂₄H₂₈BrNO: C, 67.61; H, 6.62; N, 3.29.

Found: C, 67.70; H, 6.79; N, 3.13.

This compound was prepared by the method described

for

(S_p)-4-(4,4-dimethyl-4,5-dihydrooxazolyl)-12-

hydroxymethyl[2.2]paracyclophane using (S,R_p)-6b (5.2

g, 12.6 mmol), t-BuLi (19 mL, 28.5 mmol), THF (350

mL) and LiAlH₄(1.1 g, 29.2 mmol). After puriﬁcation

by column chromatography on silica gel (hex-

ane:EtOAc, 5:1), the title compound was obtained as a

white solid (2.37 g, 52% yield). Mp 80°C; [h]²_D⁵=−79 (c

3.8. Synthesis of (S_p)-1-{4-(4,4-dimethyl-4,5-dihydrooxa-

zolyl)[2.2]paracyclophane-12-yl-methyl}-3-methyl imida-

zolium bromide (S_p)-8a

1

1.1, CHCl₃); H NMR (400 MHz, CDCl₃) l 1.15 (s,

9H, CH₃), 2.79–2.87 (m, 1H, CH₂), 2.91–3.09 (m, 3H,

CH₂), 3.11–3.18 (m, 2H, CH₂), 3.26–3.33 (m, 1H, CH₂),

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

1741

A solution of methyl bromide (S_p)-7a (0.77 g, 1.93

mmol) and 1-methylimidazole (0.24 mL, 3.0 mmol) in

DMF (5 mL) was stirred at 80°C for 48 h. After

cooling to room temperature, diethyl ether was added.

Puriﬁcation of the precipitate by column chromatogra-

phy on silica gel (CH₂Cl₂:MeOH, 95:5 to 90:10), treat-

ment of the residue with benzene, and drying in vacuo

at elevated temperature yielded 0.73 g of the title

compound (79% yield) as a white, hygroscopic powder.

128.8 (qC), 131.0 (C-5), 132.2 (qC), 133.1 (C-13),

134.2, 135.5, 135.8, 136.3 (CH), 137.4 (NCHN), 139.6,

138.9, 140.7, 141.5 (qC), 163.9 (CꢁN); IR (KBr) w˜ 2952,

2864, 1638, 1571, 1165 cm⁻¹; MS (SIMS-FAB, pos) m/z

(%) 429 (25), 428 (100, M⁺), 426 (15), 347 (11), 346 (51);

MS (SIMS-FAB, neg) m/z (%) 81 (93), 79 (100). Anal.

calcd for C₂₈H₃₄BrN₃O·H₂O: C, 63.87; H, 6.89; N, 7.98.

Found: C, 63.83; H, 7.22; N, 8.11.

1

Mp 110–113°C; [h]_D²⁵=+67 (c 1.0, CHCl₃); H NMR

3.10. Synthesis of (S,R_p)-1-{4-(4-tert-butyl-4,5-dihy-

drooxazolyl)[2.2]paracyclophane-12-yl-methyl}-3-methyl

imidazolium bromide (S,R_p)-8b

(400 MHz, CDCl₃) l 1.42 (s, 3H, CH₃), 1.45 (s, 3H,

CH₃), 2.78–2.92 (m, 3H, CH₂), 3.09–3.27 (m, 3H, CH₂),

3.42–3.49 (m, 1H, CH₂), 4.06 (s, 3H, NCH₃), 4.07 (d,

1H, J=8.2 Hz, OCH₂), 4.11–4.17 (m, 1H, CH₂), 4.24

(d, 1H, J=8.2 Hz, OCH₂), 5.04 (d, 1H, J=14.5 Hz,

CH₂N), 5.63 (d, 1H, J=14.5 Hz, CH₂N), 6.50 (d, 1H,

J=1.4 Hz, 13-H), 6.53–6.62 (m, 4H, Aryl-CH), 7.02 (t,

1H, J=1.8 Hz, NCHꢁCH), 7.11 (d, 1H, J=1.7 Hz,

5-H), 7.53 (t, 1H, J=1.7 Hz, NCHꢁCH), 10.30 (s, 1H,

NCHN); ¹³C NMR (100 MHz, CDCl₃) l 28.8, 28.9

(CH₃), 33.5, 34.3, 34.4, 35.6 (CH₂), 37.1 (CH₃), 52.2

(CH₂N), 68.1 (C(CH₃)₂), 78.9 (OCH₂), 121.8

(NCHꢁCH), 123.8 (NCHꢁCH), 129.3 (qC), 131.3 (C-

5), 131.9 (qC), 133.4, 134.4, 135.0, 136.0, 136.2 (CH),

137.3 (NCHN), 138.9, 139.5, 140.6, 141.5 (qC), 162.2

(CꢁN); IR (KBr) w˜ 3031, 2927, 2861, 1637, 1590, 1565,

1302, 1161, 1040, 682, 619 cm⁻¹; MS (SIMS-FAB, pos)

m/z (%) 401 (28), 400 (100, M⁺), 318 (41); MS (SIMS-

FAB, neg) m/z (%) 81 (99), 79 (100).

This compound was prepared by the same procedure as

described for (S_p)-8a using (S,R_p)-7b (0.5 g, 1.2 mmol),

1-methylimidazole (0.19 mL, 2.4 mmol), and DMF (1

mL). After puriﬁcation of the precipitate by column

chromatography on silica gel (CH₂Cl₂:MeOH, 95:5 to

90:10) and drying in vacuo at elevated temperature, the

product was obtained as a white solid (0.56 g, 93%

1

yield). Mp 136–138°C; [h]²_D⁵=−91 (c 1.0, CHCl₃); H

NMR (400 MHz, CDCl₃) l 1.00 (s, 9H, C(CH₃)₃),

2.83–2.91 (m, 2H, CH₂), 2.95–3.02 (m, 1H, CH₂), 3.05–

3.11 (m, 1H, CH₂), 3.15–3.21 (m, 1H, CH₂), 3.23–3.31

(m, 1H, CH₂), 3.45–3.53 (m, 1H, CH₂), 4.01 (ddd, 1H,

J=12.3, 10.2, 2.0 Hz, CH₂), 4.05 (s, 3H, NCH₃), 4.11–

4.18 (m, 2H, CHtBu, OCH₂), 4.42–4.48 (m, 1H,

OCH₂), 4.99 (d, 1H, J=14.3 Hz, CH₂N), 5.63 (d, 1H,

J=14.3 Hz, CH₂N), 6.54–6.64 (m, 5H, Aryl-CH), 6.95

(t, 1H, J=1.7 Hz, NCHꢁCH), 7.07 (d, 1H, J=1.7 Hz,

5-H), 7.58 (t, 1H, J=1.7 Hz, NCHꢁCH), 10.31 (s, 1H,

NCHN); ¹³C NMR (100 MHz, CDCl₃) l 26.4 (3C,

C(CH₃)₃), 33.4, 34.0, 34.1, 34.2, 35.2 (CH₂, C(CH₃)₃),

37.0 (NCH₃), 52.2 (CH₂N), 68.5 (OCH₂), 76.9

(CHtBu), 121.6, 124.0 (NCHꢁCH), 129.1 (qC), 131.3

(C-5), 131.9 (qC), 133.8, 134.6, 135.1, 136.0, 136.1

(CH), 137.1 (NCHN), 139.1, 139.7, 140.6, 141.6 (qC),

163.6 (CꢁN); IR (KBr) w˜ 3030, 2952, 2865, 1642, 1570,

1163 cm⁻¹; MS (SIMS-FAB, pos) m/z (%) 429 (30), 428

(100, M⁺), 426 (26), 347 (11), 346 (48), 344 (13); MS

(SIMS-FAB, neg) m/z (%) 81 (96), 79 (100). Anal. calcd

for C₂₈H₃₄BrN₃O·0.5H₂O: C, 64.99; H, 6.82; N, 8.12.

Found: C, 64.59; H, 7.00; N, 8.00.

3.9. Synthesis of (S,S_p)-1-{4-(4-tert-butyl-4,5-dihydro-

oxazolyl)[2.2]paracyclophane-12-yl-methyl}-3-methyl

imidazolium bromide (S,S_p)-8b

This compound was prepared by the method described

for (S_p)-8a using (S,S_p)-7b (0.8 g, 1.9 mmol), 1-

methylimidazole (0.3 mL, 3.8 mmol), and DMF (4

mL). The precipitate was treated several times with

diethyl ether in a super sonic bath and dried in vacuo at

elevated temperature to give 0.8 g (83% yield) of the

title compound as a white solid. Mp 185–188°C; [h]²_D⁵=

+43 (c 0.6, CHCl₃); ¹H NMR (400 MHz, CDCl₃) l 1.05

(s, 9H, C(CH₃)₃), 2.85–3.00 (m, 4H, CH₂), 3.06–3.12

(m, 1H, CH₂), 3.15–3.25 (m, 2H, CH₂), 4.07 (s, 3H,

NCH₃), 4.04–4.16 (m, 2H, CH₂, CHtBu), 4.32 (t, 1H,

J=8.4 Hz, OCH₂), 4.43 (t, 1H, J=9.5 Hz, OCH₂), 5.05

(d, 1H, J=14.8 Hz, CH₂N), 5.63 (d, 1H, J=14.6 Hz,

CH₂N), 6.41 (s, 1H, 13-H), 6.57–6.65 (m, 4H, Aryl-

CH), 7.06 (s, 1H, NCHꢁCH), 7.21 (s, 1H, 5-H), 7.53 (s,

1H, NCHꢁCH), 10.23 (s, 1H, NCHN); ¹³C NMR (100

MHz, CDCl₃) l 26.6 (3C, C(CH₃)₃), 33.5, 34.3, 34.4,

34.7, 35.1 (CH₂, C(CH₃)₃), 37.2 (NCH₃), 52.0 (CH₂N),

68.9 (OCH₂), 76.4 (CHtBu), 122.0, 123.8 (NCHꢁCH),

3.11. Synthesis of (S_p)-1-{4-(4,4-dimethyl-4,5-dihydro-

oxazolyl)[2.2]paracyclophane-12-yl-methyl}-3-(2,4,6-

trimethylphenyl) imidazolium bromide (S_p)-8c

1742

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

NCHꢁCH), 7.29 (s, 1H, 5-H), 7.43 (s, 1H, NCHꢁCH),

10.44 (s, 1H, NCHN); ¹³C NMR (100 MHz, CDCl₃) l

18.1 (2C, Mesityl-CH₃), 21.4 (Mesityl-CH₃), 26.5 (3C,

C(CH₃)₃), 33.5, 34.2, 34.5, 34.6, 35.1 (CH₂, C(CH₃)₃),

52.8 (CH₂N), 68.7 (OCH₂), 76.4 (CHtBu), 123.3, 123.4

(NCHꢁCH), 128.8 (qC), 129.9, 130.1 (Mesityl-CH),

130.9 (qC), 131.0 (C-5), 132.3 (C-13), 132.7 (qC), 134.0

(CH), 134.4, 134.6 (qC), 135.5, 135.9, 136.1 (CH),

138.3 (NCHN), 139.3, 140.1, 140.4, 141.2, 141.4 (qC),

164.0 (CꢁN); IR (KBr) w˜ 2950, 2921, 1640, 1204 cm⁻¹;

MS (SIMS-FAB, pos) m/z (%) 533 (40), 532 (100, M⁺),

346 (21); MS (SIMS-FAB, neg) m/z (%) 81 (97), 79

(100). Anal. calcd for C₃₆H₄₂BrN₃O·0.25H₂O: C, 70.06;

H, 6.94; N, 6.81. Found: C, 69.92; H, 7.02; N, 6.89.

This compound was prepared by the same procedure as

described for (S_p)-8a using methyl bromide (S_p)-7a (1.2

g, 3.0 mmol), 1-mesitylimidazole (0.84 g, 4.5 mmol) and

DMF (5 mL). The precipitate was treated several times

with diethyl ether in a super sonic bath and dried in

vacuo at elevated temperature to give 1.71 g (97% yield)

of the title compound as a white solid. Mp 268°C;

1

[h]²_D⁵=+63 (c 1.1, CHCl₃); H NMR (400 MHz, CDCl₃)

l 1.39 (s, 3H, CH₃), 1.45 (s, 3H, CH₃), 2.02 (s, 3H,

Mesityl-CH₃), 2.05 (s, 3H, Mesityl-CH₃), 2.30 (s, 3H,

Mesityl-CH₃), 2.82–2.96 (m, 3H, CH₂), 3.10–3.17 (m,

2H, CH₂), 3.48–3.54 (m, 1H, CH₂), 3.59–3.65 (m, 1H,

CH₂), 4.05 (d, 1H, J=8.2 Hz, OCH₂), 4.16–4.21 (m,

1H, CH₂), 4.26 (d, 1H, J=8.3 Hz, OCH₂), 5.17 (d, 1H,

J=14.6 Hz, CH₂N), 6.27 (d, 1H, J=14.5 Hz, CH₂N),

6.55–6.64 (m, 5H, Aryl-CH), 6.95 (s, 2H, Mesityl-CH),

7.18 (bs, 2H, NCHꢁCH, 5-H), 7.35 (t, 1H, J=1.7 Hz,

NCHꢁCH), 10.49 (s, 1H, NCHN); ¹³C NMR (125

MHz, CDCl₃) l 17.6, 17.7, 21.0 (Mesityl-CH₃), 28.3,

28.6 (CH₃), 33.0 (CH₂), 34.0 (2C, CH₂), 35.2 (CH₂),

52.6 (CH₂N), 67.7 (C(CH₃)₂), 78.5 (OCH₂), 122.5

(NCHꢁCH), 123.0 (NCHꢁCH), 128.9 (qC), 129.6 (2C,

Mesityl-CH), 130.5 (qC), 131.3 (C-5), 132.0 (qC),

133.2 (CH), 133.9, 134.0 (qC), 134.1, 134.7, 135.6,

135.8 (CH), 137.5 (NCHN), 139.1, 139.6, 140.1, 140.9,

141.1 (qC), 161.8 (CꢁN); IR (KBr) w˜ 2967, 2917, 1631,

1208, 1045 cm⁻¹. MS (ESI, pos) m/z (%) 505 (29), 504

(100, M⁺), 318 (10); MS (ESI, neg) m/z (%) 81 (96), 79

(100). Anal. calcd for C₃₄H₃₈BrN₃O·0.5 H₂O: C, 68.80;

H, 6.62; N, 7.08. Found: C, 68.47; H, 6.81, N, 7.40.

3.13. Synthesis of (S,R_p)-3-{4-(4-tert-butyl-4,5-dihydroox-

azolyl)[2.2]paracyclophane-12-yl-methyl}-1-(2,4,6-

trimethylphenyl) imidazolium bromide (S,R_p)-8d

This compound was prepared by the same procedure as

described for (S_p)-8a using (S,R_p)-7b (0.7 g, 1.64 mmol),

1-mesitylimidazole (0.46 g, 2.47 mmol), and DMF (2

mL). After addition of diethyl ether, treatment of the

precipitate with diethyl ether and pentane in a super

sonic bath, and drying in vacuo at elevated tempera-

ture, the product was obtained as a white solid (0.85 g,

85% yield). Mp 151–154°C (dec); [h]²_D⁵=−87 (c 0.7,

3.12. Synthesis of (S,S_p)-3-{4-(4-tert-butyl-4,5-dihydro-

oxazolyl)[2.2]paracyclophane-12-yl-methyl}-1-(2,4,6-

trimethylphenyl) imidazolium bromide (S,S_p)-8d

1

CHCl₃); H NMR (400 MHz, CDCl₃) l 0.96 (s, 9H,

C(CH₃)₃), 2.00 (s, 3H, Mesityl-CH₃), 2.02 (s, 3H,

Mesityl-CH₃), 2.27 (s, 3H, Mesityl-CH₃), 2.80–2.87 (m,

2H, CH₂), 2.97–3.16 (m, 3H, CH₂), 3.47–3.54 (m, 1H,

CH₂), 3.61–3.67 (m, 1H, CH₂), 4.02 (ddd, 1H, J=12.4,

10.2, 2.7 Hz, CH₂), 4.07–4.13 (m, 2H, CHtBu, OCH₂),

4.37–4.44 (m, 1H, OCH₂), 5.17 (d, 1H, J=14.6 Hz,

CH₂N), 6.22 (d, 1H, J=14.5 Hz, CH₂N), 6.51–6.63 (m,

4H, Aryl-CH), 6.67 (bs, 1H, 13-H), 6.92 (s, 2H,

Mesityl-CH), 7.06 (bs, 1H, NCHꢁCH), 7.11 (bs, 1H,

5-H), 7.19 (bs, 1H, NCHꢁCH), 10.50 (s, 1H, NCHN);

¹³C NMR (100 MHz, CDCl₃) l 18.1 (2C, Mesityl-

CH₃), 21.4 (Mesityl-CH₃), 26.6 (3C, C(CH₃)₃), 33.5,

34.1, 34.2, 34.5, 35.4 (CH₂, C(CH₃)₃), 52.9 (CH₂N),

68.4 (OCH₂), 77.3 (CHtBu), 122.4, 123.1 (NCHꢁCH),

129.3 (qC), 130.0 (2C, Mesityl-CH), 130.9 (qC), 131.7

(C-5), 132.4 (qC), 133.9 (C-13), 134.6 (CH), 134.2,

134.4 (qC), 135.0, 135.8, 136.0 (CH), 138.0 (NCHN),

139.7, 140.1, 140.3, 141.4, 141.7 (qC), 163.4 (CꢁN); IR

(KBr) w˜ 2950, 2865, 1641, 1198; MS (SIMS-FAB, pos)

m/z (%) 533 (35), 532 (M⁺, 100), 346 (16); MS (SIMS-

FAB, neg) m/z (%) 81 (97), 79 (100). Anal. calcd for

C₃₆H₄₂BrN₃O·0.75H₂O: C, 69.05, H, 7.00; N, 6.71.

Found: C, 69.09; H, 6.76; N, 6.72.

This compound was prepared by the same procedure as

described for (S_p)-8a using (S,S_p)-7b (0.7 g, 1.64 mmol),

1-mesitylimidazole (0.46 g, 2.47 mmol), and DMF (4

mL). After addition of diethyl ether, treatment of the

precipitate with the same solvent in a super sonic bath,

and drying in vacuo at elevated temperature, the

product was obtained as a white solid (0.94 g, 94%).

Mp 270–271°C (dec); [h]²_D⁵=+29 (c 0.6, CHCl)]; ¹H

NMR (400 MHz, CDCl₃) l 0.98 (s, 9H, C(CH₃)₃), 2.03

(s, 3H, Mesityl-CH₃), 2.08 (s, 3H, Mesityl-CH₃), 2.32

(s, 3H, Mesityl-CH₃), 2.83–2.95 (m, 3H, CH₂), 3.09–

3.18 (m, 2H, CH₂), 3.42–3.48 (m, 1H, CH₂), 3.60–3.66

(m, 1H, CH₂), 3.90 (bt, 1H, J=9.0 Hz, CHtBu), 4.11–

4.16 (m, 1H, CH₂), 4.25–4.35 (m, 2H, OCH₂), 5.15 (d,

1H, J=15.1 Hz, CH₂N), 6.31 (d, 1H, J=15.1 Hz,

CH₂N), 6.34 (s, 1H, 13-H), 6.57–6.65 (m, 4H, Aryl-

CH), 6.98 (s, 2H, Mesityl-CH), 7.23 (s, 1H,

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

1743

3.14. Synthesis of (S_p)-(h⁴-1,5-cyclooctadiene){1-[4-(4,4-

dimethyl-4,5-dihydrooxazolyl)[2.2]paracyclophane-12-yl-

methyl]-3-methylimidazolin-2-ylidene}iridium(I)

318 (12), 197 (27); MS (SIMS-FAB, neg) m/z (%) 863

(100, M⁻). Anal. calcd for C₆₆H₅₃BF₂₄IrN₃O: C, 50.71;

H, 3.42; N, 2.69. Found: C, 50.71; H, 3.74; N, 2.56.

tetrakis[3,5-bis(triﬂuoromethyl)phenyl]borate (S_p)-9a

3.15. Synthesis of (S,S_p)-(h⁴-1,5-cyclooctadiene){1-[4-(4-

tert-butyl-4,5-dihydrooxazolyl)[2.2]paracyclophane-12-

yl-methyl]-3-methylimidazolin-2-ylidene}iridium(I)

tetrakis[3,5-bis(triﬂuoromethyl)phenyl]borate (S,S_p)-9b

To a suspension of imidazolium salt (S_p)-8a (0.192 g,

0.4 mmol) and [Ir(COD)Cl]₂(0.134 g, 0.2 mmol) in

THF (10 mL) was added at room temperature a solu-

tion of KOt-Bu in THF (0.6 mL, 0.6 mmol) via syringe.

The resulting mixture was heated to 60°C for 18 h.

After cooling to room temperature, the volatiles were

removed in vacuo. NaBARF (0.54 g, 0.6 mmol),

degassed water (10 mL) and dichloromethane (15 mL)

were added, and the mixture was stirred vigorously for

20 h. After phase separation, the aqueous layer was

washed with CH₂Cl₂(3×10 mL). The combined organic

layers were dried (MgSO₄), evaporated and the residue

was puriﬁed by column chromatography using a short

silica gel column and CH₂Cl₂:pentane (1:1 to 7:3) as the

eluent. Complex (S_p)-9a was isolated as a bright yellow

solid in 59% yield (0.371 g). Mp 221–222°C; [h]²_D⁵=−15

This compound was prepared by the same procedure

described for 9a using imidazolium salt (S,S_p)-8b (0.203

g, 0.4 mmol), [Ir(COD)Cl]₂(0.134 g, 0.2 mmol), KOt-

Bu (0.6 mL, 0.6 mmol) and NaBARF (0.54 g, 0.6

mmol). After puriﬁcation using a short silica gel

column (CH₂Cl₂:pentane, 7:3), complex (S,S_p)-9b was

obtained as a bright yellow solid (0.306 g, 48% yield).

1

Mp 193–195°C; [h]_D²⁵=+78 (c 1.0, CHCl₃); H NMR

(400 MHz, CDCl₃) l 1.19 (s, 9H, C(CH₃)₃), 1.19–1.28

(m, 1H, COD-CH₂), 1.34–1.44 (m, 1H, COD-CH₂),

1.95–2.06 (m, 2H, COD-CH₂), 2.23–2.30 (m, 2H, COD-

CH₂), 2.32–2.52 (m, 2H, CH₂, COD-CH₂), 2.54–2.68

(m, 2H, CH₂, COD-CH₂), 2.86–2.93 (m, 1H, CH₂),

3.07–3.12 (m, 1H, CH₂), 3.20–3.33 (m, 2H, CH₂, COD-

CH), 3.35–3.39 (m, 2H, CH₂), 3.44–3.48 (m, 1H, COD-

CH), 3.78–3.83 (m, 1H, CH₂), 3.85 (dd, 1H, J=10.6,

6.5 Hz, CHtBu), 4.04 (s, 3H, NCH₃), 4.22 (t, 1H,

J=10.1 Hz, CH₂O), 4.34–4.38 (m, 1H, COD-CH),

4.41–4.47 (m, 1H, COD-CH), 4.48 (dd, 1H, J=9.6, 6.3

Hz, CH₂O), 5.08 (d, 1H, J=17.0 Hz, CH₂N), 5.13 (s,

1H, 13-H), 5.96 (d, 1H, J=17.0 Hz, CH₂N), 6.45 (d,

1H, J=7.6 Hz, 16-H), 6.54 (bd, 1H, J=8.0 Hz, 15-H),

6.62 (d, 1H, J=7.9 Hz, 8-H), 6.65 (d, 1H, J=1.9 Hz,

NCHꢁCH), 6.71 (dd, 1H, J=8.0, 1.7 Hz, 7-H), 6.80 (d,

1H, J=2.2 Hz, NCH=CH), 7.45 (s, 4H, BARF-CH),

7.65 (bs, 8H, BARF-CH), 10.27 (d, 1H, J=1.7 Hz,

5-H); ¹³C NMR (100 MHz, CDCl₃) l 26.2 (COD-

CH₂), 28.2 (3C, C(CH₃)₃), 29.2, 31.2, 32.3, 33.1, 34.2,

35.3, 36.6 (CH₂, COD-CH₂, C(CH₃)₃), 38.6 (NCH₃),

40.8 (CH₂), 53.2 (CH₂N), 57.7, 61.9 (COD-CH), 69.1

(OCH₂), 78.4 (CHtBu), 86.5, 87.3 (COD-CH), 117.7

(m, 4C, BARF-CH), 123.1, 124.0 (NCHꢁCH), 124.8 (q,

8C, J_FC=272.1 Hz, CF₃), 124.3 (qC), 126.9 (C-13),

129.1 (q, 8C, J_FC=32.3 Hz, CCF₃), 131.3 (C-15), 135.0

(b, 8C, BARF-CH), 135.2 (C-5), 135.3 (C-16), 135.6,

136.1 (qC), 137.8 (C-7), 138.7 (C-8), 139.3, 141.5, 145.7

(qC), 161.9 (q, 4C, J_CB=49.9 Hz, BC), 170.6 (CꢁN),

174.2 (NCN); ¹⁹F NMR (376 MHz, CDCl₃) l –62.8 (s);

IR (KBr) w˜ 1356, 1280, 1127 cm⁻¹; MS (SIMS-FAB,

pos) m/z (%) 728 (100, M⁺), 618 (25), 428 (11), 197 (10);

MS (SIMS-FAB, neg) m/z (%) 863 (100, M⁻). Anal.

calcd for C₆₈H₅₇BF₂₄IrN₃O: C, 51.33; H, 3.61; N, 2.64.

Found: C, 51.23; H, 3.58; N, 2.56.

1

(c 1.0, CHCl₃); H NMR (400 MHz, CDCl₃) l 1.10 (s,

3H, CH₃), 1.53–1.62 (m, 1H, COD-CH₂), 1.68–1.75 (m,

1H, COD-CH₂), 1.77–1.83 (m, 1H, COD-CH₂), 1.95–

2.00 (m, 1H, COD-CH₂), 1.97 (s, 3H, CH₃), 2.07–2.16

(m, 1H, COD-CH₂), 2.30–2.42 (m, 4H, CH₂, COD-

CH₂), 2.70 (ddd, 1H, J=13.7, 9.2 Hz, CH₂), 2.88 (ddd,

1H, J=13.5, 10.7, 6.9 Hz, CH₂), 3.11 (dd, 1H, J=13.4,

9.2 Hz, CH₂), 3.17–3.40 (m, 5H, CH₂, COD-CH),

3.75–3.80 (m, 1H, COD-CH), 3.80 (d, 1H, J=8.5 Hz,

OCH₂), 3.81–3.86 (m, 1H, CH₂), 4.04 (s, 3H, NCH₃),

4.20–4.25 (m, 1H, COD-CH), 4.27 (d, 1H, J=8.5 Hz,

OCH₂), 5.10 (d, 1H, J=17.0 Hz, CH₂N), 5.35 (bs, 1H,

13-H), 5.90 (d, 1H, J=17.0 Hz, CH₂N), 6.47 (d, 1H,

J=7.7 Hz, 16-H), 6.54 (dd, 1H, J=7.7, 1.1 Hz, 15-H),

6.64 (d, 1H, J=7.7 Hz, 8-H), 6.67–6.69 (m, 1H, 7-H),

6.68 (d, 1H, J=1.9 Hz, NCHꢁCH), 6.84 (d, 1H, J=1.9

Hz, NCHꢁCH), 7.45 (s, 4H, BARF-CH), 7.65 (t, 8H,

J=2.4 Hz, BARF-CH), 9.59 (d, 1H, J=1.6 Hz, 5-H);

¹³C NMR (100 MHz, CDCl₃) l 26.9, 27.2 (CH₃), 28.3,

29.6 (COD-CH₂), 32.0, 32.4, 33.4, 33.5, 35.7 (CH₂,

COD-CH₂), 38.5 (NCH₃), 38.8 (CH₂), 52.9 (CH₂N),

60.8, 63.0 (COD-CH), 72.3 (C(CH₃)₂), 78.9 (OCH₂),

86.9, 87.5 (COD-CH), 117.7 (m, 4C, BARF-CH),

123.1, 123.9 (NCHꢁCH), 124.8 (q, 8C, J_FC=272.1 Hz,

CF₃), 125.0 (qC), 127.0 (C-13), 129.1 (q, 8C, J_FC=32.8

Hz, CCF₃), 131.3 (C-16), 132.2 (C-5), 135.0 (b, 8C,

BARF-CH), 135.1 (C-15), 136.3 (qC), 136.8 (C-8),

138.0 (C-7), 139.3, 141.0, 144.0 (qC), 161.9 (q, 4C,

J

_CB=49.8 Hz, BC), 167.4 (CꢁN), 176.0 (NCN); ¹⁹F

NMR (376 MHz, CDCl₃) l 62.8 (s); IR (KBr) w˜ 1564,

1356, 1279, 1127, 896, 714, 682, 672 cm⁻¹; MS (SIMS-

FAB, pos) m/z (%) 700 (100, M⁺), 590 (45), 400 (10),

1744

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

3.16. Synthesis of (S,R_p)-(h⁴-1,5-Cyclooctadiene){1-[4-(4-

tert-butyl-4,5-dihydrooxazolyl)[2.2]paracyclophane-12-

yl-methyl]-3-methylimidazolin-2-ylidene}iridium(I)

tetrakis[3,5-bis(triﬂuoromethyl)phenyl]borate (S,R_p)-9b

mmol), [Ir(COD)Cl]₂(0.134 g, 0.2 mmol), KOt-Bu (0.6

mL, 0.6 mmol) and NaBARF (0.54 g, 0.6 mmol). After

column chromatography on silica gel (CH₂Cl₂:pentane,

1:1 to 2:1), complex (S_p)-9c was obtained as a bright

yellow solid in 74% yield (0.494 g). Mp 172–173°C;

This compound was prepared by the method described

for 9a using imidazolium salt (S,R_p)-8b (0.203 g, 0.4

mmol), [Ir(COD)Cl]₂(0.134 g, 0.2 mmol), KOt-Bu (0.6

mL, 0.6 mmol) and NaBARF (0.54 g, 0.6 mmol). After

column chromatography on silica gel (CH₂Cl₂:pentane,

7:3), complex (S,R_p)-9b was obtained as a bright yellow

solid (0.440 g, 69% yield). Mp 180–183°C; [h]_D=+26 (c

1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃) l 1.20 (s, 9H,

C(CH₃)₃), 1.36–1.46 (m, 1H, COD-CH₂), 1.50–1.58 (m,

1H, COD-CH₂), 1.87–1.92 (m, 2H, COD-CH₂), 2.06–2.15

(m, 1H, COD-CH₂), 2.32–2.43 (m, 2H, CH₂, COD-CH₂),

2.45–2.54 (m, 1H, COD-CH₂), 2.67–2.74 (m, 1H, CH₂),

2.86–2.95 (m, 2H, CH₂), 2.99–3.06 (m, 3H, CH₂), 3.22–

3.32 (m, 3H, CH₂, COD-CH), 3.34–3.40 (m, 1H, CH₂),

3.78–3.82 (m, 1H, COD-CH), 3.92 (s, 3H, NCH₃), 4.08

(t, 1H, J=9.6 Hz, CHtBu), 4.18 (d, 1H, J=9.3 Hz,

CH₂O), 4.23 (d, 1H, J=10.2 Hz, CH₂O), 4.27–4.31 (m,

1H, COD-CH), 5.02 (d, 1H, J=16.8 Hz, CH₂N), 5.15

(s, 1H, 13-H), 5.87 (d, 1H, J=16.7 Hz, CH₂N), 6.48 (bd,

1H, J=7.7 Hz, 7-H), 6.54 (d, 1H, J=7.9 Hz, 8-H),

6.57–6.59 (m, 2H, NCHꢁCH, 16-H), 6.63 (bd, 1H, J=7.7

Hz, 15-H), 6.80 (d, 1H, J=1.9 Hz, NCHꢁCH), 7.45 (s,

4H, BARF-CH), 7.65 (bs, 8H, BARF-CH), 9.33 (s, 1H,

5-H); ¹³C NMR (100 MHz, CDCl₃) l 27.4 (3C, C(CH₃)₃),

27.7, 30.3, 31.4 (COD-CH₂), 32.3 (CH₂), 33.0, 33.5, 33.8

(CH₂, COD-CH₂, C(CH₃)₃), 34.7, 34.8 (CH₂), 39.3

(NCH₃), 53.0 (CH₂N), 60.2, 60.8 (COD-CH), 68.9

(OCH₂), 79.5 (CHtBu), 83.6, 85.8 (COD-CH), 117.7 (m,

1

[h]²_D⁵=+89 (c 1.0, CHCl₃); H NMR (400 MHz, CDCl₃)

l 0.64 (s, 3H, CH₃), 0.84 (s, 3H, CH₃), 1.18–1.27 (m, 1H,

COD-CH₂), 1.41–1.50 (m, 1H, COD-CH₂), 1.84–1.92 (m,

1H, COD-CH₂), 1.90 (s, 3H, Mesityl-CH₃), 2.14–2.23 (m,

2H, COD-CH₂), 2.23 (s, 3H, Mesityl-CH₃), 2.26–2.37 (m,

2H, COD-CH₂), 2.34 (s, 3H, Mesityl-CH₃), 2.62–2.72 (m,

1H, COD-CH₂), 2.78–2.82 (m, 2H, CH₂), 2.99 (ddd, 1H,

J=14.1, 11.6, 5.3 Hz, CH₂), 3.11–3.22 (m, 4H, CH₂,

COD-CH), 3.26–3.38 (m, 2H, CH₂), 3.48 (t, 1H, J=6.5

Hz, COD-CH), 3.65 (d, 1H, J=8.5 Hz, OCH₂), 3.89 (d,

1H, J=8.5 Hz, OCH₂), 4.33 (q, 1H, J=7.6 Hz, COD-CH)

4.46 (t, 1H, J=7.0 Hz, COD-CH) 4.61 (s, 1H, 13-H), 5.21

(d, 1H, J=16.2 Hz, CH₂N), 6.02 (d, 1H, J=16.2 Hz,

CH₂N), 6.40 (dd, 1H, J=7.9, 1.6 Hz, 7-H), 6.45 (d, 1H,

J=7.7 Hz, 8-H), 6.61 (d, 1H, J=7.7 Hz, 16-H), 6.66 (dd,

1H, J=7.6, 1.5 Hz, 15-H), 6.73 (d, 1H, J=1.9 Hz,

NCHꢁCH), 6.75 (d, 1H, J=1.9 Hz, NCHꢁCH), 6.89 (s,

1H, Mesityl-CH), 7.08 (s, 1H, Mesityl-CH), 7.44 (s, 4H,

BARF-CH), 7.64 (t, 8H, J=2.2 Hz, BARF-CH), 9.41 (d,

1H, J=1.6 Hz, 5-H); ¹³C NMR (100 MHz, CDCl₃) l 18.3,

19.2, 21.1 (Mesityl-CH₃), 21.8 (CH₃), 26.5 (COD-CH₂),

27.9 (CH₃), 29.3 (COD-CH₂), 32.4 (2C, CH₂, COD-

CH₂), 32.5, 33.7, 34.5 (CH₂), 35.2 (COD-CH₂), 54.3

(CH₂N), 62.6, 62.9 (COD-CH), 72.0 (C(CH₃)₂), 78.6

(OCH₂), 81.2, 82.3 (COD-CH), 117.6 (m, 4C, BARF-

CH), 123.3 (NCHꢁCH), 125.1 (qC), 124.8 (q, 8C,

J_FC=272.1 Hz, CF₃), 126.0 (NCHꢁ8CH), 128.8 (C-13),

129.1 (q, 8C, J_FC=30.5 Hz, CCF₃), 129.3 (C-5), 129.8,

131.1 (Mesityl-CH), 131.8 (C-16), 133.2 (C-15), 135.0 (b,

8C, BARF-CH), 135.5, 135.7, 135.9, 136.0, 136.1 (qC),

136.2 (C-8), 137.8 (qC), 139.0 (C-7), 140.3, 141.2, 144.3

(qC), 161.8 (q, 4C, J_CB=49.8 Hz, BC), 171.1 (C=N),

178.3 (NCN); ¹¹B NMR (160 MHz, CDCl₃) l 4.29 (s);

¹⁹F NMR (376 MHz, CDCl₃) l 62.8 (s); IR (KBr) w˜ 1559,

1355, 1279, 1126, 888, 713, 682, 671 cm⁻¹; MS (APCI,

pos) m/z (%) 804 (100, M⁺), 694 (59); (APCI, neg) m/z

(%) 863 (100, M⁻). Anal. calcd for C₇₄H₆₁BF₂₄IrN₃O: C,

53.31; H, 3.69; N, 2.52. Found: C, 52.96; H, 3.96; N, 2.33.

4C, BARF-CH), 122.4 (NCHꢁCH), 124.8 (q, 8C, J_FC

=

272.6 Hz, CF₃), 125.1 (NCHꢁCH), 125.6 (qC), 127.4

(C-5), 128.7 (C-13), 129.1 (q, 8C, J_FC=30.9 Hz, CCF₃),

131.3 (C-15), 133.9 (C-16), 135.0 (b, 8C, BARF-CH),

135.3 (qC), 136.2 (C-8), 136.8 (qC), 138.1 (2C, C-7, qC),

140.5, 142.5 (qC), 161.9 (q, 4C, J_CB=49.6 Hz, BC), 169.9

(CꢁN), 175.7 (NCN); ¹⁹F NMR (376 MHz, CDCl₃) l

–62.8 (s); IR (KBr) w˜ 1356, 1279, 1129 cm⁻¹; MS

(SIMS-FAB, pos) m/z (%) 729 (100, M⁺+H), 619 (14),

197 (14); MS (SIMS-FAB, neg) m/z (%) 864 (100, M⁻+H).

Anal. calcd for C₆₈H₅₇BF₂₄IrN₃O: C, 51.33; H, 3.61; N,

2.64. Found: C, 51.16; H, 3.71; N, 2.42.

3.18. Crystal structure analysis of (S_p)-9c

3.17. Synthesis of (S_p)-(h⁴-1,5-cyclooctadiene){1-[4-(4,4-

dimethyl-4,5-dihydrooxazolyl)[2.2]paracyclophane-12-yl-

methyl]-3-(2,4,6-trimethylphenyl)imidazolin-2-ylidene}-

iridium(I) tetrakis[3,5-bis(triﬂuoromethyl)phenyl]borate

(S_p)-9c

Suitable crystals of (S_p)-9c have been obtained from a

mixture of EtOH, CH₂Cl₂, and Et₂O at 25°C. The

compound crystallizes in orthorhombic space group

P2₁2₁2₁(19) with one formula unit (C₇₄H₆₁BF₂₄N₃OIr)

in the asymmetric unit. The cell constants are a=

,

15.422(2), b=18.973(2), c=24.548(3) A. A cell volume

3

,

of V=7182.8(15) A , Z=4, and M_r=1667.31, amount to

This compound was prepared by the method described

for (S_p)-9a using imidazolium salt (S_p)-8c (0.234 g, 0.4

a calculated density of r_cal=1.542. A total number of

53665 reﬂections (−20<h<20, −25<k<25, −23<l<32,

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

1745

u_max=28.3°) have been collected at room temperature

on a Bruker SMART APEX diffractometer employing

graphite-monochromated MoK_aradiation (u=0.71073

retention times (in min)=13.7 (R), 18.9 (starting mate-

rial), 21.6 (S).²³11d: Daicel Chiracel OB-H column,

254 nm, 20°C, 0.5 mL min⁻¹, n-heptane:2-propanol,

99.5:0.5, retention times (in min)=17.1 (R), 19.5 (S).^20a

11e: Daicel Chiracel OD-H column, 254 nm, 20°C, 0.5

mL min⁻¹, n-heptane:2-propanol, 99.5:0.5, retention

times (in min)=21.5 (R), 25.4 (S).²⁴

,

A). Data have been corrected for Lorentz-, polarization

and absorption effects (v=1.967 mm⁻¹).^22aThe struc-

ture has been solved by direct methods as implemented

in the Xtal3.7 set of crystallographic routines,^22b

employing GENSIN^22cfor the generation of structure

invariant relation ships and GENTAN^22dfor the gen-

eral tangent phasing procedure. 12529 observed reﬂec-

tions (F>4|(F)) have been included in the ﬁnal

full-matrix least squares reﬁnement on F involving 705

parameters and converging at r (r_w)=0.082(0.088, w=

Acknowledgements

We are grateful to ﬁnancial support by the Fonds der

Chemischen Industrie, the BMBF, and Degussa AG.

We also thank OMG and Degussa for the generous gift

of chemicals and Dr. Chunhua Hu for the data

collection.

1/[|²(F)+0.0004F²]) a residual electron density of

−3

,

−1.98/+2.27e A , and a goodness of ﬁt of S=2.326. All

hydrogen atoms have been calculated in idealized posi-

tions. Their equivalent displacement parameters have

been ﬁxed at 1.5 U of the relevant heavy atom prior to

ﬁnal reﬁnement where all hydrogen parameters have

been kept constant. The representation is Figure 1 in an

ORTEP plot.^22e,f

References

8

1. (a) Ofele, K. J. Organomet. Chem. 1968, 12, P42; (b)

Wanzlick, H.-W.; Scho¨nherr, H.-J. Angew. Chem. 1968,

80, 154; Angew. Chem., Ind. Ed. Engl. 1968, 7, 141.

2. (a) Arduengo, A. J., III; Harlow, R. L.; Kline, M. J. Am.

Chem. Soc. 1991, 113, 361; (b) Arduengo, A. J., III Acc.

Chem. Res. 1999, 32, 913.

The CF₃groups of the anion are severely disordered.

For six groups the disorder could be split into two

components with equal occupation parameters and all

CF₃substituents have isotropically been reﬁned as rigid

groups. Moreover, a slight disorder of the COD ligand

is reﬂected by the relatively large displacement parame-

ters of C3, C4, C7, and C8 and the apparently short-

ened C3ꢀC4 and C7ꢀC8 bonds. No attempts have been

made to resolve this disorder.

3. For reviews about NHCs and NHC-metal complexes,

see: (a) Cardin, D. J.; Cetinkaya, B.; Lappert, M. F.

Chem. Rev. 1972, 72, 545; (b) Herrmann, W. A.; Ko¨cher,

C. Angew. Chem. 1997, 109, 2256; Angew. Chem., Int. Ed.

Engl. 1997, 36, 2163; (c) Bourissou, D.; Guerret, O.;

Gabba¨ı, F. P.; Bertrand, G. Chem. Rev. 2000, 100, 39; (d)

Herrmann, W. A. Angew. Chem. 2002, 114, 1342; Angew.

Chem., Ind. Ed. 2002, 41, 1290.

3.19. Procedure for the hydrogenation of substrates

10a–e and analyses of products 11a–e

4. For examples of di-N-heterocyclic carbenes and their

metal complexes, see: (a) Douthwaite, R. E.; Hau¨ssinger,

D.; Green, M. L. H.; Silcock, P. J.; Gomes, P. T.;

Martins, A. M.; Danopoulos, A. A. Organometallics

1999, 18, 4584; (b) Douthwaite, R. E.; Green, M. L. H.;

Silcock, P. J.; Gomes, P. T. Organometallics 2001, 20,

2611; (c) Douthwaite, R. E.; Green, M. L. H.; Silcock, P.

J.; Gomes, P. T. J. Chem. Soc., Dalton Trans. 2002, 1386.

5. Selected references on the use of NHCs in oleﬁn metathe-

sis: (a) Weskamp, T.; Schattenmann, W. C.; Spiegler, M.;

Herrmann, W. A. Angew. Chem. 1998, 110, 2631; Angew.

Chem., Int. Ed. 1998, 37, 2490; (b) Weskamp, T.; Kohl,

F. J.; Herrmann, W. A. J. Organomet. Chem. 1999, 582,

362; (c) Scholl, M.; Trnka, T. M.; Morgan, J. P.; Grubbs,

R. H. Tetrahedron Lett. 1999, 40, 2247; (d) Scholl, M.;

Ding, S., Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1,

953; (e) Huang, J.; Schanz, H. Z.; Stevens, E. D.; Nolan,

S. P. Organometallics 1999, 18, 5375; (f) Fu¨rstner, A.;

Ackermann, L.; Gabor, B.; Goddard, R.; Lehmann, C.

W.; Mynott, R.; Stelzer, F.; Thiel, O. R. Chem. Eur. J.

2001, 7, 3236; (g) Trnka, T. M.; Grubbs, R. H. Acc.

Chem. Res. 2001, 34, 18; (h) Sanford, M. S.; Love, J. A.;

Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 6543; (i)

Wakamatsu, H.; Blechert, S. Angew. Chem. 2002, 114,

2509; Angew. Chem., Int. Ed. 2002, 41, 2403; (j) Connon,

S. J.; Dunne, A. M. Blechert, S. Angew. Chem. 2002, 114,

3989; Angew. Chem., Int. Ed. 2002, 41, 3835; (k) Choi,

T.-L.; Rutenberg, M.; Grubbs, R. H. Angew. Chem. 2002,

114, 3995; Angew. Chem., Int. Ed. 2002, 41, 3839; (l) See

also Ref. 3d.

Substrate 10, iridium complex 9, and dichloromethane

(1 mL) were added to a small tube containing a mag-

netic stirring bar, which was then placed in 100 mL

autoclave. The autoclave was sealed and pressurized to

10–50 bar of hydrogen. One sequence of experiments

was carried out at 50°C using a heating mantle. After

stirring for several hours at the appropriate tempera-

ture, the reactor was vented. Reaction times were not

optimized. If necessary, it was cooled to room tempera-

ture before venting. Hydrogenations at ambient pres-

sure were carried out in a Schlenk tube using a ballon.

The tube containing the catalyst and the substrate was

evacuated and reﬁlled with hydrogen gas several times

before adding the solvent.

The reaction mixture was diluted with pentane and

passed through a short silica gel plug using hex-

ane:ethyl acetate (3:1) as the eluent. After evaporation

of the solvents, the conversion and the ee was deter-

1

mined by H NMR and HPLC using a chiral column,

respectively. 11a: Daicel Chiracel OJ column, 254 nm,

20°C, 0.5 mL min⁻¹, n-heptane:2-propanol, 99:1, reten-

tion times (in min)=15.5 (R), 25.7 (S), 29.5 (starting

material).^20a11b: Daicel Chiralcel OD-H column, 254

nm, 40°C, 0.5 mL min⁻¹, n-heptane:2-propanol, 95:5,

retention times (in min)=15.2, 16.9, 19.2 (starting

material).^20a11c: Daicel Chiracel OD-H column, 215

nm, 20°C, 0.5 mL min⁻¹, n-heptane:2-propanol, 96:4,

1746

C. Bolm et al. / Tetrahedron: Asymmetry 14 (2003) 1733–1746

Angew. Chem. 2001, 113, 4747; Angew. Chem., Int. Ed.

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Article Doi

Synthesis of iridium complexes with novel planar chiral chelating imidazolylidene ligands

DOI: 10.1016/S0957-4166(03)00353-7

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Full text of DOI:10.1016/S0957-4166(03)00353-7

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