Novel multichiral diols and diamines by highly stereoselective pinacol coupling of planar chiral [2.2]paracyclophane derivatives

DOI: 10.1002/chem.200500413

Novel Multichiral Diols and Diamines by Highly Stereoselective Pinacol

Coupling of Planar Chiral [2.2]Paracyclophane Derivatives

Elena V. Sergeeva,^[a]Valeria I. Rozenberg,*^[a]Dmitrii Yu. Antonov,^[a]

Evgenii V. Vorontsov,^[a]Zoya A. Starikova,^[a]Ivan V. Fedyanin,^[a]and Henning Hopf*^[b]

Abstract: The TiCl₄/Zn-mediated inter-

molecular pinacol coupling of the

planar chiral carbonyl compounds

[2.2]paracyclophane-4-carbaldehyde, 4-

acetyl[2.2]paracyclophane (ketone) and

the four regioisomeric 5-, 7-, 12- and

13-methoxy[2.2]paracyclophane-4-carb-

aldehydes as well as the pTosOH–Zn/

Cu-promoted coupling of their N-sub-

stituted imines is described. Coupling

of the enantiomerically pure substrates

(most of carbonyl compounds and all

imines) occurs stereoselectively giving

rise to diastereomerically pure 1,2-diols

and 1,2-diamines. Racemic aldehydes

and ketone react with different degrees

of stereoselectivity (depending on the

substituents in certain positions) and

produce one to three diastereomers. 7-

Methoxy[2.2]paracyclophane-4-carbal-

dehyde undergoes a tandem pinacol

coupling–pinacol rearrangement to

stereoselective formation of the asym-

metric centres is governed by the

planar

chiral

[2.2]paracyclophanyl

moiety. The techniques elaborated are

extended to the intramolecular cou-

pling of [2.2]paracyclophane-4,13-dicarb-

aldehyde and its bis-N-phenylimine, re-

sulting in stereoselective formation of

the chiral triply-bridged diol and exclu-

sive formation of the meso-diamine. X-

Ray investigations of several diols and

diamines have been carried out and the

structural features of these derivatives

are discussed.

yield

bis-(7-methoxy[2.2]paracyclo-

phane-4-yl)acetaldehyde. Coupling of

the racemic imines produces a mixture

of single racemic d,l-diamine and

single meso-diamine in each case. The

Keywords: cyclophanes · diastereo-

selectivity

·

pinacol coupling

·

planar chirality

Introduction

and diamines.^[3]The aim of these studies is to develop more

effective catalytic systems providing chiral target compounds

with high stereoselectivity and in high chemical yields. The

possibility to carry out the pinacol coupling of a,w-bis-car-

bonyl derivatives makes this reaction an excellent tool to

prepare cyclic compounds in highly stereoselective fashion

which may be useful for natural product and drug synthe-

sis.^[4]Another promising direction is the application of the

pinacol coupling to the construction of novel multichiral li-

gands, bearing—apart from two chiral centres—additional

elements of central, axial or planar chirality and/or having

the diol, diamine or amino alcohol fragments incorporated

in rigid frameworks. Several interesting ligands were syn-

thesised by intermolecular coupling of planar chiral (h⁶-are-

ne)tricarbonylchromium complexes, ferrocenecarbaldehydes

or formylphosphaferrocenes,^[5]cyclopentadiene- or cyclobu-

tene-based ketones^[6]or by intramolecular coupling of axially

chiral 2,2’-biarylcarbaldehydes and their diimines, planar

chiral mono-(h⁶-arene)tricarbonylchromium complexes of

such biaryls, diferrocenylcarboxaldehyde and its diimine.^[7]

The pinacol cross-coupling of the metal-coordinated planar

chiral arylaldehydes with imines has also recently been re-

The prominent role of diols and diamines as chiral inductors

in a wide range of stereoselective processes is evident and

well documented in the literature.^[1]A notable part of these

ligands are compounds possessing C₂symmetry.^[1,2]The pina-

col coupling of carbonyl compounds and their imino deriva-

tives is presently accepted as one of the most rational and

convenient methods for the synthesis of such chiral diols

[a] Dr. E. V. Sergeeva, Dr. V. I. Rozenberg, D. Yu. Antonov,

Dr. E. V. Vorontsov, Dr. Z. A. Starikova, I. V. Fedyanin

A. N. Nesmeyanov Institute of Organoelement Compounds

Russian Academy of Science

Vavilova 28, 119991 Moscow (Russia)

Fax : (+7)095-135-50-85

E-mail: ineos-ghkl@yandex.ru

[b] Prof. Dr. H. Hopf

Institute of Organic Chemistry

Technical University of Braunschweig

Hagenring 30, 38106, Braunschweig (Germany)

Fax : (+49)531-391-5388

E-mail: h.hopf@tu-bs.de

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Chem. Eur. J. 2005, 11, 6944 – 6961

FULL PAPER

ported.^[8]Selected examples of such types of ligands are pre-

sented in Figure 1 (I–VI). Reductive coupling of aromatic

diimines effectively produces a variety of diazacrown esters

and other nitrogen-containing macrocycles.^[9]

4-carbaldehyde (1), 4-acetyl[2.2]paracyclophane (2, ketone)

and four regioisomeric hydroxy[2.2]paracyclophane-4-carb-

aldehydes, all of which are chiral and have a variable sub-

stitution pattern, that is, 5-hydroxy- (ortho-, FHPC, 3), 12-

hydroxy- (pseudo-ortho-, pseudo-FHPC, 4), 13-hydroxy-

(pseudo-gem-,

iso-FHPC,

5)

and

7-hydroxy-

[2.2]paracyclophane-4-carbaldehydes (para-, para-FHPC, 6)

(Figure 2). This selection will help us to understand how the

substituents effect reactivity and stereoselectivity of these

model carbonyl compounds.

Figure 2. Carbonyl derivatives of [2.2]paracyclophane and enhanced ste-

reochemical descriptors for disubstituted compounds.

Figure 1. Selected examples of multichiral and rigid diols, diamines and

amino alcohols.

In the course of our studies directed at the elaboration of

planar chiral [2.2]paracyclophanes as ligands for asymmetric

synthesis we have already reported on a number of efficient

methods providing easy access to the enantiomerically pure

ortho-acylhydroxy-, ortho- and pseudo-gem-formylhydroxy-

[2.2]paracyclophanes, their imines, amino alcohols, salene-

type ligands, chiral b-diketones, and others.^[10]Moreover,

two novel types of planar chiral bisphenols (namely, bridged

and aryl [2.2]paracyclophane-type) were suggested by us re-

cently.^[11]In continuation of these studies we became inter-

ested in other chiral diols and diamines of the [2.2]paracy-

clophane series. Here we present the application of intra-

and intermolecular pinacol coupling of planar chiral [2.2]para-

cyclophane carbonyl derivatives and their imines to the syn-

thesis of novel potential ligands of type VII and VIII

(Figure 1).^[12]The structures and the determination of the

relative configurations of these new compounds are also

presented and the stereoselectivity of the coupling reactions

is discussed.

All compounds are easily available either in racemic or in

enantiomerically pure form. Aldehydes rac- and (R_p)-1^[13]

and ketones rac- and (R_p)-2^[10d]were obtained as described

previously. For the synthesis of each chiral regioisomeric

hydroxy[2.2]paracyclophane-4-carbaldehydes specific syn-

thetic techniques were applied. rac-3 (FHPC) was obtained

from 4-hydroxy[2.2]paracyclophane in three steps with its

ortho-regioselective oxaloylation as a key reaction.^[10f]The

procedure for the synthesis of rac-5 (iso-FHPC)^[10i]was

based on the pseudo-gem-regioselective TiCl₄-catalysed for-

mylation of methyl[2.2]paracyclophane-4-carboxylate with

a,a-dichloromethyl methyl ether.^[14]Aldehyde rac-4

(pseudo-FHPC) was synthesised from 4,12-dibromo-

[2.2]paracyclophane by stepwise exchange of the bromine

atoms for the respective functional group.^[15]All three hy-

droxy-substituted [2.2]paracyclophane-derived aldehydes

were resolved into enantiomers through their Schiff bases

by using the enantiomers of a-phenylethylamine (a-

PEAM). Subsequently rac- and (R)-3–5 were transformed

into the respective methoxy derivatives rac- and (R)-7–9 by

methoxylation with methyl iodide in the presence of K₂CO₃

in acetone.^[10c]

Results and Discussion

For the synthesis of 7-methoxy[2.2]paracyclophane-4-carb-

aldehyde (10) two different techniques starting from either

4-hydroxy[2.2]paracyclophane (11; Scheme 1, route A) or 4-

Synthesis of the starting materials: As substrates we have

chosen different carbonyl compounds: [2.2]paracyclophane-

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6945

V. I. Rozenberg, H. Hopf et al.

methoxy[2.2]paracyclophane (12; Scheme 1, route B) were

investigated. We have found that formylation of phenol 11

with Cl₂CHOCH₃(1.3 equiv TiCl₄, CH₂Cl₂, 2 h) was para-re-

gioselective rather than ortho-regioselective (unlike the acy-

lation of 11^[10e]) and thus afforded the respective 7-hydroxy-

[2.2]paracyclophane-4-carbaldehyde (6) (para-FHPC, isolat-

ed yield 60%) predominantly, whereas the ortho-substituted

compound 3 was formed only in traces (isolated yield less

than 5%). At the same time formylation of 11 in the pres-

ence of other Lewis acids (1 to 5 equiv SnCl₄or 1.3 equiv

FeCl₃) was neither effective nor regioselective and produced

in all cases (reaction time 2–8 h) mixtures of the correspond-

ing ortho- and para-hydroxyaldehydes 3 and 6 together with

unreacted starting phenol. From the combined reaction mix-

tures of these transformations we have isolated 3 (30%), 6

(36%) and the remaining 11 (25%) by preparative chroma-

tography. Racemic 10 was obtained from 6 by the standard

methoxylation procedure mentioned above. Next an alterna-

tive route to 10 was developed which included the formyla-

tion of racemic 4-methoxy[2.2]paracyclophane 12 under the

conditions found by us earlier for the para-regioselective

acylation^[10e,f]of this compound. The reaction of 12 with

Cl₂CHOCH₃, carried out in the presence of 1.3 equiv TiCl₄

in CH₂Cl₂, has provided a high level of para-regioselectivity

and furnished 10 exclusively in a chemical yield of 90%

(Scheme 1).

Figure 3. Racemic and enantiomerically pure imines 14–19.

from aniline hydrochloride in the presence of Et₃N, other

imines 15–17 were synthesised from the free amines. All re-

actions were carried out in toluene with Et₂SnCl₂as a cata-

lyst^[10f]allowing in all cases to reach full consumption of the

starting aldehydes. Most of the compounds were found to be

quite unstable on silica gel and hence were purified by re-

crystallisation from hexane.

For all disubstituted compounds under investigation, the

absolute configurations are defined by the carbon atom to

which OCH₃group is attached (due to its priority over

CHO or imino groups). In order to locate the positions of

the carbonyl- or imino-substituents which are the reaction

centres in the pinacol coupling reaction, we here introduce a

set of enhanced stereochemical descriptors. Thus, in pseudo-

ortho- and para-substituted carbonyl compounds (12R_p)-8,

(7R_p)-10 (Figure 2) and imine (7R_p)-19 (Figure 3) the de-

scriptors for the carbon atoms bearing CHO or CH=NHPh

groups are of the same configuration (namely, 4R_p) as the

descriptor for OCH₃-substituted carbon (12R_por 7R_p) and

those of monosubstituted compounds (R_p)-1, (R_p)-2

(Figure 2) and (R_p)-14 (Figure 3). However, in the ortho-

((5R_p)-7, (5R_p)-18) and pseudo-gem-derivatives ((13R_p)-9)

the formyl- or imino-substituted carbons could be described

as 4S_p. As will be seen below the application of these en-

hanced descriptors will be necessary when discussing the

stereoselectivity of the coupling process. The descriptors

which describe the positions for the corresponding carbonyl

and imino groups will be marked there by bold letters.

Scheme 1. Two routes to racemic carbaldehyde 10 and its resolution into

enantiomers. i) Cl₂CHOCH₃, TiCl₄, CH₂Cl₂; ii) CH₃I, K₂CO₃, acetone; iii)

(R)-PEAM, molecular sieves 4 , recrystallisation; iv) 2n HCl, MeOH.

Diastereoselective pinacol coupling of the [2.2]paracy-

clophane-derived aldehydes 1, 7–10 and ketone 2:

A

number of efficient techniques have been described for the

pinacol coupling of aldehydes and ketones, by using, for ex-

ample, SmI₂or other rare earth metal derivatives,^{[5a,7a–c,8,16a]}

low-valent Ti particles (generated in various ways)^{[5b,6b,16b–g]}

or titanocene derivatives.^[16h,i]The enantioselective version

of the coupling reaction was also elaborated.^[16k–m]Very re-

cently, environmentally friendly techniques of Sm^II-mediated

pinacol coupling in water^[17a]and even by sunlight^[17b]were

suggested. We have applied several of these techniques em-

ploying TiCl₄(an inexpensive and readily available reagent)

Racemic 10 was resolved into enantiomers through the di-

astereomeric Schiff bases 13 with enantiomers of a-PEAM

(Scheme 1, the representative example is given for (R)-a-

PEAM as a reagent). The absolute configuration of the en-

antiomer obtained from (R_p,R)-13 (isolated in 40% chemi-

cal yield as a pure diastereomer by two successive recrystal-

lisations from hexane) was determined as (R_p)-10 by com-

parison of its specific rotation with that of an authentic

sample in turn synthesised by para-regioselective formyla-

tion of (R_p)-12 (Scheme 1).

to the racemic unsubstituted aldehyde

1 (Scheme 2,

Starting from aldehydes 1, 7 and 10 we have synthesised a

number of novel racemic and enantiomerically pure imines

14–19 (Figure 3). Phenylimines 14, 18 and 19 were obtained

Table 1). The reaction mixtures were worked up and ana-

lysed by H NMR spectroscopy to determine the ratio of the

diastereomers obtained.

1

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Chem. Eur. J. 2005, 11, 6944 – 6961

Paracyclophane Derivatives

FULL PAPER

While beginning the discussion of the results of the cou-

pling reaction, we would like to make the following intro-

ductory remarks. The pinacol coupling of [2.2]paracy-

clophane-derived carbonyl compounds (as well as their

imines) produces multichiral diols (or diamines), bearing

two planar chiral moieties and two newly formed chiral cen-

tres. Therefore starting from racemic compounds a mixture

of six diastereomers (four chiral enantiomeric d,l-pairs and

two achiral meso-compounds) could in principle be obtained

(Scheme 2, the representative example is given for the po-

tential diols obtained from rac-1). From these diastereomers

two chiral d,l-pairs (20a and b) and two meso-compounds

(20e and f) possess symmetry (C₂and C_s, respectively) and

hence should give a half set of NMR signals, whether in the

¹H or ¹³C NMR spectrum. The diastereomeric chiral d,l-

pairs 20c and d, because of their C₁symmetry should dem-

onstrate in the spectrum a full set of signals and multiplets

(with corresponding coupling constants) for the protons of

the -CH(OH) fragment, however. This allows us to carry

out the initial determination of the stereoselectivity of the

reaction on the basis of NMR data.

Scheme 2. Pinacol coupling of rac-1 (top), and relative configurations of

six potential diastereomers of diol 20 with four chiral elements (bottom).

[a] For example, (R_p,S,S,R_p)*-20a stands for (R_p,S,S,R_p) + (S_p,R,R,S_p).

Table 1. Pinacol coupling of racemic aldehydes 1, 7–10 and ketone 2 (car-

Thus careful analysis of the proton spectra of the reaction

mixtures showed that in both cases three compounds of the

six possible were formed. Two singlets for CH(OH) groups

at d 4.50 and 4.56 ppm and two broad singlets of OH groups

at 2.36 and 1.96, respectively, were assigned to the symmetri-

cal chiral diol 20 and the achiral meso-20. At the same time,

four signals of equal intensity, namely two doublets (J=

3.4 Hz) at 2.00 and 2.61 ppm (two nonequivalent OH pro-

tons) pairwise with two doublets (J=3.4 Hz) at 4.87 and

5.00 ppm, respectively, (two nonequivalent CH(OH) pro-

tons) were attributed to the unsymmetrical chiral diol 20 ac-

cording to the data of a homonuclear double proton reso-

nance experiment. Among the three diastereomers the un-

symmetrical diol was the major product in both reactions,

while two symmetrical diols were formed as minor products,

slightly differing in their ratio. After purification of the reac-

tion mixtures by preparative chromatography all three dia-

stereomers were isolated together (for they have similar

chromatographic mobility) with an almost unchanged ratio.

Some olefin as a mixture of two diastereomers (chiral

(R_p,R_p)* and meso (R_p,S_p), approximately 5–7% yield) were

also isolated; they were formed as a by-products of the com-

peting McMurry reaction.

Next we turned our attention to the enantiomerically

pure aldehyde (R_p)-1 and carried out its coupling under the

optimal conditions (1 (1 equiv), TiCl₄(2 equiv), Zn

(4 equiv), THF). In this reaction three (all chiral) diaster-

eomers could arise, namely two C₂-symmetrical diols differ-

ing by the configurations at the benzylic centres

((R_p,S,S,R_p)-20 and (R_p,R,R,R_p)-20) and one C₁-symmetrical

diastereomer (R_p,R,S,R_p)-20. In fact, a single C₂-symmetrical

product (R_p,S,S,R_p)-20 was produced (Table 2, run 1). This

absolute configuration was assigned to 20 by comparison

with that of 23 (see below). This allowed us to identify the

products of the racemic reaction as one symmetrical chiral

d,l-pair (R_p,S,S,R_p)*-20, one unsymmetrical chiral d,l-pair

bonyl compound (1 equiv), TiCl₄(2 equiv), Zn (4 equiv), THF).

Run

Carbonyl

compound

Diol

Ratio of

Isolated yield

isomers^[a]

a/b:c/d:e/f

of the diol [%]^[b]

1^[c]

2

3

4

5

1

2

7

8

20

21

22

22:56:22

11:54:35

67:0:33

0:25:75

62:23:15^[d]

100:0:0

67:33

47

72

70

72

70

75

62

23

6

7

9

10

24

25^[e]

[a] Determined by ¹H NMR analysis of the reaction mixtures. [b] In all

reactions some olefinic products of the formula PC-CH=CH-PC (PC is

for the respective [2.2]paracyclophane unit) were formed (as a mixture of

two diastereomers) and isolated (3–7%). [c] The reaction was carried out

with [TiCl₄(thf)₂], Zn (4 equiv) in THF. [d] The reduction product (5%)

was detected in the reaction mixture by ¹H NMR analysis. [e] For the

structure of the product see Scheme 3.

TiCl₄/nBu₄NI^[16f]proved to be unsuitable for coupling of

1. The reaction, carried out under the described conditions

(CH₂Cl₂, ꢀ788C to room temperature, 12 h), or for a longer

(up to 20 h) periods of time, or even under reflux, produced

no target product, not even in traces. The reaction of 1 with

the TiCl₄/Et₃N^[16e]for 24 h proceeded only halfway and fur-

nished a mixture of several unidentified compounds.

Satisfactory results were obtained when the reaction was

promoted by the system TiCl₄/Zn in THF. The active species

was generated in two ways here: i) by reduction with zinc of

the [TiCl₄(thf)₂] solution, prepared in advance, and ii) by

careful addition of TiCl₄to precooled THF (08C), producing

the yellow complex in situ, followed by Zn addition (1/

TiCl₄/Zn 1:2:4, modification of the reported tech-

niques.^[6b,16g]) The second approach gave higher yields of the

mixture of the diastereomeric diols (cf. 72 versus 47%,

Table 1, runs 2 and 1).

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6947

V. I. Rozenberg, H. Hopf et al.

(R_p,R,R,S_p)*-20 (with the threo-arrangement of the newly

formed asymmetric centres and configurationally different

paracyclophanyl moieties) and one meso-compound

(R_p,S,R,S_p)-20.

active diols 22 by chromatography and recrystallisation. The

TLC-pure compound, with an acceptable elemental analysis,

always showed the presence of two diastereomers in varia-

1

ble ratios in its H NMR spectra. Recrystallisation of the re-

action mixture produced by

coupling of racemic 7 furnished

Table 2. Pinacol coupling of the carbonyl compounds (R_p)-1, 2, 7–10 (carbonyl compound (1 equiv), TiCl₄

(2 equiv), Zn (4 equiv), THF)).

a single crystal of the major

product, suitable for X-ray

analysis. This yielded the rela-

tive configuration of this dia-

stereomer as meso-(R_p,S,R,S_p)-

22 (see Figure 7).

The coupling of the racemic

pseudo-ortho substituted alde-

hyde 8 was as not as selective

as that of rac-1, and the mixture

of three diastereomers of 23

was formed again (Table 1, run

5). However, in this case the

chiral symmetrical diastereomer

Run

Carbonyl

compound

Descriptor for the

carbonyl group

Diol (confi-

guration)

Isolated

yield [%]

[a]²_D²

1

2

3

(4R_p)-1

(4R_p)-2

(5R_p)-7

4R_p

4S_p

(R_p,S,S,R_p)-20^[a]

(R_p,R,R,R_p)-21

(R_p,S,S,R_p)-22

(R_p,R,S,R_p)-22

(R_p,S,S,R_p)-23^[b]

(R_p,R,R,R_p)-24^[c]

(R_p,R_p)-25^[d]

77

ꢀ88.2 (c 0.2, CHCl₃)

ꢀ14.6 (c 0.2, CHCl₃)

+116.3 (c 0.2, CHCl₃)^[e]

52 (92)

57^[e](58:42)

4

5

6

(12R_p)-8

(13R_p)-9

(7R_p)-10

4R_p

4S_p

4R_p

70

83

57

ꢀ36.6 (c 0.23, CHCl₃)

+104.0 (c 0.3, CHCl₃)

ꢀ69.6 (c 0.2, CHCl₃)

[a] An olefinic product was isolated in 22% yield. [b] The reduction product (14%) was detected in the reac-

1

tion mixture by H NMR analysis. [c] Olefin (10%) was detected in the reaction mixture by H NMR analysis.

[d] For the structure of the product see Scheme 3. [e] Mixture of two diastereomers.

was the dominating product.

1

The pinacol coupling of the racemic (Table 1) and (R_p)-

enantiomers of regioisomeric aldehydes 7–10 and ketone

(R_p)-2 (Table 2) under similar conditions constituted the

next experiments.

The analysis of the CH region in the H NMR spectrum of

the reaction mixture revealed the presence of two singlets at

d 4.51 and 4.66 ppm responsible for the CH(OH) groups of

achiral meso-23 and the symmetrical chiral diol 23, respec-

tively, and two multiplets with equal intensity at 4.43 and

4.73 ppm (two nonequivalent CH(OH) protons), originating

from the unsymmetrical chiral diol 23. The reaction of (R_p)-

The coupling of the racemic methylketone 2 produced a

mixture of two symmetrical diastereomers of diol 21 (chiral

1

and meso according to H NMR data, Table 1, run 3), from

1

which the major isomer was isolated by preparative chroma-

tography in 30% chemical yield. For the coupling of (R_p)-2

¹H NMR spectra of the reaction mixture (obtained in 92%

chemical yield) revealed the formation of the single sym-

metrical diol 21 without any noticeable side products

(Table 2, run 2). However, the isolated yield after chromato-

graphic purification was remarkably low (52%), although

small amounts (not more than 10%) of unidentified side

8 produced the single chiral diol 23 (according to H NMR

analysis) which was isolated by preparative chromatography

and recrystallisation (Table 2, run 4). The appropriate single

crystal was subjected to X-ray analysis and the absolute con-

figuration of 23 was established as (R_p,S,S,R_p) (see Figure 7).

It should be noted that in the case of this substrate the cou-

pling was accompanied by reduction (5 and 14% for the rac-

emic and optically pure substrates, respectively).

The coupling of the racemic pseudo-gem-aldehyde rac-9

occurred at a high level of stereoselectivity and resulted in a

single symmetrical diol (Table 1, run 6). Enantiomerically

pure (R_p)-9 produced the single symmetrical product 24 as

1

products were isolated. The H NMR spectra of this chiral

diol 21 and maj-21 were identical, and hence the latter con-

stitutes the racemic chiral diol. An X-ray diffraction study,

carried out for a single crystal of the optically pure sample,

allowed us to determine the absolute configuration as

(R_p,R,R,R_p)-21 (see Figure 7).

1

well (Table 2, run 5), and the H NMR spectra of both race-

mic and optically pure products were identical. Both com-

pounds were isolated by preparative chromatography, and

from the latter single crystals suitable for X-ray diffraction

workwere obtained (see Figure 7). The absolute configura-

tion hence determined was (R_p,R,R,R_p)-24.

In the reactions of the ortho-substituted aldehydes rac-7

and (R_p)-7, mixtures of two isomers of 22 were formed in

25:75 (Table 1, run 4) and 58:42 ratios (Table 2, run 3), re-

1

spectively. In both cases the H NMR spectra of the reaction

mixtures clearly displayed the dominating sharp singlets of

the OCH₃groups at 3.26 or 3.24 ppm as well as singlets at

5.19 or 5.18 ppm, attributable to -CH(OH) groups, thus indi-

cating that the symmetrical diols had been generated. The

second diastereomers in both cases have unsymmetrical

structures. This was established by careful analysis of the

¹H NMR spectra of the reaction mixtures where two dou-

blets of protons of nonequivalent CH(OH) groups at 4.65

and 5.05 ppm and a broadened multiplet in the range 4.77–

4.87 ppm (tentatively attributed to one of OH groups) were

clearly indicated. We were unable to separate the optically

In all reactions of 7–9 (as well as 1) small amounts of the

corresponding olefins (near 3–7%) were detected and were

isolated as the first fractions during the chromatographic

separation of the product mixtures.

Surprisingly, the reaction of racemic 10 as well as its (R_p)-

enantiomer produced the aldehydes 25 (Table 1, run 7,

Table 2, run 6, Scheme 3) rather than the anticipated diols,

as was unambiguously confirmed by X-ray crystallography

1

(Figure 4), H and ¹³C NMR spectrum, mass and IR-spectral

data. The coupling of racemic 10 produced a 63:37 mixture

of two isomers (maj-25 and min-25), while (R_p)-10 gave rise

6948

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Chem. Eur. J. 2005, 11, 6944 – 6961

Paracyclophane Derivatives

FULL PAPER

migratory aptitude of the respective [2.2]paracyclophanyl

fragment.^[19]

The experimental results obtained so far allow the follow-

ing conclusions and generalisations:

1) Almost in all cases (except for the coupling of substrate

7) the stereoselective formation of a single chiral sym-

metrical diol from an optically pure carbonyl compound

was observed, correspondingly the respective d,l-pairs

were produced from the racemic substrates. This sup-

ports the assumption that the planar chiral paracyclo-

phanyl unit governs the stereoselective formation of the

asymmetric centres both for the enantiomerically pure

and racemic substrates.

2) With this assumption in mind two mechanisms, proposed

for the pinacol coupling of carbonyl compounds mediat-

ed by low-valent Ti species, may be considered. The first

mechanism (a conventional one, as referred to in the lit-

erature) assumes the generation of ketyl radicals, fol-

lowed by their dimerisation in a manner, favouring the

minimisation of steric interaction between aryl substitu-

ents attached to the reaction centres. The stereoselective

formation of the chiral d,l-pairs is generally attributed

to the additional bridging of these intermediates by the

low-valent Ti species (Figure 5, left). For our case with

Figure 4. The structure of the aldehyde (R_p,R_p)-25 in the crystal. Here

and below the hydrogen atoms of all the aromatic rings, ethano bridges

of [2.2]paracyclophanyl moieties and Me-groups are omitted for clarity.

All structures are presented as ORTEP plots with ellipsoids plotted at

the 30% probability level.

1

to (R_p,R_p)-25, the H NMR spectrum of which was identical

to that of the maj-25. We assume that in this particular case

(unlike the other ones studied) a tandem pinacol coupling–

Lewis acid promoted pinacol rearrangement^[18]takes place.

The suggested mechanism of such a sequence (similar to the

one described for the coupling/rearrangement of arylke-

tones^[18a]) is summarised in Scheme 3. The expected coupling

product (respective diol) would exist in the reaction mixture

as the metal coordinated (Zn, Ti) cyclic intermediate, a sym-

bolised by structure A. This would subsequently afford the

cationic intermediate B, then produce the stable intermedi-

ate C as a result of a 1,2-migration of the 7-methoxy-

[2.2]paracyclophane-4-yl-moiety and, finally, release the al-

dehyde 25 upon hydrolysis. The driving force of such a pro-

cess could be attributed to the para-methoxy substituent of

the starting aldehyde 6, which should greatly facilitate the

Figure 5. The possible intermediates of the pinacol coupling reaction.

additional planar chiral paracyclophanyl moieties such a

reaction pathway determines (assuming the stereoselec-

tive formation of the anion radicals), that only symmetri-

cal diastereomers (chiral d,l-pairs or chiral diastereo-

mers and achiral meso-compounds) can be obtained. The

coupling of substrates 2 and 9 (Table 1, entries 3 and 6,

Table 2, entries 2 and 5) agrees with such an explanation.

However, chiral unsymmetrical diastereomers found in

the reaction mixtures of all other cases (for substrates 1,

7 and 8, Table 1, entries 1, 2, 4 and 5, Table 2, entry 3)

support an alternative reaction path,^[20]based on initial

formation of a titanooxirane intermediate (Figure 5,

right), followed by insertion of a second aldehyde into

ꢀ

the Ti C bond. The configuration of the second asym-

metric centre formed in this case could be favoured by

the more appropriate threo-arrangement of the bulky

substituents at the two developing asymmetric centres.

Accordingly, for the coupling of the racemic carbonyl

derivatives of [2.2]paracyclophane (again having in mind

the diastereoselective formation of the titanooxirane),

all three types of diastereomers (achiral meso-, symmet-

Scheme 3. Synthesis of 25 from 6 by tandem pinacol coupling–pinacol re-

arrangement process. R = 7-methoxy[2.2]paracyclophan-4-yl-; M = Zn

or Ti; L = (THF) or Cl.

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6949

V. I. Rozenberg, H. Hopf et al.

rical and unsymmetrical chiral) are in principle possible,

and this was in fact observed for racemic substrates 1

and 8 (Table 1, runs 1, 2, and 5). Enantiomers of these

substrates stereoselectively gave rise to the single sym-

metrical diols 20 and 23 (Table 2, entries 1 and 4). The

selectivity of the coupling of substrate 7 contarsts that of

the other derivatives because the chiral diastereomer

was not formed from the racemic substrate at all, and

the unsymmetrical chiral diastereomer was produced

ers (4R_p,S,R,4S_p)-20, 22 and 23, or (4R_p,R,S,4S_p)-21,

whereas coupling between two homonymous fragments

would produce chiral diols (R_p,S,S,R_p)*-20 and 23 or

(R_p,R,R,R_p)-21 and 24. If the insertion mechanism is as-

sumed to be operative, the formation of the unsymmetri-

cal chiral diols is governed by the more appropriate

mutual arrangement of the substituents at the two asym-

metric centres. It results in the formation of the threo-

diols bearing configurationally different paracyclophanyl

moieties from substrates 1 and 8, and the erythro-diol

with configurationally equal paracyclophanyl fragments

from 7. The presence of bulky substituents in selected

positions affects the stereochemistry of the processes

considerably. Thus, the formation of the chiral d,l-21

from the racemic ketone 2 (bearing a methyl group in-

stead of hydrogen at the carbonyl group) was approxi-

mately twice as favoured as that of meso-21 (Table 1,

run 3). The methoxy group in pseudo-gem-position of

the [2.2]paracyclophane moiety (aldehyde 9) prevents all

reactions except the formation of the chiral diol d,l-24

(Table 1, run 6). The methoxy substituent in pseudo-

ortho-position to the carbonyl group (aldehyde 8) causes

a less pronounced influence on the stereoselectivity, but

the formation of the chiral d,l-23 still predominates

(Table 1, run 5). Note that in the case of the racemic

ortho-substituted aldehyde 3 the preferred product was

meso-22 (together with smaller amounts of the unsym-

metrical chiral d,l-22), whereas the chiral C₂-symmetri-

cal diol d,l-22 was not formed at all, probably because

of steric hindrance effects (Table 1, run 4). This awkward

product was, however, obtained in the coupling reaction

with (R)-7, although the contribution of the unsymmetri-

cal d,l-22 in this case significantly increased (Table 2,

run 3).

even when coupling the enantiomerically pure

7

(Table 1, run 4, Table 2, run 3). Thus it appears that both

reaction pathways and participating intermediates are

reasonable for different substrates and a further detailed

discussion of the stereoselectivity of the pinacol coupling

will have to take this duality into account.

3) We now return to the assumption that the initial forma-

tion of the intermediate (either ketyl radical or titanoox-

irane) occurs stereoselectively and we will discuss the

role of the planar chiral [2.2]paracyclophanyl moiety

more thoroughly. Here the enhanced stereochemical de-

scriptors mentioned above will be useful. To explain the

observed selectivity, we assume that the carbonyl group

of each aldehyde (4R_p)-1, (12R_p,4R_p)-8 or (13R_p,4S_p)-9

coordinated to Ti takes up a conformation anti to the

nearest ethano bridge, thus reducing steric interactions

within the particular intermediate generated. Moreover,

in the case of 8 and 9 the additional fixation of such con-

formations is possible by coordination of Ti with me-

thoxy groups. In such conformations the Si faces of the

carbonyl groups in 1 and 8, as well as the Re face in 9,

are not shielded by the protons of the unsubstituted

[2.2]paracyclophane ring, and in this way the intermedi-

ate species (radical anion or titanooxirane, see above)

may be formed with the asymmetric centre of the oppo-

site configuration, namely, (S) from (4R_p)-1 and

(12R_p,4R_p)-8 and (R) from (13R_p,4S_p)-9 (Table 2, runs 1,

4 and 5). At the same time for the carbonyl group of the

ketone (4R_p)-2 and of the ortho-substituted aldehyde

(5R_p,4S_p)-7, the syn orientation with respect to the

ethano bridge^[21]helps to avoid undesired repulsive inter-

actions and hence induces formation of the asymmetric

centre of homonymous configuration [(R)- from (4R_p)-2

and (S)- from (5R_p,4S_p)-7). Then, for practically all reac-

tions (except for 7, see below), either coupling between

two (4R_p,S)- or (4R_p,R)-paracyclophanyl fragments or in-

sertion of the second paracyclophanyl moiety with for-

mation of the second asymmetric centre of the same

configuration (which demands threo arrangement of the

bulky substituents) produces the corresponding

(4R_p,R,R,4R_p)- or (4R_p,S,S,4R_p)-diols. The formation of

the unsymmetrical diol from (5R_p,4S_p)-7 provides evi-

dence for the more favourable erythro arrangement of

two configurationally equal ortho-substituted paracyclo-

phanyl moieties. Concerning the racemic compounds, it

should be noted that the coupling between two stereose-

lectively formed ketyl radicals of opposite planar chirali-

ty ((4R_p)- and (4S_p)-) could lead to the meso diastereom-

Diastereoselective pinacol coupling of [2.2]paracy-

clophane-derived imines:^[12]For the synthesis of chiral dia-

mines by pinacol coupling of imino derivatives a variety of

[5a,7b,7c]

reducing agents such as SmI₂

and its combinations

with other reagents,^[22]Zn-based reagents^[9,23]and a few

others systems^[24]have been described. We have carried out

the coupling reactions of imines 14–19 in DMF with excess

Zn/Cu couple and pTosOH at 08C, followed by maintaining

the reaction mixture at room temperature for 24 h. After

work-up the ratio of the obtained diastereomers (Table 3)

1

was analysed by H NMR spectroscopy. Subsequently the di-

amines 26–31 were purified by silica gel chromatography

and characterised as diastereomeric mixtures or individual

compounds by the usual spectroscopic and analytical data.

1

According to the H NMR data coupling of the racemic

imines 14, 15, 17 and 19 occurs with formation of mixtures

of only two diastereomers in 1:1 ratio (Table 3, entries 1, 2,

4, 6), while in the case of imines 16 and 18, which contains

bulky substituents close to the reaction centre, the ratio

shifts towards one diastereomer considerably (Table 3, runs

3 and 5). No traces of the reduction product (corresponding

amines) were detected. The presence of only a half set of

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Chem. Eur. J. 2005, 11, 6944 – 6961

Paracyclophane Derivatives

FULL PAPER

signals in the proton spectra of diamines 26–31 indicates the

formation of symmetrical compounds. Diamines 26, 30 and

31 (Table 3, runs 1, 5, 6) were isolated and characterised as

mixtures of diastereomers. Recrystallisation of diamines 27

(Table 3, run 2) and 28 (Table 3, run 3), having sterically de-

manding N-substituents, allowed the isolation of individual

crystalline diastereomers, the structures of which were deter-

mined by X-ray studies^[12]as meso-27 and meso-28 (major)

of (R_p,S,R,S_p)-relative configuration. The chromatographic

separation of the mixture of the N-benzylimine-derived di-

amine 29 (Table 3, run 4) resulted in only one meso diaste-

reomer in 49% yield. We have failed in the isolation of the

chiral racemic isomer either by recrystallisation or prepara-

tive chromatography due to its extremely low solubility and

low chromatographic mobility.

Next we have carried out the coupling of imines (R_p)-14,

(5R_p,4S_p)-18 and (7R_p,4R_p)-19 (Table 4, runs 1–3) and ob-

served in each case the stereoselective formation of the

single chiral products 26, 30, 31. This indicates that the

second diastereomers formed in the coupling of the racemic

14, 18 and 19 unequivocally were achiral meso compounds.

Diamines 26, 30 and 31 were readily purified on silica gel.

The relative configuration of the diastereomerically pure 30

was determined as (4R_p,S,S,4R_p) by 2D ¹H NMR experi-

ments. For diamine 31 a single crystal X-ray diffraction

study revealed (4R_p,S,S,4R_p)-configuration (see Figure 7).

Relying on the established relative configurations of

meso-27 and 28 and chiral 30 and 31, we assume that the

planar chiral [2.2]paracyclophane moiety plays a key role in

the stereochemical outcome of the reaction. It is accepted

that the reaction proceeds by electron transfer from the

metal to the substrate which is activated by the sulfonic

acid.^[20,22c]Thus if the activated imine fragments of 14–17

and 19 react in their anti conformations with respect to the

Figure 6. Structures of the imines rac-15 (top) and (R_p)-18 (bottom) in

the solid state.

nearest ethano bridge (as is also supported by the X-ray

structural data of the starting imine 15, Figure 6, top), then

the Si faces for (4R_p)-14 and (7R_p,4R_p)-19 (as well as for ra-

cemic 15 and 16) will not be

shielded by the protons of the

Table 3. Pinacol coupling of the racemic imines 14–19 with Zn/Cu couple and pTosOH.

unsubstituted

[2.2]paracy-

clophane ring. The coupling be-

tween (R_p)- and (S_p)-paracyclo-

phanyl fragments should lead to

the meso diastereomer with

(R_p,S,R,S_p)-configuration as was

unequivocally shown for 27 and

28. In turn, coupling between

two (R_p)- or two (S_p)-paracyclo-

phanyl fragments should give

chiral d,l-pairs (R_p,S,S,R_p)* 26–

29 and 31 from racemic sub-

strates 14–17 and 19 or

(R_p,S,S,R_p)-diastereomers from

(R_p)-14 and 19. At the same

time the X-ray structure of the

imine 18^[12](Figure 6, bottom)

bearing an ortho-substituent re-

veals that now the more pref-

erable conformation of the

imine fragment is the one with

Run

R

R¹

Imine

Diamine

Isolated yield [%]

d,l/meso^[a]

1

2

3

4

5

6

H

Ph

14

15

16

26

60

80

50:50

51:49

15:85

50:50

25:75

50:50

2-BrC₆H₄

2,6-Me₂-C₆H₃

CH₂C₆H₅

Ph

27^[12]

28^[12]

29

79

17

49^[b]

45

o-OCH₃

p-OCH₃

18^[12]

19

30

31

Ph

64

1

[a] Determined by H NMR analysis. [b] Yield of the meso-diamine isolated after purification on silica gel.

Table 4. Pinacol coupling of the imines (R_p)-14, 18 and 19 with Zn/Cu couple and pTosOH.

Run

Imine

Diamine

Isolated yield [%]

[a]²_D²

1

2

3

(4R_p)-14

(4R_p,S,S,4R_p)-26

(4R_p,S,S,4R_p)-30

(4R_p,S,S,4R_p)-31

64

52

46

ꢀ15.7 (c 0.36, C₆H₆)

+28.7 (c 0.27, C₆H₆)

+49.4 (c 0.23, C₆H₆)

(5R_p,4S_p)-18

(7R_p,4R_p)-19

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6951

V. I. Rozenberg, H. Hopf et al.

Figure 7. Structures of the diols a) (R_p,R,R,R_p)-21, b) (R_p,S,R,S_p)-22, c) (R_p,S,S,R_p)-23, d) (R_p,R,R,R_p)-24, and e) diamine (R_p,S,S,R_p)-31 in the crystal.

the N-Ph substituent in syn-orientation with respect to the

ethano bridge, owing to the repulsive interaction with the

OCH₃group. Thus the stereochemical result of the coupling

reaction should be the opposite of that of the reaction of

the imines 14–17 and 19, and formation of the asymmetric

centre of homonymous configuration (namely, (R)- from

(R_p)-paracyclophanyl moiety) is expected. However, the

configuration of the imine (5R_p,4S_p)-18 (and thereby of the

diamine 30) is defined by the descriptor of the OCH₃group.

Hence the coupling of two paracyclophanyl fragments

having opposite configurations should give (R_p,S,R,S_p)-30

whereas the coupling of two paracyclophanes with the same

configurations should afford (R_p,S,S,R_p)-/(S_p,R,R,S_p)-30.

X-ray crystallographic study and structural features of diols

(R_p,R,R,R_p)-21, (R_p,S,R,S_p)-22, (R_p,S,S,R_p)-23 and

(R_p,R,R,R_p)-24, and diamines meso-27, meso-28 and

(R_p,S,S,R_p)-31: The general views of diols (R_p,R,R,R_p)-21,

(R_p,S,R,S_p)-22, (R_p,S,S,R_p)-23 and (R_p,R,R,R_p)-24, and di-

amine (R_p,S,S,R_p)-31 are summarised in Figure 7. The data

for diamines meso-27 and meso-28 are taken from ref. [12].

We have undertaken a comparative analysis of the solid-

state structures of the newly synthesised diols and diamines

with other similar compounds described in the literature.

The structural data for compounds with the formula

[25]

[26]

ꢀ

Ar(OH)CH CH(OH)Ar,

Ar(OH)C(R) C(R)(OH)Ar

1

[27]

ꢀ

and Ar(NHR )CH CH(NHR )Ar

were taken from the

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Chem. Eur. J. 2005, 11, 6944 – 6961

Paracyclophane Derivatives

FULL PAPER

Ar = C₆H₅, R = CH₃,^[26a]Ar = C₆H₅, R = (CH₂)₂C(O)N-

[26b]

(CH₂)₃

and Ar = 4-CH₃C₆H₅, R = CH₂N(CH₂)₅,^[26c]

(with gauche hydroxy and aryl groups and anti-alkyl sub-

stituents) and for the diol with Ar = C₆H₅, R = 2-naph-

thyl^[26d](where the hydroxy groups were in anti position).

Among the meso-diols of such structure (Ar = C₆H₅, R =

[26e]

CH₃

and Ar = R = C₆H₅),^[26f]only anti conformers have

been reported. Apparently, such sterically hindered diols

adopt in each particular case (and depending on the sub-

stituents at the tetrahedral carbon atom) conformations that

prevent unfavourable steric interactions.

The crystal structures of diamines with the formula Ar-

1

ꢀ

(NHR )CH CH(NHR )Ar are represented in the CSD da-

tabase by a considerably smaller number of examples and

no distinct regularities have been noticed. Thus, [2.2]paracy-

clophane-derived meso-diamines 27 and 28^[12]have all

gauche conformations of like substituents, whereas diamines

[27a,b]

with Ar

BrC₆H₄

=

2-OH-C₆H₄and R¹

=

2-ClC₆H₄

or 4-

[27a,c]

prefer anti conformations. The crystal structure

[27a,d]

of the diamine with Ar = 4-Cl-C₆H₄and R¹= C₆H₅

contains both gauche and anti conformers. Among the chiral

diamines the [2.2]paracyclophane-derived 31 has anti confor-

mation of the NH-R¹substituent (R¹= C₆H₅) as well as the

Figure 8. The conformations and characteristic torsion angles for diols

and diamines in the crystal (PC: [2.2]paracyclophan-4-yl-; PC^ortho: 5-

methoxy[2.2]paracyclophan-4-yl-; PC^ps: 12-methoxy[2.2]paracyclophan-4-

yl-;. PC^iso

:

13-methoxy[2.2]paracyclophan-4-yl-; PC^para

:

7-methoxy-

diamine with Ar = C₆H₅and R¹= C₆F₅,^[27f]whereas those

[2.2]paracyclophan-4-yl-).

with Ar = 2,6-Cl₂-C₆H₃and R¹= C₆H₅

displays gauche

[27f]

CSD.^[28]First, we have considered the conformations in the

solid state of the central core of the molecules of diols 21–

24 and diamines 27, 28 and 31 and presented them as

Newman projections with the key torsion angles (Figure 8).

It should be noted, that all chiral compound of this type

could adopt three different conformations (in order to mini-

mise steric strain), in which one pair of the identical groups

usually will be in anti orientation, whereas two others will

pairwise be in gauche conformations. At the same time, for

the achiral meso compounds two other conformations (all

identical groups anti or all gauche) are preferred. From this

point of view we have analysed the molecular conformations

of our compounds. Thus for the centrosymmetric molecule

meso-22 the conformation of all substituents was anti. A

similar conformational behaviour has been described for

orientation of the NH-R¹and Ar substituents.

The key geometric parameters of the [2.2]paracy-

clophane-derived diols and diamines are collected in

Tables 5–7. To unify the numbering of the atoms (for they

have different numeration in Figure 7 due to nomenclature

rules) we present a generalised view of the central frag-

ments (see Table 5). It is clear from the data that bond

lengths and dihedral angles have the values expected for the

tetrahedral carbon atoms (C_sp₃). The only exceptions were

1

2

ꢀ

found for the length of the central C C bonds in diol 21

and diamines 27, 28 and 31, which were clearly longer than

the standard C_sp₃C_sp₃bond (1.530 ).^[29]The greatest length

ꢀ

1

2

ꢀ

of a C C bond was observed for diol 21 (Table 5, entry 1,

1.601 ) with [2.2]paracyclophanyl and Me substituents at

1

ꢀ

the tetrahedral carbon atoms. Similar elongations of the C

most meso-diols of the general formula Ar(OH)CH

C²bond have been, for example, registered for the chiral

ꢀ

CH(OH)Ar (Ar = 4-Br-, 4-Cl, 4-I- or 4-CH₃C₆H₄,^[25a]4-

diols (Ar(OH)C(R) C(R)(OH)Ar) with Ar = C₆H₅, R =

ꢀ

[25b]

OCH₃C₆H₄or 3,4-(OCH₃)₂C₆H₃

or (7-tert-butyl-

CH₃(1.591 ),^[26a]Ar = C₆H₅, R = (CH₂)₂C(O)N(CH₂)₃

(1.594 ),^[26b]and Ar = 4-CH₃C₆H₅, R = CH₂N(CH₂)₅

(1.592 ),^[26c]and meso-diols with Ar = C₆H₅, R = CH₃

(1.584 ),^[26e]Ar = C₆H₅, R = 2-naphthyl-(1.619 ),^[11]and

Ar = R = C₆H₅(1.59 ).^[26f]In all these cases the lengthen-

[2.2]metacyclophan-4-yl-).^[25c]In only one special case^[25d]

(Ar=2-BrC₆H₄·Cr(CO)₃) the conformation of the corre-

sponding meso-diol in the crystal was gauche. The solid-state

structures of the chiral diols 23 and 24 are very similar to

each other, with gauche orientations of the hydroxy groups

and paracyclophanyl moieties, and anti orientation of the

hydrogen atoms (consistent with the conformational struc-

1

2

ꢀ

ing of the C C bond is caused by the increase of the steric

strain in the molecules. In [2.2]paracyclophane-derived di-

1

2

ꢀ

amines 27, 28 and 31 the lengths of the C C bonds were in

the range of 1.55–1.56 (Table 5, entries 5–7), similar to those

of the aryl-derived diamines (1.53–1.56 ).^[27]

ꢀ

tures of the chiral diols Ar(OH)CH CH(OH)Ar with Ar=

C₆H₅

[25e]

or 3,4-(OCH₃)C₆H₃^[25f]). At the same time, the

The values of the O¹-C¹-C²-O²torsion angles for the

chiral [2.2]paracyclophane-derived diols 23 and 24 (50.0 and

53.28, Table 7, entries 3 and 4) were comparable with the

angles of the parent hydrobenzoin (54.88)^[25a]and the diol

with Ar = 4-CH₃C₆H₅, R = CH₂N(CH₂)₅(53.48),^[26c]and

ꢀ

chiral diol 21 (having the formula (Ar(OH)C(R)

C(R)(OH)Ar)) revealed a gauche orientation of the hy-

droxy groups and hydrogen atoms together with an anti con-

formation of the paracyclophanyl units. Two other possible

conformations were presented in the literature for diols with

Chem. Eur. J. 2005, 11, 6944 – 6961

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6953

V. I. Rozenberg, H. Hopf et al.

Table 5. Selected bond lengths [] for [2.2]paracyclophane-derived diols and diamines.

ꢀ

O1 O1’ 2.80 and 2.80 , O1

ꢀ

H10’ and O1 H10’ 1.81 and

2.33 , OHO 161 and 1068 in

two independent molecules)

thus forming a dimeric struc-

ture, whereas the methoxy

groups do not participate in the

hydrogen bonding.

1

2

1

3

2

4

1

2

ꢀ

Entry

Bond length

C

O

C or N

C

O C or N C

Intramolecular diastereoselec-

tive pinacol coupling of pseudo-

gem-disubstituted [2.2]paracy-

clophanes leading to triply-

bridged diols and diamines: As

mentioned above several inter-

esting examples of intramolecu-

lar coupling leading to rigid

diol and diamine frameworks

have been described.^[7]In all

these cases axial or planar chir-

ality of the substrate has gov-

erned the stereochemistry of

the reactions studied and has

controlled the formation of the

asymmetric centres.

We also would like to present

some preliminary results on the

preparation of rigid, bridged

compounds by intramolecular

pinacol coupling of some para-

cyclophane derivatives. For this

purpose we have optimised the

1

2

(R_p,R,R,R_p)-21

meso-22

1.601(3)

1.542(7)

1.524(8)

1.534(5)

1.538(5)

1.554(11)

1.570(12)

1.560(3)

1.573(3)

1.565(3)

1.528(3)

1.522(6)

1.524(5)

1.508(5)

1.516(5)

1.533(12)

1.537(12)

1.526(3)

1.534(3)

1.505(3)

1.536(3)

1.522(6)

1.524(5)

1.480(5)

1.508(5)

1.528(12)

1.515(13)

1.523(3)

1.516(3)

1.429(3)

1.452(6)

1.439(5)

1.415(4)

1.430(4)

1.444(10)

1.465(11)

1.466(2)

1.442(2)

1.451(2)

1.433(3)

1.452(6)

1.439(5)

1.442(4)

1.448(4)

1.466(10)

1.478(11)

1.467(2)

1.463(2)

1.462(2)

3

4

5

(R_p,S,S,R_p)-23

(R_p,R,R,R_p)-24

meso-27^[12]

6

7

meso-28^[12]

(R_p,S,S,R_p)-31

Table 6. Selected bond angles [8] for [2.2]paracyclophane-derived diols and diamines.

Entry

Angles

O¹-C¹-C²or N¹-C¹-C²

O²-C²-C¹or N²-C²-C¹

C³-C¹-C²

C⁴-C²-C¹

1

2

(R_p,R,R,R_p)-21

meso-22

109.9 (2)

107.6(5)

107.8(5)

111.1(3)

108.5(3)

109.8(7)

111.1(8)

105.5(2)

112.5(2)

110.1(2)

109.3(2)

107.6(5)

107.8(5)

108.7(3)

104.6(3)

112.0(7)

107.1(7)

106.7(2)

108.6(2)

109.5(2)

108.6(2)

111.1(4)

111.5(4)

111.8(3)

110.1(3)

113.1(7)

109.8(7)

110.1(2)

109.8(2)

112.1(2)

110.2(2)

111.1(4)

111.5(4)

113.4(3)

113.1(3)

110.7(7)

111.9(7)

111.5(2)

112.5(2)

112.0(2)

3

4

5

(R_p,S,S,R_p)-23

(R_p,R,R,R_p)-24

meso-27^[12]

6

7

meso-28^[12]

(R_p,S,S,R_p)-31

Table 7. Selected torsion angles [8] for [2.2]paracyclophane-derived diols and diamines.

synthesis

of

[2.2]paracy-

Entry

Angles

O¹-C¹-C²-O²

O²-C²-C¹-C³

N²-C²-C¹-C³

O¹-C²-C¹-C⁴

C³-C¹-C²-C⁴

or N¹-C¹-C²-N²

N¹-C²-C¹-C⁴

clophane-4,13-dicarbaldehyde

(34).^[30]Following previously

developed protocols^[31]the pro-

cedure involves the successive

reduction of the pseudo-gem di-

substituted compound 32 with

LiAlH₄followed by oxidation

of the resultant dicarbinol 33

with DDQ (Scheme 4). Di-

aldehyde 34 was converted into

the corresponding bis(phenyl-

imine) 35 as described for the

1

2

(R_p,R,R,R_p)-21

meso-22

60.4(2)

180

56.2(2)

59.3(5)

57.8(5)

174.3(3)

175.7(3)

54.2(10)

55.5(1)

59.1(2)

60.9(2)

66.6(3)

56.7(2)

59.3(5)

57.8(5)

174.5(3)

173.9(2)

161.5(9)

163.7(8)

162.7(2)

63.6(3)

64.4(3)

173.3(2)

180

3

4

5

(R_p,S,S,R_p)-23

(R_p,R,R,R_p)-24

meso-27^[12]

50.0(4)

53.2(3)

71.8(9)

70.4(10)

67.3(2)

170.8(2)

165.9(2)

61.2(4)

63.6(4)

72.8(10)

70.3(10)

70.8(2)

64.7(3)

63.1(2)

6

7

meso-28^[12]

(R_p,S,S,R_p)-31

notably smaller than those for other chiral diols (21: 60.48,

Table 7, entry 2; 3,4-(OCH₃)₂C₆H₃:^[25b]66.38; Ar = C₆H₅, R

= CH₃:^[26a]61.58; Ar = C₆H₅, R = (CH₂)₂C(O)N(CH₂)₃:^[26b]

65.28). For diols 23 and 24 such conformations could addi-

tionally be stabilised by hydrogen bonding. Thus in the crys-

tal of 24 both hydroxy and methoxy groups are involved in

the intermolecular hydrogen bonds (parameters of the hy-

synthesis of other imines; it was obtained in analytically

pure form by recrystallisation. Needless to note both 34 and

35 are achiral, and only two possible diastereomers can

result from the coupling, namely, a chiral d,l-pair, (R,R)*,

and a meso-diastereomer, (R,S).

Coupling of 34 was carried out with TiCl₄and Zn in THF

under standard conditions. As a result of the coupling, clo-

sure of the third, vicinally hydroxy-substituted ethano

bridge occurred.^[32]The product was obtained in quantitative

ꢀ

drogen bonds for O2 H20’···O1: O2 O1 2.81 , O1 H20’

ꢀ

1.89 , O2-H20’-O1 1518 and for O2’ H10’···O2: O2 O2’

1

2.66 , O2 H10’ 2.16 , O2’-H10’-O2 1138). In contrast, in

diol 23 only OH groups participate in intramolecular O1

yield, H and ¹³C NMR spectra of the reaction mixture dem-

ꢀ

onstrated the presence of two compounds in 77:23 ratio. An-

alytically pure major isomer 36 was obtained in 72% yield

ꢀ

H10···O1’ and O1’ H10’···O1 bonds (the parameters are:

6954

www.chemeurj.org

ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2005, 11, 6944 – 6961

Paracyclophane Derivatives

FULL PAPER

Conclusion

The pinacol coupling of enantiomerically pure planar chiral

carbonyl derivatives of [2.2]paracyclophane and their N-sub-

stituted imines occurs stereoselectively and gives rise to dia-

stereomerically pure diols and diamines. The stereoselectivi-

ty of the coupling reaction (i.e., possible formation of one to

three diastereomers) depends on the substituents of the aro-

matic ring for the racemic aldehydes and on the presence of

a methyl substituent at the carbonyl group for the racemic

ketone. In a particular case, a substituent in para-position to

the carbonyl group induces a tandem pinacol coupling–pina-

col rearrangement with formation of the corresponding acet-

aldehyde. Coupling of the racemic imines in each case pro-

duces a mixture of a single racemic d,l-diamine and a single

meso-diamine. The intramolecular coupling of the pseudo-

gem-dialdehyde stereoselectively produces a chiral racemic

diol, whereas its bis-phenylimine gives rise to the meso-di-

amine exclusively. All newly synthesised chiral compounds

are potential chiral ligands for a wide range of stereoselec-

tive reactions proceeding with participation of chiral diols

and diamines. The application of these compounds for the

construction of phosphites, phosphoroamidites, and related

ligands as well as further investigation of the inter- and in-

tramolecular coupling of appropriate [2.2]paracyclophane

derivatives are currently in progress.

Scheme 4. Preparation and stereoselective intramolecular pinacol cou-

pling of pseudo-gem-disubstituted [2.2]paracyclophane derivatives 36 and

37. i) LiAlH₄, THF, 95%; ii) DDQ, dioxane, 92%; iii) PhNH₂·HCl, Et₃N,

toluene, 79%, iv) TiCl₄, THF, Zn; v) Zn/Cu, pTosOH, DMF.

by recrystallisation of the reaction mixture from toluene. In

1

the H NMR spectrum of this compound two sets of signals

of all characteristic protons (broad singlets of CH at d 4.72

and 5.06 ppm, doublets of OH at 5.66 and 5.83 ppm and

ABX systems of aromatic rings) were clearly visible, allow-

ing to designate this major product as the chiral diol 36. The

structure of the second product was not established. Analyt-

ical chiral HPLC resolution of 36 showed the two peaks of

the corresponding enantiomers. This diol, in principle, could

be resolved into enantiomers or dissymmetry could be intro-

duced into the starting dialdehyde by substitution of any

proton in the aromatic rings or the ethano bridges.

Experimental Section

General methods: Dichloromethane was washed successively with conc.

H₂SO₄, water and saturated aq. Na₂CO₃, dried with CaCl₂and successive-

ly distilled from P₂O₅and CaH₂. THF, dioxane and toluene were distilled

from sodium/benzophenone under argon before use. DMF was distilled

under reduced pressure from P₂O₅and stored over molecular sieves 3 .

(R)-a-Phenylethylamine was purchased from Merck. Aldehydes rac- and

(R_p)-1,^[13]3,^[10e]4,^[15]5,^[10i]ketones rac- and (R_p)-2^[10d]and rac- and (R_p)-4-

methoxy[2.2]paracyclophane 12^[10f]were synthesised according to de-

scribed procedures. NMR: Bruker AMX-400 (400.13 for ¹H) and Bruker

Avance 300 (75.47 MHz for ¹³C). The ¹H NMR signals of the residual

protons of deuterated solvents were used as internal standards. MS:

KRATOS MS890 A (70 eV). Optical rotations were measured with a

Perkin–Elmer-241 and EPO-1 polarimeters in a thermostated cell at 20

or 258C. TLC analyses were performed on silica gel precoated plates Si-

lufol UV-254 (Chemapol) and SORBFIL plates PTLC-A-UV (Sorbpo-

limer). Column chromatography was performed on Kieselgel 60 (Merck).

Enantiomeric and diastereomeric analyses were carried out by HPLC on

Chiracel-OD-H chiral column (hexane/iPrOH 9:1, 1 mLmin^ꢀ1).

The coupling of bisimine 35 occurs smoothly with an

excess of Zn/Cu couple and pTosOH in DMF at 08C for 2 h.

1

The analysis of the reaction mixture by H NMR spectrosco-

py (one set of signals of the characteristic protons) and

chiral HPLC (one peak) showed that in this case the meso-

diastereomer of the bridged diamine 37 was stereoselective-

ly formed. The crude compound was purified by preparative

chromatography on silica gel. For the pinacol coupling of ar-

omatic oximes and azines it has been found that the applica-

tion of the Zn/MsOH system affords predominantly meso-

diamines, whereas Zn/TiCl₄gave rise to d,l-diamines.^[22b]

This selectivity has been rationalised by differences in the

nature of the active species involved. Therefore we have car-

ried out the pinacol coupling of 35 under the reaction condi-

tions elaborated for the coupling of aldehydes. However, in

this case meso-37 was formed stereoselectively again (ac-

General procedure for the formylation of 4-hydroxy[2.2]paracyclophane

(11): TiCl₄(1.2 equiv, 0.05 mL, 0.087 g, 0.46 mmol) (or SnCl₄, FeCl₃or

BF₃(OEt)₂, 1.2 to 5 equiv) and CH₃OCHCl₂(0.04 mL, 0.053 g,

0.46 mmol) of were added successively at 08C to

a solution of 11

(0.082 g, 0.37 mmol) in CH₂Cl₂(3 mL) and the resulting coloured solution

was stirred at room temperature for 2 to 8 h. The reaction mixture was

diluted with CH₂Cl₂(5 mL), cooled to 08C, and water and 2n HCl were

successively added to the mixture. The organic layer was washed with

H₂O (210 mL), NaHCO₃solution, and dried with Na₂SO₄. The mixture

of products obtained after removal of the solvent in vacuo was separated

by preparative chromatography (CH₂Cl₂).

1

cording to H NMR data), the isolated yield of the product

was noticeably lower. Possibly with both the Zn/Cu–

pTosOH or the Zn/TiCl₄system the two imino substituents

react out of conformations with the NPh groups anti with re-

spect to the nearest ethano bridge. Probably pinacol cou-

pling of less hindered imino derivatives (for example, diox-

imes) will allow one to carry out the process with d,l-stereo-

selectivity.

7-Hydroxy[2.2]paracyclophane-4-carbaldehyde (6): Yield 0.056 g (60%);

analytically pure sample was obtained by recrystallisation from hexane/

toluene 3:2; R_f=0.2 (CH₂Cl₂); m.p. 180–181.58C; ¹H NMR (400 MHz,

Chem. Eur. J. 2005, 11, 6944 – 6961

ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

6955

V. I. Rozenberg, H. Hopf et al.

CDCl₃): d=2.64–2.84 (m, 2H, -CHH-CH₂-), 2.98–3.30 (m, 4H, -CHH-

CH₂-), 3.36–3.46 (m, 1H, -CHH-CH₂-), 4.00–4.12 (m, 1H, -CHH-CH₂-),

and then H₂O and 2n HCl were successively added to the mixture. The

organic layer was washed with H₂O (230 mL), NaHCO₃solution and

dried with Na₂SO₄. The crude product obtained after removal of the sol-

vent in vacuo was purified by preparative chromatography (silica gel,

CH₂Cl₂) to yield 10 (1.15 g, 93%). Analytically pure sample was obtained

by recrystallisation from hexane. M.p. 141–1428C; elemental analysis

calcd (%) for C₁₈H₁₈O₂(266.34): C 81.17, H 6.81; found C 80.99, H 6.80.

3

5.72 (s, 1H, PC aromatic 5-H), 5.98 (brs, 1H, OH), 6.41 (dd, 1H, J=7.8,

⁴J=1.8 Hz, PC aromatic H), 6.47 (dd, 1H, ³J=7.8, ⁴J=1.8 Hz, PC aro-

3

4

matic H), 6.54 (dd, 1H, J=7.8, J=1.8 Hz, PC aromatic H), 7.00 (s, 1H,

3

4

aromatic 8-H), 7.02 (dd, 1H, J=7.8, J=1.8 Hz, PC aromatic H), 9.85 (s,

1H, CHO); ¹³C NMR (75 MHz, CDCl₃): d=30.9, 33.0, 33.4, 35.2 (C-1, 2,

9, 10), 125.1, 126.4, 128.5, 130.5, 131.8, 132.4, 132.7, 138.7, 139.6, 140.3,

146.9 (C-OH), 159.2 (C=O); MS (70 eV): m/z (%): 252 (100) [M ⁺], 148

(22), 104 (22); elemental analysis calcd (%) for C₁₇H₁₆O₂(252.31): C

80.93, H 6.39; found: C 80.78, H 6.37.

Resolution of 7-methoxy[2.2]paracyclophane-4-carbaldehyde (10): A so-

lution of racemic 10 (1.15 g, 4.32 mmol) and (R)-a-PEAM (0.65 g,

0.67 mL, 5.39 mmol) in toluene (40 mL) was heated under reflux in a

flaskequipped with a Dean–Starktrap filled with molecular sieves 4

for 6 h. The solvent was removed and the resulting mixture of diastereo-

meric 7-{[(1-phenylethyl)imino]methyl}-[2.2]paracyclophan-4-ols (R_p,R_c)-

and (S_p,R_c)-13 was recrystallised from hexane. The resulting precipitate

was recrystallised from hexane to give (R_p,R_c)-13 (0.32 g, 20%) (de

Methoxylation of hydroxyaldehydes 3–6 was carried out by a standard

procedure.^[10c]

(R)-12-Methoxy[2.2]paracyclophane-4-carbaldehyde [(R)-(8)]: Yield

0.287 g (96%); analytically pure sample was obtained by recrystallisation

from hexane; m.p. 176–177.58C; [a]_D²⁵

=

ꢀ51.98 (c=0.27, CHCl₃);

1

> 98% by H NMR analysis); m.p. 172.5–173.58C; [a]²_D⁰= ꢀ2228 (c=0.27

¹H NMR (400 MHz, CDCl₃): d=2.58–2.65 (m, 1H, -CHH-CH₂-), 2.88–

2.98 (m, 2H, -CHH-CH₂-), 3.10–3.25 (m, 3H, -CHH-CH₂-), 3.43–3.50 (m,

1H, -CHH-CH₂-), 3.64 (s, 3H, OCH₃), 3.98–4.08 (m, 1H, -CHH-CH₂-),

5.62 (s, 1H, PC aromatic 5-H), 5.60 (d, ⁴J=1.8 Hz, 1H, PC aromatic 5-

in C₆H₆); ¹H NMR (400 MHz, C₆D₆): d=1.71 (d, J=6.5 Hz, 3H, CH₃),

2.42–2.61 (m, 2H, CH₂-CH₂), 2.90–3.10 (m, 4H, CH₂-CHH), 3.28 (s, 3H,

OCH₃), 3.47–3.57 (m, 1H, CH₂-CHH), 4.00–4.14 (m, 1H, CH₂-CHH),

4.41–4.51 (q, J=6.5 Hz, 1H, CH), 5.48 (s, 1H, 5-H), 6.30–6.39 (m, 2H),

3

4

3

H), 6.37 (dd, 1H, J=7.5, J=1.8 Hz, PC aromatic 7-H), 6.49 (d, 1H, J=

3

6.62 (d, J=7.8, 1H), 6.73 (d, J=7.8, 1H), 7.10 (s, 1H, 8-H), 7.16–7.21 (t,

³J=7.5 Hz, 1H, p-H, Ph), 7.31–7.39 (t, ³J=7.5 Hz, 2H, m-H, Ph), 7.61–

7.68 (d, ³J=7.5 Hz, 2H, o-H, Ph), 8.28 (s, 1H, CH=N); ¹³C NMR

(75 MHz, C₆D₆): d=26.0 (CH₃), 31.6, 34.0, (2C), 35.2 (C-1, -2, -9, -10),

54.0 (OCH₃), 71.2 (N-CH), 118.7, 129.99, 127.03, 128.7, 129.1, 129.8,

131.7, 132.1, 133.1, 137.2, 138.9, 140.1, 143.4, 146.5, 158.5 (C-OCH₃),

159.4 (C=N); MS (70 eV): m/z (%): 369 (100) [M ⁺], 264 (100), 250 (16),

248 (20), 219 (8), 160 (72), 132 (25), 105 (26), 104 (11); elemental analysis

calcd (%) for C₂₆H₂₇NO (369.51): C 84.51, H 7.37, N 3.79; found: C

84.24, H 7.25, N 3.90.

7.8 Hz, PC aromatic 8-H), 6.65 (d, 1H, ³J=7.5, PC aromatic 16-H), 6.69

3

4

(dd, 1H, J=7.8, J=1.8 Hz, PC aromatic 15-H), 7.39 (d, J=1.8 Hz, 1H,

PC aromatic 13-H); ¹³C NMR (75 MHz, CDCl₃): d=27.7, 29.1, 29.3, 31.2

(C-1, -2, -9, -10), 50.3 (OCH₃), 112.1, 119.7, 123.2, 127.05, 130.9, 131.9,

132.3, 134.7, 137.3, 138.0, 138.6, 153.4 (COCH₃), 187.6 (C=O); MS

(70 eV): m/z (%): 266 (100) [M ⁺], 134 (25), 104 (20); elemental analysis

calcd (%) for C₁₈H₁₈O₂(266.34): C 81.17, H 6.81; found 81.19, H 6.77.

Racemic 8: Yield 0.177 g (82%); m.p. 177–1788C; elemental analysis

calcd (%) for C₁₈H₁₈O₂(266.34): C 81.17, H 6.81; found: C 81.32, H 6.77.

(R)-13-Methoxy[2.2]paracyclophane-4-carbaldehyde [(R)-(9)]: Yield

Compound (R_p,R_c)-13 was hydrolysed by heating under reflux with aq.

HCl solution in methanol. The organic material was extracted by CH₂Cl₂

(230 mL), the combined extracts were dried with Na₂SO₄, and after re-

moval of solvent (R)-10 was isolated as colourless crystals (0.3 g, 19%).

M.p. 138–139.58C; [a]²_D⁰= ꢀ738 (c=0.32 in C₆H₆); elemental analysis

calcd (%) for C₁₈H₁₈O₂(266.34): C 81.17, H 6.81; found: C 81.28, H 6.75.

0.42 g (90%); analytically pure sample was obtained by recrystallisation

from hexane; m.p. 186–187.58C; [a]_D²⁵

= +301 (c=0.2 in CHCl₃);

¹H NMR (400 MHz, CDCl₃): d=2.66–2.75 (m, 1H, -CHH-CH₂-), 2.94–

3.17 (m, 5H, -CHH-CH₂-), 3.45–3.54 (m, 1H, -CHH-CH₂-), 3.48 (s, 3H,

4

OCH₃), 3.89–3.99 (m, 1H, -CHH-CH₂-), 5.60 (d, J=1.8 Hz, 1H, PC aro-

matic 5-H), 6.34 (dd, 1H, ³J=7.5, ⁴J=1.8 Hz, PC aromatic H), 6.48 (d,

1H, ³J=7.8 Hz, PC aromatic H), 6.47 (d, 1H, ³J=7.5 Hz, PC aromatic

H), 6.77 (dd, 1H, ³J=7.8, ⁴J=1.8 Hz, PC aromatic H), 7.10 (d, ⁴J=

1.8 Hz, 1H); ¹³C NMR (75 MHz, CDCl₃): d=29.8, 30.0, 34.7, 34.9 (C-1,

-2, -9, -10), 54.2 (OCH₃), 116.3, 123.8, 127.0, 130.7, 134.7, 135.8, 137.3,

139.5, 141.9, 144.2, 157.6, 189.3 (C=O); MS (70 eV): m/z (%): 266 (65)

[M ⁺], 134 (100), 104 (96); elemental analysis calcd (%) for C₁₈H₁₈O₂

(266.34): C 81.17, H 6.81; found: 81.15, H 6.81.

The combined hexane filtrates, containing partially enriched (R_p,S_c)-13,

after evaporation and hydrolysis gave partially resolved (S)-10 (0.86 g,

75%). This compound and (S)-a-PEAM (0.41 g, 0.43 mL, 3.40 mmol) af-

forded (S_p,S_c)-13 (0.31 g, 19.5%) after two successive recrystallisations of

the diastereomeric mixture from hexane. M.p. 172–1738C; [a]²_D⁰=+2238

(c=0.31 in C₆H₆); elemental analysis calcd (%) for C₂₆H₂₇NO (369.51): C

84.51, H 7.37, N 3.79; found: C 84.57, H 7.48, N 3.71.

Racemic 9: Yield 0.334 g (90%); m.p. 141–1428C; elemental analysis

Representative procedures for the synthesis of imines

calcd (%) for C₁₈H₁₈O₂(266.34): C 81.17, H 6.81; found: C 81.29, H 6.86.

From aldehyde and aniline hydrochloride

Racemic 7-methoxy[2.2]paracyclophane-4-carbaldehyde (10) by methox-

ylation of 6: Yield 0.047 g (80%); analytically pure sample was obtained

by recrystallisation from hexane; m.p. 141–1428C; ¹H NMR (400 MHz,

CDCl₃): d=2.59–2.69 (m, 1H, -CHH-CH₂-), 2.77–2.87 (m, 1H, -CHH-

CH₂-), 3.00–3.27 (m, 4H, -CHH-CH₂-), 3.37–3.46 (m, 1H, -CHH-CH₂-),

3.80 (s, 3H, OCH₃), 4.05–4.14 (m, 1H, -CHH-CH₂-), 5.74 (s, 1H, PC aro-

matic 5-H), 6.38 (dd, 1H, ³J=7.8, ⁴J=1.8 Hz, PC aromatic H), 6.43 (dd,

1H, ³J=7.8, ⁴J=1.8 Hz, PC aromatic H), 6.52 (dd, 1H, ³J=7.8, ⁴J=

1.8 Hz, PC aromatic H), 6.72 (dd, 1H, ³J=7.8, ⁴J=1.8 Hz, PC aromatic

H), 7.00 (s, 1H), 9.90 (s, 1H, CHO); ¹³C NMR (75 MHz, C₆D₆): d=27.1,

29.1, 29.5, 31.0 (C-1, -2, -9, -10), 50.0 (OCH₃), 114.9, 124.4, 126.8, 127.2,

128.7, 128.8, 134.6, 135.2, 135.7, 142.5 (C-OH), 157.5 (C-OCH₃), 185.7

(C=O); IR (nujol): n˜ =1670 cm^ꢀ1(C=O); IR (KBr): n˜ =2854 cm^ꢀ1

(OCH₃); MS (70 eV): m/z (%): 266 (30) [M ⁺], 162 (44), 134 (40), 104

(100); elemental analysis calcd (%) for C₁₈H₁₈O₂(266.34): C 81.17, H

6.81; found: C 81.28, H 6.75.

(R)-N-([2.2]Paracyclophane-4-ylmethylene)aniline (14):

A mixture of

(R)-1 (0.49 g, 2.08 mmol), aniline hydrochloride (0.48 g, 4.15 mmol), Et₃N

(0.45 g, 0.62 mL, 4.15 mmol) and a catalytic amount of Et₂SnCl₂in tolu-

ene (12 mL) was heated under reflux for 12 h. The hydrochlorides were

removed by filtration, the solvent was removed in vacuo and the solid

was recrystallised from hexane to yield (R)-14 as colourless crystals

(0.46 g, 73%). Analytically pure material was obtained by further recrys-

tallisation from the same solvent. M.p. 101–101.58C; [a]_D=+3518 (c=

0.4 in C₆H₆); ¹H NMR (400 MHz, C₆D₆): d=2.60–3.10 (m, 7H, -CH₂-

CH₂-), 3.84 (m, 1H, -CHH-CH₂-), 6.34–6.46 (m, 7H, PC aromatic H),

6.64 (dd, ³J=7.8, ⁴J=1.8 Hz, 1H, PC aromatic 5-H), 7.13–7.18 (m, 1H,

aromatic p-H), 7.22 (brs, 2H, aromatic o-H), 7.32 (d, ³J=8.0 Hz, 2H, ar-

omatic m-H), 8.38 (s, 1H, CH=N); ¹³C NMR (75 MHz, C₆D₆): d=30.0,

30.9, 31.3 (2C), 116.9, 121.6, 125.3, 127.5, 128.2, 128.9, 129.3, 130.2, 131.0,

131.5, 132.5, 135.3, 136.1, 137.5, 149.6, 155.3; MS (70 eV): m/z (%): 311

(52) [M ⁺], 207 (95), 206 (100), 130 (17), 104 (49); elemental analysis

calcd (%) for C₂₃H₂₁N (311.43): C 88.71, H 6.80, N 4.50; found: C 88.75,

H 6.84, N 4.34.

Racemic 7-methoxy[2.2]paracyclophane-4-carbaldehyde (10) by para-re-

gioselective formylation of (12): TiCl₄(0.6 mL, 1.04 g, 5.48 mmol) and

CH₃OCHCl₂(0.42 mL, 0.54 g, 4.7 mmol) were added successively at 08C

to a solution of 12 (1.1 g, 4.66 mmol) in CH₂Cl₂(20 mL) and the resulting

darkcherry coloured solution was stirred at room temperature for 4 h.

The reaction mixture was diluted with CH₂Cl₂(20 mL), cooled to 08C

Racemic 14: Yield 0.605 g (96%); m.p. 99.0–100.58C; elemental analysis

calcd (%) for C₂₃H₂₁N (311.43): C 88.71, H 6.80, N 4.50; found C 88.74,

H 6.81, N 4.59.

6956

www.chemeurj.org

ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2005, 11, 6944 – 6961

Paracyclophane Derivatives

FULL PAPER

(R)-N-{5-Methoxy([2.2]paracyclophane-4-yl)methylene}aniline

Yield 0.34 g (74%); m.p. 123.5–1258C (from hexane); [a]_D²⁵

(18):

+1198

(21); elemental analysis calcd (%) for C₂₅H₂₅N (339.48): C 88.45, H 7.42,

N 4.13; found C 88.21, H 7.35, N 4.05.

=

(c=0.37 in C₆H₆); ¹H NMR (400 MHz, C₆D₆): d=2.41–2.51 (m, 1H,

-CHH-CH₂-), 2.66–2.75 (m, 1H, -CHH-CH₂-), 2.78–2.89 (m, 1H, -CHH-

CH₂-), 2.98–3.18 (m, 3H, -CHH-CH₂-), 3.19–3.30 (m, 1H, -CHH-CH₂-),

3.25 (s, 3H, OCH₃), 4.73–4.85 (m, 1H, -CHH-CH₂-), 6.33–6.42 (m, 3H,

PC aromatic H), 6.53 (d, ⁴J=1.8 Hz, 1H, PC aromatic H), 6.73 (d, ⁴J=

1.8 Hz, 1H, PC aromatic H), 7.00 (d, ⁴J=1.8 Hz, 1H, PC aromatic H),

7.17 (m, 1H, aromatic p-H), 7.27–7.38 (m, 4H, aromatic o-H and m-H),

8.72 (s, 1H, CH=N); ¹³C NMR (75 MHz, C₆D₆): d=26.9, 30.0, 30.3, 31.32,

57.2, 116.8, 121.5, 125.3, 125.3, 126.0, 126.9, 127.2, 127.7, 128.7, 129.5,

133.5, 135.0, 135. 8, 139.4, 150.0, 154.8, 157.0; MS (70 eV): m/z (%): 341

(11) [M ⁺], 237 (34), 236 (100), 233 (13), 222 (11), 208 (27), 195 (16), 145

(8), 104 (16), 91 (14); elemental analysis calcd (%) for C₂₄H₂₃NO

(341.45): C 84.42, H 6.79, N 4.10; found: C 84.25, H 6.65, N 4.14.

Racemic

1-phenyl-N-([2.2]paracyclophane-4-ylmethylene)methamine

(17): The title compound was obtained from 1 (0.19 g, 0.805 mmol) and

benzylamine (0.087 g, 0.09 mL, 0.815 mmol) after 5 h. The solvent was re-

moved in vacuo and the solid was recrystallised from hexane to yield 17

(0.213 g, 99%). Analytically pure sample was obtained by recrystallisa-

tion from the same solvent. M.p. 95.5–978C; ¹H NMR (400 MHz, C₆D₆):

d=2.61–2.70 (m, 1H, -CHH-CH₂-), 2.72–2.93 (m, 5H, -CH₂-CH₂-), 2.96–

3.06 (m, 1H, -CHH-CH₂-), 3.82–3.92 (m, 1H, -CHH-CH₂-), 4.76 (s, 2H,

N-CH₂), 6.33–6.43 (m, 5H, PC aromatic H), 6.59 (d, 1H, ³J=7.8 Hz, PC

aromatic H), 7.14–7.20 (m, 2H, PC aromatic and phenyl aromatic H),

7.27–7.34 (m, 2H, aromatic H), 7.48 (m, 2H, aromatic H), 8.22 (s, 1H,

CH=N); ¹³C NMR (75 MHz, C₆D₆): d=30.0, 31.0, 31.2, 31.3, 61.9, 122.9,

124.5, 127.3, 128.2, 128.9, 129.2, 130.0, 130.3, 131.4, 132.4, 135.3, 135.9,

136.4, 136.5, 156.6; MS (70 eV): m/z (%): 325 (71) [M ⁺], 234 (10), 224

(41), 221 (88), 220 (83), 218 (127), 104 (73); elemental analysis calcd (%)

for C₂₄H₂₃N (325.45): C 88.57, H 7.12, N 4.30; found: C 88.60, H 7.18, N

4.32.

Racemic 17: Yield 0.257 g (88%); m.p. 139.5–140.58C (from hexane); el-

emental analysis calcd (%) for C₂₄H₂₃NO (341.45): C 84.42, H 6.79, N

4.10; found: C 84.49, H 6.94, N 4.10.

(R)-N-{7-Methoxy([2.2]paracyclophane-4-yl)methylene}aniline

(19):

(R_p)-17: Yield 0.238 g (97%); m.p. 100–101.58C; [a]_D=ꢀ2608 (c=0.43 in

C₆H₆); elemental analysis calcd (%) for C₂₄H₂₃N (325.45): C 88.57, H

7.12, N 4.30; found: C 88.61, H 7.05, N 4.26.

Yield 0.102 g (77%) as orange coloured oil; [a]_D=ꢀ1348 (c=0.56 in

C₆H₆); ¹H NMR (400 MHz, C₆D₆): d=2.43–2.57 (m, 1H, -CHH-CH₂-),

2.86–3.10 (m, 4H, -CHH-CH₂-), 3.25 (s, 3H, OCH₃), 3.45–3.55 (m, 1H,

-CHH-CH₂-), 3.82–3.92 (m, 1H, -CHH-CH₂-), 5.45 (s, 1H, PC aromatic

5-H), 6.33 (dd, ³J=8.1, ⁴J=1.87 Hz, 1H, PC aromatic H), 6.36–6.43 (m,

2H, PC aromatic H), 6.69 (dd, ³J=7.78, ⁴J=1.87 Hz, 1H, PC aromatic

H), 6.73 (dd, ³J=7.78, ⁴J=1.87 Hz, 1H, PC aromatic H), 7.10–7.19 (m,

1H, aromatic p-H), 7.31–7.41 (m, 4H, aromatic o-H and m-H), 8.44 (s,

1H, CH=N); ¹³C NMR (75 MHz, C₆D₆): d=27.3, 29.6, 29.8, 31.2, 49.9,

114.4, 117.0, 121.2, 124.82, 125.2, 125.7, 127.4, 128.2, 128.9, 132.7, 134.5,

136.0, 140.4, 150.0, 154.7, 156.0; MS (70 eV): m/z (%): 341 (47) [M ⁺],

248 (17), 237 (88), 236 (100), 222 (28), 208 (75), 193 (29), 183 (9), 178

(14), 165 (20), 154 (14), 104 (58).

General procedure for pinacol coupling of aldehydes: TiCl₄(0.38 g,

0.22 mL, 2 mmol) was carefully added to THF at 08C under argon atmos-

phere. To the formed yellow suspension Zn (0.26 g, 4 mmol) was added

and the greenish-brown mixture was stirred for 5 min. A solution of the

carbonyl compound (1 mmol) in THF (3–6 mL) was added by syringe

and the reaction mixture was stirred at room temperature for 2–4 h (TLC

control). The mixture was diluted with CH₂Cl₂(10 mL) and vigorously

shaken with saturated aq. NaHCO₃solution until the darkblue colour of

the mixture vanished. The mixture was passed through a Celite pad, the

organic layer was separated and dried with Na₂SO₄. The solvent was

evaporated, the ratio of the products was determined by ¹H NMR spec-

troscopy, and the mixture was separated by chromatography on silica gel.

Racemic 19: Yield 0.188 g (68%); m.p. 105–105.58C (from hexane); ele-

mental analysis calcd (%) for C₂₄H₂₃NO (341.45): C 84.42, H 6.79, N

4.10; found: C 84.32, H 6.83, N 3.95.

(R_p,S,S,R_p)-1,2-Bis([2.2]paracyclophane-4-yl)ethane-1,2-diol [(R_p,S,S,R_p)-

20]: Yield 0.182 g (77%); m.p. 2178C (decomp); [a]_D=ꢀ888 (c=0.23 in

CHCl₃); ¹H NMR (400 MHz, CDCl₃): d=2.38 (s, 2H, 2 OH), 2.36–2.50

(m, 4H), 2.55–2.68 (m, 2H), 2.78–2.90 (m, 2H), 2.95–3.20 (m, 12H), 4.50

From aldehyde and pure amine

Racemic 2-bromo-N-([2.2]paracyclophane-4-ylmethylene)aniline (15): A

mixture of racemic

1 (0.72 g, 3.05 mmol), 2-bromoaniline (0.65 g,

3

(s, 2H, 2CH), 6.26 (d, J=7.8 Hz, 2H), 6.36–6.60 (m, 10H), 6.80 (s, 2H);

3.76 mmol) of and a catalytic amount of Et₂SnCl₂in toluene (10 mL) was

heated under reflux for 10 h. The solvent was removed in vacuo. The res-

idue (pale yellow oil) was precipitated by pentane at ꢀ208C to yield 15

(0.96 g, 81%). Analytically pure sample was obtained by recrystallisation

from hexane. M.p. 105–1078C; ¹H NMR (400 MHz, C₆D₆): d=2.62–3.09

(m, 7H, -CH₂-CH₂-), 3.87–4.00 (m, 1H, -CHH-CH₂-), 6.30–6.47 (m, 4H,

PC aromatic H), 6.54 (d, 1H, ³J=7.8 Hz, PC aromatic H), 6.70–6.79 (m,

2H, PC aromatic H), 6.87 (d, 1H, ³J=7.8 Hz), 7.20–7.28 (m, 1H), 7.60

(d, ³J=7.8 Hz, 1H), 8.10 (s, 1H, CH=N); ¹³C NMR (75 MHz, C₆D₆): d=

30.0, 30.9, 31.3, 114.6, 115.8, 122.3, 124.3, 127.9, 128.5, 129.0, 129.1, 129.2,

130.8, 131.5, 131.6, 132.0, 135.3, 135.5, 136.2, 137.9, 148.2, 156.8; MS

(70 eV): m/z (%): 391 (30), 389 (30), 287 (98), 285 (100), 207 (95), 206

(23), 204 (21), 104 (38); elemental analysis calcd (%) for C₂₃H₂₀BrN

(390.32): C 70.78, H 5.16, Br 20.47, N 3.59; found: C 70.81, H 5.21, Br

20.52, N 3.57.

¹³C NMR (75 MHz, CDCl₃): d=29.3, 30.2, 31.3, 31.4 (2C-1, -2, -9, -10),

71.6 (2C-OH), 126.4, 127.1, 128.3, 128.5 (4C), 129.4, 130.8, 133.0, 134.3,

135.3, 135.5, 135.8; MS (70 eV): m/z (%): 237 (27) [¹= M ⁺], 220 (10), 219

2

(14), 134 (14), 117 (12); elemental analysis calcd (%) for C₃₄H₃₄O₂

(474.64): C 86.04, H 7.22; found C 85.89, H 7.21.

(R_p,R,R,R_p)-2,3-Bis([2.2]paracyclophane-4-yl)-2,3-butanediol

[(R_p,R,R,R_p)-21]: Yield 0.13 g (52%); m.p. 213–214.58C; [a]_D=ꢀ158 (c=

0.2 in CHCl₃); ¹H NMR (400 MHz, CDCl₃): d=1.07 (s, 6H, 2CH₃), 2.16

(s, 2H, 2 OH), 2.80–3.25 (m, 14H), 3.95–4.05 (m, 2H), 6.30–6.37 (m,

4H), 6.45–6.60 (m, 14H); ¹³C NMR (75 MHz, CDCl₃): d=22.0 (2CH₃),

31.3, 31.5, 32.7, 36.0 (2C-1, -2, -9, -10), 77.9 (2C-OH), 127.7, 128.10,

128.13, 128.7, 128.8, 128.9, 133.5, 133.8, 135.0, 135.1, 135.3, 136.6; MS

(70 eV): m/z (%): 251 (20) [¹= M ⁺], 147 (36), 131 (28), 119 (36), 117 (27),

2

115 (17), 104 (100); elemental analysis calcd (%) for C₃₆H₃₈O₂(502.70):

C 86.02, H 7.62; found: C 86.04, H 7.65.

Racemic

2,6-dimethyl-N-([2.2]paracyclophane-4-ylmethylene)aniline

meso-1,2-Bis(5-methoxy[2.2]paracyclophane-4-yl)ethane-1,2-diol (meso-

22): The title compound (0.020 g, 13%) was isolated from the mixture of

diastereomers by recrystallisation from toluene. M.p. 122–1248C;

¹H NMR (400 MHz, CDCl₃): d=2.40 (s, 2H, OH), 2.62–2.73 (m, 2H),

2.82–3.24 (m, 6H), 3.24 (s, 6H, 2OCH₃), 3.65–3.75 (m, 2H), 5.18 (s, 2H,

2CH), 6.11 (d, ³J=7.8 Hz, 2H), 6.18 (d, ³J=7.8 Hz, 2H), 6.50–6.70 (m,

8H); MS (70 eV): m/z (%): 517 (13), 500 (19), 487 (18), 415 (24), 394

(16): The title compound was obtained by treating 1 (0.246 g, 1.04 mmol)

with 2,6-dimethylaniline (1.04 g, 0.62 mL, 5.04 mmol) for 8 h. The solvent

was removed in vacuo and the solid was recrystallised from hexane to

yield 16 (0.31 g, 87%). Analytically pure material was obtained by fur-

ther recrystallisation from the same solvent. M.p. 127–128.58C; ¹H NMR

(400 MHz, C₆D₆): d=2.32 (s, 6H, 2CH₃), 2.60–3.03 (m, 7H, -CH₂-CH₂-),

3

3.59–3.64 (m, 1H, -CHH-CH₂-), 6.34 (d, 1H, J=7.8 Hz, PC aromatic H),

(69), 291 (18), 277 (23), 267 (82) [¹= M ⁺], 239 (56), 205 (12), 161 (100),

6.39–6.45 (m, 3H, PC aromatic H), 6.49 (d, 1H, ³J=7.8 Hz, PC aromatic

2

3

104 (41); elemental analysis calcd (%) for C₃₆H₃₈O₄(534.70): C 80.87, H

7.16; found C 80.93, H 7.40.

H), 6.75 (d, 1H, J=7.8 Hz, PC aromatic H), 7.03–7.09 (m, 1H, aromatic

p-H), 7.12–7.18 (m, 2H, aromatic m-H), 7.34 (brs, 1H, PC aromatic H),

8.10 (s, 1H, CH=N); ¹³C NMR (75 MHz, C₆D₆): d=14.7, 29.4, 31.0, 31.4,

31.5, 119.7, 123.0, 124.3, 127.9, 128.3, 128.9, 129.2, 129.3, 131.3, 131.6,

132.2, 135.3, 135.4, 136.2, 137.1, 148.4, 157.4; MS (70 eV): m/z (%): 339

(70) [M ⁺], 236 (48), 235 (100), 233 (21), 218 (23), 204 (9), 130 (14), 104

(R_p,S,S,R_p)-1,2-Bis(12-methoxy[2.2]paracyclophane-4-yl)ethane-1,2-diol

[(R_p,S,S,R_p)-23]: Yield 0.07 g (62%); m.p. 269–2708C; [a]_D=ꢀ378 (c=

0.26 in CHCl₃); ¹H NMR (400 MHz, CDCl₃): d=2.10 (brs, 2H, 2 OH),

2.50–2.63 (m, 2H), 2.64–2.75 (m, 2H), 2.76–2.87 (m, 2H), 2.98–3.17 (m,

Chem. Eur. J. 2005, 11, 6944 – 6961

ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

6957

V. I. Rozenberg, H. Hopf et al.

8H), 3.34–3.46 (m, 2H), 3.68 (s, 6H, 2 OCH₃), 4.60 (s, 2H, 2CH), 5.77 (s,

2H, 5-H), 6.23 (d, ³J=7.8 Hz, 2H), 6.38–6.50 (m, 6H), 7.02 (s, 2H, 13-

H); ¹³C NMR (75 MHz, CDCl₃): d=31.8, 33.52, 33.54, 34.2 (2C-1, -2, -9,

-10), 54.8 (2OCH₃), 75.3 (2C-OH), 116.1, 123.7, 126.2, 127.4, 132.7, 135.1,

135.2, 138.4, 140.8, 141.5, 158.0 (2COCH₃); MS (70 eV): m/z (%): 534 (3)

[M ⁺], 517 (24), 516 (20), 487 (11), 381 (13), 367 (16), 365 (17), 353 (17),

268 (54), 251 (20), 239 (31), 235 (11), 219 (22), 205 (21), 149 (37), 135

(100), 119 (10), 105 (28), 104 (16); elemental analysis calcd (%) for

C₃₆H₃₈O₄(534.70): C 80.87, H 7.16; found C 80.97, H 7.37.

(100), 207 (39), 104 (67); elemental analysis calcd (%) for C₄₆H₄₂Br₂N₂

(782.66): C 70.59, H 5.41, Br 20.42, N 3.58; found: C 70.49, H 5.57, Br

20.00, N 3.31.

Analysis of the filtrate from recrystallisation allowed to determine the

¹H NMR spectrum of chiral 27: ¹H NMR (400 MHz, [D₆]acetone): d=

2.57–2.64 (m, 2H), 2.66–2.80 (m, 2H), 2.80–3.20 (m, 10H), 3.28–3.36 (m,

2H), 4.87 (brd, 2H, 2CH), 5.06 (brd, 2H, 2NH), 5.66 (brs, 2H, 5-H),

5.98 (d, ³J=7.8 Hz, 2H), 6.09 (d, ³J=7.8 Hz, 2H), 6.38–6.48 (m, 6H),

6.52 (d, ³J=7.8 Hz, 2H), 6.60–6.68 (m, 2H), 7.00 (d, ³J=8.0 Hz, 2H),

3

4

(R_p,R,R,R_p)-1,2-Bis(13-methoxy[2.2]paracyclophane-4-yl)ethane-1,2-diol

[(R_p,R,R,R_p)-24]: Yield 0.114 g (83%); m.p. 209–2118C; [a]_D=+1048

(c=0.3 in CHCl₃); ¹H NMR (400 MHz, CDCl₃): d=2.00–2.11 (m, 2H),

2.35–2.49 (m, 4H), 2.87–3.17 (m, 10H), 3.63 (s, 6H, 2 OCH₃), 3.79 (brs,

2H, 2 OH), 4.60 (s, 2H, 2CH), 5.86 (s, 2H, 25-H), 6.05 (d, ³J=7.8 Hz,

2H), 6.25 (d, ³J=7.8 Hz, 2H), 6.34 (d, ³J=7.8 Hz, 2H), 6.40 (d, ³J=

7.8 Hz, 2H), 6.89 (s, 2H, 2 12-H); ¹³C NMR (75 MHz, CDCl₃): d=25.2,

27.2, 31.1, 31.3 (2C-1, 2, 9, 10), 54.0 (2OCH₃), 71.5 (2C-OH), 116.5,

122.1, 124.7, 124.9, 128.0, 130.1, 130.6, 133.8, 133.9 (4C), 137.9, 153.9

(2COCH₃); MS (70 eV): m/z (%): 516 (76), 487 (31), 381 (20), 367 (21),

353 (30), 339 (19), 325 (17), 267 (59), 265 (16), 250 (14), 233 (14), 219

(40), 205 (66), 189 (19), 161 (16), 149 (39), 135 (100), 131 (49), 104 (82);

elemental analysis calcd (%) for C₃₆H₃₈O₄(534.70): C 80.87, H 7.16;

found C 80.97, H 7.34.

7.25–7.32 (m, 2H), 7.52 (dd, J=8.0, J=1.3 Hz, 2H).

meso-N,N-Bis(2,6-dimethylphenyl)-1,2-bis([2.2]paracyclophane-4-yl)-

ethane-1,2-diamine (meso-28): Analytically pure product (0.138 g, 61%)

was obtained by recrystallisation of the mixture of diastereomers from

EtOH/C₆H₆/AcOEt 5:2:1; m.p. 202–2048C; ¹H NMR (400 MHz, CDCl₃):

d=2.39–2.52 (m, 2H), 2.45 (s, 12H, 4CH₃), 2.64–2.98 (m, 12H), 3.05–

3.15 (m, 2H), 4.10 (brd, J=11.5 Hz, 2H, 2CH), 5.18 (brd, J=11.52 Hz,

2H, 2NH), 5.33 (d, ³J=7.8 Hz, 2H), 5.60 (d, ³J=7.8 Hz, 2H), 5.98 (brs,

2H, 5-H), 16 (d, 2H), 6.26 (d, 2H), 6.40–6.55 (m, 4H), 6.81–6.87 (m, 2H,

Ar-para-H), 7.52 (d, ³J=7.8 Hz, 4H, Ar-meta-H); ¹³C NMR (75 MHz,

CDCl₃): d=16.1 (4CH₃), 28.1, 31.3, 31.4 (4C) (2C-1, -2, -9, -10), 57.1

(2CH-NH), 116.5, 122.5, 125.4, 125.8, 127.7, 128.0, 128.5, 128.8, 129.2,

131.1, 132.8, 134.0, 134.1, 134.7, 134.9, 140.9 (2C-NH); MS (70 eV): m/z

(%): 560 (11), 440 (5), 339 (35), 340 (15) [¹= M ⁺], 335 (10), 220 (11),

2

(R_p,R_p)-Bis-(7-methoxy[2.2]paracyclophan-4-yl)acetaldehyde

[(R_p,R_p)-

218(30), 121 (51), 104 (53); elemental analysis calcd (%) for C₅₀H₅₂N₂

(680.98): C 88.19, H 7.70, N 4.11; found C 87.21, H 7.71, N 3.70.

25]: Yield 0.084 g (57%); m.p. 202.5–203.58C; [a]²_D⁵= ꢀ708 (c=0.23 in

CHCl₃); ¹H NMR (400 MHz, CDCl₃): d=2.15–2.24 (m, 1H), 2.43–2.61

(m, 1H), 2.72–2.94 (m, 3H), 3.00–3.28 (m, 8H), 3.35–3.52 (m, 2H), 3.60–

3.75 (m, 1H), 3.68 (s, 3H, 20-OCH₃), 3.80 (s, 3H, 19-OCH₃), 4.89 (d, J=

meso-N,N-Dibenzyl-1,2-bis([2.2]paracyclophane-4-yl)ethane-1,2-diamine

(meso-29): Yield 0.049 g (49%); m.p. 210–211.58C; ¹H NMR (400 MHz,

CDCl₃): d=1.82 (brs, 2H, 2NH), 2.45–2.55 (m, 2H), 2.72–3.10 (m, 14H),

4.06 (brs, 2H, 2CH-NH), 4.06–4.16 (m, 4H, 2CH₂-NH), 6.15 (d, ³J=

7.8 Hz, 2H), 6.19 (brs, 2H, 5-H), 6.25 (brd, ³J=7.8 Hz, 2H), 6.31 (brd,

3

4.7 Hz, 1H, CH-OH), 5.63 (s, 1H, 5’-H), 5.68 (s, 1H, 8’-H), 5.79 (dd, J=

7.8, ⁴J=1.8 Hz, 1H, 15’-H), 5.81 (s, 1H, 5-H), 6.25 (dd, ³J=7.8, ⁴J=

1.8 Hz, 1H, 16’-H), 6.29 (dd, ³J=7.8, ⁴J=1.8 Hz, 1H, 15-H), 6.37 (s, 1H,

8-H), 6.42 (dd, ³J=7.8, ⁴J=1.8 Hz, 1H, 12’-H), 6.54 (dd, ³J=7.8, ⁴J=

3

³J=7.8 Hz, 2H), 6.36 (brd, J=7.8 Hz, 2H), 6.45–6.53 (m, 4H), 7.31–7.38

(m, 2H, Ar-para-H), 7.40–7.47 (m, 4H, Ar-meta-H), 7.52 (m, 4H, Ar-

ortho-H), ¹³C NMR (75 MHz, CDCl₃): d=25.7 (2CH₂-NH), 29.3, 31.0,

31.3, 31.4 (2C-1, -2, -9, -10), 49.2 (CH₂-NH), 58.8 (2CH-NH), 123.1,

124.2, 124.6, 126.1, 127.2, 127.60, 128.1, 128.3, 129.0, 130.9, 132.9, 134.6,

3

4

3

1.8 Hz, 1H, 16-H), 6.58 (dd, J=7.8, J=1.8 Hz, 1H, 12-H), 6.69 (dd, J=

4

7.8, J=1.8 Hz, 1H, 13’-H), 6.86 (dd, ³J=7.8, J=1.8 Hz, 1H, 13-H), 9.78

(d, J=4.7 Hz, 1H, OH); ¹³C NMR (75 MHz, CDCl₃): d=31.3, 31.6, 33.2

(2C), 33.5 (2C), 34.4, 35.3 (C-1, -1’, -2, -2’, -9, -9’, -10, -10’), 54.2, 54.3,

55.4 (2 OCH₃, CH-CHO), 119.0 (C-5’), 119.1 (C-5), 126.3, 127.2, 127.5,

128.4, 128.5, 131.0 (4C), 131.5, 132.9, 133.1, 134.0 (C-8), 134.4, 138.1,

138.2, 140.0 (2C), 140.3 (C-6’), 156.4 (C-4), 156.8 (C-4’), 199.0 (CHO);

MS (70 eV): m/z (%): 517 (21), 516 (56), 488 (50), 487 (100), 411 (14),

384 (23), 383 (65), 369 (17), 307 (8), 279 (21), 266 (11), 265 (41), 251 (16),

221 (11), 205 (16), 191 (17), 165 (11), 161 (11), 131 (15), 119 (15), 104

(42); IR (KBr): n˜ =1713 cm^ꢀ1(HC=O); elemental analysis calcd (%) for

C₃₆H₃₆O₃(516.68): C 83.69, H 7.02; found C 82.80, H 7.08.

134.7, 135.4, 135.5, 137.3; MS (70 eV): m/z (%): 326 (27) [¹= M ⁺], 221

2

(83), 220 (56), 104 (45), 91 (100); elemental analysis calcd (%)

forC₄₈H₄₈N₂(652.92): C 88.30, H 7.41, N 4.29; found C 88.10, H 7.61, N

4.12.

[2.2]Paracyclophane-4,13-dicarbaldehyde (34): LiAlH₄(1.2 g, 50 mmol)

was added under argon to a solution of 32 (3.7 g, 12.6 mmol) in anhy-

drous THF (300 mL). The reaction mixture was stirred at 608C for 5 h.

Unreacted LiAlH₄was destroyed by addition of wet AcOEt and water,

and the reaction mixture was acidified with 2n aqueous HCl solution

until the precipitate had entirely dissolved. The organic phase was sepa-

rated and the aqueous phase was extracted with CH₂Cl₂(3100 mL).

The combined organic solutions were washed with water, saturated aq.

NaHCO₃solution, water (15 mL), and dried with MgSO₄. The solvent

was evaporated to yield diol 33 (3.20 g, 95%). This compound

(11.9 mmol) was dissolved in anhydrous dioxane (180 mL) and a solution

of DDQ (2.70 g, 11.9 mmol) in anhydrous dioxane (120 mL) was added

dropwise at room temperature. The reaction mixture was stirred at room

temperature for 3 h, and the precipitated DDQH₂was filtered off. The

solvent was removed in vacuo, the residue was dissolved in CH₂Cl₂and

separated from the remaining DDQH₂by filtration. Silica gel column

chromatography (CH₂Cl₂) gave dialdehyde 34 (2.90 g, 92%). Analytically

pure sample was obtained by recrystallisation from cyclohexane. M.p.

209–2108C (lit.^[26]m.p. 207–2098C).

General procedure for pinacol coupling of imines: A suspension of Zn/

Cu couple (0.13 g, 2 mmol) in DMF (2.5 mL) was cooled to 08C and solu-

tions of pTosOH (0.38 g, 2 mmol) in DMF (5 mL) and imines 14–19

(0.5 mmol) in the same solvent (1.5–3 mL) were added simultaneously

dropwise during 1.5 h. The mixture was allowed to stand at room temper-

ature for 1 h, then saturated aq. NaHCO₃solution was added, and the

mixture was filtered through a thin layer of silica gel or Celite pad. The

filtrate was extracted with Et₂O (315 mL), the organic solution was

thoroughly washed with H₂O (340 mL) and the combined extracts were

dried with Na₂SO₄. The solvent was evaporated, the ratio of the products

1

was determined by H NMR spectroscopy, and the mixture was separated

by chromatography on silica gel.

Chiral diamines 26, 30, and 31 were described in a previous paper.^[12]

meso-N,N-Bis(2-bromophenyl)-1,2-bis([2.2]paracyclophane-4-yl)ethane-

1,2-diamine (meso-27): Analytically pure sample (0.022 g, 28%) was ob-

tained by recrystallisation of the mixture of diastereomers from acetone.

M.p. 1928C (decomp); ¹H NMR (400 MHz, CDCl₃): d=2.52–2.62 (m,

2H), 2.71–3.18 (m, 14H), 4.83 (brd, 2H, 2CH), 4.98 (brd, 2H, 2NH),

5.94–6.01 (m, 4H), 6.07 (d, ³J=7.8 Hz, 2H), 6.25 (d, ³J=7.8 Hz, 2H),

N,N’-{[2.2]Paracyclophane-4,13-diyldimethylylidene}dianiline (35) was

obtained as described above from 34 and aniline hydrochloride in quanti-

tative yield. Analytically pure product was obtained by recrystallisation

from heptane: Yield 0.37 g (79%). M.p. 1238C; ¹H NMR (400 MHz,

C₆D₆): d=2.78–2.95 (m, 6H, -CH₂-CH₂-), 4.16–4.25 (m, 2H, -CH₂-CH₂-),

6.43 (dd, ³J=7.8, ⁴J=1.8 Hz, 2H,), 6.47 (d, ³J=7.8 Hz, 2H, PC aromatic

H), 7.02–7.12 (m, 10H, phenyl aromatic H), 7.31 (d, ⁴J=1.8 Hz, 2H, PC

aromatic H), 8.40 (s, 2H, CH=N); ¹³C NMR (75 MHz, C₆D₆): d = 32.9

(2C), 34.8 (2C), 121.2 (4C), 125.6 (2C), 129.1 (4C), 133.6 (2C), 135.1

(2C), 135.6 (2C), 136.8 (2C), 139.7 (2C), 141.3 (2C), 152.5 (2C), 159.2

3

6.34–6.43 (m, 6H), 6.62–6.70 (m, 2H), 6.93 (d, J=8.0 Hz, 2H), 7.24–7.30

(m, 2H), 7.52 (d, ³J=8.0 Hz, 2H); ¹³C NMR (75 MHz, CDCl₃): d=33.6,

34.9, 35.3 (4C) (2C-1, -2, -9, -10), 58.0 (2CH-NH), 110.7, 111.9, 118.1,

128.7, 130.7, 132.0, 132.1, 132.2, 132.5, 132.7, 133.0, 134.8, 135.4, 136.8,

138.7, 139.1, 139.2; MS (70 eV): m/z (%): 391 (49) [¹= M ⁺], 311 (9), 287

2

6958

www.chemeurj.org

ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2005, 11, 6944 – 6961

Paracyclophane Derivatives

FULL PAPER

(2C); MS (70 eV): m/z (%): 414 (21) [M ⁺], 337 (30), 322 (18), 209 (8),

1, -2, -9, -10), 80.3 and 89.5 (2C-OH), 129.2, 131.2, 133.6, 133.9, 134.6,

136.6, 137.5, 139.5, 140.1, 140.6, 145.1, 146.1; MS (70 eV): m/z (%): 266

207 (100) [¹= M ⁺], 77 (8); elemental analysis calcd (%) for C₃₀H₂₆N₂

2

(414.55): C 86.92, H 6.32, N 6.76; found C 86.95, H 6.21, N 6.58.

(52) [M ⁺], 249 (24), 219 (12), 205 (16), 190 (8), 133 (100) [¹= M ⁺], 119

2

(80), 105 (87); IR (KBr): n˜ =2947 and 2926 cm^ꢀ1(OH); elemental analy-

sis calcd (%) for C₁₈H₁₈O₂(266.34): C 81.17, H 6.81; found: C 81.04, H

6.87; analytical HPLC resolution: t_R= 17:56.0 and 21:56.4 min, respec-

tively.

1,2-Dihydroxy[2.2.2][1,2,4]cyclophane (36): TiCl₄(12.08 mmol, 1.33 mL,

2.30 g) was carefully added to THF (15 mL) at 08C under argon. Then

Zn (30.02 mmol, 1.96 g) was added to the yellow suspension, and the

greenish-brown mixture was stirred for 5 min. A solution of dialdehyde

34 (0.82 g, 3.11 mmol) in THF (30 mL) was added dropwise and the reac-

tion mixture was stirred at room temperature for 3 h (TLC control). The

mixture was diluted with Et₂O (40 mL), the organic layer was washed

with saturated aq. NaHCO₃, H₂O and dried with Na₂SO₄. The solvent

was evaporated to yield crude 36 (0.82 g, 98%). Analytically pure materi-

al was obtained by purification of the reaction mixture on silica gel

(CHCl₃) and recrystallisation from toluene. Yield 0.60 g (72%); m.p.

232–2348C (lit.^[27]m.p. 2348C); ¹H NMR (400 MHz, [D₆]DMSO): d=

2.57–2.63 (m, 1H, CH₂), 2.70–2.83 (m, 1H, CH₂), 2.88–3.17 (m, 5H,

CH₂), 3.66–3.76 (m, 1H, CH₂), 4.72 (brs, 1H, CH), 5.06 (brs, 1H, CH),

5.66 (d, J_CH-OH=3.9 Hz, 1H, OH), 5.83 (d, J_CH-OH=2.9 Hz, 1H, OH), 6.13

1,2-Bis(N-phenylamino)[2.2.2][1,2,4]cyclophane (37):

A suspension of

Zn/Cu couple (0.047 g, 0.73 mmol) in DMF (1 mL) was cooled to 08C

and solutions of pTosOH (0.14 g, 0.73 mmol) in DMF (1.5 mL) and bisi-

mine 35 (0.1 g, 0.24 mmol) in the same solvent (1.5 mL) were added si-

multaneously dropwise during 0.5 h. The mixture was allowed to stand at

room temperature for 2 h. The reaction mixture was diluted with H₂O,

extracted twice with CH₂Cl₂, the combined organic layers were washed

with H₂O and dried with Na₂SO₄. The solvent was evaporated and excess

DMF was removed under reduced pressure to yield crude 37 in quantita-

tive yield. The ¹H NMR spectrum of this product showed the formation

of a single meso-isomer. An analytically pure sample (0.08 g, 80%) was

obtained after chromatography on silica gel (toluene). M.p. 1928C

(decomp); ¹H NMR (400 MHz, CDCl₃): d=2.80–2.90 (m, 2H, 1-H^b, 2-

H^b), 2.95–3.03 (m, 2H, 9-H^b, 10-H^b), 3.09–3.16 (m, 2H, 9-H^a, 10-H^a),

3.33–3.41 (m, 2H, 1-H^a, 1-H^a), 5.00 (brs, 2H, 2NH), 5.20 (brs, 2H, 17-H,

4

3

(d, J=1.8 Hz, 1H, 5- or 12-H), 6.18 (d, J=7.8 Hz, 1H, 8- or 15-H), 6.19

(d, ³J=7.8 Hz, 1H, 8- or 15-H), 6.41 (dd, ³J=7.8, ⁴J=1.8 Hz, 1H, 7- or

16-H), 6.46 (dd, ³J=7.8, ⁴J=1.8 Hz, 1H, 7- or 16-H), 6.56 (d, ⁴J=1.8 Hz,

1H, 5- or 12-H); ¹³C NMR (75 MHz, CDCl₃): d=31.5, 33.8, 36.1, 36.2 (C-

Table 8. Summary of crystal data, data collection and refinement parameters for the structures of the compounds reported in this paper.

(R_p,R,R,R_p)-21

(R_p,S,R,S_p)-22

(R_p,S,S,R_p)-23 (R_p,R,R,R_p)-24 (R_p,R_p)-25

(R_p,S,S,R_p)-31

15

formula

C₃₆H₃₈O₂

C₄₃H₄₆O₄

C₃₆H₃₉O₄·

0.5H₂O

543.67

C₃₆H₃₈O₄

C₃₅H₃₅O₃·

CHCl₃

636.02

C₄₈H₄₈N₂O₂·

0.125(C₆H₁₄)

695.66

C₂₃H₂₀BrN

M_r

502.66

626.80

534.66

390.31

crystal habit

colourless prism colourless

needle

colourless

plate

colourless

plate

colourless

plate

colourless

prism

colourless

plate

crystal size [mm]

crystal system

space group

cell constants

a []

b []

c []

a [8]

b [8]

0.10.30.5

monoclinic

P2₁

0.30.20.05

0.40.50.6

orthorhombic orthorhombic monoclinic

P2₁2₁2

0.40.30.2

0.30.40.5

0.30.50.5

monoclinic

C2/c

0.40.30.2

orthorhombic

P2₁2₁2₁

triclinic

¯

P1

P2₁2₁2₁

P2₁

8.0035(12)

11.4165(16)

15.367(2)

90

102.455(4)

90

1371.0(3)

2

1.218

9.893(5)

13.598(6)

13.786(5)

72.89(3)

88.45(4)

72.81(4)

1689.6(13)

2

17.535(7)

17.728(7)

9.152(4)

90

2845(2)

4

1.269

120

9.397(11)

15.68(2)

19.18(2)

90

2825(6)

4

1.257

110

12.5390(7)

8.5160(5)

28.6420(17)

90

91.690(1)

90

3057.1(3)

4

1.382

20.126(3)

19.473(4)

38.962(7)

90

94.457(5)

90

15224(5)

16

1.214

7.697(2)

13.155(4)

17.508(4)

90

1772.7(7)

4

1.462

163

g [8]

V [³]

Z

1_calcd[mgm^ꢀ3

T [K]

]

1.232

163

293

120

110

2q_max[8]

56.1

0.073

semiempirical

from equiva-

lents

46.5

0.077

none

58.0

0.082

56.2

0.080

52.0

0.338

56.0

0.073

52.0

2.323

none

m(Mo_Ka) [mm^ꢀ1

absorption

]

semiempirical from equivalents

correction

T_min/T_max

no. indep. reflns

R_int

no. reflns refined

no. obsd reflns (I>2s(I))

abs. structure

0.499/0.969

6850

0.0191

5659

3241

ꢀ0.2(2)

–

0.123/0.928

24251

0.1087

7470

2593

ꢀ6.0(2)

0.478/0.968

16629

0.586

6823

3330

0.607/0.862

21549

0.0541

10505

6827

0.797/0.928

54480

0.0803

18115

6268

–

3754

0.0477

3429

2016

–

3709

0.0388

3244

2389

0.02(2)

ꢀ0.8(2)

0.4(8)

–

parameter

no. parameters

343

0.0545

432

0.0606

0.1536

371

0.0735

0.1266

479

0.0601

0.1228

829

0.0656

0.1267

964

0.598

0.0757

226

0.0565

0.1228

R₁(on F for obsd reflns)^[a]

wR²(on F²for all reflns)^[b]0.1331

weighting scheme

w^ꢀ1=1/[s²(F ²)+(aP)²+bP, P=¹= (F ²+2F²)

3

o o c

a

b

0.0611

–

540

1.020

0.169/

ꢀ0.133

0.0853

0.3174

672

1.013

0.257/

ꢀ0.268

0.0155

–

1164

0.981

0.339/

ꢀ0.346

0.0400

0.2800

1144

0.0132

3.5110

1336

0.0016

0.0500

5956

0.0481

2.9500

F(000)

GOOF

largest diff. peak/hole

0.984

1.013

0.977

0.972

0.328/

ꢀ0.186

0.573/

ꢀ0.479

0.923/

ꢀ0.249

1.450/

ꢀ0.621

ꢀ3

[e

]

[a] R₁= ꢀjjF_ojꢀꢀF_cjj/j(F_o) for observed reflections. [b] wR₂= {[w(F_o²ꢀF_c²)²/[w(F_o²)²]}^0.5for all reflections.

Chem. Eur. J. 2005, 11, 6944 – 6961

ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

6959

V. I. Rozenberg, H. Hopf et al.

18-H), 6.36 (d, ³J=7.8 Hz, 2H, 8-H, 15-H), 6.47 (dd, ³J=7.8, ⁴J=1.8 Hz,

2H, 7-H, 16-H), 6.64 (d, ⁴J=1.8 Hz, 2H, 5-H, 12-H), 6.69 (brd, 4H, 4-o-

H-Phenyl), 6.73–6.78 (m, 2H, 2-p-H-Phenyl), 7.12–7.20 (m, 4H, 4-m-H-

Phenyl); ¹³C NMR (75 MHz, CDCl₃): d=33.1 (2C), 36.6 (2C) (C-1, -2,

-9, -10), 60.2 (2CH-NH), 114.3 (4C), 118.4 (2C), 129.2 (4C), 130.2 (2C),

133.4 (2C), 134.2 (2C), 138.0 (2C), 141.3 (2C), 142.9 (2C), 147.9 (2C);

MS (70 eV): m/z (%): 416 (27) [M ⁺], 415 (45), 339 (66), 324 (100), 297

(15), 206 (73), 191 (28), 104 (20), 77 (15); elemental analysis calcd (%)

for C₃₀H₂₈N₂(416.57): C 86.50, H 6.77, N 6.72; found: C 86.48, H 6.71, N

6.64; analytical HPLC resolution: t_R=10:41.6 min.

[3] T. Hirao, Synlett 1999, 175–181, see also original papers (refs. [5]–

[8], [16] for the synthesis of diols and refs. [5], [7], [21]–[23] for the

synthesis of diamines) and other references therein.

[4] a) B. Kammermeier, G. Beck, D. Jacobi, H. Jendralla, Angew. Chem.

1994, 106, 719–721; Angew. Chem. Int. Ed. Engl. 1994, 33, 685–687;

b) J. L. Chiara, N. Valle, Tetrahedron: Asymmetry 1995, 6, 1895–

1898; c) C. S. Swindell, W. Fan, Tetrahedron Lett. 1996, 37, 2321–

2324; d) I. Shiina, H. Iwadare, H. Sakoh, M. Hagesawa, Yu-i. Tani,

T. Mukaiyama, Chem. Lett. 1998, 1–2; e) A. I. R. N. A. Barros,

A. M. S. Silva, Tetrahedron Lett. 2003, 44, 5893–5896.

[5] a) N. Taniguchi, M. Uemura, Tetrahedron 1998, 54, 12775–12788;

b) S. O. Agustsson, C. Hu, U. Englert, T. Marx, L. Westmann, C.

Ganter, Organometallics 2002, 21, 2993–3000.

[6] a) G. Borsato, O. De Lucchi, F. Fabris, V. Lucchini, P. Frascella, A.

Zambon, Tetrahedron Lett. 2003, 44, 3517–3520; b) J. Wang, X.

Jiang, M. Chen, Y. Hu, H. Hu, J. Organomet. Chem. 2001, 629, 213–

218.

[7] a) K. Ohmori, M. Kitamura, K. Suzuki, Angew. Chem. 1999, 111,

1304–1307; Angew. Chem. Int. Ed. 1999, 38, 1226–1229; b) N. Tani-

guchi, T. Hata, M. Uemura, Angew. Chem. 1999, 111, 1311–1314;

Angew. Chem. Int. Ed. 1999, 38, 1232–1235; c) A. O. Larsen, R. A.

Taylor, P. S. White, M. R. GangØ, Organometallics 1999, 18, 5157–

5162; d) R. Annunziata, M. Benaglia, M. Caporate, L. Raimondi,

Tetrahedron: Asymmetry 2002, 13, 2727–2734.

[8] a) N. Taniguchi, M. Uemura, J. Am. Chem. Soc. 2000, 122, 8301–

8302; b) Y. Tanaka, N. Taniguchi, T. Kimura, M. Uemura, J. Org.

Chem. 2002, 67, 9227–9237.

X-ray crystallographic study of imine 15, diols 21–24, aldehyde 25 and di-

amine 31: Single-crystal X-ray diffraction experiments for 21–25 and 31

were carried out with a Bruker SMART 1000 CCD area detector, using

graphite monochromated Mo_Karadiation (l=0.71073 , w scans with a

0.38 step in w and 10 s per frame exposure, 2q <608) at 110–120 K with

the exception of 21 (at 293 K). The low temperature of the crystals was

maintained with a Cryostream (Oxford Cryosystems) open-flow N₂gas

cryostat. Reflection intensities were integrated using SAINT software^[33]

and semiempirical method SADABS.^[34]Single-crystal X-ray diffraction

experiments for 22 and 15 were carried out with a rebuilt Syntex P2₁

four-circle diffractometer, using graphite monochromated Mo_Karadiation

(q/2q scans) at 163 K, the reflection intensities were integrated using Sie-

mens P3/PC software.^[35]

The structures were solved by direct methods and refined by the full-

matrix least-squares against F²in anisotropic (for non-hydrogen atoms)

approximation. The hydrogen atoms of the OH and NH groups were lo-

cated from the difference Fourier syntheses and refined in isotropic ap-

proximation in rigid model, the positions of the hydrogen atoms of CH₂

and CH₃groups and the phenyl rings were calculated and included in the

refinement using the riding model approximation with the U_iso(H)=

1.2U_eq(C) for the methyne and U_iso(H)=1.5U_eq(C) for methylene and

methyl groups, where the U_eq(C) is the equivalent isotropic temperature

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All calculations were performed on an IBM PC/AT using the SHELXTL

software.^[36]

The crystallographic data for compounds 15, 21–25 and 31 are represent-

ed in the Table 8. Some geometrical parameters are represented in the

Tables 5–7.

CCDC-266839 (15), -266840 (21), -266841 (22), -266842 (23), -266843

(24), -266844 (25) and -266845 (31) contain the supplementary crystallo-

graphic data for this paper. These data can be obtained free of charge

from The Cambridge Crystallographic Data Centre via www.ccdc.cam.

ac.uk/data_request/cif/

Acknowledgements

Financial support of this workby Russian Science Foundation (03-03-

32957 and 03-03-32214) and funds provided by the Descartes Prize are

gratefully acknowledged.

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Chem. Eur. J. 2005, 11, 6944 – 6961

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Received: April 13, 2005

Published online: September 2, 2005

Chem. Eur. J. 2005, 11, 6944 – 6961

ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

6961

Article Doi

Novel multichiral diols and diamines by highly stereoselective pinacol coupling of planar chiral [2.2]paracyclophane derivatives

DOI: 10.1002/chem.200500413

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Article abstract of DOI:10.1002/chem.200500413

Full text of DOI:10.1002/chem.200500413

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