Preparation of amino acid-bridged dicatechol ligands for dinuclear titanium(IV) complexes

PAPER

1125

Preparation of Amino Acid-Bridged Dicatechol Ligands for Dinuclear

Titanium(IV) Complexes

A

mino Acid-Bridged D

a

icatechola

r

k

lexes us Albrecht,*^aRainer Nolting,^aPatrick Weis^b

a

Institut für Organische Chemie der RWTH-Aachen, Professor-Pirlet-Straße 1, 52074 Aachen, Germany

Fax +49(241)8092385; E-mail: markus.albrecht@oc.rwth-aachen.de

b

Institut für Physikalische Chemie der Universität Karlsruhe, Fritz-Haber-Weg, 76128 Karlsruhe, Germany

Received 30 November 2004; revised 4 January 2005

substrates occurs by hydrogen bonding, electrostatic, hy-

drophobic/hydrophilic and charge-transfer interactions

with amino acid side chains which are appropriately ar-

ranged on the surface or in cavities of the enzyme.¹In

Abstract: Amino acid-bridged dicatechol ligands 2a–e-H₄were

prepared by peptide coupling reactions. Under special conditions,

an unusual BBr₃-promoted amide to methyl ester transformation

was observed for the asparagine and glutamine side chain functions.

The ligands were used in coordination studies with titanium(IV) metalloenzymes, the metal centers are not only able to

ions in the presence of an alkali metal carbonate. Double-stranded

complexes Li₂[(2a–e)₂(OR)₂Ti₂] which have alcoholate coligands

(R = CH₃, C₂H₅, C₃H₅) bridging the metals were selectively formed

site for substrates or even a catalytically active center.²

with lithium counter cations. On the other hand, with potassium

support a specific folding of the peptide chains, but also

might introduce an additional metal-coordination binding

Recently we described the preparation of the dicatechol

derivatives 1-H₄, which possess the nonpolar, hydropho-

bic amino acids glycine (a), alanine (b), valine (c), leucine

(d) or phenylalanine (e) as spacers.³The derivatives 1

form dinuclear complexes [(1)₂Ti₂(OCH₃)₂]^2–with titani-

um(IV) ions in the presence of an alkali metal carbonate

as base in methanolic solution (Figure 1). They have some

common structural features with the active centers of di-

nuclear metalloenzymes.⁴The amino acids form a chiral

pocket in which the alkoxide coligands were fixed by co-

ordination to the two metal centers. Triple-stranded heli-

cate-type complexes [(1)₃Ti₂]^4–could not be observed

with the ligands 1.^5,6

or sodium cations triple-stranded complexes M₄[(2b,c,e)₃Ti₂]

were obtained in addition to the double-stranded

M₂[(2b,c,e)₂(OCH₃)₂Ti₂] (M = Na, K).

Key words: peptide coupling, amino acid, ligands, metal complex,

template effect

Introduction

Enzymes are nature’s molecular machines to catalyze

chemical reactions which are essential for the functioning

of organisms on a molecular level. Despite their high

complexity they are made from a small pool of approxi-

mately 20 amino acid building blocks. Hereby binding of

OH

2-

HO

OH

O

R

H

HO

N

H

N

HN

N

H

O

1a-e-H₄

O

CH₃

O

R = nonpolar, hydrophobic

H (a), Me (b), i-Pr (c),

CH₂i-Pr (d), CH₂Ph (e)

∆

Λ

Ti

O

CH₃

O

HN

N

H

[(1e)₂Ti₂(OCH₃)₂]^2-

Figure 1 Amino acid-bridged dicatechol ligands 1a–e-H₄and a complex, which is formed from the phenylalanine-bridged ligand 1e. Only

the thermodynamically most favored isomer of [(1e)₂Ti₂(OCH₃)₂]^2–out of seven possible isomers is shown.

SYNTHESIS 2005, No. 7, pp 1125–1135

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Advanced online publication: 10.03.2005

DOI: 10.1055/s-2005-861865; Art ID: Z22504SS

1126

M. Albrecht et al.

PAPER

All our recent synthetic, metal coordination and structural

studies were performed with nonpolar, hydrophobic ami- 2a–e-H₄

no acids as spacers of the ligands 1a–e-H₄. However, to

Preparation of the Amino Acid-Bridged Dicatechols

enable some additional weak secondary interactions be- The earlier preparation of the ligands 1a–e-H₄was done

tween the amino acids and functionalized alkoxide coli- by use of the unprotected amino acid. First 2,3-dimeth-

gands, we need to substitute the alkyl-bearing amino acids oxybenzoic acid (7) and then 2,3-(dimethoxy)benzyl-

by others, which possess appropriate functionalities in the amine (4) were attached. The reactions were performed in

side chain.

DMF/CH₂Cl₂with DCC/NHS (dicyclohexylcarbodiim-

ide/N-hydroxysuccinimide) or EDC/HOBt [ethyl(dimeth-

ylaminopropyl)carbodiimide/hydroxybenzotriazole] as

coupling reagent. Following this protocol we obtained the

compounds 1a–e-H₄with up to 10–20% racemization at

the a-position of the amino acid residue.^3,6An indepen-

dent study with isoleucine as amino acid revealed that the

partial epimerization takes place during the second cou-

pling step. To suppress this epimerization, we tested sev-

eral solvents and found out that, e.g. acetone leads to a full

epimerization during the second amide coupling.

In this study we present the synthesis of seven new amino

acid-bridged dicatechol ligands 2a–e-H₄, which bear po-

lar, uncharged (amide: 2a, 2b; ester: 2a¢, 2b¢; phenol: 2c),

basic (imidazole: 2d), or conformationally constrained

(proline: 2e) amino acids as spacers (Figure 2). Prelimi-

nary coordination studies which were monitored by

FT-ICR MS show that the ligands 2 form dinuclear metal

complexes with titanium(IV) ions and that we are able to

introduce different types of alkoxides as coligands. For

the first time we observed triple-stranded complexes

which are formed in addition to the double-stranded ones. The epimerization can be suppressed by inverting the cou-

pling procedure. Therefore, in our new approach we start-

polar, uncharged

side-chains:

ed with an N-Fmoc-protected amino acid 3 and attached

O

2,3-(dimethoxy)benzylamine (4) to the C-terminus.^7,8Af-

OH

X

HO

ter removal of the Fmoc group, 2,3-dimethoxybenzoic

(CH₂)_n

OH

O

H

acid (7) was connected to the C-terminus. In preliminary

studies with isoleucine derivatives it was found, that the

use of HBTU/Hünig’s base (i-Pr₂NEt)⁹as coupling re-

agents in acetonitrile as solvent was most appropriate for

amide bond formation without epimerization at the a-car-

bon.

HO

N

H

O

n = 1: 2a-H₄(X = NH₂), 2a'-H₄(X = OMe)

n = 2: 2b-H₄(X = NH₂), 2b'-H₄(X = OMe)

HO

Following this strategy, we prepared the ligands 2a–d-H₄

(Scheme 1). We used Fmoc-protected amino acids

(Fmoc-Asn-OH: 3a, Fmoc-Gln-OH: 3b, Fmoc-Tyr(Me)-

OH: 3c, Fmoc-His(Mtt)-OH: 3d) as starting materials.

Hereby the tyrosine derivative 3c bore an additional meth-

yl group to protect the phenolic OH, while the imidazole

of 3d was protected by an Mtt (methyltrityl) group.¹⁰Cou-

pling with 2,3-(dimethoxy)benzylamine (4) proceeded

smoothly by use of HBTU/Hünig’s base in acetonitrile to

afford the derivatives 5a–d in 82–95% yield. The Fmoc

protecting group of 5 was removed by reaction with

piperidine⁸in acetonitrile. The advantage of this solvent

was that we could obtain pure amines by simple extraction

of the reaction mixture with hot n-hexane. The amines 6a–

d remained in the acetonitrile phase and were obtained in

very high yields (91%–quant.).

OH

HO

OH

O

H

HO

N

H

O

2c-H₄

basic

side-chains:

N

OH

HN

HO

OH

O

H

HO

N

H

O

2d-H₄

conformationally

constrained:

A second amide coupling with HBTU/Hünig’s base was

performed in acetonitrile to attach 2,3-dimethoxybenzoic

acid (7) to the amines 6. The protected ligand precursors

8a–d were obtained in 63–96% yield.

OH

HO

H

OH

N

The methyl ethers of 8a,b were cleaved by reaction with

BBr₃¹¹in chloroform to give the asparagine- (2a-H₄, 73%)

and glutamine-bridged ligands (2b-H₄, 80%). However,

this procedure highly depends on the reaction conditions

N

HO

O

2e-H₄

Figure 2 Ligands 2a–e-H₄described in this study, which bear polar, and the work-up of the reaction mixture. Following the

uncharged, or basic, or conformationally constraining amino acid side

chains.

general procedure for methyl ether cleavage, side prod-

ucts 2a¢-H₄and 2b¢-H₄(vide infra) were observed. How-

ever, 2a-H₄and 2b-H₄were obtained by reaction with

Synthesis 2005, No. 7, 1125–1135 © Thieme Stuttgart · New York

PAPER

Amino Acid-Bridged Dicatecholate Complexes

1127

OCH₃

O

OCH₃

HBTU, i-Pr₂NEt,

MeCN, 4

H₂N

OCH₃

1. BBr₃, CH₂Cl₂, reflux 2 d

2. methanol, reflux 5 h

H₃CO

R

O

(CH₂)_n

H

N

H

N

H₃CO

Fmoc

R:

N

CO₂H

Fmoc

N

H

O

n = 1: 8a

n = 2: 8b

O

5a (95%)

5b (87%)

5c (82%)

5d (87%)

CH₂CONH₂3a

(CH₂)₂CONH₂3b

CH₂(p-C₆H₄-OMe) 3c

O

OH

Mtt

H₃CO

O

HO

N

3d

OH

(CH₂)_n

n = 1: 2a'-H₄("20%")

n = 2: 2b'-H₄(60%)

H₂C

H

HO

N

OCH₃

H

O

H₃CO

HBTU, i-Pr₂NEt,

MeCN, 7

R

H

N

piperidine,

MeCN

Scheme 2 BBr₃-promoted amide to ester transformation.

H₂N

O

The Mtt protecting group of 8d was not affected by BBr₃.

Only the methyl groups were removed and the intermedi-

ate 9 was formed in 43%. However, ligand 2d-H₄was fi-

nally obtained in quantitative yield by cleavage of the

Mtt-group of 9 with trifluoroacetic acid and triisopropyl-

silane in dichloromethane¹⁰(Scheme 1).

6a (quant.)

6b (quant.)

6c (91%)

6d (96%)

OCH₃

BBr₃,

CH₂Cl₂or CHCl₃

H₃CO

OCH₃

O

R

H

N

Due to solubility problems, the methyl ethers of the ty-

rosine derivative 8c had to be removed by reaction with

BBr₃in chloroform. Compound 2c-H₄was obtained in

98% yield by concomitant ether cleavage at the catechol

as well as at the tyrosine moiety.

H₃CO

N

H

8a (63%)

8b (88%)

8c (87%)

8d (96%)

O

OH

R':

HO

OCH₃

OH

O

R'

CH₂CONH₂2a-H₄(73%)

(CH₂)₂CONH₂2b-H₄(80%)

CH₂(p-C₆H₄-OH) 2c-H₄(98%)

HBTU, i-Pr₂NEt,

CH₃CN, 4

H

N

H₃CO

HO

N

H

N

Mtt

CO₂H

N

O

Fmoc

N

9 (43%)

H₂C

Fmoc

O

3e

5e (99%)

N

OCH₃

N

piperidine,

CH₃CN

HBTU, i-Pr₂NEt,

CH₃CN, 7

OH

H₃CO

F₃CCOOH,

(i-Pr)₃SiH,

CH₂Cl₂

HN

O

HO

H

N

OH

N

H

9

H

HO

N

O

H

6e (quant.)

O

2d-H₄(quant.)

OCH₃

H₃CO

Scheme 1 Preparation of the asparagine, glutamine, tyrosine, and

histidine-bridged dicatechol ligands 2a–e-H₄.

BBr₃,

CH₂Cl₂

H

N

O

8e (87%)

BBr₃at 0 °C followed by work-up with ethanol instead of

methanol.

H₃CO

OCH₃

OH

The formation of the side products could be maximized by

performing the cleavage and quenching the reaction mix-

ture at high temperatures. Hereby an amide to methyl ester

transformation occurred at the side chain of the amino

acid residues (Scheme 2). In case of the asparagine

bridged derivative 8a, the corresponding ester 2a¢-H₄was

observed as the minor component of a 1:4 mixture with

2a-H₄. We were able to obtain the corresponding ester of

the glutaric acid derivative 2b¢-H₄in 60% yield in pure

form.

HO

H

N

O

2e-H₄(84%)

HO

OH

Scheme 3 Preparation of the proline-bridged ligand 2e-H₄.

Synthesis 2005, No. 7, 1125–1135 © Thieme Stuttgart · New York

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M. Albrecht et al.

PAPER

Table 1 Results of Negative ESI MS Spectrometry of the Complex-

ation Studies of Ligands 2a–e-H₄with Titanium(IV) Ions in the Pres-

ence of Alkali Metal Carbonate with Methanolate (CH₃O), Ethanolate

(C₂H₅O), or Allyl Alcoholate (C₃H₅O) as Coligands

Scheme 3 shows that the sterically constrained proline-

bridged ligand 2e-H₄was obtained as was described for

the corresponding derivatives 2a–d-H₄. The attachment of

the amine 4 to Fmoc-protected proline 3e proceeded in

99% yield to form 5e. After quantitative cleavage of the

Fmoc-group, the benzoic acid 7 was coupled to 6e and the

ligand precursor was obtained in 87% yield. Final ether

cleavage afforded the ligand 2e-H₄in 84%.

L¹/X/L²

X₂[(L¹)₂(L²)₂Ti₂] X₄[(L¹)₃Ti₂] (m/z)

(m/z)

– 2X⁺

464

478

493

– X⁺– 3X⁺– 2X⁺– X⁺

2a/Li/CH₃O

2b/Li/CH₃O

2b/Na/CH₃O

2b/K/CH₃O

2b¢/Li/CH₃O

935

963

–

Preparation of Amino Acid-Bridged Dinuclear

Titanium(IV) Complexes

979

–

995

686

–

We investigated the coordination behavior of the ligands

2a–e-H₄with titanium(IV) ions in methanol and tested

some selected examples in the presence of ethanol or allyl

993

–

2b¢/Na/CH₃O 493

1009

1025

1033

–

1

alcohol as solvent (Scheme 4). In most cases H NMR

spectroscopy showed complicated and broad spectra,

which were due to the presence of many different spe-

cies.⁶As an exceptionally well resolved spectrum the one

of Li₂[(2c)₂(OCH₃)₂Ti₂] in methanol-d₄has to be men-

tioned which shows the presence of only one isomer (see

Experimental section).

2b¢/K/CH₃O

2c/Li/CH₃O

2c/Na/CH₃O

2c/K/CH₃O

2d/Li/CH₃O

2e/Li/CH₃O

2e/Na/CH₃O

2e/K/CH₃O

2b/Li/C₂H₅O

2c/Li/C₃H₅O

2e/Li/C₃H₅O

493

513

–

1049 474

1065 479

722

738

–

1467

1515

–

978

901

–

OH

447

492

539

473

–

OH

TiO(acac)₂

917 408

623

639

–

1269

1317

–

X₂CO₃

ROH

O

N

933

991

–

R'

NH

OH

1085

953

–

OH

2a-e-H₄

–

O

methanol resulted in the exclusive formation of Li₂[(2a–

e)₂(OCH₃)₂Ti₂]. Negative ESI MS showed the corre-

sponding peaks for the dianions [(2a–e)₂(OCH₃)₂Ti₂]^2–

and the monoanions Li[(2a–e)₂(OCH₃)₂Ti₂]^–with correct

isotopic pattern.

Ti

O

N

O

N

OR

X₂

+ X₄

R'

RO

NH

If sodium or potassium carbonate were used as base, the

corresponding dinuclear double-stranded complexes

[(2b,c,e)₂(OCH₃)₂Ti₂]^2–were observed as well by ESI MS

(Figure 3). However, the potassium derivatives of 2b

showed a characteristic peak for the triple-stranded

K₂[(2b)₃Ti₂]^2–at m/z = 686. In case of the sodium and po-

tassium salts of the titanium complexes of 2c and 2e al-

ways the triple-stranded complex [(2c,e)₃Ti₂]^4–was

observed in addition to the double-stranded

[(2c,e)₂(OCH₃)₂Ti₂]^2–.¹²For the glutaric ester only dou-

ble-stranded complexes [(2b¢)₂(OCH₃)₂Ti₂]^2–are ob-

served independent of the counter ions.

O

Ti

O

2

3

X₂[(2)₂(OR)₂Ti₂]

X₄[(2)₃Ti₂]

X = Li, Na, K

X = Na, K

Scheme 4 Formation of titanium(IV) complexes of the ligands [2a–

e]^4–(only one isomer of double- and triple-stranded dinuclear comple-

xes is indicated).

Because the NMR spectra were often not sufficiently in-

formative, we performed extensive ESI MS studies, to

find out if the complex formation was successful and what

kind of species was formed. The results are listed in

Table 1. Coordination studies of the ligands 2a–e-H₄with

titanium(IV) ions in the presence of lithium carbonate in

Our observations show that a specific formation of the

double-stranded coordination compounds with two coli-

gands is only guaranteed, if lithium is the counter cation.

This template effect¹³by the small Li⁺cation is not under-

stood yet, but has to be considered in the preparation of

Synthesis 2005, No. 7, 1125–1135 © Thieme Stuttgart · New York

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Amino Acid-Bridged Dicatecholate Complexes

1129

Currently, we are investigating whether more functional-

ized coligands can be introduced and whether we finally

can perform chemical reactions in the ligand sphere of our

double-stranded dinuclear coordination compounds.

¹H and ¹³C NMR spectra were recorded on a Varian Mercury 300 or

Inova 400 spectrometer. FT-IR spectra were recorded by diffuse re-

flection (KBr) or neat on a Bruker IFS spectrometer. Mass spectra

(EI, 70 eV; FAB) were taken on a Finnigan MAT 95 or 212 mass

spectrometer. FT-ICR ESI mass spectra were measured on a Bruker

Bioapex II FTMS equipped with a 7 Tesla magnet. Elemental anal-

yses were obtained with a Heraeus CHN-O-Rapid analyzer. Melting

points: Büchi B-540 (uncorrected).

Coupling of Fmoc-Amino Acids 3 with 2,3-(Dimethoxy)benzyl-

amine (4); General Procedure

To a solution of the Fmoc-protected amino acid derivative 3 (1

equiv) in MeCN (50–200 mL) were added HBTU (1.2 equiv) and

diisopropylethylamine (1.1 equiv). The mixture was stirred for 20

min at r.t. and 2,3-(dimethoxy)benzylamine (4; 1 equiv) was added.

After 18–24 h at rt., work-up was done by isolation of the precipi-

tated product 5 by filtration and purification by washing with cold

MeCN. Eventually the precipitate can be dissolved in EtOAc, and

the EtOAc layer was washed successively with aq NH₄Cl, NaHCO₃,

H₂O, and brine, dried (MgSO₄) and the solvent removed in vacuum

(Method A). If the product did not precipitate from MeCN, the sol-

vent was removed and purification of the residue was done as de-

scribed for method A (Method B).

Figure 3 ESI MS spectra of Li₂[(2c)₂(OCH₃)₂Ti₂] and of the mix-

ture of Na₄[(2c)₃Ti₂] and Na₂[(2c)₂(OCH₃)₂Ti₂]. In 2c* the phenolic

side group of tyrosine is deprotonated.

5a

Method A; yield: 1.49 g (95%); colorless solid; mp 200 °C.

double-stranded complexes with coligands of the type

[(2)₂(OR)₂Ti₂]^2–. In addition, we performed the complex

formation of ligand 2b-H₄with titanium(IV) ions in etha-

nol in the presence of lithium carbonate, which smoothly

produced Li₂[(2b)₂(OC₂H₅)₂Ti₂] containing bridging eth-

anolate coligands.

IR (KBr): 3303, 3208, 1695, 1634, 1514, 1483, 1279, 1263 cm^–1.

¹H NMR (300 MHz, DMSO-d₆): d = 8.19 (t, J = 5.7 Hz, 1 H, NH),

7.82 (dd, J = 7.5, 2.7 Hz, 4 H), 7.53 (d, J = 7.5 Hz, 1 H), 7.42 (t,

J = 7.1 Hz, 2 H), 6.92 (m, 3 H), 4.40 (m, 1 H), 4.29 (m, 2 H), 4.22

(m, 2 H), 3.77 (s, 3 H), 3.71 (s, 3 H), 2.43 (m, 2 H).

¹³C NMR (130 MHz, DMSO-d₆): d = 174.2 (C), 172.1 (C), 171.9

(C, double intensity), 152.7 (C, double intensity), 144.5 (C, double

intensity), 141.4 (C), 139.7 (C), 133.2 (CH, double intensity), 128.3

(CH, double intensity), 127.8 (CH, double intensity), 124.4 (CH,

double intensity), 120,7 (CH), 120.5 (CH), 112.2 (CH), 66,5 (CH₂),

60.6 (CH₃), 56.3 (CH₃), 47.3 (CH), 41.0 (CH), 40.7 (CH₂), 31.8

(CH₂).

Allyl alcoholate-bridged dinuclear titanium complexes

Li₂[(2c,e)₂(OC₃H₅)₂Ti₂] were obtained, if the reaction of

the ligands 2c,e-H₄with titanium(IV) and lithium carbon-

ate proceeded in allyl alcohol as solvent. Here the purifi-

cation of the complex salts had to be performed in allyl

alcohol to prevent an exchange of the coligands.

MS (LCMS-ESI, MeOH): m/z = 504 [M + H]⁺.

Anal. Calcd for C₂₈H₂₉N₃O₆: C, 66.79; H, 5.81; N, 8.34. Found: C,

66.32; H, 6.03; N, 8.29.

Conclusion

In this paper, we have presented the preparation of amino

acid-bridged dicatechol ligands, which bear functional

groups in the side chain. With our new procedure, the

preparation proceeds smoothly with acceptable to good

yields without racemization. All ligands specifically form

double-stranded coordination compounds Li₂[(2a–

e)₂(OR)₂Ti₂] in the presence of lithium carbonate. Howev-

er, in the presence of sodium and potassium carbonate tri-

ple-stranded complexes [(2b,c,e)₂(OCH₃)₂Ti₂]^4–are

observed in addition. Introduction of alternative alcohol-

ates as coligands can be achieved by use of alcohols other

than methanol as solvent. In preliminary experiments we

were able to introduce ethanolate as well as allyl alcohol-

ate.

5b

Method A; yield: 2.44 g (87%); colorless solid; mp 194 °C.

IR (KBr): 3290, 1663, 1541, 1279, 757 cm^–1.

¹H NMR (400 MHz, DMSO-d₆): d = 7.90 (d, J = 7.4 Hz, 2 H), 7.74

(d, J = 7.2 Hz, 2 H), 7.53 (d, J = 7.5 Hz, 1 H), 7.40 (t, J = 7.5 Hz, 2

H), 7.31 (m, 2 H), 6.97 (m, 1 H), 6.76 (m, 1 H), 4.26 (m, 2 H), 4.21

(m, 3 H), 4.10 (t, J = 6.8 Hz, 1 H), 3.77 (s, 3 H), 3.69 (s, 3 H), 2.06

(m, 2 H), 1.80 (m, 2 H).

¹³C NMR (100 MHz, DMSO-d₆): d = 174.7 (C), 174.1 (C), 156.4

(C, double intensity), 152.6 (C), 146.6 (C), 144.3 (C), 144.2 (C),

139.8 (C), 137.8 (C), 129.4 (CH, double intensity), 127.7 (CH, dou-

ble intensity), 124.6 (CH, double intensity), 123.8 (CH), 121.8 (CH,

double intensity), 120.5 (CH), 112.1 (CH), 66.15 (CH₂), 60.5 (CH₃),

56.1 (CH₃), 54.9 (CH), 47.1 (CH), 39.4 (CH₂), 31.5 (CH₂), 28.2

(CH₂).

MS (FAB, DMSO): m/z = 518 [M + H]⁺.

Synthesis 2005, No. 7, 1125–1135 © Thieme Stuttgart · New York

1130

M. Albrecht et al.

PAPER

Anal. Calcd for C₂₉H₃₁N₃O₆: C, 67.30; H, 6.04; N, 8.12. Found: C,

67.72; H, 6.00; N, 8.67.

Anal. Calcd for C₂₉H₃₀N₂O₅·MeCN·H₂O: C, 68.24; H, 6.17; N,

7.70. Found: C, 68.79; H, 6.03; N, 8.26.

5c

Removal of the Fmoc-Protecting Group from 5; General Proce-

dure

Method B; yield: 1.67 g (82%); colorless solid; mp 188 °C.

The Fmoc-protected compounds 5 (1 equiv) were suspended in

MeCN (100 mL) and piperidine (6 equiv) was added. The mixture

was stirred for 24 h at r.t. The MeCN phase was extracted with hot

n-hexane (5 × 30 mL) and the MeCN was removed in vacuum to

obtain the amines 6.

IR (KBr): 3420, 3299, 1693, 1644 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 7.81 (d, J = 7.6 Hz, 2 H), 7.60 (d,

J = 7.4 Hz, 2 H), 7.52 (m, 2 H), 7.41 (m, 2 H), 7.32 (m, 2 H), 7.02

(d, J = 7.8 Hz, 2 H), 6.95 (t, J = 8.1 Hz, 1 H), 6.83 (t, J = 8.1 Hz, 1

H), 6.74 (d, J = 7.8 Hz, 1 H), 4.33 (m, 5 H), 4.17 (t, J = 6.5 Hz, 1

H), 3.83 (s, 3 H), 3.75 (s, 6 H), 2.98 (d, J = 6.1 Hz, 2 H).

6a

¹³C NMR (100 MHz, CDCl₃): d = 172.1 (C), 170.3 (C), 158.5 (C),

155.8 (C), 152.5 (C), 147.1 (C), 143.8 (C), 143.7 (C), 141.3 (C),

131.1 (C), 130.3 (CH, double intensity), 129.4 (CH, double intensi-

ty), 128.1 (CH, double intensity), 127.7 (CH, double intensity),

127.1 (CH, double intensity), 125.6 (CH, double intensity), 124.1

(CH), 121.2 (CH, double intensity), 120.0 (C), 114.0 (CH), 112.0

(CH), 66.9 (CH₂), 60.6 (CH₃), 55.7 (CH₃), 55.2 (CH₃), 38.9 (CH₂),

37.9 (CH₂).

Yield: 1.49 g (quant.); colorless solid; mp 137 °C (dec.).

IR (KBr): 3443, 3421, 3312, 1665, 1637, 1548, 1482, 1085, 1057,

988 cm^–1.

¹H NMR (300 MHz, DMSO-d₆): d = 6.98 (m, 2 H), 6.83 (m, 1 H),

4.27 (d, J = 5.7 Hz, 2 H), 3.79 (s, 3 H), 3.74 (s, 3 H), 3.53 (dd,

J = 8.9, 4.1 Hz, 1 H), 2.47 (m, 1 H).

¹³C NMR (130 MHz, DMSO-d₆): d = 174.4 (C), 173.2 (C), 153.6

(C), 147.7 (C), 124.3 (CH), 121.4 (CH), 120.5 (C), 112.1 (CH), 60.5

(CH₃), 56.1 (CH₃), 52.1 (CH), 39.5 (CH₂), 34.2 (CH₂).

MS (EI): m/z = 567 [M + H]⁺.

Anal. Calcd for C₃₄H₃₄N₂O₆: C, 72.07; H, 6.05; N, 4.94. Found: C,

71.87; H, 6.11; N, 5.23.

MS (EI): m/z = 282 [M + H]⁺.

Anal. Calcd for C₁₃H₁₉N₃O₄·0.5H₂O: C, 53.78; H, 6.94; N, 14.47.

Found: C, 53.61; H, 6.66; N, 14.99.

5d

Method B; yield: 2.14 g (87%); colorless solid; mp 103 °C.

6b

IR (KBr): 3305, 3061, 2937, 1723, 1671, 1481, 1273, 1243, 742

cm^–1.

Yield: 860 mg (ca. 100%); colorless solid; mp 183 °C (dec.).

¹H NMR (400 MHz, CDCl₃): d = 7.05 (m, 1 H), 6.85 (d, J = 7.4 Hz,

2 H), 4.45 (m, 2 H), 3.85 (s, 6 H), 3.50 (t, J = 6.6 Hz, 1 H), 2.35 (m,

2 H), 2.01 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): d = 174.2 (C), 170.4 (C), 152.6 (C),

147.1 (C), 123.8 (CH), 120.9 (C), 120.7 (CH), 112.7 (CH), 59.3

(CH₃), 56.5 (CH₃), 48.7 (CH), 39.5 (CH₂), 32.0 (CH₂), 25.7 (CH₂).

¹H NMR (400 MHz, CDCl₃): d = 7.74 (d, J = 7.4 Hz, 2 H), 7.55 (t,

J = 8.0 Hz, 2 H), 7.36 (m, 3 H), 7.29 (m, 7 H), 7.07 (m, 6 H), 6.96

(d, J = 8.2 Hz, 3 H), 6.70 (m, 3 H), 6.66 (s, 1 H), 4.59 (m, 1 H), 4.51

(m, 3 H), 4.33 (d, J = 8.1 Hz, 2 H), 3.80 (s, 6 H), 3.02 (m, 2 H), 2.33

(s, 3 H).

¹³C NMR (100 MHz, CDCl₃): d = 172.3 (C), 156.0 (C, double in-

tensity), 153.7 (C, double intensity), 147.8 (C), 143.6 (C), 142.2

(C), 140.5 (C), 139.8 (C), 139.2 (C), 137.0 (C), 136.0 (C), 134.9

(CH, double intensity), 132.9 (CH, double intensity), 130.6 (CH,

double intensity), 129.7 (CH, double intensity), 129.6 (CH, double

intensity), 128.0 (CH, quadruple intensity), 127.3 (CH, quadruple

intensity), 126.1 (CH, double intensity), 123.3 (CH), 122.3 (CH,

double intensity), 121.2 (CH), 121.1 (CH), 120.0 (C), 113.4 (CH),

74.5 (C), 66.7 (CH₂), 60.2 (CH₃), 56.4 (CH₃), 51.3 (CH), 47.1 (CH),

46.5 (CH), 39.6 (CH₂), 29.8 (CH₂), 21.1 (CH₃).

MS (EI): m/z = 296 [M + H]⁺.

Anal. Calcd for C₁₄H₂₁N₃O₄: C, 56.94; H, 7.17; N, 14.23. Found: C,

57.67; H, 6.78; N, 13.89.

6c

Yield: 414 mg (91%); colorless solid; mp 128 °C.

¹H NMR (400 MHz, CDCl₃): d = 7.05 (d, J = 7.5 Hz, 1 H), 6.93 (m,

2 H), 6.74 (m, 4 H), 4.43 (d, J = 6.0 Hz, 2 H), 3.81 (s, 3 H), 3.76 (s,

3 H), 3.69 (s, 3 H), 3.56 (m, 1 H), 2.98 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): d = 170.2 (C), 158.5 (C), 151.8 (C),

147.3 (C), 131.9 (C), 130.6 (C), 130.5 (CH), 129.8 (CH, double in-

tensity), 123.2 (CH, double intensity), 114.2 (CH), 113.4 (CH), 60.8

(CH₃), 56.7 (CH₃), 55.4 (CH₃), 54.1 (CH), 39.4 (CH₂), 37.8 (CH₂).

MS (FAB, DMSO): m/z = 783 [M + H]⁺.

Anal. Calcd for C₅₀H₄₆N₄O₅: C, 76.70; H, 5.92; N, 7.15. Found: C,

76.31; H, 5.79; N, 7.22.

5e

MS (EI): m/z = 345 [M + H]⁺.

Method A; yield: 2.86 g (99%); colorless solid; mp 144 °C.

IR (KBr): 3368, 3282, 1711, 1688, 1646, 1539, 1480, 1448, 1429,

1349, 1122, 739 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 7.76 (d, J = 7.4 Hz, 2 H), 7.57 (m,

2 H), 7.39 (t, J = 7.5 Hz, 2 H), 7.30 (m, 2 H), 6.83 (m, 3 H), 4.52 (m,

1 H), 4.49 (m, 2 H), 4.44 (d, J = 6.2 Hz, 2 H), 3.85 (s, 3 H), 3.84 (s,

3 H), 3.73 (m, 1 H), 2.93 (m, 2 H), 2.02 (m, 2 H), 1.67 (m, 2 H).

6d

Yield: 3.33 g (96%); colorless solid; mp 73 °C.

¹H NMR (400 MHz, CDCl₃): d = 7.35 (m, 2 H), 7.32 (s, 1 H), 7.31

(m, 5 H), 7.11 (m, 5 H), 6.97 (m, 3 H), 6.83 (d, J = 7.9 Hz, 2 H),

6.63 (s, 1 H), 4.45 (m, 2 H), 3.85 (s, 3 H), 3.84 (s, 3 H), 3.65 (m, 1

H), 3.02 (m, 2 H), 2.35 (s, 3 H).

¹³C NMR (130 MHz, DMSO-d₆): d = 174.8 (C), 172.3 (C), 152.9

(C), 152.3 (C, double intensity), 147.8 (C, double intensity), 143.6

(C), 140.5 (C), 130.6 (CH), 127.2 (CH, double intensity), 126.1

(CH, double intensity), 123.0 (CH, double intensity), 121.6 (CH,

double intensity), 119.7 (CH), 113.3 (CH), 67.8 (CH₂), 60.2 (CH₃),

58.6 (CH), 56.5 (CH₃), 47.2 (CH), 46.9 (CH₂), 39.2 (CH₂), 28.7

(CH₂), 23.8 (CH₂).

¹³C NMR (100 MHz, CDCl₃): d = 174.2 (C), 152.6 (C), 147.1 (C),

142.5 (C), 139.4 (C, double intensity), 138.5 (C), 138.0 (CH), 137.9

(C), 134.2 (CH, double intensity), 134.1 (CH), 132.1 (CH), 132.0

(CH, double intensity), 129.6 (CH, quadruple intensity), 128.0 (CH,

quadruple intensity), 124.4 (CH), 124.1 (CH), 120.0 (C), 119.5

(CH), 113.6 (CH), 75.1 (C), 60.8 (CH₃), 55.7 (CH), 55.6 (CH₃),

38.2 (CH₂), 33.0 (CH₂), 21.0 (CH₃).

MS (FAB, DMSO): m/z = 488 [M + H]⁺.

MS (FAB, DMSO): m/z = 561 [M + H]⁺.

Synthesis 2005, No. 7, 1125–1135 © Thieme Stuttgart · New York

PAPER

Amino Acid-Bridged Dicatecholate Complexes

1131

Anal. Calcd for C₃₅H₃₆N₄O₃: C, 74.98; H, 6.47; N, 9.99. Found: C,

73.99; H, 6.23; N, 10.15.

8c

Yield: 400 mg (87%); yellow oil.

IR (KBr): 3266, 2945, 2837, 1653, 1633, 1512, 1479, 1271, 1082,

1001, 750 cm^–1.

6e

Yield: 543 mg (quant.); brown oil.

IR (neat): 3315, 3218, 1725, 1644, 1518, 1493, 1289 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 7.00 (t, J = 8.0 Hz, 1 H), 6.84 (d,

J = 8.0 Hz, 2 H), 4.44 (d, J = 6.0 Hz, 2 H), 3.85 (s, 3 H), 3.84 (s, 3

H), 3.73 (m, 1 H), 2.02 (m, 2 H), 1.91 (m, 2 H), 1.68 (m, 2 H).

¹H NMR (400 MHz, CD₃OD): d = 7.49 (m, 2 H), 7.07 (m, 3 H), 6.94

(t, J = 8.0 Hz, 1 H), 6.85 (t, J = 8.0 Hz, 1 H), 6.73 (d, J = 8.0 Hz, 2

H), 6.68 (m, 1 H), 4.78 (t, J = 6.8 Hz, 1 H), 4.37 (m, 2 H), 3.85 (s,

3 H), 3.81 (s, 3 H), 3.74 (s, 3 H), 3.72 (s, 3 H), 3.70 (s, 3 H), 3.05

(m, 2 H).

¹³C NMR (130 MHz, CDCl₃): d = 170.8 (C), 152.8 (C), 148.0 (C),

123.9 (CH), 120.9 (C), 120.5 (CH), 113.4 (CH), 60.5 (CH₃), 58.9

(CH), 56.5 (CH₃), 47.9 (CH₂), 39.7 (CH₂), 31.9 (CH₂), 26.9 (CH₂).

¹³C NMR (100 MHz, CD₃OD): d = 171.3 (C), 165.5 (C), 158.5 (C),

155.5 (C), 152.4 (C), 147.9 (C), 146.7 (C), 131.2 (CH), 130.2 (C),

128.3 (C), 125.6 (CH), 124.2 (CH), 124.0 (CH), 121.0 (CH), 120.9

(C), 115.9 (CH), 113.8 (CH), 111.8 (CH), 61.5 (CH), 61.1 (CH₃),

60.3 (CH₃), 55.8 (CH₃), 55.5 (CH₃), 55.4 (CH₃), 55.3 (CH), 38.1

(CH₂), 37.5 (CH₂).

MS (EI): m/z = 265 [M + H]⁺.

Anal. Calcd for C₁₄H₂₀N₂O₃: C, 63.37; H, 7.98; N, 10.56. Found: C,

62.99; H, 7.84; N, 11.31.

MS (EI): m/z = 509 [M + H]⁺.

Coupling of 2,3-Dimethoxybenzoic Acid (7) with the Amines 6;

General Procedure

Anal. Calcd for C₂₈H₃₂N₂O₇: C, 66.13; H, 6.34; N, 5.51. Found: C,

65.65; H, 6.24; N, 5.31.

2,3-Dimethoxybenzoic acid (7; 1 equiv) was dissolved in MeCN

(50–100 mL) and HBTU (1.2 equiv) and diisopropylethylamine

(1.1 equiv) were added. The mixture was stirred for 20 min at r.t.

and the amine 6 was added. After 2 d at r.t., the precipitate was re-

moved by filtration and washed with cold MeCN. The crude prod-

uct was dissolved in EtOAc and successively washed with aq

NH₄Cl, aq NaHCO₃, H₂O, and brine. After drying (MgSO₄) the

EtOAc was removed by distillation to afford 8.

8d

Yield: 3.61 g (84%); colorless solid; mp 124 °C (dec.).

IR (KBr): 2949, 2840, 2808, 1674, 1532, 845 cm^–1.

¹H NMR (400 MHz, CD₃OD): d = 8.13–6.79 (22 H_arom), 4.46 (m, 2

H), 3.86 (s, 3 H), 3.85 (s, 3 H), 3.84 (s, 3 H), 3.82 (s, 3 H), 3.65 (m,

1 H), 3.02 (m, 2 H), 2.15 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): d = 175.8 (C), 166 (C), 152,7 (C),

146.9 (C), 146.6 (C), 144.2 (C), 142.2 (C), 140.2 (C), 139.3 (C, dou-

ble intensity), 136.9 (C), 134.1 (CH, double intensity), 133.6 (CH,

double intensity), 133.4 (CH, double intensity), 130.8 (CH, quadru-

ple intensity), 127.4 (CH, quadruple intensity), 124.3 (CH), 124.1

(C), 123.8 (CH), 123.4 (CH), 120.9 (CH), 120.6 (CH), 118.5 (C),

113.7 (CH), 77.9 (C), 60.6 (CH₃), 59.9 (CH₃), 55.5 (CH₃), 55.2

(CH₃), 49.4 (CH), 38.0 (CH₂), 27.4 (CH₂), 21.7 (CH₃).

8a

Yield: 1.28 g (63%); colorless solid; mp 192 °C.

IR (KBr): 3419, 3291, 3256, 2180, 1663, 1636, 1534, 1481.51,

1434, 1267, 1221, 1084 cm^–1.

¹H NMR (300 MHz, DMSO-d₆): d = 8.90 (br, 1 H, NH), 8.25 (t, 1

H, J = 6.2 Hz, NH), 7.40 (m, 1 H), 7.20 (m, 1 H), 6.95 (m, 4 H), 4.79

(dd, J = 8.1, 2.3 Hz, 1 H), 4.29 (d, J = 6.2 Hz, 2 H), 3.84 (s, 3 H),

3.80 (s, 3 H), 3.78 (s, 3 H), 3.71 (s, 3 H), 2.60 (md, J = 8.1 Hz, 2 H).

MS (FAB, DMSO): m/z = 725 [M + H]⁺.

¹³C NMR (130 MHz, DMSO-d₆): d = 174.3 (C), 169.6 (C), 158.3

(C), 152.3 (C), 150.0 (C), 148.2 (C), 147.1 (C), 128.2 (C), 126.3

(CH), 124.1 (CH), 121.9 (CH), 120.4 (C), 118.3 (CH), 114.9 (CH),

61.5 (CH), 60.4 (CH₃), 56.6 (CH₃), 56.5 (CH₃), 56.1 (CH₃), 50.6

(CH), 39.4 (CH₂), 37.5 (CH₂).

8e

Yield: 147 mg (87%); yellow solid; mp 146 °C (dec.).

IR (KBr): 3420, 2924, 1623, 1535, 1480, 1430, 1305, 1271, 1229,

1072, 1004, 844, 797, 751, 557 cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 7.16–6.75 (6 H_arom), 4.49 (d,

J = 4.1 Hz, 2 H), 3.89 (s, 3 H), 3.88 (s, 3 H), 3.86 (s, 3 H), 3.85 (s,

3 H), 3.74 (m, 1 H), 2.02 (m, 2 H), 1.90 (m, 2 H), 1.67 (m, 2 H).

¹³C NMR (130 MHz, CD₃OD): d = 172.7 (C), 172.6 (C), 168.7 (C),

152.7 (C, double intensity), 144.8 (C), 131.5 (C), 130.9 (C), 124.6

(CH), 124.5 (CH), 120,4 (CH), 120.4 (CH), 113.8 (CH), 111.7

(CH), 60.7 (CH₃), 60.6 (CH₃), 60.2 (CH), 55.2 (CH₃), 54.6 (CH₃),

42.3 (CH₂), 26.1 (CH₂), 25.6 (CH₂), 24.2 (CH₂).

MS (ESI, pos): m/z = 446 [M + H]⁺.

Anal. Calcd for C₂₂H₂₇N₃O₇·1/3H₂O: C, 58.53; H, 6.18; N, 9.31.

Found: C, 58.64; H, 6.08; N, 9.95.

8b

The reaction took 4 instead of 2 d to yield 1.27 g (88%) of a color-

less solid; mp 167 °C (dec.).

IR (KBr): 3299, 1662, 1626, 1539, 1429, 1355, 1332, 1172, 942,

989, 868 cm^–1.

MS (EI): m/z = 429 [M + H]⁺.

¹H NMR (400 MHz, CDCl₃): d = 7.21 (t, J = 7.9 Hz, 2 H), 7.04 (dd,

J = 8.0, 1.6 Hz, 1 H), 6.99 (t, J = 8.0 Hz, 1 H), 6.97 (m, 1 H), 6.85

(m, 1 H), 4.79 (m, 1 H), 4.52 (m, 2 H), 3.77 (s, 3 H), 3.73 (s, 3 H),

3.68 (s, 3 H), 3.67 (s, 3 H), 2.15 (m, 2 H), 1.84 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): d = 176.0 (C), 171.2 (C), 165.7 (C),

152.6 (C), 152.4 (C), 147.7 (C), 146.7 (C), 131.1 (C), 125.6 (CH),

124.1 (CH), 121.8 (CH), 120.7 (CH), 120.4 (C), 115.7 (CH), 111.7

(CH), 61.3 (CH₃), 60.4 (CH₃), 55.8 (CH₃), 55.5 (CH₃), 49.1 (CH),

38.2 (CH₂), 31.3 (CH₂), 29.3 (CH₂).

Anal. Calcd for C₂₃H₂₈N₂O₆·3H₂O: C, 57.25; H, 7.10; N, 5.81.

Found: C, 57.37; H, 6.99; N, 6.47.

Cleavage of the Methyl Ethers of 8; General Procedure

The protected derivatives 8 (1 equiv) were dissolved in CH₂Cl₂(20

mL). At 0 °C, BBr₃(6-10 equiv) was added and the resulting mix-

ture was stirred for 24 h at r.t. MeOH (15 mL) was added and the

solvents were removed in vacuum. The residue was dissolved in

EtOAc and the EtOAc layer was washed with H₂O and brine. The

organic phase was dried (MgSO₄) and the solvent was removed to

obtain 2a,b,c,e and 9.

MS (EI): m/z = 460 [M + H]⁺.

Anal. Calcd for C₂₃H₂₉N₃O₇: C, 60.12; H, 6.36; N, 9.14. Found: C,

59.01; H, 6.33; N, 9.08.

1132

M. Albrecht et al.

PAPER

Cleavage of the Methyl Ethers 8a,b; Optimized Procedure

The derivatives 8a,b (1 equiv) were dissolved in CHCl₃(10 mL). At

0 °C, BBr₃(8 eq) was added and the suspension was stirred at r.t.

for 24 h. The mixture was slowly hydrolyzed with EtOH (10 mL) at

0 °C. After the solvents were removed, the residue was dissolved in

EtOAc and washed with H₂O and brine. The organic phase was

dried (MgSO₄) and the solvent was removed to obtain 2a,b.

EtOAc. This procedure was repeated two more times to obtain the

product as a colorless solid; yield: 150 mg (60%); white solid.

IR (KBr): 3359, 2866, 2487, 1726, 1639, 1587, 1536, 1478, 1447,

1350, 1263, 1176, 1078, 840, 783, 741 cm^–1.

¹H NMR (400 MHz, CD₃OD): d = 7.20 (dd, J = 1.5, 8.2 Hz, 1 H),

6.86 (dd, J = 1.5, 8.1 Hz, 1 H), 6.59 (m, 4 H), 4.55 (t, J = 5.4 Hz, 1

H), 4.26 (d, J = 8.2 Hz, 2 H), 3.52 (s, 3 H), 2.34 (m, 1 H), 2.26 (m,

1 H), 2.11 (m, 1 H), 1.98 (m, 1 H).

2a-H₄

¹³C NMR (100 MHz, CD₃OD): d = 173.6 (C), 172.5 (C), 169.5 (C),

145.7 (C) double intensity, 145.1 (C) double intensity, 143.1 (C),

124.6 (C), 119.9 (CH), 119.1 (CH), 118.4 (CH), 118.3 (CH), 118.1

(CH), 114.2 (CH), 53.0 (CH), 50.9 (CH₃), 38.7 (CH₂), 30.0 (CH₂),

27.1 (CH₂).

Yield: 190 mg (73%); slightly brown solid; mp 72 °C.

IR (KBr): 3380, 2983, 1699, 1641, 1594, 1549, 1482, 1457, 1335,

1268, 1169, 743 cm^–1.

¹H NMR (400 MHz, CD₃OD): d = 7.19 (d, J = 7.4 Hz, 1 H), 6.94 (d,

J = 7.4 Hz, 1 H), 6.75 (m, 4 H), 4.74 (t, J = 3.2 Hz, 2 H), 4.68 (m, 1

H), 2.99 (m, 2 H).

MS (EI): m/z = 419.1 [M + H]⁺.

¹³C NMR (100 MHz, CD₃OD): d = 177.0 (C), 169.5 (C), 158.4 (C),

152.4 (C), 149.3 (C), 148.3 (C), 145.9 (C), 142.8 (C), 131.1 (C),

124.8 (CH), 122.6 (CH), 119.4 (CH), 118.9 (CH), 114.6 (CH),

114.3 (CH), 51.9 (CH), 38.4 (CH₂), 35.6 (CH₂).

Anal. Calcd for C₂₀H₂₂N₂O₈·H₂O: C, 55.04; H, 5.54; N, 6.42.

Found: C, 54.98; H, 5.48; N, 6.63.

2c-H₄

CHCl₃was used as the solvent instead of CH₂Cl₂; yield: 93 mg

(98%); slightly brown solid; mp 98 °C.

MS (FAB, DMSO): m/z = 390 [M + H]⁺.

Anal. Calcd for C₁₈H₁₉N₃O₇: C, 55.53; H, 4.92; N, 10.79. Found: C,

55.90; H, 5.03; N, 9.93.

IR (KBr): 3347, 2944, 1636, 1515, 1332, 1261, 743 cm^–1.

¹H NMR (400 MHz, CD₃OD): d = 7.26 (d, J = 8.5 Hz, 2 H), 7.00 (d,

J = 8.5 Hz, 2 H), 6.94 (m, 1 H), 6.71 (m, 2 H), 6.61 (m, 2 H), 6.53

(m, 1 H), 4.77 (t, J = 7.2 Hz, 1 H), 4.30 (m, 2 H), 3.09 (dd, J = 13.9,

6.5 Hz, 1 H), 2.99 (dd, J = 13.9, 6.5 Hz, 1 H).

¹³C NMR (100 MHz, CD₃OD): d = 172.7 (C), 168.9 (C), 158.4 (C),

155.8 (C), 148.0 (C), 145.7 (C), 143.2 (C), 130.0 (CH), 127.2 (C),

126.9 (C), 125.9 (CH), 124.6 (CH), 120.9 (CH), 120.0 (C), 119.2

(CH), 118.4 (CH), 118.8 (CH), 117.7 (CH), 114.8 (CH), 114.2

(CH), 55.3 (CH), 38.5 (CH₂), 37.0 (CH₂).

2a¢-H₄

Compound 8a (100 mg, 1 equiv) was dissolved in CH₂Cl₂(10 mL).

At r.t., BBr₃(10 eq) was added and the mixture was refluxed for 48

h. MeOH was added to the hot mixture and refluxed for an addition-

al 5 h. The solution was allowed to cool down and the solvents were

removed in vacuum. The residue was dissolved in EtOAc and

washed with H₂O and brine. The organic phase was dried (MgSO₄)

and the solvent was removed under reduced pressure. So far it was

not possible to obtain the product in pure form. ¹H NMR spectrum

shows a mixture of 20% of 2a¢-H₄and 80% of 2a-H_4.

MS (EI): m/z = 440 [M + H]⁺.

Anal. Calcd for C₂₃H₂₃N₂O₇: C, 62.86; H, 5.28; N, 6.37. Found: C,

62.83; H, 5.12; N, 6.64.

¹H NMR (400 MHz, CD₃OD): d = 7.23 (dd, J = 1.5, 7.9 Hz, 1 H),

6.98 (dd, J = 1.5, 7.9 Hz), 6.70 (m, 4 H), 4.77 (d, J = 3.5 Hz, 2H),

4.73 (m, 1 H), 3.65 (s, 3 H, 20% int), 3.15 (dd, J = 9.1, 17.8 Hz, 1

H), 2.93 (dd, J = 5.7, 17.8 Hz, 1 H).

9

Yield: 40 mg (43%); brown oil.

MS (EI): m/z = 405.2 [M + H]⁺.

IR (KBr): 3402, 2948, 2838, 2806, 1671, 1585, 1462, 1433, 1030

cm^–1.

¹H NMR (400 MHz, CD₃OD): d = 8.15–6.50 (22 H_arom), 4.72 (m, 2

H), 4.46 (m, 2 H), 3.02 (m, 1 H), 2.15 (s, 3 H).

2b-H₄

Yield: 140 mg (80%); colorless solid; mp 142 °C (dec.).

IR (KBr): 3304, 1646, 1539, 1236 cm^–1.

¹³C NMR (100 MHz, CD₃OD): d = 174.8 (C), 166.7 (C), 152.8 (C),

152.6 (C), 146.9 (C), 146.3 (C), 142.3 (C), 142.1 (C), 137.0 (C, dou-

ble intensity), 136.8 (C), 134.2 (CH, double intensity), 133.7 (CH,

double intensity), 133.4 (CH, double intensity), 130.9 (CH, quadru-

ple intensity), 127.5 (CH, quadruple intensity), 124.8 (C), 123.9

(CH, double intensity), 123.4 (CH, double intensity), 120.5 (CH,

double intensity), 120.1 (C), 113.5 (CH), 112.1 (CH), 77.9 (C), 49.4

(CH), 38.4 (CH₂), 27.3 (CH₂), 21.8 (CH₃).

¹H NMR (400 MHz, CD₃OD): d = 7.31 (d, J = 8.0 Hz, 1 H), 6.94 (d,

J = 8.0 Hz, 1 H), 6.71 (m, 4 H), 4.61 (m, 1 H), 4.37 (m, 2 H), 2.37

(m, 2 H), 1.84 (m, 2 H).

¹³C NMR (100 MHz, CD₃OD): d = 176.7 (C), 173.8 (C), 169.9 (C),

148.6 (C), 148.4 (C), 145.8 (C), 145.1 (C), 124.7 (CH), 120.0 (CH),

119.2 (CH), 118.6 (CH), 118.5 (CH), 118.4 (CH), 115.4 (C), 114.3

(C), 48.0 (CH), 38.6 (CH₂), 31.5 (CH₂), 27.5 (CH₂).

MS (EI): m/z = 404 [M + H]⁺.

MS (FAB, DMSO): m/z = 669 [M + H]⁺.

Anal. Calcd for C₁₉H₂₁N₃O₇: C, 56.57; H, 5.25; N, 10.42. Found: C,

56.89; H, 4.91; N, 11.63.

2e-H₄

Compound 8e (500 mg, 1 equiv) was dissolved in CH₂Cl₂(15 mL).

At 0 °C, BBr₃(8 equiv) was added and the mixture was stirred for

8 h at 0 °C. MeOH was slowly added to the cooled suspension. The

solvents were removed in vacuum, the residue was dissolved in

EtOAc and washed with H₂O and brine. The organic phase was

dried (MgSO₄) and the solvent was removed under reduced pres-

sure; yield: 364 mg (84%); slightly brown solid; mp 67 °C (dec.).

¹H NMR (300 MHz, CD₃OD): d = 6.87 (dd, J = 8.2, 2.1 Hz, 1 H),

6.76 (m, 4 H), 6.65 (dd, J = 8.2, 2.1 Hz, 1 H), 4.42 (d, J = 6.3 Hz, 2

H), 3.72 (m, 1 H), 2.92 (m, 2 H), 2.05 (m, 2 H), 1.67 (m, 2 H).

2b¢-H₄

Compound 8b (250 mg, 1 equiv) was dissolved in CH₂Cl₂(20 mL).

At r.t., BBr₃(10 eq) was added and the mixture was refluxed for 48

h. MeOH was added to the hot mixture and refluxed for an addition-

al 5 h. The solution was allowed to cool down and the solvents are

removed in vacuum. The residue was dissolved in EtOAc and

washed with H₂O and brine. The organic phase was dried (MgSO₄),

concentrated and slowly added to Et₂O. The solid was collected by

filtration and the filtrate was concentrated again and dissolved in

PAPER

Amino Acid-Bridged Dicatecholate Complexes

1133

¹³C NMR (130 MHz, CD₃OD): d = 175.3 (C), 162.9 (C), 151.3 (C),

150.9 (C), 148.9 (C), 146.6 (C), 125.0 (CH), 121.4 (CH), 120.4

(CH), 119.5 (CH), 114.5 (CH), 113.6 (CH), 108.9 (C), 103.8 (C),

58.3 (CH), 38.7 (CH₂), 29.4 (CH₂), 26.3 (CH₂), 25.9 (CH₂).

MS (ESI): m/z = Na₂[(2b)₂(OCH₃)₂Ti₂]: 478 [M – 2 Na]^2–, 979

[M – Na]^–.

Anal. Calcd for C₄₀H₄₀N₆Na₂O₁₆Ti₂·4 H₂O: C, 44.71; H, 4.50; N,

7.82. Found: C, 44.98; H, 4.56; N, 5.77.

MS (EI): m/z = 373 [M + H]⁺.

K₂[(2b)₂(OCH₃)₂Ti₂] + K₄[(2b)₃Ti₂]

Red solid.

Anal. Calcd for C₁₉H₂₀N₂O₆: C, 61.28; H, 5.41; N, 7.53. Found: C,

60.99; H, 5.22; N, 7.90.

IR (KBr): 3408, 1728, 1667, 1527, 1445, 1345, 1251, 1219, 1027,

845, 741, 670, 633 cm^–1.

Deprotection of 9 to 2d-H₄

Compound 9 (22 mg, 0.033 mmol) was dissolved in CH₂Cl₂(20

mL) and trifluoroacetic acid (0.2 mL) and triisopropylsilane (1 mL)

were added. The mixture was stirred for 2 h at r.t. The precipitate

was collected by filtration, washed with CH₂Cl₂and dried; yield:

14 mg (ca. 100%); slightly brown solid.

¹H NMR (400 MHz, CD₃OD): d = 7.46 (s, 1 H), 7.37 (d, J = 7.4 Hz,

2 H), 6.92 (m, 1 H), 6.76–6.69 (m, 4 H), 4.30 (m, 2 H), 3.04 (m, 1

H), 1.80 (m, 2 H).

¹³C NMR (100 MHz, CD₃OD): d = 174.4 (C), 160.7 (C), 152.5 (C),

151.4 (C), 147.8 (C), 145.3 (C), 134.8 (CH), 133.7 (CH, double in-

tensity), 131.0 (C), 124.3 (CH), 199.7 (CH), 118.0 (CH), 113.2

(CH), 113.2 (CH), 104.9 (C), 101.4 (C), 48.7 (CH), 38.2 (CH₂), 29.1

(CH₂).

¹H NMR (300 MHz, CD₃OD): d = 7.60 (m, 1 H), 7.11 (m, 1 H),

6.59–6.15 (br m, 4 H), 4.41 (m, 1 H), 4.05 (d, J = 14.7 Hz, 1 H), 4.15

(m, 1 H), 1.91 (br m, 2 H), 1.32 (br m, 2 H).

MS (ESI): m/z = K₂[(2b)₂(OCH₃)₂Ti₂]: 478 [M – 2 K]^2–, 995 [M –

K]^–; K₄[(2b)₃Ti₂]: 686 [M –2 K]^2–.

Li₂[(2b¢)₂(OCH₃)₂Ti₂]

Yield: quant.; red solid.

IR (KBr): 3403, 1639, 1525, 1448, 1254, 1219, 1064, 853, 742, 488

cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 7.24 (dd, J = 1.5, 8.2 Hz, 1 H),

6.63 (t, J = 8.2, 1 H), 6.54 (dd, J = 1.5, 7.7 Hz, 2 H), 6.48 (m, 1 H),

6.42, (m, 1 H), 4.83 (m, 1 H), 4.53 (m, 1 H), 4.16 (m, 1 H), 3.75 (s,

3 H), 3.38 (s, 3 H), 2.68 (m, 2 H), 2.48 (m, 1 H), 2.12 (m, 1 H).

Dinuclear Complexes with Methoxide Coligands; General Pro-

cedure

MS (ESI): m/z = 493 [M – 2 Li]^2–, 993 [M – Li]^–.

The amino acid-bridged ligand 2-H₄(1 equiv, ca. 0.1 mmol),

TiO(acac)₂(1 equiv) and alkali metal carbonate (1 equiv) were dis-

solved in MeOH. The mixture was stirred for 20 h and the solvent

was removed in vacuum. The residue was dissolved in MeOH and

filtered over Sephadex LH20 and the orange red band was collected.

Anal. Calcd for C₄₂H₄₂Li₂N₄O₁₈Ti₂·8H₂O: C, 44.07; H, 5.11; N,

4.89. Found: C, 44.37; H, 5.06; N, 5.24.

Na₂[(2b¢)₂(OCH₃)₂Ti₂]

Yield: 54%; red solid.

IR (KBr): 3410, 3245, 1719, 1642, 1539, 1446, 1250, 1218, 1064,

851, 740, 680, 632, 485 cm^–1.

Li₂[(2a)₂(OCH₃)₂Ti₂]

Yield: 91%; red solid.

¹H NMR (300 MHz, CD₃OD): d = 9.67 (d, 1 H, J = 9.4, NH), 7.25

(d, J = 8.2, 1 H), 6.63 (t, J = 7.9, 1 H), 6.53 (m, 1 H), 6.41 (d,

J = 4.9, 2 H), 6.28 (m, 1 H), 4.62 (m, 1 H), 4.50 (d, J = 14.1, 1 H),

4.15 (m, 1 H), 3.75 (s, 3 H), 3.38 (s, 3 H), 2.68 (m, 2 H), 2.47 (m, 1

H), 2.10 (m, 1 H).

IR (KBr): 3425, 1707, 1633, 1592, 1525, 1451, 1356, 1255, 1022,

931, 801, 744, 664 cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 7.15–6.80 (m, 2 H), 6.30–5.95

(m, 4 H), 3.04 (m, 2 H), 5.05 (m, 1 H), 3.65 (m, 2 H).

MS (ESI): m/z = 464 [M – 2 Li]^2–, 935 [M – Li]^–.

MS (ESI): m/z = 493 [M – 2 Na]^2–, 1009 [M – Na]^–.

Anal. Calcd for C₃₈H₃₆Li₂N₆O₁₆Ti₂·5H₂O·8CH₃OH: C, 41.43; H,

5.82; N, 6.74. Found: C, 41.14; H, 4.85; N, 3.27.

Anal. Calcd for C₄₂H₄₂Na₂N₄O₁₈Ti₂·6H₂O·CH₃OH: C, 44.04; H,

4.99; N, 4.78. Found: C, 43.99; H, 4.98; N, 5.31.

Li₂[(2b)₂(OCH₃)₂Ti₂]

Yield: 91%; a red solid.

K₂[(2b¢)₂(OCH₃)₂Ti₂]

Yield: quant.; red solid.

IR (KBr): 3378, 2927, 1646, 1593, 1527, 1447, 1252, 1219, 741

cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 7.12 (dd, 1 H, J = 8.2, 2.1 Hz,

NH), 6.61 (t, J = 8.2 Hz, 1 H), 6.55–6.43 (m, 2 H), 6.39 (d, J = 5.3

Hz, 2 H), 6.30–6.20 (m, 1 H), 4.46 (d, J = 15.2 Hz, 2 H), 4.10 (d,

J = 4.1 Hz, 1 H), 2.65–1.95 (br m, 4 H).

IR (KBr): 3390, 3241, 1720, 1642, 1536, 1445, 1251, 1218, 1062,

851, 740, 680, 632, 484 cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 9.66 (d, 1 H, J = 9.4 Hz, NH),

7.24 (m, 1 H), 6.63 (m, 1 H), 6.52 (m, 1 H), 6.42 (d, J = 4.2 Hz, 2

H), 6.30 (m, 1 H), 4.82 (t, J = 4.7 Hz, 1 H), 4.17 (m, 1 H), 3.76 (s,

3 H), 3.38 (s, 3 H), 2.68 (m, 2 H), 2.48 (m, 1 H), 2.12 (m, 1 H).

MS (ESI): m/z = 478 [M – 2 Li]^2–, 957 [M – 2 Li + H]^–, 963 [M –

MS (ESI): m/z = 493 [M – 2 K]^2–, 1025 [M – Li]^–.

Li]^–.

Anal. Calcd for C₄₂H₄₂K₂N₄O₁₈Ti₂·8.5H₂O: C, 41.42; H, 4.88;

N,.4.60. Found: C, 41.25; H, 4.71; N, 5.15.

Anal. Calcd for C₄₀H₄₀Li₂N₆O₁₆Ti₂·6H₂O·2CH₃OH: C, 44.15; H,

5.29; N, 7.35. Found: C, 44.13; H, 5.09; N, 6.38.

Li₂[(2c)₂(OCH₃)₂Ti₂]

Yield: 88%; red solid.

Na₂[(2b)₂(OCH₃)₂Ti₂]

Yield: 90%; red solid.

IR (KBr): 3591, 3430, 1640, 1602, 1517, 1451, 1255, 1221, 1019,

919, 742, 521 cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 7.27 (d, J = 8.4 Hz, 2 H), 7.19

(m, 1 H), 6.81 (d, J = 8.4 Hz, 2 H), 6.61 (m, 2 H), 6.40 (d, J = 5.2

Hz, 2 H), 6.26 (m, 1 H), 5.01 (m, 1 H), 4.48 (d, J = 14.3 Hz, 1 H),

4.12 (d, J = 14.3 Hz, 1 H), 3.21 (m, 2 H).

IR (KBr): 3408, 1724, 1651, 1591, 1527, 1447, 1361, 1251, 1219,

1027, 739, 674, 634 cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 7.25 (m, 1 H), 6.34 (t, J = 7.9 Hz,

1 H), 6.54 (m, 1 H), 6.42 (d, J = 5.0 Hz, 2 H), 6.29 (t, J = 5.0 Hz, 1

H), 4.87 (m, 1 H), 4.49 (d, J = 13.3 Hz, 1 H), 4.15 (d, J = 13.3 Hz,

1 H), 2.56 (m, 2 H), 2.17 (m, 2 H).

1134

M. Albrecht et al.

PAPER

MS (ESI): m/z = 513 [M – 2 Li]^2–, 1033 [M – Li]^–.

MS (ESI): m/z = K₂[(2e)₂(OCH₃)₂Ti₂]: 447 [M – 2 K]^2–, 933 [M –

K]^–; K₄[(2e)₃Ti₂]: 639 [M –2 K]^2–, 1317 [M – K]^–.

Anal. Calcd for C₄₈H₄₂Li₂N₄O₁₆Ti₂·6H₂O·CH₃OH: C, 49.85; H,

4.95; N, 4.75. Found: C, 49.76; H, 5.24; N, 3.17.

Ethoxide-Bridged Complex Li₂[(2b)₂(OCH₂CH₃)₂Ti₂]

The ethoxide-bridged complex is prepared as described for the cor-

responding methoxide derivative, with the exception that all proce-

dures were performed in EtOH; yield: 90%; red solid.

Na₂[(2c)₂(OCH₃)₂Ti₂] + Na₄[(2c)₃Ti₂]

Red solid.

IR (KBr): 3412, 1645, 1594, 1517, 1451, 1360, 1251, 1220, 1023,

741, 664, 632, 517 cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 7.14 (d, J = 8.4 Hz, 2 H), 7.05

(m, 1 H), 6.67 (d, J = 8.4 Hz, 2 H), 6.47 (m, 2 H), 6.26 (d, J = 5.2

Hz, 2 H), 6.13 (m, 1 H), 4.78 (m, 1 H), 4.34 (d, J = 14.3 Hz, 1 H),

4.09 (d, J = 14.3 Hz, 1 H), 3.05 (m, 2 H).

MS (ESI): m/z = Na₂[(2c)₂(OCH₃)₂Ti₂]: 513 [M – 2Na]^2–, 1049

[M – Na]^–; Na₄[(2c)₃Ti₂]: 474 [M – 3Na]^3–, 722 [M – 2 Na]^2–, 1467

Na₃[M – Na]^–.

IR (KBr): 3395, 2935, 1642, 1591, 1545, 1448, 1252, 1220, 1025,

1000, 744, 631, 517 cm^–1.

¹H NMR (300 MHz, DMSO-d₆): d = 7.38 (br, 1 H, NH), 7.05 (d,

J = 8.2 Hz, 1 H), 6.50–6.00 (m, 5 H), 4.78 (m, 1 H), 4.52 (m, 1 H),

4.05 (m, 1 H), 3.43 (br m, 2 H), 2.30-1.75 (br m, 4 H) 1.06 (t, J = 7.1

Hz, 3 H).

MS (ESI): m/z = 492 [M – 2 Li]^2–, 991 [M – Li]^–.

Anal. Calcd for C₄₂H₄₆N₆O₁₆Ti₂Li₂·13H₂O·3C₂H₅OH: C, 42.15; H,

6.26; N, 6.14. Found: C, 41.95; H, 6.31; N, 5.31.

K₂[(2c)₂(OCH₃)₂Ti₂] + K₄[(2c)₃Ti₂]

Red solid.

Allyloxy-Bridged Complexes

The allyloxy-bridged complexes were prepared as described for the

corresponding methoxide derivatives, with the exception that all

procedures were performed in allyl alcohol.

IR (KBr): 3424, 1636, 1554, 1447, 1252, 1221, 745 cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 7.24–6.10 (m, 10 H), 4.62 (m, 1

H), 4.23 (d, J = 14.7 Hz, 1 H), 4.11 (d, J = 14.7 Hz, 2 H), 3.01 (br

m, 2 H).

Li₂[(2c)₂(OCH₂CH=CH₂)₂Ti₂]

Yield: 67%; a red solid.

MS (ESI): m/z = K₂[(2c)₂(OCH₃)₂Ti₂]: 513 [M – 2 K]^2–, 1065 [M –

K]^–; K₄[(2c)₃Ti₂]: 479 [M – 3 K]^3–, 738 [M – 2 K]^2–, 1515 [M – K]^–.

IR (KBr): 3401, 2926, 2865, 1639, 1559, 1519, 1448, 1251, 1221,

1059, 1031, 743 cm^–1.

¹H NMR (300 MHz, DMSO-d₆): d = 7.16–6.20 (m, 10 H), 6.09–578

(m, 3 H), 5.32–4.90 (m, 2 H), 4.68 (m, 1 H), 3.95 (m, 2 H), 3.01 (br

m, 2 H).

Li₂[(2d)₂(OCH₃)₂Ti₂]

Yield: 90%; red solid.

¹H NMR (300 MHz, CD₃OD): d = 7.28–7.14 (m, 3 H), 7.09 (s, 1 H),

6.58–6.30 (m, 4 H), 3.58 (br s, 2 H), 3.04 (br s, 1 H), 1.83 (br m, 2

H).

MS (ESI): m/z = 539 [M – 2 Li]^2–, 1085 [M – Li]^–.

Anal. Calcd for C₅₂H₄₆Li₂N₄O₁₆Ti₂·11H₂O·7(HOCH₂CH=CH₂): C,

51.66; H, 6.53; N, 3.30. Found: C, 51.76; H, 6.06; N, 2.45.

MS (ESI): m/z = 981 [M – Li]^–.

Li₂[(2e)₂(OCH₃)₂Ti₂]

Yield: 85%; red solid.

Li₂[(2e)₂(OCH₂CH=CH₂)₂Ti₂]

Yield: 93%; red solid.

IR (KBr): 3386, 2928, 1592, 1527, 1446, 1254, 1223, 1026, 740

cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 6.71 (dd, J = 7.6, 1.8 Hz, 1 H),

6.56–6.30 (m, 4 H), 6.23 (dd, J = 7.6, 1.8 Hz, 1 H), 4.61 (m, 1 H),

4.61 (m, 1 H), 4.25 (m, 1 H), 2.20–1.45 (br m, 6 H).

IR (KBr): 3404, 1588, 1529, 1443, 1353, 1254, 1026, 740, 651

cm^–1.

¹H NMR (300 MHz, DMSO-d₆): d = 6.42–6.00 (m, 6 H), 5.94 (br

m, 3 H), 5.19 (m, 1 H), 5.02 (m, 1 H), 4.72 (t, J = 7.2 Hz, 1 H), 4.52

(d, J = 13.3 Hz, 1 H), 4.30 (d, J = 13.3 Hz, 1 H), 3.93 (m, 2 H),

2.18–1.80 (m, 6 H).

MS (ESI): m/z = 447 [M – 2 Li]^2–, 901 [M – Li]^–.

MS (ESI): m/z = 473 [M – 2 Li]^2–, 953 [M – Li]^–.

Na₂[(2e)₂(OCH₃)₂Ti₂] + Na₄[(2e)₃Ti₂]

Red solid.

Anal. Calcd for C₄₄H₄₄Li₂N₄O₁₄Ti₂·6H₂O·HOCH₂CH=CH₂: C,

50.01; H, 5.54; N, 4.96. Found: C, 50.15; H, 5.17; N, 4.22.

IR (KBr): 3392, 1589, 1528, 1445, 1357, 1253, 1222, 740, 520

cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 6.47–6.18 (br m, 6 H), 4.44 (m,

1 H), 4.37 (d, J = 14.3 Hz, 1 H), 4.12 (d, J = 14.3 Hz, 1 H), 2.15–

1.32 ( m, 6 H).

MS (ESI): m/z = Na₂[(2e)₂(OCH₃)₂Ti₂]: 447 [M – 2 Na]^2–, 917

[M – Na]^–; Na₄[(2e)₃Ti₂]: 408 [M – 3 Na]^3–, 623 [M – 2 Na]^2–, 1269

[M – Na]^–.

Acknowledgment

Financial support by the Deutsche Forschungsgemeinschaft (SPP

1118) is gratefully acknowledged. We thank Professor Dr. M. Kap-

pes and the Nanotechnology Institute, Forschungszentrum Karls-

ruhe, for facilitating the ESI-MS measurements.

K₂[(2e)₂(OCH₃)₂Ti₂] + K₄[(2e)₃Ti₂]

Red solid.

References

(1) Fersht, A. Structure and Mechanism in Protein Science; W.

H. Freeman: New York, 1998.

IR (KBr): 3423, 1656, 1594, 1525, 1445, 1359, 1253, 1222, 1025,

740 cm^–1.

¹H NMR (300 MHz, CD₃OD): d = 6.51–6.19 (br m, 6 H), 4.60 (m,

1 H), 4.29 (d, J = 13.4 Hz, 1 H), 4.08 (d, J = 13.4 Hz, 1 H), 2.21 (br

m, 1 H), 1.83 (br m, 2 H), 1.47 (br m, 2 H).

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PAPER

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Article Doi

Preparation of amino acid-bridged dicatechol ligands for dinuclear titanium(IV) complexes

DOI: 10.1055/s-2005-861865

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