complexes containing the...

Inorganica Chimica Acta 357 (2004) 3493–3502

www.elsevier.com/locate/ica

Complexes containing the (R;R)-N ;N 0-bis(2-hydroxy-3-functionalised-benzylidene)-1,2-diaminocyclohexane ligand:

synthesis and X-ray analyses of titanium chloro and oxo derivatives

Amber Davis, Colin A. Kilner, Terence P. Kee *

Department of Chemistry, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK

Received 29 December 2003; accepted 28 January 2004

Available online 17 June 2004

Abstract

Titanium complexes based on the (R;R)-N ;N 0-bis(2-hydroxy-3-functionalised-benzylidene)-1,2-diaminocyclohexane ligand and

containing either chloro or bridged oxo co-ligands have been prepared, subjected to single crystal X-ray analysis and examined as

pre-catalysts for the asymmetric phospho-aldol (PA) reaction. Catalysis does take place although at a much slower rate than with

related aluminium complexes and then only to afford racemic products; significant observations that lead to an important design

point in PA pre-catalysts.

� 2004 Elsevier B.V. All rights reserved.

Keywords: Salcyen; Titanium; Complexes; Asymmetric

1. Introduction

The salen class of Schiff base molecule has found

widespread use as a ligand framework in coordination

chemistry and as a support ligand for metal-based cat-

alysts [1]. Moreover, the incorporation of asymmetry

within the salen backbone allows for chiral ligands of a

type which have seen considerable recent success inenantioselective transition metal based oxidation and

related catalysis [2].

We have been interested in the potential of such sa-

len-based ligands as components of asymmetric transi-

tion and main-group element complex catalysts for the

stereoselective phospho-aldol reaction [3]. This, some-

what oft-neglected reaction, is one of the most valuable

processes for the synthesis of medicinally relevant

* Corresponding author. Tel.: +44-113-243-1751; fax: +44-113-343-

6565.

E-mail address: [email protected] (T.P. Kee).

0020-1693/$ - see front matter � 2004 Elsevier B.V. All rights reserved.

doi:10.1016/j.ica.2004.01.048

a-funcationalised (most commonly hydroxo and amino)

phosphonate esters [4–8] and the currently accepted

mechanistic picture for the process is outlined in

Scheme 1 (CAT¼ catalyst) [9].

We have recently found that salen complexes con-

taining the (R;R)-cyclohexyldiamine backbone (salcyen)

and the closely related tetrahydro-(R;R)-salcyen (or

salcyan) ligands have led to effective stereocontrolwithin the phospho-aldol reaction; especially when

coupled with a metal complex combining both Lewis

acidic and Lewis basic properties such as the aluminium

hydroxo function [3]. We were interested therefore, to

expand the scope of metals from main-group to the

transition series, especially attractive being the class of

salcyen oxo complexes of titanium exploited previously

by North, Belokon and co-workers [10] so elegantly inasymmetric carbonyl hydrocyanation. Here we describe

the synthesis, characterisation and single crystal X-ray

analysis of some oxo and chloro complexes based on the

(R;R)-N ;N 0-bis(2-hydroxy-3-functionalised-benzylidene)-1,2-diaminocyclohexane ligand, along with studies of

their catalytic potential in the phospho-aldol reaction.

mail to: [email protected]

OP

HOO

R

R

OP

OO

R

R

OP

OO

R

R

O

R'H

O O

POO

HR'R

R

OP

OO

CAT

CAT

R

R

CAT

CATOH

R'

R'CHO

DMHP

DMHP

Scheme 1. Mechanistic outline of the phospho-aldol (PA) reaction.

3494 A. Davis et al. / Inorganica Chimica Acta 357 (2004) 3493–3502

2. Results and discussion

2.1. Syntheses of dichloro and dioxo complexes of

titanium containing (R,R)-N ,N 0-bis(2-hydroxy-3-func-

tionalised-benzylidene)-1,2-diaminocyclohexane ligands

Salcyen ligands were synthesised using existing liter-

ature methods from the condensation reaction of (R;R)-(+)-1,2-diaminocyclohexane-LL-tartrate and respective

salicylaldehyde derivative as described by Jacobsen and

coworkers [11].

Subsequent condensation of the salcyen ligands 1–3

with TiCl4 in CH2Cl2 solution afforded the red [(R;R)-salcyen]TiCl2 complexes 4–6 in excellent yields [10]. Thechloro-substituted derivative 6 has proved somewhat

difficult to purify as a result of its low solubility; con-

sequently, we have focused on the tert-butyl systems 4

and 5. All three chloro derivatives are stable under at-

NN

OH HO

R = H; R' = tBu 1;R = R' = tBu 2R = R' = Cl 3

(ii)

R'

RR

R'R'

R

O

HO R

R'

(i)

R =R =R =

Scheme 2. Syntheses of compounds 1–8: (i) (R;R)-(+)-1,2-diaminocyclohex

mospheric aerobic conditions but, upon treatment with

water (1 equiv.) in the presence of a base such as NEt3, 4

and 5 convert to oxo-bridged dimers (7–8) as reported

previously by North and Belokon (Scheme 2) [10]. In

our hands, we find that chloro derivative 6 does notafford an oxo dimer cleanly whereas even with 7 and 8,

product separation and purification is frequently made

difficult due to the formation of a intermediate dimeric

species, which we identify as a second oxo-bridged dimer

containing residual halogen. In all cases where we have

used homogeneous molecular bases, commonly trieth-

ylamine, we find that this intermediate is invariably

present. However, use of a solid phase, polystyrene-supported piperidine base circumvents this problematic

impurity.

2.2. Single-crystal X-ray diffraction analyses of dichloro

and dioxo complexes of titanium containing(R,R)-N ,N 0-

bis(2-hydroxy-3-functionalised-benzylidene)-1,2-diamino

cyclohexane ligands

Compounds 3, 5, 6 and 7 have been subjected to

single-crystal X-ray diffraction analysis. Molecular pa-

rameters for Schiff base compound 3 [12] are summar-

ised in Table 1 with a molecular view in Fig. 1. The usual

cyclohexyldiamine chair structure with equatorial imino

functions is in evidence as well as intramolecular H-

bonding between O(24)H(88)–N(15) and O(23)H(89)–

N(8) of 1.786 and 1.817 �A, respectively. Titaniumdichloro complexes 5 and 6 are illustrated in Figs. 2 and

3 with respective intramolecular parameters summarised

in Tables 2 and 3. Both molecules display somewhat

distorted octahedral coordination geometries at tita-

nium whilst the salcyen ligands occupy meridinial posi-

tions in both cases as is usual for such ligands [13]. In

NN

O O

NN

O O

TiO

ON

O

N

O

TiO

N

O

N

(iii)

R'

R

R'

RR

R'

Ti Ti

Cl Cl

H; R' = tBu 4; R' = tBu 5 R' = Cl 6

R = H; R' = tBu 7;R = R' = tBu 8

O

2

ane-LL-tartrate, K2CO3; (ii) TiCl4, CH2Cl2; (iii) H2O, Base (see text).

Table 1

Interatomic distances (�A) for 3 with e.s.d.s in parentheses

C(1)–O(23) 1.339(2) C(1)–C(2) 1.401(2)

C(1)–C(6) 1.411(2) C(2)–C(3) 1.382(2)

C(2)–Cl(25) 1.7281(17) C(3)–C(26) 1.386(2)

C(5)–C(26) 1.380(2) C(5)–C(6) 1.394(2)

C(6)–C(7) 1.467(2) C(7)–N(8) 1.272(2)

N(8)–C(9) 1.4724(19) C(9)–C(14) 1.534(2)

C(9)–C(10) 1.535(2) C(10)–C(11) 1.532(2)

C(11)–C(12) 1.521(3) C(12)–C(13) 1.530(2)

C(13)–C(14) 1.537(2) C(14)–N(15) 1.463(2)

N(15)–C(16) 1.280(2) C(16)–C(17) 1.468(2)

C(17)–C(18) 1.393(2) C(17)–C(22) 1.412(2)

C(18)–C(19) 1.388(2) C(19)–C(20) 1.385(2)

C(19)–Cl(27) 1.7416(17) C(20)–C(21) 1.379(2)

O(23)–C(1)–C(2) 119.49(15) O(23)–C(1)–C(6) 122.14(15)

C(2)–C(1)–C(6) 118.37(15) C(3)–C(2)–C(1) 121.31(15)

C(3)–C(2)–Cl(25) 119.98(13) C(1)–C(2)–Cl(25) 118.69(13)

C(2)–C(3)–C(26) 119.20(15) C(26)–C(5)–C(6) 119.72(15)

C(5)–C(6)–C(1) 120.14(15) C(5)–C(6)–C(7) 119.92(15)

C(1)–C(6)–C(7) 119.93(15) N(8)–C(7)–C(6) 121.16(15)

C(7)–N(8)–C(9) 119.04(14) N(8)–C(9)–C(14) 107.91(13)

N(8)–C(9)–C(10) 109.31(13) C(14)–C(9)–C(10) 110.37(13)

C(11)–C(10)–C(9) 110.59(14) C(12)–C(11)–C(10) 111.13(14)

C(11)–C(12)–C(13) 110.90(14) C(12)–C(13)–C(14) 110.94(14)

N(15)–C(14)–C(9) 108.15(13) N(15)–C(14)–C(13) 109.52(13)

C(9)–C(14)–C(13) 110.20(13) C(16)–N(15)–C(14) 118.68(14)

N(15)–C(16)–C(17) 120.88(15) C(18)–C(17)–C(22) 120.07(15)

C(18)–C(17)–C(16) 119.64(15) C(22)–C(17)–C(16) 120.28(14)

C(19)–C(18)–C(17) 119.64(15) C(20)–C(19)–C(18) 121.07(15)

C(20)–C(19)–Cl(27) 119.01(13) C(18)–C(19)–Cl(27) 119.91(13)

C(21)–C(20)–C(19) 119.23(15) C(20)–C(21)–C(22) 121.56(15)

C(20)–C(21)–Cl(28) 119.53(13) C(22)–C(21)–Cl(28) 118.91(13)

O(24)–C(22)–C(21) 119.57(15) O(24)–C(22)–C(17) 122.02(14)

Fig. 1. Molecular structure of 3.

A. Davis et al. / Inorganica Chimica Acta 357 (2004) 3493–3502 3495

each case the Cl–Ti–Cl bond angles of 170� and 169�,respectively, are similar to that reported by North andBelokon for the analogue with an (R;R)-N ;N 0-bis(2-hydroxy-3,5-di-tert-butyl-benzylidene)-1,2-diaminocyclo-

hexane (169�) [13]. Oxo-bridged dimeric compound 7,

(Fig. 4 and Table 4) possesses a similar structure to the

related unsubstituted derivative [10], where each tita-

nium coordination environment is twisted into a squareantiprismatic arrangement with its partner. The princi-

pal difference between 7 and its unsubstituted cousin

appears to be a sterically induced asymmetry in 7 re-

sulting in an increased spacial separation between each




intramolecular ligand separated by the metal bridge as

summarised in Table 5.

2.3. Phospho-aldol catalysis mediated via complexes 7and 8

In two earlier papers, we have reported on the ap-

plications of enantiopure, dimeric salcyan complexes of

aluminium as catalytic precursors for the addition of

dimethyl-H-phosphonate (DMHP) to benzaldehydes

(the phospho-aldol or PA reaction of Scheme 1) [3c,14].In each of these cases, we envisaged that cleavage of an

[Al(l-OH)Al] moiety was an important feature in initi-

ating the reaction shown in Scheme 1. We were, conse-

quently, interested to see how related complexes

containing the same ligand stereochemistry and closely

related [Ti(l-O)Ti] moiety would behave as potential PA

precursor complexes. Intriguingly, neither compound7 or 8 were effective catalytic precursors for the PA

reaction. For example, after treating a mixture of

dimethyl-H-phosphonate (MeO)2P(O)H (DMHP) and

benzaldehyde with oxo dimer 8 (5 mol%) for 24 h, only

14% conversion to product phosphonate (MeO)2P(O)-

CHPh(OH) was achieved and this product was racemic!

Although surprised by this somewhat, there are certain

points which we feel could be relevant to these obser-vations. In order to initiate phospho-aldol catalysis,

DMHP must first be deprotonated and the resulting

phosphito species stabilised by coordination to the metal

centre. This is a process which requires a reagent suffi-

Table 2


Ti(1)–O(1) 1.830(3) Ti(1)–O(1) 1.830(3)

Ti(1)–N(1) 2.140(3) Ti(1)–N(1) 2.140(3)

Ti(1)–Cl(1) 2.3563(10) Ti(1)–Cl(1) 2.3563(10)

O(1)–C(10) 1.336(4) N(1)–C(4) 1.288(5)

N(1)–C(3) 1.480(5) C(1)–C(1) 1.533(8)

C(1)–C(2) 1.534(5) Ti(2)–O(2) 1.827(3)

Ti(2)–O(2) 1.827(3) Ti(2)–N(2) 2.139(3)

Ti(2)–N(2) 2.139(3) Ti(2)–Cl(2) 2.3551(9)

Ti(2)–Cl(2) 2.3551(9) O(2)–C(24) 1.337(5)

N(2)–C(18) 1.288(5) N(2)–C(17) 1.484(5)

O(1)–Ti(1)–O(1) 111.38(17) O(1)–Ti(1)–N(1) 162.40(13)

O(1)–Ti(1)–N(1) 86.12(12) O(1)–Ti(1)–N(1) 86.12(12)

O(1)–Ti(1)–N(1) 162.40(13) N(1)–Ti(1)–N(1) 76.45(17)

O(1)–Ti(1)–Cl(1) 91.64(9) O(1)–Ti(1)–Cl(1) 93.83(9)

N(1)–Ti(1)–Cl(1) 85.17(9) N(1)–Ti(1)–Cl(1) 87.20(9)

O(1)–Ti(1)–Cl(1) 93.83(9) O(1)–Ti(1)–Cl(1) 91.64(9)

N(1)–Ti(1)–Cl(1) 87.20(9) N(1)–Ti(1)–Cl(1) 85.17(9)

Cl(1)–Ti(1)–Cl(1) 170.29(7) C(10)–O(1)–Ti(1) 139.8(3)

C(4)–N(1)–C(3) 120.7(3) C(4)–N(1)–Ti(1) 124.1(3)

C(3)–N(1)–Ti(1) 115.3(2) C(1)–C(1)–C(2) 111.2(3)

O(2)–Ti(2)–O(2) 109.76(17) O(2)–Ti(2)–N(2) 163.34(12)

O(2)–Ti(2)–N(2) 86.73(12) O(2)–Ti(2)–N(2) 86.73(12)

O(2)–Ti(2)–N(2) 163.34(12) N(2)–Ti(2)–N(2) 76.92(17)

O(2)–Ti(2)–Cl(2) 93.55(9) O(2)–Ti(2)–Cl(2) 92.12(9)

N(2)–Ti(2)–Cl(2) 88.05(9) N(2)–Ti(2)–Cl(2) 84.23(9)

O(2)–Ti(2)–Cl(2) 92.12(9) O(2)–Ti(2)–Cl(2) 93.55(9)

N(2)–Ti(2)–Cl(2) 84.23(9) N(2)–Ti(2)–Cl(2) 88.05(9)

Cl(2)–Ti(2)–Cl(2) 170.14(6) C(24)–O(2)–Ti(2) 139.6(3)

C(18)–N(2)–C(17) 120.8(3) C(18)–N(2)–Ti(2) 124.0(3)

C(17)–N(2)–Ti(2) 115.1(2) C(3)–C(2)–C(1) 109.8(3)

N(1)–C(3)–C(3) 107.4(2) N(1)–C(3)–C(2) 116.1(3)

C(3)–C(3)–C(2) 111.1(3) N(1)–C(4)–C(5) 126.6(4)


ciently basic to remove a proton from a species with

calculated pKa of ca. 14 [15]. We envisage that effective

deprotonation of DMHP will be achieved only after

binding of this reagent to the metal centre as illustrated

in Scheme 3. We envisage further that titanium oxo

complexes such as 7 and 8 may behave significantly

differently to their aluminium hydroxo-bridged ana-

logues (Scheme 3) upon which we have reported previ-ously [3c,12]. It is clear that the aluminium system is far

more active as a PA catalyst than the titanium analogue

and we suspect that this is a reflection of the fact that K2

is significantly larger than K1; the result of solvent dis-

placement of the protonated oxygen atom as water for

aluminium. This is not possible in the titanium case as

the hydroxo function must still remain metal-coordi-

nated and hence in the same coordination sphere as thehighly reactive phosphito species (Scheme 3). By the

same token, this lack of a vacant coordination site at

titanium should also preclude carbonyl binding to the

metal centre simultaneous with phosphite generation.

Consequently, we envisage little or no stereocontrol in

the titanium-mediated reaction as both phosphite and

carbonyl are prevented from interacting within an in-

herently chiral coordination geometry. The conclusionto draw is any such PA pre-catalyst must be capable of

(i) deprotonating DMHP and thus generating the active

phosphito species whilst also (ii) enabling both phos-

phito and carbonyl moieties to interact in a cis-orien-

tation within a chiral environment.

3. Experimental

3.1. General

All reactions and manipulations were performed us-

ing standard techniques of synthetic organometallic

chemistry, as reported previously [12]. Commercial

compounds were either recrystallised, chromatographed

on a short column of Brockmann Grade I basic alumina

or distilled under nitrogen prior to use; as appropriate.1H, 13C and 31P NMR spectra were recorded on a

Bruker DPX300 spectrometer (operating frequency

300.1 MHz for 1H and 75.48 MHz for 13C) or Bruker

DRX500 spectrometer (operating frequency 500.13

MHz for 1H) or a Bruker ARX250 spectrometer (op-

erating frequency 101.26 MHz for 31P). All spectra were

recorded at 298 K, chemical shifts ðdÞ are given in parts

per million (ppm) downfield of tetramethylsilane (TMS)at zero for 1H resonances and referenced to the centre

Table 3


C(1)–C(1) 1.519(5) C(1)–C(2) 1.529(4)

C(2)–C(3) 1.523(4) C(3)–N(4) 1.476(3)

C(3)–C(3) 1.540(5) N(4)–C(5) 1.283(4)

N(4)–Ti(13) 2.156(2) C(5)–C(6) 1.454(4)

C(6)–C(7) 1.396(4) C(6)–C(11) 1.419(4)

C(7)–C(8) 1.382(4) C(8)–C(9) 1.374(4)

C(8)–Cl(15) 1.739(3) C(9)–C(10) 1.378(5)

C(10)–C(11) 1.395(4) C(10)–Cl(16) 1.730(3)

C(11)–O(12) 1.321(4) O(12)–Ti(13) 1.856(2)

Ti(13)–O(12) 1.856(2) Ti(13)–N(4) 2.156(2)

Ti(13)–Cl(14) 2.3436(7) Ti(13)–Cl(14) 2.3436(7)

C(17)–C(18) 1.443(10) C(18)–O(19) 1.194(6)

C(18)–C(20) 1.520(8)

C(1)–C(1)–C(2) 110.7(2) C(3)–C(2)–C(1) 109.9(2)

N(4)–C(3)–C(2) 116.1(2) N(4)–C(3)–C(3) 106.62(16)

C(2)–C(3)–C(3) 111.23(18) C(5)–N(4)–C(3) 120.8(2)

C(5)–N(4)–Ti(13) 124.28(19) C(3)–N(4)–Ti(13) 114.68(17)

N(4)–C(5)–C(6) 126.0(3) C(7)–C(6)–C(11) 119.8(3)

C(7)–C(6)–C(5) 118.2(3) C(11)–C(6)–C(5) 121.9(3)

C(8)–C(7)–C(6) 120.1(3) C(9)–C(8)–C(7) 120.6(3)

C(9)–C(8)–Cl(15) 118.6(2) C(7)–C(8)–Cl(15) 120.8(2)

C(8)–C(9)–C(10) 119.8(3) C(9)–C(10)–C(11) 121.8(3)

C(9)–C(10)–Cl(16) 119.6(2) C(11)–C(10)–Cl(16) 118.6(3)

O(12)–C(11)–C(10) 120.7(3) O(12)–C(11)–C(6) 121.6(3)

C(10)–C(11)–C(6) 117.7(3) C(11)–O(12)–Ti(13) 135.48(19)

O(12)–Ti(13)–O(12) 112.79(13) O(12)–Ti(13)–N(4) 85.50(9)

O(12)–Ti(13)–N(4) 161.71(9) O(12)–Ti(13)–N(4) 161.71(9)

O(12)–Ti(13)–N(4) 85.50(9) N(4)–Ti(13)–N(4) 76.22(12)

O(12)–Ti(13)–Cl(14) 94.59(7) O(12)–Ti(13)–Cl(14) 91.47(7)

N(4)–Ti(13)–Cl(14) 86.67(6) N(4)–Ti(13)–Cl(14) 84.70(6)

O(12)–Ti(13)–Cl(14) 91.47(7) O(12)–Ti(13)–Cl(14) 94.59(7)

N(4)–Ti(13)–Cl(14) 84.70(6) N(4)–Ti(13)–Cl(14) 86.67(6)

Cl(14)–Ti(13)–Cl(14) 169.04(5) O(19)–C(18)–C(17) 128.3(8)

O(19)–C(18)–C(20) 118.9(6) C(17)–C(18)–C(20) 112.5(6)



triplet peak of deuterated chloroform (d 77.16 ppm) as

secondary standard for the 13C resonances, using CHCl3d 7.24 ppm as an internal standard, and coupling con-

stants J are given in Hertz (Hz). Multiplicities are re-

ported as singlet (s), doublet (d), triplet (t), quartet (q)

and some combination of these, broad (br) or multiplet

(m). Attribution of the 1H and 13C signals were per-

formed by 1H–1H and 13C–1H correlation techniques.

Table 4


Ti(1)–O(6) 1.843(2) Ti(1)–O(5) 1.875(2)

Ti(1)–O(1) 1.884(2) Ti(1)–O(2) 1.952(2)

Ti(1)–N(2) 2.208(3) Ti(1)–N(1) 2.263(3)

Ti(1)–Ti(2) 2.8122(7) O(1)–C(10) 1.336(3)

N(1)–C(11) 1.287(4) N(1)–C(12) 1.485(4)

C(1)–C(4) 1.531(5) Ti(2)–O(5) 1.822(2)

Ti(2)–O(6) 1.859(2) Ti(2)–O(3) 1.877(2)

Ti(2)–O(4) 1.983(2) Ti(2)–N(4) 2.176(3)

Ti(2)–N(3) 2.279(3) O(2)–C(19) 1.327(4)

N(2)–C(18) 1.282(4) N(2)–C(17) 1.476(4)

C(2)–C(4) 1.531(5) O(3)–C(38) 1.338(4)

N(3)–C(39) 1.283(4) N(3)–C(40) 1.489(4)

C(3)–C(4) 1.535(5) O(4)–C(47) 1.330(4)

N(4)–C(46) 1.283(4) N(4)–C(45) 1.473(4)

C(4)–C(5) 1.537(5) C(5)–C(6) 1.395(5)

C(5)–C(10) 1.424(4) C(6)–C(7) 1.383(5)

C(7)–C(8) 1.376(5) C(8)–C(9) 1.397(5)

C(9)–C(10) 1.395(5) C(9)–C(11) 1.459(4)

O(6)–Ti(1)–O(5) 80.48(9) O(6)–Ti(1)–O(1) 95.61(9)

O(5)–Ti(1)–O(1) 116.15(10) O(6)–Ti(1)–O(2) 88.82(10)

O(5)–Ti(1)–O(2) 148.56(10) O(1)–Ti(1)–O(2) 94.16(9)

O(6)–Ti(1)–N(2) 118.25(9) O(5)–Ti(1)–N(2) 80.87(9)

O(1)–Ti(1)–N(2) 144.85(10) O(2)–Ti(1)–N(2) 78.39(10)

O(6)–Ti(1)–N(1) 157.11(9) O(5)–Ti(1)–N(1) 81.24(9)

O(1)–Ti(1)–N(1) 80.26(9) O(2)–Ti(1)–N(1) 113.86(9)

N(2)–Ti(1)–N(1) 71.95(9) O(6)–Ti(1)–Ti(2) 40.77(7)

O(5)–Ti(1)–Ti(2) 39.77(6) O(1)–Ti(1)–Ti(2) 112.32(7)

O(2)–Ti(1)–Ti(2) 122.50(7) N(2)–Ti(1)–Ti(2) 100.27(7)

N(1)–Ti(1)–Ti(2) 120.18(7) C(10)–O(1)–Ti(1) 143.0(2)

C(11)–N(1)–C(12) 117.2(3) C(11)–N(1)–Ti(1) 125.5(2)

C(12)–N(1)–Ti(1) 117.15(19) O(5)–Ti(2)–O(6) 81.48(9)

O(5)–Ti(2)–O(3) 101.04(10) O(6)–Ti(2)–O(3) 107.95(9)

O(5)–Ti(2)–O(4) 88.90(9) O(6)–Ti(2)–O(4) 155.64(9)

O(3)–Ti(2)–O(4) 95.80(9) O(5)–Ti(2)–N(4) 108.20(10)

O(6)–Ti(2)–N(4) 83.03(10) O(3)–Ti(2)–N(4) 150.07(9)

O(4)–Ti(2)–N(4) 78.80(9) O(5)–Ti(2)–N(3) 164.56(10)

O(6)–Ti(2)–N(3) 83.27(9) O(3)–Ti(2)–N(3) 81.42(9)

O(4)–Ti(2)–N(3) 106.10(9) N(4)–Ti(2)–N(3) 72.13(9)

O(5)–Ti(2)–Ti(1) 41.18(7) O(6)–Ti(2)–Ti(1) 40.35(6)

O(3)–Ti(2)–Ti(1) 110.89(7) O(4)–Ti(2)–Ti(1) 125.63(6)

N(4)–Ti(2)–Ti(1) 95.58(7) N(3)–Ti(2)–Ti(1) 123.62(7)

C(19)–O(2)–Ti(1) 132.8(2) C(18)–N(2)–C(17) 121.2(3)

C(18)–N(2)–Ti(1) 127.0(2) C(17)–N(2)–Ti(1) 111.77(19)

C(38)–O(3)–Ti(2) 137.9(2) C(39)–N(3)–C(40) 119.6(3)

C(39)–N(3)–Ti(2) 123.3(2) C(40)–N(3)–Ti(2) 116.15(18)

C(47)–O(4)–Ti(2) 123.86(18) C(46)–N(4)–C(45) 121.8(3)

C(46)–N(4)–Ti(2) 124.7(2) C(45)–N(4)–Ti(2) 113.49(18)

Table 5

Trans-bridge parameters (�A) for 7 and {[(R;R)-salcyenTi](l-O)}2

Distance (�A) [SalcyenTi(l-O)]2 [Salcyen(tBu)2Ti(l-O)]2 D�A

Ti–Ti 2.79 2.81 0.02

N–N 3.58 N(1)–N(4) 3.87 N(2)–(N4) 0.29

O–O 4.00 O(4)–O(5) 4.25 O(1)–O(3) 0.25

No e.s.d.s are given in the ref for {[(R;R)-salcyenTi](l-O)}2 so have been omitted for 7.


Mass spectra were recorded on a VG Autospec instru-

ment operating in the electron impact (70 eV) or fast

atom bombardment (FAB) modes or a LCTK111 in-

strument operating in the electrospay mode. Infraredspectra were recorded using a MIDAC FT-IR spec-

trometer (4000–600 cm�1) as KBr discs and recorded in

wavenumbers (cm�1) and referenced to the polystyrene

vibration 1601 cm�1. Only principal absorptions are

reported. Melting points were recorded on a BibbyStuart Scientific Melting Point Apparatus SMP3 and

TiO

ON

O

N

O

TiO

N

O

N

TiO

ON

O

N

O

PH

OMeOMe

TiOH

ON

O

N

O

POMe

OMe

AlOH

OHN

O

N

O

AlO

N

O

N

AlOH

ON

O

N

O

PH

OMeOMe

AlTHF

ON

O

N

O

POMe

OMe

THF

K1

K2

THF

+ H2O

Scheme 3. Proposed initiation step for the phospho-aldol reaction mediated by bridged, six-coordinate titanium and aluminium complexes.


recorded uncorrected, in degrees Celsius (�C). Rotation

of reaction mixtures containing based-functionalised

resins was carried out on a Bibby Stuart scientific blood

tube rotator SB1. Thin Layer Chromatography wascarried out using Merck silica TLC plates which were

visualised using ultraviolet light. The intensity data for

determination of the X-ray structures were collected at

125 K using an Enarf-Nonius Kappa CCD diffractom-

eter with Mo K radiation (k ¼ 0:71073 �A). The struc-

tures were solved by direct methods and refined by

full-matrix least-squares on F 2 with SHELXSHELX software.

(R;R)-(+)-1,2-Diaminocyclohexane-LL-tartrate, (opticalrotation ½a�D ¼ þ12; c ¼ 2, H2O; 96% optical purity;

Optical Activity AA 10 polarimeter operating at 589.44

nm; sodium d-line.) and all salcyen ligands were syn-

thesised according to literature methods [11].

3.2. [(R,R)-salcyen-Rn]TiCl2. R¼ tBu, n ¼ 4; R¼ tBu,

n ¼ 2; R¼Cl, n ¼ 4

The following procedure is representative [10]. Tita-

nium tetrachloride (0.230 ml, 0.230 mmol) (1 M solution

in CH2Cl2) was added to (R;R)-[salcyen-tBu2] (0.10 g,

0.230 mmol) in CH2Cl2 (ca. 5 ml) under nitrogen and

stirred at ambient temperature for 4 h. The volatiles

were subsequently removed under reduced pressure to

afford a red precipitate that was extracted via soxhlet

into toluene from solvent from which the title com-pound crystallised as red crystals.

3.2.1. [(R, R)-salcyen-Rn]TiCl2. R¼ tBu, n ¼ 4 (5)MP ca. 330 �C (decomp.). 1H NMR (300 MHz,

CDCl3 300 K): d ¼ 8:29 (s, 2H, C4H, C40H), 7.60 (d, 2H,

J2 ¼ 2:63 Hz, C8H, C80H), 7.33 (d, 2H, J 2 ¼ 2:19 Hz,

C6H, C60H), 4.05 (m, 2H, C3H, C30H), 2.57 (m, 2H,

C1Heq, C10Heq, C2Heq, C20Heq, C1Hax, C10Hax, C2Hax,C20Hax), 2.08 (m, 2H, C1Heq, C10Heq, C2Heq, C20Heq;

C1Hax, C10Hax, C2Hax, C20Hax), 1.52 (s, 18H, C14H,

C140H), 1.40–1.65 (m, 6H, C1Heq, C10Heq, C2Heq, C20Heq;

C1Hax, C10Hax, C2Hax, C20Hax), 1.33 (s, 18H, C12H,

C120H). 13C{1H} NMR (300 MHz, CDCl3, 300 K):

d ¼ 160:90 (C4), 160.16 (C10), 144.97 (C7), 137.20 (C9),

131.57 (C8), 130.40 (C6), 126.14 (C5), 68.06 (C3), 35.94(C11), 34.90 (C13), 31.76 (C12), 30.27 (C14), 28.91 (C1=2),

24.54 (C1=2). m/z (ESþ, 70 eV, 200 �C) 662 [M]þ ¼ 662.3.

Found: C, 66.5; H, 8.0; N, 3.9. C36H52Cl2N2O2Ti.1/2

toluene requires; C, 66.9; H, 8.0; N, 4.0 (0.5 equiv. tol-

uene confirmed by 1H NMR).

3.2.2. [(R,R)-salcyen-Rn]TiCl2. R¼ tBu, n ¼ 2 (4)MP ca. 200 �C (decomp.). IR data (cm�1; KBr):

3550–3400 (broad OH, hydrogen bonded); 3000–2800

(CH3, CH2, CH stretch); 1615, 1579, 1559 (CN stretch).1H NMR (300 MHz, CDCl3, 300 K): d ¼ 8:31 (s, 2H,

C4H, C40H), 7.57 (dd, 2H, J 2 ¼ 7:8 Hz, J 3 ¼ 1:5 Hz,

C6H, C60H), 7.39 (dd, 2H, J 2 ¼ 7:5 Hz, J 3 ¼ 1:5 Hz,

C8H, C80H), 7.01 (t, 2H, J 2 ¼ 7:7 Hz, C7H, C70H), 4.05

(d, 2H, J2 ¼ 8:4 Hz, C3H, C30H), 2.56 (d, 2H, J2 ¼ 12:3Hz, C1H, C10H, C2H, C20H), 2.09 (d, 2H, J 2 ¼ 8:7 Hz,C1H, C10H, C2H, C20H), 1.53 (s, 18 H, C12H, C120H),

1.44 (m, 4H, C1H, C10H, C2H, C20H). 13C{1H} NMR

(300 MHz, CDCl3, 300 K): d ¼ 160:55 (C9, C90), 138.10

(C7, C70 ), 134.10 (C6, C60), 130.10 (C4, C40), 129.01 (C3,

C30), 126.82 (C8, C80 ), 122.548 (C5, C50 ), 68.09 (C10, C100 ),

35.79 (C2, C20), 30.22 (C1, C10), 28.84 (C11, C110 ), 24.49

(C12, C120 ). m/z (EI, 70 eV, 200 �C) 551 [M]þ. Found: C,60.8; H, 6.7; N, 4.9. C28H36Cl2N2O2Ti requires; C, 61.0;H, 6.6; N, 5.1.

3.2.3. [(R,R)-salcyen-Rn]TiCl2. R¼Cl, n ¼ 4 (6)1H NMR (300 MHz, CDCl3 300 K): d ¼ 8:29 (s, 2H,

C4H, C40H), 7.64 (d, 2H, J 2 ¼ 2:4 Hz, C8H, C80H), 7.45

(d, 2H, J2 ¼ 2:6 Hz, C6H, C60H), 4.15 (m, 2H, C3H,

C30H), 2.56 (m, 2H, C1Heq, C10Heq, C2Heq, C20Heq,

C1Hax, C10Hax, C2Hax, C20Hax), 2.33 (m, 2H, C1Heq,C10Heq, C2Heq, C20Heq, C1Hax, C10Hax, C2Hax, C20Hax),

2.12 (m, 4H, C1Heq, C10Heq, C2Heq, C20Heq, C1Hax,

C10Hax, C2Hax, C20Hax).

Table 6

Crystal data and refinement for compounds 3, 5, 6 and 7

3 5 6 7

Formula C27H26Cl4N2O2 C38:50H48Cl2N2O2Ti C13H14Cl3NO2Ti0:50 C56H72N4O6Ti2Formula weight 552.3 689.59 346.55 992.98

Size (mm) 0.46� 0.4� 0.26 0.51� 0.36� 0.28 0.56� 0.23� 0.18 0.44� 0.18� 0.1

Crystal morphology yellow crystal pink/red prism red prism yellow prism

Temperature (K) 150(2) 150(2) 150(2) 150(2)

Wavelength (�A) (Mo Ka) 0.71073 0.71073 0.71073 0.71073

Crystal system monoclinic orthorhombic hexagonal monoclinic

Space group P21 P21212 P6122 P21Unit cell dimensions

a (�A) 8.33930(10) 12.7583(3) 11.885(3) 13.7927(3)

b (�A) 18.3141(3) 12.8800(3) 11.885(3) 10.0211(2)

c (�A) 9.19210(10) 21.6306(6) 37.048(5) 18.7191(5)

a (�) 90 90 90 90

b (�) 107.8770(10) 90 90 90.8780(10)

c (�) 90 90 120 90

Volume (�A3) 1336.10(3) 3554.49(15) 4532.0(17) 2587.01(10)

Z 2 4 12 2

Dcalc (Mg/m3) 1.373 1.289 1.524 1.275

Absorption coefficient (mm�1) 0.47 0.427 0.849 0.362

F (0 0 0) 572 1460 2124 1056

Data collection range (�) 3:096 h6 26 2:466 h6 26 3:396 h6 26 2:736 h6 26

Index ranges �106 h6 10; �226 k6 22;

�116 l6 11

�136 h6 15; �136 k6 15;

�266 l6 26

�146 h6 14; �146 k6 14;

�456 l6 45

�176 h6 17; �126 k6 12;

�226 l6 23

Reflections collected 25 200 24 078 45 394 23 833

Independent reflections (Rint) 5221 (0.0493) 6959 (0.0671) 2976 (0.1064) 9861 (0.0669)

Observed reflections [I > 2rðIÞ] 5079 5691 2649 7675

Absorption correction none none none none

Maximum and minimum

transmission

0.8875 and 0.8127 0.8898 and 0.8117 0.9647 and 0.857

Refinement method full full full full

Data/restraints/parameters 5221/1/325 6959/0/421 2976/0/179 9861/1/625

Goodness of fit 1.032 1.037 1.054 1.009

Final R indices [I > 2rðIÞ] R1 ¼ 0:0262, wR2 ¼ 0:0672 R1 ¼ 0:0583, wR2 ¼ 0:1602 R1 ¼ 0:0366, wR2 ¼ 0:0901 R1 ¼ 0:0443, wR2 ¼ 0:0936

R indices (all data) R1 ¼ 0:0282, wR2 ¼ 0:0681 R1 ¼ 0:073, wR2 ¼ 0:1734 R1 ¼ 0:0448, wR2 ¼ 0:0946 R1 ¼ 0:0696, wR2 ¼ 0:1042

Largest difference peak

and hole (e/�A3 )

0.237 and )0.175 0.697 and )0.394 0.338 and )0.252 0.259 and )0.321

Absorption structure parameter 0.00(3) )0.02(5) )0.03(5) )0.015(19)

A.Davis

etal./Inorganica

Chim

icaActa

357(2004)3493–3502

3501


3.3. {[(R,R)-salcyen-Rn]Ti(l-O)}2. R¼ tBu, n ¼ 2 (7);R¼ tBu, n ¼ 4 (8)

The following procedure is again representative and a

modification of previously published method [10]. Amixture comprising (R;R)-[salcyen-tBu2]TiCl2 (0.05 g,

0.09 mmol), piperidinomethyl polystyrene HL (0.01 g,

0.02 mmol) and water (0.02 ml, 0.12 mmol) was rotated

in THF (2 ml) at room temperature for 24 h. The yellow

solution was subsequently washed with water and dried

over magnesium sulfate. The volatiles were removed

under reduced pressure to afford a yellow solid which

was crystallised from toluene to afford the product ascolourless crystals.

3.3.1. Compound 71H NMR (300 MHz, CDCl3, 300 K): d ¼ 8:21 (s, 2H,

C4H), 7.87 (s, 2H, C16H), 7.42 (d, 2H, J ¼ 6:84 Hz,

C8H), 7.29 (d, 2H, J ¼ 7:69 Hz, C20H), 7.20 (d, 2H,

J ¼ 7:69 Hz C18H), 7.11 (d, 2H, J ¼ 6:84 Hz, C6H), 6.72

(6.74–6.74, m, 4H, C7H and C19H), 4.04 (t, 2H,J ¼ 11:25 Hz, C15H), 2.75 (t, 2H, J ¼ 11:25 Hz, C3H),

2.39 (d, 2H, J ¼ 2:7 Hz, C2eqH), 1.87 (d, 2H, J ¼ 4:05Hz, C1eqH), 1.69 (d, 2H, J ¼ 3:9 Hz C13eqH), 1.58 (m,

2H, C14eqH), 1.47 (s, 18H, C24H), 1.32 (m, 2H, C2axH),

1.15 (m, 2H, C1axH), 1.14 (s, 18H, C12H), 1.05 (m, 2H,

C14axH), 0.83 (m, 2H, C13eqH).

3.3.2. Compound 8Compound 8 was prepared as above, which is a slight

variant on the previously published procedure [10].

Identity was established by 1H and 13C{1H} NMR

spectroscopy upon comparison to that of the previously

reported data [10].

3.3.3. Phospho-aldol catalysis with complexes 7 and 8Dimethyl-H-phophonate (1 mmol) and benzaldehyde

(1mmol) were added to a stirred solution of the catalyst

precursor (x mol%) in dry distilled THF (4 cm3) under

an aerobic atmosphere in a vessel maintained at the

temperature of interest. The mixture was subsequently,

stirred at that temperature for a period of 2–24 h. After

the required reaction time, all volatile materials were

removed from a 1 cm3 aliquot under reduced pressure

and the residue dissolved in CDCl3 and analysed first by31P{1H} NMR spectroscopy to ascertain the extent of

reaction during the period studies and then secondly, re-

analysed in the presence of quinine (4 mmol) from which

enantioselectivities were readily calculated as described

previously [3c].

3.4. Molecular structure determinations of 3, 5, 6 and 7

Data were collected at temperatures of 150(2) K; for

compounds 3, 4, 5, 6 and 7, respectively, on crystals

mounted under oil on a Nonius KappaCCD with Mo

Ka radiation (k ¼ 0:71073 �A). Data reduction was

performed using DENZO and data were corrected for

Lorenztian and polarisation effects but not absorption.

The structure was solved by direct methods with

SHELXSSHELXS-97 and refined with full-matrix least squares onF 2 with SHELXLSHELXL-97. All non-hydrogen atoms were re-

fined anisotropically. Carbon positions within each

phenyl ring were restrained to be coplanar using the

FLAT command of SHELXLSHELXL-97. Hydrogen atoms were

included at calculated positions using a riding refine-

ment. Further details of the data collection and struc-

ture refinement are given in Table 6.

Acknowledgements

We thank the EPSRC for their financial support.

References

[1] See for example N.E. Leadbeater, M. Marco, Chem. Rev. 102

(2002) 3217, and references therein.

[2] See for exampleE.N. Jacobsen, A. Pfaltz, H. Yamamoto (Eds.),

Comprehensive Asymmetric Catalysis, vols. I–III, Springer, Ber-

lin, 1999.

[3] (a) J.P. Duxbury, A. Cawley, M. Thornton-Pett, L. Wantz, J.N.D.

Warne, R. Greatrex, D. Brown, T.P. Kee, Tetrahedron Lett. 40

(1999) 4403;

(b) J.P. Duxbury, J.N.D. Warne, R. Mushtaq, C. Ward, M.

Thornton-Pett, M. Jiang, R. Greatrex, T.P. Kee, Organometallics

19 (2000) 4445;

(c) C.V. Ward, M. Jiang, T.P. Kee, Tetrahedron Lett. 41 (2000)

6181.

[4] D.V. Patel, K. Rielly-Gauvin, D.E. Ryono, Tetrahedron Lett. 31

(1990) 5587.

[5] D. Green, G. Patel, S. Elgendy, J.A. Baban, G. Claeson, V.V.

Kakkar, J. Deadman, Tetrahedron Lett. 34 (1993) 6917.

[6] J.A. Sikorski, M.J. Miller, D.S. Braccolini, D.G. Cleary, S.D.

Corey, J.L. Font, K.J. Gruys, C.Y. Han, K.C. Lin, P.D.

Pansegrau, J.E. Ream, D. Schnur, A. Shah, M.C. Walker,

Phosphorus Sulfur Silicon 76 (1993) 115.

[7] B. Stowasser, K.-H. Budt, L. Jian-Qi, A. Peyman, D. Ruppert,

Tetrahedron Lett. 33 (1992) 6625.

[8] Y.-L. Zhang, Z.-J. Yao, M. Sarmiento, L. Wu, T.R. Burke, Z.-Y.

Zhang, J. Biol. Chem. 275 (2000) 34205.

[9] For a recent review on the phospho-aldol reaction see, T.D.

Nixon, T.P. Kee, Top. Curr. Chem. 223 (2003) 45.

[10] Y.N. Belekon, S. Caveda-Cepas, B. Green, N.S. Ikonnikov, V.N.

Khrustalev, V.S. Larichev, M.A. Moscalenko, M. North, C.

Orizu, V.I. Tararov, M. Tasinazzo, G.I. Timofeeva, L.V. Yashk-

ina, J. Am. Chem. Soc. 121 (1999) 3968.

[11] J.F. Larrow, E.N. Jacobsen, Y. Gao, Y. Hong, X. Nie, C.M.

Zepp, J. Org. Chem. 59 (1994) 1939.

[12] Y.N. Belokon, M. Flego, N.S. Ikonnikov, M. Margarita, M.

North, C. Orizu, V.I. Tararov, M. Tasinazzo, J. Chem. Soc.,

Perkin Trans. 1 (1997) 1293.

[13] V.I. Tararov, D.E. Hibbs, M.B. Hursthouse, N.S. Ikonnikov,

K.M.A. Malik, M. North, C. Orizu, Y.N. Belokon, Chem.

Commun. (1998) 387.

[14] T.D. Nixon, S. Dalgarno, C.V. Ward, M. Jiang, M.A. Halcrow,

C.A. Kilner, M. Thornton-Pett, T.P. Kee, C. R. Chim., in press.

[15] J.P. Guthrie, Can. J. Chem. 57 (1979) 236.

complexes containing the...

Documents