Stereomanipulation of (η5-1-arylcyclohexadienyl)iron complexes

FULL PAPER

DOI: 10.1002/ejoc.200700919

Stereomanipulation of (η⁵-1-Arylcyclohexadienyl)iron Complexes

Christopher E. Anson,^[a][‡]Andrei V. Malkov,^[a][‡‡]Caroline Roe,^[a]Elizabeth J. Sandoe,^[a]and

G. Richard Stephenson*^[a]

Keywords: Iron / Cations / X-ray structure characterisation / Nucleophilic addition / Regioselectivity

A crystallographic investigation comparing five 1-aryl-sub-

stituted tricarbonyl[(1–5-η)-cyclohexadienyl]iron(1+) salts

demonstrates that introducing additional electron density on

the aromatic ring increases π overlap between the arene and

the cyclohexadienyl ligand, thus flattening the structures suf-

ficiently to make available a conformation in which nucleo-

philes can approach the site of substitution, despite the steric

blockade of o-benzyl substituents.

Germany, 2008)

Introduction

The 100% stereoselectivity available in the reactions of

chiral (cyclohexadienyl)iron complexes^[1]offers a powerful

strategy for asymmetric synthesis,^[2]especially in reaction

sequences that make multiple use of the organoiron group.

Consequently, the use of organoiron complexes in synthe-

sis^[3]has become established as a valuable and effective ap-

proach to promote bond formation and stereocontrol. We

have recently described^[4]a generally applicable methodol-

ogy to gain efficient access to both (1- and 2-arylcyclo-

hexadienyl)iron electrophilic carbonylmetal complexes,

which offer a convenient “C₁₂building block strategy”^[5]for

use in alkaloid synthesis. This is illustrated in Figure 1 with

examples which make iterative use of the metal in two dif-

ferent ways. When the two C–C bond-formation steps take

place at the same position in the multihapto ligand, this is

referred to as a “1,1 strategy”^[6](the product of the 1,1 se-

quence has a single stereogenic quaternary centre, as for

example in target molecules 1^[7]and 4^[8]). When the reac-

tions take place at adjacent positions (a “1,2 strategy”^[6])

two adjacent stereogenic centres are formed (this is illus-

trated in our work towards target molecules 2^[10]and 5^[11]).

In these synthetic routes, the 1-arylcyclohexadienyl ligand

in 3^[4]corresponds to a central portion of the target struc-

ture.

Figure 1. Examples of alkaloid target molecules to illustrate a gene-

ral organoiron-mediated approach that makes multiple use of the

metal: a “C₁₂building block” based on an arylcyclohexadienyl

complex corresponds to the central pair of six-membered rings in

structures of this type (the requirements for iterative^[9]metal-medi-

ated bond formation are indicated as 1,1 or 1,2^[6,7]by the dashed

circles).

Figure 2 gives an example of a more advanced target

structure that combines iterative 1,1 and 1,2 bond-forma-

tion strategies, and like many alkaloid targets (e.g. lycoram-

ine,^[12]or hippeastrine^[10]and lycorine^[11]shown in Figure 1)

the structure also contains an additional challenge. The aryl

substituents in these cases bear a benzylic carbon atom ad-

jacent to their attachment to the (cyclohexadienyl)iron com-

plex. Often in alkaloid synthesis, this type of feature is in-

troduced quite late in the synthetic route (e.g. by a Pictet–

Spengler reaction^[13]), but to ensure a high degree of conver-

[a] Wolfson Materials and Catalysis Centre, School of Chemical

Sciences and Pharmacy, University of East Anglia

Norwich, NR4 7TJ, UK

Fax: +44-1603-592003

E-Mail: g.r.stephenson@uea.ac.uk

[‡] Present address: Institut für Anorganische Chemie der Uni-

versität Karlsruhe,

Engesserstrasse Geb. 30.45, 76128 Karlsruhe, Germany

[‡‡] Present address: WestChem, Department of Chemistry, Joseph

Black Building, University of Glasgow,

Glasgow, G12 8QQ, UK

196

Eur. J. Org. Chem. 2008, 196–213

Stereomanipulation of (η⁵-1-Arylcyclohexadienyl)iron Complexes

Figure 2. Example of a retrosynthetic analysis for pretazettine combining an iterative sequence of three metal-mediated bond-formation

steps (and using both 1,1 and 1,2 patterns^[6,7]). For a convergent approach that includes the additional benzylic carbon atom [see also

hippeastrine and lycorine (Figure 1)] there is a need for ipso addition adjacent to the aryl group in a “C₁₃building block”.

gence in our synthetic strategy (Figure 2) we have set our- formation. When all the substituents on the dienyl complex

selves the more difficult task of bringing this ortho substitu- are mutually reinforcing, the use of the organoiron electro-

ent in at an early stage of the route. Thus ideally, the “C₁₂” philes is now well understood. The introduction of the aro-

building blocks (Figure 1) that suit O-methyljoubertiam- matic group leaves the C(1)–OMe substituent correctly

ine^[7]and the Ackland–Pinhey–Martin intermediate for ly- placed as a leaving group to facilitate the return to the η⁵-

coramine,^[14]develop into a “C₁₃” central building block cyclohexadienyl form of the complex. Acids,^[18]tri-

strategy (Figure 2) corresponding to a [(1–5-η)-1-(o-substi- phenylcarbenium ion reagents,^[19]and trialkyloxonium ion

tuted-aryl)cyclohexadienyl]iron complex, for the more reagents^[20]are all suitable to promote this reaction, and

highly substituted target structures. To establish this chem- our alkoxide abstraction approach overcomes the problem

istry we have now carried out a detailed study of the regi- that conventional hydride abstraction is usually^[21]blocked

ocontrol properties of this class of structures, on the basis after the first nucleophile addition step. A considerable ef-

of an extensive X-ray crystallographic investigation of the fort^[5,22]has been made to understand the step that intro-

effects of substituents on the orientation of the aryl group duces the aryl group, and the reaction has been shown to

relative to the plane of the haptyl section of the (cyclohexa- be compatible with flanking substituents such as OMe and

dienyl)iron complex. These results are reported in this pa- CH₂OMe.

per.^[15]The requirement for success is the presence of suit-

able electron-donating substituents on the aromatic ring,

which is the case for most of the typical biologically

active^[16]natural target structures of this type.

For the “C₁₃building block” strategy summarised in Fig-

ure 2, it would be useful to have a formyl group as the

flanking substituent, to allow later elaboration at this posi-

tion by reductive amination. This has now been addressed

by addition of o-LiC₆H₄CH(-OCH₂CH₂O-) (11)^[23]to 8,

followed by reaction with triphenylcarbenium tetrafluo-

roborate which afforded the o-benzaldehyde derivative 12

as the BF₄^–salt 12b. Use of TFA and ammonium hexafluo-

Results and Discussion

General Access to 4-Methoxy-Substituted (1-Arylcyclo-

hexadienyl)iron(1+) Complexes

–

rophosphate gave the corresponding PF₆salt 12a. The

BF₄^–salt 12b was crystallized from acetonitrile/diethyl ether

The extension of our general method^[4,8]for the prepara- to obtain crystals suitable for X-ray analysis. To provide a

tion of (1-arylcyclohexadienyl)iron complexes to examples comparison, an example was chosen with a protected donor

with a methoxy directing group on the dienyl complex has substituent in the place of the formyl group in 12. The re-

already been described.^[4,5,7,12]The parent example,^[5]tri- quired aryl nucleophile was prepared from 2-bromophenol

carbonyl[(1–5-η)-1-phenyl-4-(methoxycyclohexadienyl)]- by allylation and conversion into the organolithium reagent

iron(1+) hexafluorophosphate(1–) salt (10) has been ob- 13. Reaction of 13 with 8, and demethoxylation with HPF₆

tained from tricarbonyl[(1–5-η)-1,4-(dimethoxycyclohexadi- in acetic anhydride gave the expected product 14 which was

enyl)]iron(1+) hexafluorophosphate(1–) (8) by reaction with crystallized from acetone/diethyl ether for X-ray analysis. A

phenyllithium and demethoxylation, and the method has more hindered doubly flanked example with an o-CH₂OMe

been successfully employed in our synthesis of O-methyl- group was also prepared. Initially, directed metallation^[24]

joubertiamine (1)^[7]and to prepare a more highly substi- of 3-methoxybenzyl methyl ether was examined as a means

tuted example with a methylenedioxy group correctly to produce the required organolithium reagent, but this

placed^[4]on the aromatic ring for the target molecule crin- procedure proved difficult (even trapping with BrCF₂–

ine. The success of this approach (Figure 2) stems from the CF₂Br gave none of the expected 2-bromo product) and

initial combination of the ipso-directing C(1)–OMe group would also produce an organolithium reagent of a different

and the ω-directing C(4)–OMe group in a mutually rein- type to that made by the lithium/bromine exchange reac-

forcing fashion^[17]to ensure nucleophile addition at C(1) of tion, so an alternative was developed. Metallation of 3-

8. We now report the successful use of this strategy with a methoxybenzyl alcohol with 2 equiv. of n-butyllithium was

wide range of aryllithium reagents, including examples with followed by quenching with BrCF₂–CF₂Br to give the 2-

significant steric hindrance around the site of C–C bond bromo derivative, which was then converted into the methyl

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197

C. E. Anson, A. V. Malkov, C. Roe, E. J. Sandoe, G. R. Stephenson

Table 1. Preparation of (1-arylcyclohexadienyl)iron complexes and the regioselectivity of their reactions with nucleophiles.

FULL PAPER

Entry Substitution pattern

Ar

Preparation of the η⁵electrophile

Step (I) Yield (%) Step (II)

Reaction with nucleophiles

Yield (%) Step (III) Yield ipso^[a](%) Yield ω^[a](%)

–

1

2

3

4

5

C₆H₅

2-(MeOCH₂)C₆H₄

2-MeOC₆H₄

2-(H₂C=CHCH₂O)C₆H₄

2-(OHC)C₆H₄

(i)^[b]

(iv)

(i)

70^[b]

58^[b]

67^[b]

53

(ii) X– = PF₆

98^[b]

80^[b]

82

69/70

73

(iii)

82

0

80

79

0

71

0

–

(ii) X^–= PF₆

–

(v) X^–= PF₆

(iii)

0

–

87^[c]

(ii)/(v) X^–= PF₆

(iii)^[d]

72^[e]

–

(vi) X^–= BF₄

–

6

7

2-(MeOCH₂)-6-MeOC₆H₃

2-(MeOCH₂)-4,5-(MeO)₂C₆H₂(iv)

(iv)

66^[f]

46

(vii) X^–= PF₆

64

(iii)

0

61

84^[g]

16^[h]

(vii) X^–= PF₆^–/K₂CO₃65

[a] ipso/ω (see ref.^[4]) with the aryl group as the reference substituent. [b] See ref.^[5][c] 2:1 mixture of OMe and OH. [d] X^–= PF₆. [e] A

second molecule of methyl 2-cyanoacetate added to the aldehyde. [f] Tricarbonyl[(2–5-η)-4-methoxycyclohexadien-1-one]iron also formed

(37% yield). [g] 4,6Ј-Dimethoxy-2Ј-(methoxymethyl)biphenyl also formed (4% yield). [h] 4,4Ј,5Ј-Trimethoxy-2Ј-(methoxymethyl)biphenyl

also formed (9% yield). Reaction conditions: (i): CH₂Cl₂, –78 °C; (ii): TFA, then NH₄PF₆, 0 °C; (iii): NaCH(CO₂Me)CN, THF, 0 °C;

(iv): CH₂Cl₂, –100 °C; (v): HPF₆, Ac₂O, 0 °C; (vii) Ph₃C⁺X^–, CH₂Cl₂, 0 °C.

–

Scheme 1. Prepartion of (1-arylcyclohexadienyl)iron complexes.

ether. Formation of the organolithium reagent 15 from this into the salt 18 by the Ph₃CPF₆method. Details of these

ether by our usual procedure, reaction with 8 and demeth- synthetic routes are presented in Table 1 (columns 2–6) and

oxylation using Ph₃CPF₆, afforded the η⁵salt 16. The cor- Scheme 1.

responding benzyl methyl ether 18 with OMe groups at the

meta and para positions was also prepared. This lacks the

flanking substituent present in 16, and so provides a more

X-ray Crystallographic Investigation of (1-Arylcyclohexa-

dienyl)iron(1+) Complexes

direct comparison with the simple o-benzyl methyl ether

case described in our earlier work.^[5]The required arylli-

thium reagent 17 is available by standard methods^[25](re-

Selected bond lengths from the structures of 10, 12b, 14,

duction, ether formation, and lithium/bromine exchange) 16 and 18 are compared in Table 2. To quantify the degree

from 2-bromo-4,5-dimethoxybenzaldehyde, and reacted of rotation of the aryl ligand about the C(1)–C(8) bond

with 8 to afford the expected adduct which was converted relative to the plane of the dienyl unit, we determined the

Table 2. Selected bond lengths [Å] for the dienyliron portion of the electrophiles.

Fe–C(1)

Fe–C(2)

Fe–C(3)

Fe–C(4)

Fe–C(5)

C(1)–C(2)

C(2)–C(3)

C(3)–C(4)

C(4)–C(5)

C(4)–O

10^[a]

10^[b]

12^[a]

12^[b]

14

2.233(2)

2.249 2)

2.225(3)

2.234(3)

2.304(2)

2.303(4)

2.313(3)

2.123(3)

2.125(3)

2.152(4)

2.126(3)

2.118(2)

2.326(5)

2.136(3)

2.158

2.094(2)

2.095(3)

2.080(3)

2.083(3)

2.100(2)

2.093(4)

2.093(3)

2.091

2.204(2)

2.207(2)

2.190(3)

2.188(3)

2.185(2)

2.171(3)

2.181(3)

2.189

2.168(2)

2.171(3)

2.149(3)

2.148(3)

2.134(2)

2.128(4)

2.139(3)

2.148

1.411(3)

1.405(4)

1.389(5)

1.385(5)

1.397(3)

1.417(5)

1.403(4)

1.401

1.413(3)

1.412(4)

1.407(5)

1.410(5)

1.422(3)

1.426(6)

1.422(4)

1.416

1.422(3)

1.418(4)

1.408(5)

1.411(5)

1.412(3)

1.417(5)

1.412(4)

1.414

1.405(3)

1.397(4)

1.390(5)

1.397(5)

1.403(3)

1.404(5)

1.409(4)

1.401

1.336(3)

1.337(3)

1.339(4)

1.331(4)

1.340(3)

1.346(4)

1.341(4)

1.339

16

18

Mean 2.266

[a] Molecule 1. [b] Molecule 2 in asymmetric unit.

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Stereomanipulation of (η⁵-1-Arylcyclohexadienyl)iron Complexes

dihedral angle between the two planes. A positive dihedral

angle indicates that, for the enantiomer shown (which is

consistent for all structures) the aryl moiety is rotated antic-

lockwise about the C(1)–C(8) bond. This corresponds to the

side of the aryl ring that is cis to the methylene carbon atom

C(6) on the cyclohexadienyl ring being rotated up and away

from the iron centre. Because the cyclohexadienyl ring itself

is not flat, the flattest overall structure for the arylcyclo-

hexadienyl moiety is obtained with a dihedral angle of ca.

+20°.

The X-ray crystallographic study of this series of aryl-

substituted electrophiles began with an examination of the

simplest of the (1-arylcyclohexadienyl)iron complexes (10),

which was available from our earlier work.^[5]This has only

a phenyl substituent opposite to the 4-methoxy-directing

group on the dienyl ligand. Compound 10 crystallises with

two independent molecules in the asymmetric unit, which

have rather similar structures. The cyclohexadienyl ring was

found to have the expected form (Figure 3), with the satu-

rated CH₂position bent away from the iron atom. One of

the three carbonyl ligands lies directly below the CH₂

group, placing the other two CO groups in positions that

eclipse the C(2) and C(4) inner sp²carbon atoms on the

dienyl section. The five carbon atoms of each η⁵-dienyliron

moiety are coplanar to within 0.055 Å, and the aromatic

rings are rotated out of this plane, with dihedral angles of

+26.99(7)° and +14.01(10)° for molecules 1 and 2, respec-

tively. From Figure 3 it is clear that positive angles of this

magnitude give an overall conformation that is the most

open in terms of access to C(1) of the dienyl group.

With the allyloxy donor substituent installed at the ortho

position of the aromatic ring in 14, the general form of the

structure remains the same (Figure 4), but the aromatic ring

is now twisted further away from the plane of the dienyl

carbon atoms at +36.15(7)°. In the solid state, the arene

takes up a conformation in which the ortho substituent lies

below the plane, and the unsubstituted CH–CH edge is

roughly aligned with the CH₂group of the cyclohexadienyl

ligand, now lying slightly above it as a consequence of the

bulk of the OCH₂CH=CH₂group below the ring. The al-

lyloxy oxygen atom is perhaps interacting with the carbon

atom of one of the carbonyl ligands, because O(2)···C(22)

at 2.914 Å is less than the sum of the van der Waals radii.

Although any such interaction would be very weak, it might

be sufficient to stabilize the observed conformation com-

pared to the alternative with the allyloxy group above the

dienyl plane.

Switching from an electron-donating substituent to an

electron-withdrawing formyl group at the ortho position in

12b proved to have a large effect on the solid-state structure

(Figure 5). There are again two independent molecules in

the asymmetric unit, but in both cases the substituted side

of the aromatic ring now lies above the plane, with dihedral

angles of +78.38° and 85.18° for molecules 1 and 2, respec-

tively. The two planes have now become much closer to per-

Figure 3. ORTEP and space-filling representations of molecules 1

(top) and 2 (bottom) in the X-ray structure of tricarbonyl[(1–5-η)-

4-methoxy-1-phenylcyclohexadienyl]iron hexafluorophosphate (10).

pendicular. In molecule 1, the oxygen atom [O(2)] of the the sum of the van der Waals radii for carbon and oxygen

formyl group lies directly above the terminus of the dienyl atoms (3.25 Å) suggesting a significant interaction between

system; the C(1)···O(2) separation of 2.768 Å is well within the two atoms. The formyl group is disordered in the second

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C. E. Anson, A. V. Malkov, C. Roe, E. J. Sandoe, G. R. Stephenson

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Figure 4. ORTEP and space-filling representations of the X-ray

structure of tricarbonyl[(1–5-η)-1-(2Ј-allyloxyphenyl)-4-methoxycy-

clohexadienyl]iron hexafluorophosphate (14).

molecule, between the equivalent conformation to that in

molecule 1 and the conformation resulting from a 180° ro-

tation about the aryl–formyl C–C bond [so that the formyl

oxygen atom is now directed away from the dienyl group,

and the formyl hydrogen atom now above C(1) of the dienyl

group]. These two conformers are present in a ratio of

0.45:0.55, so the conformation with the formyl oxygen atom

above C(1) predominates in the solid state in a ratio of

2.6:1.

In the crystal structure of 16 (Figure 6), the aryl ring is

again almost perpendicular to the dienyl plane, with the

dihedral angle now +95.23°, as expected because of the ste-

ric effects of the pair of flanking ortho substituents. The

methoxy group is again located below the cyclohexadienyl

ring on the side bearing the Fe(CO)₃group. However, com-

pared to 14, where the methoxy oxygen atom occupied the

space between a carbonyl ligand and the dienyl carbon

atom C(2), in 16 it is forced down into the region of the

tripod of the CO ligands. There must be a weak but signifi-

cant interaction between the lone pairs on the methoxy oxy-

gen atom and the rather electron-deficient carbon atoms

Figure 5. ORTEP and space-filling representations of molecules 1

(top) and 2 (bottom) of tricarbonyl[(1–5-η)-1-(2Ј-formylphenyl)-4-

methoxycyclohexadienyl]iron tetrafluoroborate (12b).

200

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Stereomanipulation of (η⁵-1-Arylcyclohexadienyl)iron Complexes

of the carbonyl ligands, because the distances O(2)···C(21) dicating a consistent degree of electron donation from the

(2.766 Å) and O(2)···C(22) (2.888 Å) are well within the OMe group to the cationic metal complex.

sum of the van der Waals radii. It should be noted that the

The data for the C(4)–O(1) bond length, which also

opposite conformation of the aryl ring, with the meth- shows virtually no variation in length, supports this conclu-

oxymethyl group now below the dienyl plane, is sterically sion, and at a mean length of 1.34 Å is short enough to

impossible, as the two methylene hydrogen atoms would suggest that donation of electron density to the metal com-

make totally unrealistic close approaches to the carbonyl plex is significant. This is commonly accepted as the expla-

ligands.

nation^[25,26]for the ω-directing properties of the OMe

group. As is to be expected in cases where the lone pairs

interact with the π system, and CH₃–O bond is aligned

close to the plane of the dienyl carbon atoms, and the CH₃–

O–C(4) bond angle is fairly constant at about 118°, consis-

tent with sp²hybridization at the oxygen atom. The varia-

tion of the orientation of the MeO group relative to C(3)

is ascribed to random variation in crystal packing effects.

However, the consistency of the C(4)–C(5) and C(4)–O(1)

bond lengths and the CH₃–O–C(4) bond angle all support

the view that there is a similar degree of donation of elec-

tron density from the oxygen atom across the series, regard-

less of the orientation and substitution pattern of the aro-

matic ring.

It follows from this, that differences in the additions of

nucleophiles to these structures (see below) must arise from

the effect of the aromatic ligand itself on the dienyl system.

Despite the long Fe–C(1) separation, the C(1)–C(2) bond

lengths remain quite short at about 1.4 Å. This shows that

the relative weakening of the bonding to the iron atom at

C(1) is not pre-distorting the starting material to react with

nucleophiles at this position, as to approach the neutral η⁴

structure, the C(1)–C(2) bond in the starting material will

lengthen to a C–C single bond as the Fe–C(1) bond breaks

and the bond forms between C(1) and the nucleophile. This

type of pre-distortion towards the transition state has been

proposed^[27]in some cases to account for the regioselectivity

of nucleophile addition to electrophilic π complexes. De-

spite these pronounced similarities, besides the clear

changes in the dihedral angle (Figures 3 to 7), there are also

significant variations in the bond lengths between C(1) and

the aryl substituent in these structures. This is discussed be-

low, and holds the key to understanding and manipulating

the observed patterns of regioselectivity in the reactions

with nucleophiles. A further systematic discrepancy can be

seen in the bond-length data for complex 16 which has un-

usually long C(1)–C(2) and C(2)–C(3) bonds. The Fe–C(2)

bond is also much longer (2.32 Å) than all the others (mean

2.18 Å). These effects are ascribed to distortion of the li-

Figure 6. ORTEP and space-filling representations of the X-ray

structure of tricarbonyl[(1–5-η)-1-(2Ј-methoxymethy-6Ј-meth-

oxylphenyl)-4-methoxycyclohexadienyl]iron hexafluorophosphate

(16). For clarity, only the major conformers of disordered methoxy

groups are shown.

The bonding within the dienyliron sections shows a high gand by steric effects caused by the presence of the flanking

degree of consistency across this set of five structures OMe group beside the iron atom in 16. Indeed, the mean

(Table 2), with bond lengths between the iron atom and the Fe–C distance calculated from bond lengths of the dienyli-

five carbon atoms varying only slightly. C(1), which carries ron system in 16 is 2.20 Å, significantly longer than the cor-

the aryl substituent, has the longest Fe–C bond length in responding values (2.16–2.18 Å) in the other four struc-

each case (mean Fe–C distance 2.27 Å). The distance to the tures. The consistency of these dimensions in 10, 12, 14 and

other end of the dienyl ligand is significantly shorter in each 18 shows that the transfer of electron density from the arene

case (mean Fe–C distance 2.15 Å), showing that the Fe- to the dienyliron complex (see Discussion section) has little

(CO)₃group is displaced slightly towards the unsubstituted influence on the position of the iron atom relative to the

end of the ligand. The distance between the iron atom and plane of the dienyl ligand. In contrast, steric effects from

the carbon atom bearing the OMe group [C(4)] also shows aryl substituents on the same side of the ligand as the

relatively little variation (0.04 Å between the extremes), in- Fe(CO)₃group have a large effect. Conversely, because

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Figure 7. ORTEP and space-filling representations of the X-ray structure of tricarbonyl{(1–5-η)-1-[4Ј,5Ј-dimethoxy-2Ј-(methoxymethyl)-

phenyl]-4-methoxycyclohexadienyl}iron hexafluorophosphate (18).

structure 14 fits the normal pattern, it can be concluded character. Despite the benzylic ortho substituent present in

that, despite its proximity, the allyloxy substituent has no 18, a small dihedral angle and relatively short central bond

substantial steric interaction with the Fe(CO)₃group in the have been observed in the solid state. This is consistent with

conformation adopted in the solid state.

substantial π overlap in the centre of the structure. This π

Table 3 presents a comparison of trends in dihedral overlap would be promoted by transfer of electron density

angles and the lengths of the central carbon–carbon bond from the electron-rich π system of the arene to the cationic

that joins the arene and the dienyliron moiety [C(1)–C(8)]. dienyliron compex. On this basis, it can be expected that

Large dihedral angles tend to correspond to structures with increasing the electron density on the arene will increase the

long central bonds. The shorter C(1)–C(8) distances in the extent of π overlap, and so flatten the structure, reducing

flatter structures are consistent with greater double-bond the dihedral angle. If this factor is also significant in solu-

Table 3. Central C–C bond lengths and dihedral angles for structures 10, 12, 14, 16, and 18.

Substitution pattern on aromatic ring

C(1)–C(8)

[Å]

Dihedral angle^[a]

[°]

Directing effect

R²

R⁴

R⁵

R⁶

16

CH₂OMe

CHO

CH₂OMe

H

OMe

H

OMe

H

OMe

H

1.500(5)

1.493(4)

1.490(4)

1.489(3)

1.488(4)

1.484(3)

95.93(13)^[b]

85.18(13)^[b]

78.38(15)^[b]

20.88(16)^[d]

26.99(7)^[b]

14.01(10)^[b]

36.15(7)^[b]

ω

12^[c]

18

ipso Ͼ ω^[e]

ipso

10^[c]

14

OCH₂CH=CH₂

ipso

[a] Positive values correspond to anticlockwise rotation of the aryl ring out of the dienyl plane, so that the side of the aryl ring cis to the

methylene atom C(6) is rotated away from the iron atom. [b] Positive dihedral angle. [c] Data from two independent molecules in the unit

cell. [d] Negative dihedral angle. [e] ipso/ω = 4:1.

202

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Stereomanipulation of (η⁵-1-Arylcyclohexadienyl)iron Complexes

tion, the change in conformation could account for the im- clohexadienyl)iron system, fits this conclusion, as the aryl

proved access to ipso addition products from reactions with group directed most nucleophiles to the ω position. Stabi-

nucleophiles (see below).

lized enolate nucleophiles such as malonate enolates, how-

ever, were found also to give small amounts of ipso prod-

ucts, indicating that the ipso pathway was accessible to nu-

cleophiles. This effect has been shown to vary with the na-

ture of para substituents on the aryl group (ipso pathway:

CF₃Ͼ H Ͼ OMe^[4]).

Regiocontrol in the Reactions of 1-Aryl(cyclohexadienyl)-

iron(1+) Complexes with Nucleophiles

The natural directing effect of aryl substituents on metal-

The key to the application of (1-arylcyclohexadienyl)iron

bound π systems has been a subject of considerable investi- complexes in the synthesis of structures with the quaternary

gation, because fundamental properties of this type must centres that are produced by a 1,1 addition sequence, is the

be properly understood to support efforts to apply these inclusion^[7,12,26,40]of an OMe group at the internal position

complexes in organic synthesis. A phenyl substituent at the on the cyclohexadienyl ligand opposite to the aryl group,

terminus of the haptyl section of the ligand has been thus reducing the electrophilicity of the complex.^[41]This

studied in η²-alkene,^[28]η³-allyl,^[29]η⁴-diene^[30]and η⁵-di- deactivation is most profound adjacent to the OMe group

enyl^[4,9,31]complexes, and regiocontrol is typically consis- (α to the OMe group;^[26]ω to the aryl group) switching off

tent with an ω-directing effect. There are exceptions, how- nucleophile addition ω to the aryl group and promoting the

ever, as in the η³case, steric blocking by methyl groups sterically accessible but normally disfavoured pathway for

at the ω position allows the ipso pathway to proceed.^[32]ipso-nucleophile addition next to the aryl group, which now

Palladium-catalyzed allylic substitution is the most widely dominates the nucleophile-addition process. This has been

studied case of nucleophile addition to η³complexes, which used successfully, even with the more difficult^[4]p-meth-

are electrophilic intermediates in the catalytic cycle, and oxyaryl system,^[7]and the methylenedioxy-substituted

with a phenyl group at C(1) of the allyl ligand, substituted case^[4]needed to access crinine, to effect malonate and ma-

styrenes are produced.^[33]These result from ω addition rela- lononitrile addition at the site bearing the aryl group. The

tive to the Ph group. This outcome has been shown^[34]to crystallographic study of 10 (see above) has shown that an

hold true irrespective of the position of the leaving group accessible conformation for the molecule has the aryl group

in the allyl substrate. In catalytic systems employing other slanted to one side, leaving clear the access for the nucleo-

metals, however, the control effect is less clear, and exam- phile at C(1).

ples of either ipso or ω addition can be found.^[35]Similarly

To explore the regiocontrol of nucleophile addition

in the η⁴case, although BuLi, PhLi, LiCMe₂CO₂Et, LiC- (Table 1; columns 7–9), we have chosen as a test nucleophile

Me₂CN, gave only ω products, reaction with benzyllithium a cyanoacetate-derived reagent of the type used in our syn-

followed the ipso and ω pathways with almost equal ease.^[30]thetic applications (Figure 1; see also refs.^[4,5,7,8]) to gain ac-

Results obtained with η⁵-pentadienyliron complexes are cess to the CH₂CH₂NMe and CH₂CH₂NMe₂side-chains

further complicated by the possibility of formation of (Z)- that are present in the natural product targets O-methyljou-

or (E)-alkenes in the products, indicating two different bertiamine and lycoramine. Reaction of 10 with NaCH-

mechanisms for nucleophile addition. The clearest results (CO₂Me)CN in THF at 0 °C (Scheme 2) afforded the ex-

have been obtained with PPh₃as the nucleophile,^[36,37]giv- pected^[42]product 19 in 82% yield (Table 1, Entry 1). The

ing rise to the ω-addition product with the (Z) relative good yield indicates that there is efficient access for nucleo-

stereochemistry expected for reaction with the cisoid form philes at the atom that bears the aryl group, and this reac-

of the dienyl complex. This reaction, however, has been tion is interpreted as proceeding by a reactive conformation

shown^[31]to be reversible, and so may operate under of the electrophile that resembles the conformation defined

thermodynamic control. Fortunately, kinetic control can be in the structural study (Figure 3). The simple methyl benzyl

assessed from the results reported for hydride delivery from ether system 20 (Table 1, Entry 2) was available from our

NaBH₃CN. Both pathways were observed, with ipso and ω earlier work,^[5]and offered a case where the entire “C₁₃

products isolated in a ratio of 2:5; thus, in this case the ω building block” for the more advanced targets was present.

pathway predominates.^[38]In contrast, the use of allylsilane Reaction with NaCH(CO₂Me)CN was examined, but gave

or furan as the nucleophile has been found to give (E) prod- the opposite regiochemical outcome, with the only product

ucts according to the ipso-addition pathway to the transoid 25 (71% yield) corresponding to addition of the nucleophile

pentadienyliron complex.^[36]An ipso product has also been at the end of the dienyl ligand furthest from the benzyl

obtained with LiCH(CO₂Me)₂as the nucleophile,^[37,39]and ether substituent. Compared to the unsubstituted phenyl

with the more bulky reagent LiCMe(CO₂Me)₂, a mixture group, the 2Ј-(methoxymethyl)aryl group proved to be too

of ipso-, ω- and internal addition products is formed.^[37]strongly ω-directing and easily overcame the opposed regi-

Thus, in general it is clear that although the ω pathway is odirecting effect of the OMe group on the dienyl ligand.

usually preferred, both ipso- and ω-addition pathways are The same experiment was performed with the 2-(formyl)-

possible with a phenyl group at the terminus of the haptyl aryl example (Table 1, Entry 5; electrophile 12) which re-

section of the ligand, and that the nature of the metal atom, acted with 2 equiv. of the nucleophile to afford 28 in 72%

the nucleophile, and the geometry of the ligand can influ- yield. The formation of 28 is best accounted for by initial

ence the outcome. Our initial study^[4,8]of the (1-phenylcy- addition of the nucleophile at the highly electrophilic (cy-

Eur. J. Org. Chem. 2008, 196–213

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203

C. E. Anson, A. V. Malkov, C. Roe, E. J. Sandoe, G. R. Stephenson

FULL PAPER

Scheme 2. Nucleophile addition to (1-arylcyclohexadienyl)iron complexes.

clohexadienyl)iron complex, to produce an intermediate regiocontrol (23: 80% yield) suggesting that this conforma-

diene complex, that reacts with a second equivalent of the tion is generally accessible in the o-aryl ether case. The elec-

nuclophile at the aldehyde. The structure of the product 28 trophile 16 has both CH₂OMe and OMe groups, and in the

indicates that, like the 2-CH₂OMe substituent, the presence structural study (Figure 6) had the OMe group below the

of the 2-CHO group renders the aryl group strongly ω-di- plane of the dienyl ligand. The CH₂OMe group is on the

recting. Because the CH₂OMe and CHO substituents be- side from which the nucleophile must approach (as with

have similarly, this result is ascribed to a steric effect, and 20). As expected, the reaction with NaCH(CO₂Me)CN

the nearly perpendicular conformation seen in the structure (Table 1, Entry 6) afforded only the ω product 26 (84%

of 12 in Figure 5 is proposed to give a good guide to the yield).

nature of the complex in solution. It is clear that this con-

Whereas the o-CH₂OMe substituents in electrophiles 16

formation predominates sufficiently to strongly influence and 20 are clearly sufficiently bulky to completely block

the approach of the nucleophile, and that flatter conforma- nucleophile addition at the nearby end of the dienyl com-

tions or those where the substituent lies below the plane of plex, and the conformation in which this effect operates can

the dienyl ligand, are not sufficiently available to allow the be seen to be sufficiently preferred in solution to dominate

ipso pathway relative to the aryl group to proceed. A further the regiocontrol of the reactions, the introduction of ad-

flanked example (24), with OMe groups at both ortho posi- ditional OMe groups on the aromatic ring in 18 has been

tions, was also available from earlier work,^[5]and behaved found to have a significant and useful effect. The crystallo-

similarly in reaction with NaCH(CO₂Me)CN, affording graphic study (Figure 7) identified a new conformation in

only the ω adduct 27.

the solid state, with the CH₂OMe rotated away from C(1),

With the 2-OCH₂CH=CH₂ether substituent, the crystal- potentially leaving open the path for nucleophiles to ap-

lographic study (Figure 4) had demonstrated that a confor- proach at the atom bearing the aryl group. If this conforma-

mation was possible with the ortho substituent on the side tion was also significant in solution, the ipso-addition path-

of the ligand bearing the metal atom. The reaction of 14 way required for access to the natural product targets (Fig-

with NaCH(CO₂Me)CN (Table 1, Entry 4) afforded only ures 1 and 2) might be opened up, despite the strong ω-

the ipso product 21 in 79% yield, showing that in this case directing effect identified in 16 and 20 with the o-CH₂OMe

the opposed OMe group on the dienyl ligand could over- group installed on the aryl substituent. Reaction of 18 with

come the ω-directing effect of the aryl group. From this it NaCH(CO₂Me)CN (Table 1, Entry 7) confirmed this was

is clear that the conformation identified in the solid state is the case, producing the adducts 29 and 30 in 77% yield

also available in solution, and to a sufficient degree that it (ipso/ω = 4:1). This is the first example of the required ipso

can determine the properties of the electrophile in reactions addition to the “C₁₃building block” (see Figure 2) to pro-

with nucleophiles. Addition of NaCH(CO₂Me)CN to the duce a quaternary centre. The success of this reaction is

o-anisyl structure 22^[5](Table 1, Entry 3) showed the same attributed to the effect of the additional OMe groups on

204

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Eur. J. Org. Chem. 2008, 196–213

Stereomanipulation of (η⁵-1-Arylcyclohexadienyl)iron Complexes

60 °C. Brine refers to a saturated aqueous solution of sodium chlo-

ride. Filtration refers to filtration under water-pump suction. Col-

umn chromatography was performed using Merck 7734 silica gel

and BDH alumina (Brockmann 1). TLC was performed using

Camlab Polygram^®SIL G/UV₂₅₄plates, visualized by UV irradia-

tion (254 nm) or exposure to alkaline potassium permanganate

solution followed by heating. IR spectra were recorded as a thin

film or as a solution in the specified solvent with Avatar 360, Per-

kin–Elmer BX or Perkin–Elmer 1720X FTIR spectrometers. NMR

spectra were recorded with Varian Unity Plus, Varian Gemini 2000,

Jeol GX400, Jeol EX270, Bruker AC250 or Jeol EX90 spectrome-

ters, and were referenced to Me₄Si (δ = 0 ppm). Microanalysis

(Carlo Erba EA1108) and low-resolution EI mass spectrometry

(Kratos MS25) were performed by A. W. R. Saunders at the Uni-

versity of East Anglia. CI, FAB and high-resolution mass spectra

were recorded at the EPSRC Mass Spectrometry Centre at the Uni-

versity of Wales, Swansea.

the aromatic ring and so is applicable in the proposed appli-

cations of the “C₁₃electrophiles” because the target struc-

tures typically have highly oxygenated aromatic rings.

Conclusions

The structures of (1-arylcyclohexadienyl)iron complexes

vary considerably, depending on the nature and position of

substituents on the arene portion of the ligand. This varia-

tion corresponds to differences in regioselectivity of nucleo-

phile addition reactions, which can proceed ipso to the ar-

ene when conformations are easily accessible in which the

plane of the arene lies close to the plane of the dienyl car-

bon atoms. Flanking substitution, or electron-withdrawing

substituents, twist the two planes towards a perpendicular

alignment, and in these cases the aryl group directs strongly

ω. The crystallographically defined conformations provide

models for the reactive conformations in solution. The two

examples with crystallographically distinct molecules in the

asymmetric unit give support to the argument that the de-

fined conformations are not solely artefacts of intermo-

lecular solid-state interactions, because in both cases the

two molecules show similar dihedral angles, even though

the packing environments are inequivalent. Results from

this analysis fit well with observed regiocontrol effects in

completed synthetic work in the O-methyljoubertiamine^[7]

and lycoramine series.^[12]In this conformation, increased π

overlap in the centre of the structure and increased transfer

of electron density from the arene to the dienyl ligand is

evidenced by shortening of the central C–C bond. Low di-

hedral angles and good ipso selectivity go together in this

set of structures. In general, the variability of directing ef-

fects of aryl subsituents in the entire series (η²–η⁵) is as-

cribed to variation in conformational preferences defining

the orientation of the arene relative to the haptyl section of

the ligand.

X-ray Crystallography: Data were collected with Siemens P4 (12b)

and Rigaku AFC7R (14 and 18) 4-circle diffractometers and a

Bruker SMART Apex CCD diffractometer (10 and 16). Details

of the data collection and structure refinement are summarized in

Table 4. Structures were solved by direct methods and refined by

full-matrix least-squares refinement against F²(all data) using the

SHELXTL software package.^[43]Crystallographic data (excluding

structure factors) for the structures in this paper have been de-

posited with the Cambridge Crystallographic Data Centre as sup-

plementary publication nos. CCDC-657027, -657028, -657029,

-657030 and -657031contain the supplementary crystallographic

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.

Tricarbonyl{(2ЈЈ–5ЈЈ-η)-2-[2Ј-(1βЈЈ,4ЈЈ-dimethoxycyclohexadien-1ЈЈ-

yl)phenyl]-1,3-dioxolane}iron(0) [9, R = Me, Ar = 2-(OCH₂CH₂O)-

CHC₆H₄] and Tricarbonyl{(2ЈЈ–5ЈЈ-η)-2-[2Ј-(1βЈЈ-hydroxy-4ЈЈ-meth-

oxycyclohexadien-1ЈЈ-yl)phenyl]-1,3-dioxolane}iron(0) [9, R = H, Ar

= 2-(OCH₂CH₂O)CHC₆H₄]: A solution of n-butyllithium in hex-

ane (1.2 , 2.2 mL, 2.6 mmol) was added to a stirred solution of 2-

(2Ј-bromophenyl)-1,3-dioxolane (360 mg, 1 mmol) in diethyl ether

(2 mL) at –78 °C. Diethyl ether (4 mL) was added to the resulting

suspension, and the mixture was stirred at –78 °C for 1 h. A solu-

tion of tricarbonyl[(1–5-η)-1,4-dimethoxycyclohexadienyl]iron(1+)

tetrafluoroborate(1–) (620 mg, 2.7 mmol) in dichloromethane

(30 mL) at –78 °C was added, and stirring was continued at this

temperature for 2 h. After warming to room temp., water (5 mL)

was added, and the mixture was extracted with dichloromethane

(20 mL). The extracts were washed with water, dried (MgSO₄), and

purified by chromatography on silica eluting with hexane/ethyl ace-

tate (10:1) to give tricarbonyl{(2ЈЈ–5ЈЈ-η)-2-[2Ј-(1βЈЈ,4ЈЈ-dimeth-

oxycyclohexadien-1ЈЈ-yl)phenyl]-1,3-dioxolane}iron(0) [9, R = Me,

Ar = 2-(OCH₂CH₂O)CHC₆H₄] (250 mg, 58 %) and tricarbonyl-

{(2ЈЈ–5ЈЈ-η)-2-[2Ј-(1βЈЈ-hydroxy-4ЈЈ-methoxycyclohexadien-1ЈЈ-yl)-

phenyl]-1,3-dioxolane}iron(0) [9, R = H, Ar = 2-(OCH₂CH₂O)-

CHC₆H₄] (100 mg, 29 %). Tricarbonyl[(2–5-η)-4-methoxycy-

clohexadien-1-one]iron(0)^[44](40 mg, 15%) was eluted with hexane/

ethyl acetate (2:1). Tricarbonyl{(2ЈЈ–5ЈЈ-η)-2-[2Ј-(1βЈЈ,4ЈЈ-dimeth-

This approach has led for the first time to the successful

construction of a quaternary centre at C(1) in o-substituted

(arylcyclohexadienyl)iron complexes of type 7, showing the

practicality of the proposed (Figure 2) “C₁₃building block”

approach. This is the first case in which deliberate manipu-

lation of the conformational effects in chiral electrophilic

transition metal π complexes has been used as a strategy to

gain access to the construction of hindered quaternary

centres, and sets our on-going target synthesis work on a

firm footing.

Experimental Section

General Conditions: Chemicals were reagent grade and used as sup-

plied unless otherwise stated. All chiral compounds were prepared

as racemic mixtures. All reactions were carried out in oven- or

flame-dried glassware, under dry, oxygen-free nitrogen. Diethyl

ether and THF were dried by distillation from sodium and benzo-

phenone; dichloromethane was dried by distillation from calcium

hydride. Reaction temperatures: –78 °C refers to acetone/dry ice;

0 °C refers to ice/water; –100 °C refers to diethyl ether/liquid nitro-

gen cooling. Light petroleum refers to the fraction with b.p. 40–

1

oxycyclohexadien-1ЈЈ-yl)-phenyl]-1,3-dioxolane}iron(0): H NMR

(89.5 MHz, CDCl₃): δ = 7.65 (m, 1 H, 3Ј-H or 6Ј-H), 7.41 (m, 1

H, 3Ј-H or 6Ј-H), 7.30–7.20 (m, 2 H, 4Ј-H, 5Ј-H), 6.33 (s, 1 H, 2-

3

H), 5.26 (dd, J_H,H= 6.7, 2.3 Hz, 1 H, 3ЈЈ-H), 4.2–3.9 (m, 4 H,

–CH₂–CH₂–), 3.58 (s, 3 H, 4ЈЈ-OMe), 3.28 (m, 1 H, 5ЈЈ-H), 3.00 (d,

3

³J_H,H= 6.8 Hz, 1 H, 2ЈЈ-H), 2.91 (s, 3 H, 1ЈЈ-OMe), 2.26 (d, J_H,H

= 3 Hz, 2 H, 6ЈЈα,β-H) ppm. MS (EI): m/z (%) = 372 (3) [M – 2

CO]⁺, 344 (9) [M – 3 CO]⁺, 312 (100) [M – 3 CO – CH₃OH]⁺, 284

Eur. J. Org. Chem. 2008, 196–213

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205

C. E. Anson, A. V. Malkov, C. Roe, E. J. Sandoe, G. R. Stephenson

FULL PAPER

Table 4. Crystal data.

10

12b

14

16

18

Empirical formula

Formula mass

Crystal system

Space group

a [Å]

b [Å]

c [Å]

C₁₆H₁₃F₆FeO₄P

470.08

C₁₇H₁₃BF₄FeO₅

439.93

C₁₉H₁₇F₆FeO₅P

526.15

monoclinic

P2₁/c

10.7012(8)

10.8260(10)

19.2856(15)

90

103.755(6)

90

2170.2(3)

4

C₁₉H₁₉F₆FeO₆P

544.16

monoclinic

P2₁/c

12.1223(16)

16.684(2)

11.4022(16)

90

105.447(2)

90

2222.8(5)

4

C₂₀H₂₁F₆FeO₇P

574.19

triclinic

¯

P1

10.3950(11)

10.9668(12)

16.6880(18)

74.377(2)

73.342(2)

83.411(2)

1753.8(3)

4

10.008(4)

12.421(5)

15.841(5)

95.67(3)

95.10(3)

111.36(3)

1808.3(12)

4

8.578(3)

10.878(5)

13.032(5)

97.58(4)

100.52(3)

104.39(4)

1137.8(9)

2

α [°]

β [°]

γ [°]

V [Å³]

Z

T [K]

F(000)

100

944

1.780

1.033

8933

7505

0.0173

6186

525

295

888

1.616

0.900

6784

6389

0.0279

5232

607

291

1064

1.610

0.848

6626

6310

0.0186

4158

394

100

1104

1.626

0.834

9194

3898

0.0354

2963

331

193

584

1.676

0.823

4232

4001

0.0533

3069

325

D_calcd.[Mgm^–3]

µ(Mo-K_α) [mm^–1]

Data measured

Unique data

R_int

Data with IՆ2σ(I)

Parameters

wR₂(all data)

R₁[IՆ2σ(I)]

S (all data)

Largest difference peak/hole

0.1096

0.0410

1.017

0.1161

0.0466

1.080

0.1104

0.0367

1.011

0.1298

0.0528

1.022

0.1022

0.0385

1.032

+1.79/–1.22

+0.48/–0.45

+0.37/–0.38

+0.51/–0.42

+0.74/–0.76

(45), 266 (90), 255 (47). IR (CH Cl ): ν_max= 2047 (ν_symCO), 1980, 99.72 (2-C), 71.59 (3-C), 57.87 (OMe), 44.03 (5-C), 34.70 (DEPT:

˜

2

1969 (ν_asymCO), 1667, 1603, 1495, 1230, 1105, 1075, 1025 cm^–1.

HRMS (EI): calcd. for C₁₈H₂₀FeO₅372.0660; found 372.0660 [M –

2 CO]⁺. Tricarbonyl{(2ЈЈ–5ЈЈ-η)-2-[2Ј-(1βЈЈ-hydroxy-4ЈЈ-methoxy-

cyclohexadien-1ЈЈ-yl)phenyl]-1,3-dioxolane}iron(0): ¹H NMR

CH ; 6-C) ppm. IR (acetone): ν

= 2110 (ν_symCO), 2066 (ν_asym

˜

2

max

CO), 2053 (ν_symCO^[45]), 1975 (ν_asymCO^[45]), 1703 (C=O), 1480,

1270 cm^–1. A portion of the product was crystallised from aceto-

nitrile/diethyl ether for X-ray crystallography. C₁₇H₁₃BF₄FeO₅

(89.5 MHz, CDCl₃): δ = 7.61 (m, 1 H, Ar-H), 7.41–7.16 (m, 3 H, (439.93): calcd. C 46.41, H 2.98; found C 46.43, H 2.84. The corre-

3

Ar-H), 6.36 (s, 1 H, 2-H), 5.14 (dd, J_H,H= 6.5, 2.4 Hz, 1 H, 3ЈЈ-

sponding hexafluorophosphate salt was prepared by dissolving the

H), 4.15–3.95 (m, 4 H, CH₂–CH₂), 4.0–3.6 (br. s, 1 H, OH), 3.61 same mixture of the ether and alcohol in trifluoroacetic acid (2 mL)

3

(s, 3 H, 4ЈЈ-OMe), 3.33 (m, 1 H, 5ЈЈ-H), 2.79 (d, J_H,H= 6.6 Hz, 1 at 0 °C. The mixture was stirred at this temperature for 30 min.

H, 2ЈЈ-H), 2.32 (m, 2 H, 6ЈЈα,β-H) ppm. MS (EI): m/z (%) = 358 Satd. aq. ammonium hexafluorophosphate was added until no fur-

(3) [M – 2 CO]⁺, 330 (8) [M – 3 CO]⁺, 312 (100) [M – 3 CO – ther precipitate formed. The product was collected by filtration and

H O]⁺, 284 (47), 268 (82), 266 (96), 255 (83). IR (CH Cl ): ν

=

˜

max

3450 (OH), 2046 (ν_symCO), 1974, 1965 (ν_asymCO), 1602, 1490,

1225, 1105, 1075, 1025 cm^–1. HRMS (EI): calcd. for C₁₇H₁₈FeO₅

358.0504; found 358.0504 [M – 2 CO]⁺.

purified by precipitation from acetonitrile by addition of diethyl

ether to afford tricarbonyl[(1–5-η)-1-(2Ј-formylphenyl)-4-methoxy-

2,4-cyclohexadienyl]iron(1+) hexafluorophosphate(1–) (12a) as a

yellow powder (160 mg, 69%). ¹H NMR (89.5 MHz, CD₃CN): δ =

9.87 (s, 1 H, CHO), 7.88 (m, 1 H, Ar-H), 7.76–7.63 (m, 2 H, Ar-

2

Tricarbonyl[(1–5-η)-1-(2Ј-formylphenyl)-4-methoxy-2,4-cyclohexa-

dienyl]iron(1+) Hexafluorophosphate(1–) (12a) and Tetrafluoro-

borate(1–) (12b): A 2:1 mixture of tricarbonyl{(2ЈЈ–5ЈЈ-η)-2-[2Ј-

(1βЈЈ,4ЈЈ-dimethoxycyclohexadien-1ЈЈ-yl)phenyl]-1,3-dioxolane}-

iron(0) [9, R = Me, Ar = 2-(OCH₂CH₂O)CHC₆H₄] and tri-

carbonyl{(2ЈЈ–5ЈЈ-η)-2-[2Ј-(-(1βЈЈ-hydroxy-4ЈЈ-methoxycyclo-

hexadien-1ЈЈ-yl)phenyl]-1,3-dioxolane}iron(0) [9, R = H, Ar = 2-

(OCH₂CH₂O)CHC₆H₄] (250 mg, 0.595 mmol) was dissolved in

dichloromethane and added to a solution of triphenylcarbenium

tetrafluoroborate (220 mg, 0.667 mmol) in dichloromethane (5 mL)

at 0 °C. The mixture darkened and was stirred at 0 °C for 2 h. The

reaction mixture was added dropwise to diethyl ether (50 mL), and

the precipitate was collected by filtration and dried to give the

3

H), 7.45, (m, 1 H, Ar-H), 6.89 (dd, J_H,H= 6, 2.5 Hz, 1 H, 3-H),

3

5.85 (d, J_H,H= 6 Hz, 1 H, 2-H), 4.05 (m, 1 H, 5-H), 3.80 (s, 3 H,

3

4-OMe), 3.13 (dd, J_H,H= 16, 6.1 Hz, 1 H, 6β-H), 2.70 (d, J_H,H

= 16 Hz, 1 H, 6α-H) ppm. ¹³C NMR (67.5 MHz, CD₃CN): δ =

193.4 (CHO^[46]), 150.9 (4Ј-C), 137.5 (3Ј-C or 6Ј-2), 135.6, 135.4,

133.8 (3Ј-C or 6Ј-C), 131.2, 100.1 (2-C^[46]), 92.0 (1-C), 72.1 (3-C^[46]),

44.6 (5-C^[46]), 35.1 (6-C^[46]) ppm.

Preparation of 1-Allyloxy-2-bromobenzene:^[47]A solution of 2-bro-

mophenol (1 equiv., 10.0 g, 58 mmol) in dry THF (20 mL) was

added to NaH (60% suspension in mineral oil) (2.3 g, 58 mmol) in

dry THF (20 mL) at 0 °C over 1 h. The reaction mixture was stirred

at 0 °C for 30 min to give a pale brown solution. Allyl bromide

product 12b as a yellow powder (190 mg, 73 %). ¹H NMR (10.5 g, 87 mmol) was added at 0 °C. The reaction mixture was

(89.5 MHz, CD₃CN): δ = 9.88 (s, 1 H, CHO), 7.91 (m, 1 H, Ar-

heated at reflux for 16 h. The reaction was quenched with water

(50 mL) and diethyl ether (50 mL) and the mixture extracted with

diethyl ether (3 ϫ 50 mL). The combined organic extracts were

washed with water (3ϫ25 mL), dried (MgSO₄) and filtered. The

solvent was removed under reduced pressure to afford 1-alloxy-2-

H), 7.76–7.65 (m, 2 H, Ar-H), 7.43, (m, 1 H, Ar-H), 6.95 (dd, ³J_H,H

3

= 6.15, 2.64 Hz, 1 H, 3-H), 5.89 (d, J_H,H= 6.15 Hz, 1 H, 2-H),

4.11 (ddd, ³J_H,H= 6.4, 2.6, 1.3 Hz, 1 H, 5-H), 3.80 (s, 3 H, 4-OMe),

3.13 (dd, ³J_H,H= 15.8, 6.4 Hz, 1 H, 6α-H), 2.73 (d, ³J_H,H= 15.8 Hz,

1 H, 6α-H) ppm. ¹³C NMR (22.4 MHz, CD₃CN): δ = 192.93 bromobenzene as a clear liquid (10.7 g, 87%). ¹H NMR (270 MHz,

3

(CHO), 135.13, 134.82, 133.22, 131.72, 130.65 (DEPT: 4ϫ CH),

CDCl₃): δ = 7.52 (dd, J_H,H= 7.9, 1.6 Hz, 1 H, Ar), 7.21 (ddd,

206

www.eurjoc.org

Eur. J. Org. Chem. 2008, 196–213

Stereomanipulation of (η⁵-1-Arylcyclohexadienyl)iron Complexes

³J_H,H= 8.3, 7.3, 1.6 Hz, 1 H, Ar), 6.86 (m, 2 H, Ar), 6.03 (ddt, (CD COCD ): ν

= 2098 (ν_symCO), 2049 (ν_asymCO) cm^–1

.

˜

3

max

3

³J_H,H= 17.2, 10.6, 5.0 Hz, 1 H, CH₂CH =CH₂), 5.46 (dq, J_H,H

=

C₁₉H₁₇F₆FeO₅P (526.15): calcd. C 43.4, H 3.3; found C 43.4, H

3.2.

3

17.2, 1.6 Hz, 1 H, CH₂CH=CH₂), 5.28 (dq, J_H,H= 10.6, 1.6 Hz,

3

1 H, CH₂CH=CH₂), 4.58 (dt, J_H,H= 5.0, 3.5 Hz, 1 H, OCH₂)

Preparation of 2-Bromo-3-methoxybenzyl Alcohol:^[49]According to

the method of Trost,^[23]3-methoxybenzyl alcohol (l equiv., 2 g,

14.5 mmol) was dissolved in dry hexane (50 mL). nBuLi

(31.9 mmol, 19.9 mL) was added at 0 °C with stirring. The mixture

was warmed to room temp., and a pink solution was formed. After

2 h, the solution had turned orange. The mixture was cooled to

–78 °C, and BrCF₂CF₂Br (31.9 mmol, 8.28 g, 3.8 mL) was added.

The mixture was stirred for 30 min and then warmed to 0 °C. The

mixture turned yellow after 1 h. The reaction was quenched with

water (50 mL) and diethyl ether (50 mL) and the mixture extracted

with diethyl ether (3ϫ50 mL). The combined organic extracts were

washed with water (3ϫ50 mL), dried (MgSO₄), and filtered. The

solvent was removed under reduced pressure to afford a yellow

solid. Recrystallisation (60% diethyl ether/40% cyclohexane) af-

forded l-bromo-3-methoxybenzyl alcohol as white crystals (1.262 g,

ppm. MS (EI): m/z (%) = 214 (38) [M]⁺, 212 (39) [M]⁺, 174 (19)

[M – CH₂CH=CH₂]⁺, 172 (21) [M – CH₂CH=CH₂]⁺, 133 (37) [M –

Br]⁺, 41 (100). IR (film): ν

= 2921, 1587, 1479, 1278, 1032,

˜

max

747 cm^–1. HRMS (EI): calcd. for C₉H₉OBr 211.9837; found

211.9837 [M]⁺.

[(1–4-η)-5α-(2Ј-Allyloxyphenyl)-2,5β-dimethoxy-1,3-cyclohexa-

diene]tricarbonyliron(0) [9, R = Me, Ar = 2Ј-(H₂C=CHCH₂O)-

C₆H₄]: 1-Allyloxy-2-bromobenzene (2 equiv., 1.3 g, 6.1 mmol) was

dissolved in dry diethyl ether (5 mL) and cooled to –78 °C under

nitrogen. nBuLi (1.6  in hexanes, 6 mmol, 3.8 mL) was added and

1-(allyloxy)-2-lithiobenzene^[47,48]was formed by stirring at –78 °C

for 30 min. Salt 8 (1.1 g, 3.0 mmol) was dissolved in dry dichloro-

methane (5 mL) and cooled to –100 °C. The solution of the nucleo-

phile was added through a cannula at –100 °C, and the mixture

was stirred for 10 min. The reaction was quenched at –100 °C with

water (25 mL) and diethyl ether (25 mL) and the mixture warmed

to room temp. The mixture was extracted with diethyl ether

(3 ϫ 25 mL). The combined organic extracts were washed with

water (3ϫ25 mL), dried (MgSO₄) and filtered. The solvent was

removed under reduced pressure to afford a pale brown gum. Col-

umn chromatography (20% diethyl ether/80% petroleum ether) af-

forded [(1–4-η)-5α-(2Ј-allyloxyphenyl)-2,5β-dimethoxy-1,3-cyclo-

hexadiene]tricarbonyliron(0) [9, R = Me, Ar = (2-H₂C=CHCH₂O)-

1

3

40%). H NMR (270 MHz, CDCl₃): δ = 7.30 (t, J_H,H= 8.0 Hz, 1

3

H, 5-H), 7.10 (d, J_H,H= 8.0 Hz, 1 H, 4-H), 6.86 (d., J_H,H

8.0 Hz, 1 H, 6-H), 4.77 (d, J_H,H= 6.8 Hz, 2 H, CH₂), 3.91 (s, 3

=

3

H, OMe), 2.06 (t, J_H,H= 6.8 Hz, 1 H, OH) ppm. MS (EI): m/z

(%) = 218 (96) [M]⁺, 216 (100) [M]⁺, 201 (7) [M – OH]⁺, 199 (5)

[M – OH]⁺. IR (mull): ν

= 3285 (OH), 2843, 1594, 1474, 1293,

˜

max

1047, 765 cm^–1. C₈H₉O₂Br (217.06): C 44.3, H 4.2, Br 36.8; found,

C 44.4, H 4.1, Br 36.5.

Preparation of 1-Bromo-2-Methoxy-6-(methoxymethyl)benzene:^[50]

NaH (60% suspension in mineral oil) (0.208 g, 5.23 mmol) was sus-

pended in dry THF (20 mL) at 0 °C. A solution of 2-bromo-3-

methoxybenzyl alcohol (1.13 g, 5.23 mmol) in dry THF (5 mL) was

added at 0 °C and the mixture was stirred at 0 °C for 30 min to

give a clear brown solution. Methyl iodide (0.5 mL, 7.81 mmol)

was added at 0 °C and the mixture stirred at room temp. for 18 h.

The reaction was quenched with water (50 mL) and diethyl

ether (50 mL) and the mixture extracted with diethyl ether

(3 ϫ 50 mL). The combined organic extracts were washed with

water (3ϫ50 mL), dried (MgSO₄), and filtered. The solvent was

removed under reduced pressure to afford a yellow solid. Column

chromatography (30% diethyl ether/70% cyclohexane) afforded 1-

bromo-2-methoxy-6-(methoxymethyl)benzene as a white crystalline

solid (1.038 g, 86%). ¹H NMR (250 MHz, CDCl₃): δ = 7.29 (t,

³J_H,H= 8.0 Hz, 1 H, 4-H), 7.09 (d, ³J_H,H= 8.0 Hz, 1 H, 3-H), 6.85

(d, ³J_H,H= 8.0 Hz, 1 H, 5-H), 4.55 (s, 2 H, CH₂), 3.90 (s, 3 H, Ar-

OMe), 3.47 (s, 3 H, OMe) ppm. MS (EI): m/z (%) = (EI) 232 (96)

[M]⁺, 230 (100) [M]⁺, 201 (55) [M – OMe]⁺, 199 (54) [M –

OMe]⁺, 151 (75) [M – Br]⁺, 121 (60) [M⁺– Br – OMe + H]⁺. IR

1

C₆H₄] as a pale yellow gum (649 mg, 53%). H NMR (270 MHz,

CDCl₃): δ = 7.47 (dd, J_H,H= 7.9, 2.2 Hz, 1 H, Ar), 7.22 (m, 1 H,

Ar), 6.85 (m, 2 H, Ar), 6.02 (ddt, J_H,H= 17.8, 9.6, 4.6 Hz, 1 H,

3

CH₂CH=CH₂), 5.28 (m, 2 H, CH₂CH=CH₂), 5.01 (dd, J_H,H

=

6.9, 2.3 Hz, 1 H, 3-H), 4.51 (dt, ³J_H,H= 4.0, 10.8 Hz, 1 H, OCH₂),

3.59 (s, 3 H, 2-OMe), 3.01 (m, 1 H, 1-H), 2.99 (s, 3 H, 5-OMe),

2.89 (d, J_H,H= 6.9 Hz, 1 H, 4-H), 2.47 (dd, J_H,H= 15.2, 2.3 Hz,

3

1 H, 6β-H), 2.19 (dd, J_H,H= 15.2, 3.6 Hz, 1 H, 6α-H) ppm. MS

(EI): m/z (%) = 356 (4) [M – 2 CO]⁺, 328 (9) [M – 3 CO]⁺, 286

(27), 255 (100). IR (CH Cl ): ν = 2048 (ν_symCO), 1977 (ν_asym

˜

max

2

CO) cm^–1. C₂₀H₂₀FeO₆(412.22): calcd. C 58.3, H 4.9; found C

58.5, H 4.9.

[(1–5-η)-1-(2Ј-Allyloxyphenyl)-4-methoxy-2,4-cyclohexadienyl]-

tricarbonyliron(1+) Hexafluorophosphate(1–) (14): Hexafluorophos-

phoric acid (75% in water, 1 mL) was added to a solution of tricar-

bonyl[(1–4-η)-5α-(2Ј-allyloxyphenyl)-2,5β-dimethoxy-1,3-cyclo-

hexadiene]iron(0) [9, R = Me, Ar = 2Ј-(H₂C=CHCH₂O)C₆H₄]

(567 mg, 1.38 mmol) in acetic anhydride (10 mL) at 0 °C. The reac-

tion mixture darkened and was stirred for 10 min. The reaction

mixture was added dropwise to dry diethyl ether (200 mL) cooled

to 0 °C, and a yellow precipitate formed. Recrystallisation (acetone/

diethyl ether) afforded [(1–5-η)-1-(2-allyloxyphenyl)-4-methoxy-

2,4-cyclohexadienyl]tricarbonyliron(1+) hexafluorophosphate(1–)

(14) as orange crystals (598 mg, 82 %). ¹H NMR (270 MHz,

CD₃COCD₃): δ = 7.52 (t, ³J_H,H= 7.9 Hz, 1 H, Ar), 7.44 (dd, ³J_H,H

(mull): ν

= 2932, 2820, 1593, 1469, 1294, 1126, 1029, 776 cm^–1.

˜

max

C₉H₁₁BrO₂(231.08): calcd. C 46.8, H 4.8, Br 34.6; found C 46.9,

H 4.7, Br 34.5.

Attempted Preparation of Tricarbonyl{(1–4-η)-2,5β-dimethoxy-5α-

[2Ј-methoxy-6Ј-(methoxymethyl)phenyl]-1,3-cyclohexadiene}iron(0)

(9, R = Me, Ar = 2Ј-MeO-6Ј-HOCH₂C₆H₃); Formation of

Tricarbonyl{(1–4-η)-2,5β-dimethoxy-5α-[6Ј-(hydroxymethyl)-2Ј-

3

= 7.9, 1.7 Hz, 1 H, Ar), 7.30 (dd, J_H,H= 6.3, 2.6 Hz, 1 H, 3-H),

7.15 (d, ³J_H,H= 7.9 Hz, 1 H, Ar), 7.09 (t, ³J_H,H= 7.9 Hz, 1 H, Ar),

3

6.51 (d, J_H,H= 6.3 Hz, 1 H, 2-H), 6.07 (ddt, J_H,H= 17.5, 10.6, methoxyphenyl]-1,3-cyclohexadiene}iron(0) (9, R = Me, Ar = 2Ј-

5.3 Hz, 1 H, CH₂CH=CH₂) 5.33 (m, 2 H, CH₂CH=CH₂), 4.86 (m, MeO-6Ј-HOCH₂C₆H₃) and Tricarbonyl[(2–5-η)-4-methoxy-2,4-cy-

1 H, 5-H), 4.05 (s, 3 H, OMe), 3.75 (dd., J_H,H= 15.5, 5.6 Hz, 1 clohexadienone]iron(0): According to the method of Trost,^[23]3-

3

H, 6β-H), 2.95 (d, J_H,H= 15.5 Hz, 1 H, 6α-H) ppm. ¹³C NMR

methoxybenzyl alcohol (276 mg, 2 mmol) was dissolved in dry hex-

3

(67.5 MHz, CD₃COCD₃): δ = 158.4 (2Ј-C), 151.5 (4-C), 134.2 (4Ј- ane (5 mL). nBuLi (2.6 mL, 4.1 mmol) was added at 0 °C with stir-

C), 132.1 (=CH), 131.5 (6Ј-C), 123.0 (5Ј-C), 122.6 (1Ј-C), 119.4

(=CH₂), 115.4 (3Ј-C), 95.5 (2-C), 93.5 (1-C), 73.3 (CH₂-O), 70.1 (3-

C), 43.5 (5-C), 33.9 (6-C) ppm. MS (EI): m/z (%) = 381 (100) [M –

PF₆]⁺, 353 (9) [M – PF₆– CO]⁺, 297 (5) [M – PF₆– 3 CO]⁺. IR

ring. The mixture was warmed to room temp., and a pink solution

formed. After 2 h, an orange solution had formed, and the mixture

was cooled to –100 °C. Tricarbonyl[(1–5-η)-1,4-dimethoxy-2,4-cy-

clohexadienyl]iron(1+) hexafluorophosphate(1–) (8) (1 equiv.,

Eur. J. Org. Chem. 2008, 196–213

www.eurjoc.org

207

C. E. Anson, A. V. Malkov, C. Roe, E. J. Sandoe, G. R. Stephenson

FULL PAPER

366 mg, 1.0 mmol) was dissolved in dry dichloromethane (10 mL)

and cooled to –100 °C. The solution of the nucleophile at –100 °C

was added to the salt through a cannula at –100 °C, and the mix-

ture turned black and was stirred at –100 °C for 2 h. The reaction

Triphenylcarbenium hexafluorophosphate (37 mg, 0.353 mmol)

was dissolved in freshly distilled dichloromethane (10 mL) at 0 °C.

Tricarbonyl{(1–4-η)-2,5β-dimethoxy-5α-[2Ј-methoxy-6Ј-(methoxy-

methyl)phenyl]-1,3-cyclohexadiene}iron(0) (9, R = Me, Ar = 2Ј-

was quenched with water (25 mL) and diethyl ether (25 mL) at MeO-6Ј-MeOCH₂C₆H₃) (152 mg, 0.353 mmol) was dissolved in

–100 °C and the mixture warmed to room temp. The mixture was

extracted with diethyl ether (3ϫ25 mL). The combined organic ex-

tracts were washed with water (3ϫ25 mL), dried (MgSO₄), and

filtered. The solvent was removed under reduced pressure to afford

a brown oil. Column chromatography (60% diethyl ether/40% cy-

clohexane) gave a trace of a yellow gum which was provisionally

identified as tricarbonyl{(1–4-η)-2,5β-dimethoxy-5α-[6Ј-(hy-

droxymethyl)-2Ј-methoxyphenyl]-1,3-cyclohexadiene}iron(0) (9, R

= Me, Ar = 2Ј-MeO-6Ј-HOCH₂C₆H₃) (14 mg, 3 %). ¹H NMR

dichloromethane (10 mL) and was added to the solution. The reac-

tion mixture darkened slowly while being stirred at 0 °C for 3 h.

The reaction mixture was added dropwise into dry diethyl ether

(200 mL) at 0 °C and a yellow precipitate formed. Reprecipitation

(acetone/diethyl ether) afforded tricarbonyl{(1–5-η)-4-methoxy-1-

[2Ј-methoxy-6Ј-(methoxymethyl)phenyl]-2,4-cyclohexadienyl}-

iron(1+) hexafluorophosphate(1–) (16) as a yellow solid (123 mg,

3

64 %). ¹H NMR (270 MHz, CD₃COCD₃): δ = 7.42 (t, J_H,H

=

3

8.0 Hz, 1 H, 4Ј-H), 7.12 (d, J_H,H= 8.0 Hz, 1 H, 3Ј-H), 7.06 (d,

³J_H,H= 2.5 Hz, 1 H, 3-H), 7.02 (d, ³J_H,H= 8.0 Hz, 1 H, 5Ј-H), 5.85

(d, ³J_H,H= 6.0 Hz, 1 H, 2-H), 4.38 (d, ³J_H,H= 12.3 Hz, 1 H, CH₂),

4.25 (d, J_H,H= 12.3 Hz, 1 H, CH₂), 4.12 (m, 1 H, 5-H), 4.08 (s, 3

H, 4-OMe), 3.80 (s, 3 H, Ar-OMe), 3.35 (dd, J_H,H= 16.5, 6.3 Hz,

3

(250 MHz, CDCl₃): δ = 7.20 (t, J_H,H= 7.5 Hz, 1 H, 4Ј-H), 7.09

(d, ³J_H,H= 7.5 Hz, 1 H, 3Ј-H), 6.82 (d, ³J_H,H= 7.5 Hz, 1 H, 5Ј-H),

3

5.05 (d, J_H,H= 13.5 Hz, 1 H, CH₂), 4.91 (dd, ³J_H,H= 7.0, 2.5 Hz,

3

1 H, 3-H), 4.59 (dd, J_H,H= 13.5, 7.5 Hz, 1 H, CH₂), 3.79 (s, 3 H,

3

Ar-OMe), 3.64 (s, 3 H, 2-OMe), 3.33 (m, 1 H, 1-H), 3.28 (d, J_H,H1 H, 6β-H), 3.31 (s, 3 H, CH₂OMe), 2.52 (d, ³J_H,H= 16.5 Hz, 1 H,

= 7.0 Hz, 1 H, 4-H), 3.06 (s, 3 H, 5-OMe), 2.96 (br. s, 1 H, OH),

6α-H) ppm. ¹³C NMR (75 MHz, CD₃COCD₃): δ = 156.1 (2Ј-C),

150.3 (4-C), 139.3 (6Ј-C), 131.8 (4Ј-C), 124.5 (1Ј-C), 124.2 (3Ј-C),

122.6 (5Ј-C), 100.5 (2-C^[46]), 89.8 (1-C), 73.6 (CH₂–O), 71.9 (3-

C^[46]), 58.3 (Ar-OMe), 57.9 (2Ј-OMe), 55.6 (4-OMe), 46.9 (5-C^[46]),

34.8 (6-C) ppm (the signals at δ = 58.3 and 57.9 ppm were distin-

guished by HSQC in which the ¹³C NMR signal at δ = 58.3 ppm

correlated with the CH₂–OMe methoxy resonance at δ =

3

2.61 (dd, J_H,H= 14.8, 2.5 Hz, 1 H, 6β-H), 2.25 (dd, J_H,H= 14.8,

3.0 Hz, 1 H, 6α-H) ppm. MS (EI): m/z (%) = 356 (2) [M – MeOH –

CO]⁺, 328 (6) [M – MeOH – 2 CO]⁺, 300 (10) [M – MeOH – 3

CO]⁺, 244 (15) [M – MeOH – 3 CO – Fe]⁺, 138 (100), 109 (45). IR

(acetone): ν

= 3370 (OH), 2042 (ν_symCO), 1966 (ν_asymCO),

˜

max

1490, 1260, 1074, 1031, 624 cm^–1. The main product from this reac-

tion was tricarbonyl[(2–5-η)-4-methoxy-2,4-cyclohexadienone]-

iron(0)^[48](97 mg, 37%).

3.33 ppm). IR (acetone): ν

= 2106 (ν_symCO), 2058 (ν_asymCO),

˜

max

1500, 1252, 838, 558 cm^–1. HRMS (FAB): calcd. for C₁₉H₁₉FeO₆

399.0531; found 399.0531 [M – PF₆]⁺. C₁₉H₁₉F₆FeO₆P (544.16):

calcd. C 41.9, H 3.5; found C 42.1, H 3.4.

Tricarbonyl{(1–4-η)-2,5β-dimethoxy-5α-[2Ј-methoxy-6Ј-(methoxy-

methyl)phenyl]-1,3-cyclohexadiene}iron(0) (9, R = Me, Ar = 2Ј-

MeO-6Ј-MeOCH₂C₆H₃): 1-Bromo-2-methoxy-6-(methoxymethyl)-

benzene (2 equiv., 462 mg, 2 mmol) was dissolved in dry diethyl

ether (25 mL) and cooled to –78 °C under nitrogen. nBuLi (1.6 

in hexanes, 1.25 mL, 2.0 mmol) was added and 1-lithio-2Ј-meth-

oxy-6Ј-(methoxymethyl)benzene^[51]was formed as a white suspen-

sion by stirring at –78 °C for 2 h. Tricarbonyl[(1–5-η)-1,4-dimeth-

oxy-2,4-cyclohexadienyl]iron(1+) hexafluorophosphate(1–) (8)

(366 mg, 1.0 mmol) was dissolved in dry dichloromethane (10 mL)

and cooled to –100 °C. The solution of the nucleophile at –100 °C

was added to the salt at –100 °C through a cannula, and the mix-

ture was stirred for 2 h. The reaction was quenched with water

(25 mL) and diethyl ether (25 mL) at –100 °C and the mixture

warmed to room temp. The mixture was extracted with diethyl

ether (3ϫ25 mL). The combined organic extracts were washed

with water (3ϫ25 mL), dried (MgSO₄) and filtered. The solvent

was removed under reduced pressure to afford a brown oil. Column

chromatography (40 % diethyl ether/60 % cyclohexane) afforded

tricarbonyl{(1–4-η)-2,5β-dimethoxy-5α-[2Ј-methoxy-6Ј-(methoxy-

methyl)phenyl]-1,3-cyclohexadiene}iron(0) (9, R = Me, Ar = 2Ј-

MeO-6Ј-MeOCH₂C₆H₃) (285 mg, 66 %). ¹H NMR (250 MHz,

Preparation of 2-Bromo-4,5-dimethoxybenzyl Alcohol:^[25,52]NaBH₄

(0.539 g, 13.5 mmol) was added to a solution of l-bromo-4,5-di-

methoxybenzaldehyde (3.0 g, 12.2 mmol) in dry THF (80 mL) and

methanol (20 mL) at 0 °C. The mixture was stirred at 0 °C for

20 min. The reaction was quenched with water (50 mL) and diethyl

ether (50 mL) and the mixture extracted with diethyl ether

(3 ϫ 50 mL). The combined organic extracts were washed with

water (3ϫ50 mL), dried (MgSO₄) and filtered. The solvent was

removed under reduced pressure to afford a white solid (2.957 g,

98%). Recrystallisation (ethanol/water) afforded l-bromo-4,5-di-

methoxybenzyl alcohol as fluffy fine white crystals (2.097 g, 69%).

¹H NMR (250 MHz, CDCl₃): δ = 7.02 (s, 1 H, Ar), 7.01 (s, 1 H,

3

Ar), 4.70 (d, J_H,H= 6.0 Hz, 2 H, CH₂), 3.90 (s, 3 H, OMe), 3.88

3

(s, 3 H, OMe), 1.93 (t, J_H,H= 6.0 Hz, 1 H, OH) ppm. MS (EI):

m/z (%) = 248 (98) [M]⁺, 246 (100) [M]⁺, 231 (19) [M – OH]⁺, 229

(14) [M – OH]⁺, 185 (5), 167 (9), 139 (53), 123 (11). IR (CDCl₃):

ν

= 3501 (OH), 2967, 2855, 1607, 1504, 1257, 1207, 1062, 799,

˜

max

581, 511 cm^–1. C₉H₁₁BrO₃(247.08): calcd. C 43.7, H 4.5, Br 32.3;

found C 43.6, H 4.3, Br 32.0.

Preparation of l-Bromo-3,4-dimethoxy-6-(methoxymethyl)ben-

zene:^{[2 5]}NaH (60 % suspension in mineral oil) (0.162 g,

4.045 mmol) was suspended in dry THF (20 mL) at 0 °C. A solu-

tion of 2-bromo-4,5-dimethoxybenzyl alcohol (1.0 g, 4.045 mmol)

in dry THF (5 mL) was added at 0 °C, and the mixture was stirred

at 0 °C for 30 min to give a clear solution of sodium (2-bromo-4,5-

dimethoxyphenyl)methoxide. Methyl iodide (0.3 mL, 4.453 mmol)

was added at 0 °C and the mixture stirred at room temp. for 4 h.

The reaction was quenched with water (50 mL) and diethyl ether

(50 mL) and the mixture extracted with diethyl ether (3ϫ50 mL).

The combined organic extracts were washed with water

(3ϫ50 mL), dried (MgSO₄), and filtered. The solvent was removed

under reduced pressure to afford a yellow oil. Column chromatog-

raphy (30% diethyl ether/70% cyclohexane) afforded 1-bromo-3,4-

3

CDCl₃): δ = 7.3–6.7 (m, 3 H, Ar), 4.88 (dd, J_H,H= 6.8, 2.5 Hz, 1

3

H, 3-H) ppm. 4.82 (d, J_H,H= 13.0 Hz, 1 H, CH₂), 4.61 (d, J_H,H

= 13.0 Hz, 1 H, CH₂), 4.44 (s, 3 H, Ar-OMe), 3.77 (s, 3 H,

CH₂OMe), 3.62 (s, 3 H, 2-OMe), 3.34 (m, 1 H, 1-H), 3.24 (d, ³J_H,H

3

= 6.8 Hz, 1 H, 4-H), 2.97 (s, 3 H, 5-OMe), 2.66 (dd, J_H,H= 14.7,

3.3 Hz, 1 H, 6β-H), 2.14 (dd, J_H,H= 14.7, 3.0 Hz, 1 H, 6α-H)

3

ppm. IR (CDCl ): ν

= 2044 (ν_symCO), 1976, 1966 (ν_asymCO),

˜

3

max

1489, 1262, 1104, 913, 742 cm^–1. HRMS (EI): calcd. for

C₁₈H₂₂FeO₅374.0817; found 374.0817 [M – 2 CO]⁺. Also isolated,

was tricarbonyl[(2–5-η)-4-methoxy-2,4-cyclohexadienone]iron(0)^[47]

(47 mg, 18%).

Tricarbonyl{(1–5-η)-4-methoxy-1-[2Ј-methoxy-6Ј-(methoxymethyl)-

phenyl]-2,4-cyclohexadienyl}iron(1+) Hexafluorophosphate(1–) (16):

208

www.eurjoc.org

Eur. J. Org. Chem. 2008, 196–213

Stereomanipulation of (η⁵-1-Arylcyclohexadienyl)iron Complexes

dimethoxy-6-(methoxymethyl)benzene as a white solid (0.961 g,

91%). H NMR (250 MHz, CDCl₃): δ = 7.01 (s, 1 H, Ar), 6.98 (s, 1 H, 2-H), 4.44 (m, 1 H, 5-H), 4.38 (d, J_H,H= 9.6 Hz, 2 H,

= 7.38 (m, 1 H, 3-H), 7.13 (s, 1 H, Ar), 7.06 (s, 1 H, Ar), 6.32 (m,

1

3

1 H, Ar), 4.46 (s, 2 H, CH₂), 3.88 (s, 3 H, OMe), 3.86 (s, 3 H,

CH₂OMe), 4.05 (s, 3 H, 4-OMe), 3.93 (s, 3 H, Ar-OMe), 3.88 (s, 3

OMe), 3.45 (s, 3 H, CH₂OMe) ppm. MS (EI): m/z (%) = 262 (84) H, Ar-OMe), 3.88 (m, 2 H, 6-H), 3.31 (s, 3 H, CH₂OMe) ppm. ¹³

C

[M]⁺, 260 (85) [M]⁺, 231 (99) [M – OMe]⁺, 229 (100) [M⁺

–

NMR (101 MHz, CD₃COCD₃): δ = 151.1 (4-C or 4Ј-C or 5Ј-C),

OMe]⁺, 181 (74), 151(14), 107 (12). IR (CDCl ): ν_max= 2933, 2836, 150.8 (4-C or 4Ј-C or 5Ј-C), 149.6 (4-C or 4Ј-C or 5Ј-C), 130.7 (1Ј-

˜

3

1609, 1504, 1384, 1160, 1103, 966, 804, 596 cm^–1. HRMS (EI): C or 2Ј-C), 128.1 (1Ј-C or 2Ј-C), 115.7 (3Ј-C), 114.8 (6Ј-C), 98.3

calcd. for C₁₀H₁₃BrO₃260.0048; found 260.0048 [M]⁺. C₁₀H₁₃BrO₃

(261.11): calcd. C 46.0, H 5.0; found C 45.9, H 4.8.

(1-C), 96.4 (2-C), 73.0 (CH₂-O), 72.1 (3-C), 57.9 (2 C, 4-OMe and

benzylic OMe), 56.2 (4Ј-OMe or 5Ј-OMe), 56.1 (4Ј-OMe or 5Ј-

OMe), 43.4 (5-C), 34.6 (6-C) ppm. IR (acetone): ν_max= 2105 (ν_sym

˜

Tricarbonyl{(1–4-η)-2,5β-dimethoxy-5α-[4Ј,5Ј-dimethoxy-2Ј-(meth-

oxymethyl)phenyl]-1,3-cyclohexadiene}iron(0) [9, R = Me, Ar =

4Ј,5Ј-(MeO)₂-2Ј-MeOCH₂C₆H₃]: 1-Bromo-3,4-dimethoxy-6-(meth-

oxymethyl)benzene (3.132 g, 12 mmol) was dissolved in dry diethyl

ether (50 mL) and cooled to –78 °C under nitrogen. nBuLi (1.6 

in hexanes, 7.5 mL, 12 mmol) was added, and 1-lithio-3,4-dimeth-

oxy-6-(methoxymethyl)benzene was formed as a white suspension

by stirring at –78 °C for 1 h. Tricarbonyl[(1–5-η)-1,4-dimethoxy-

2,4-cyclohexadienyl]iron(1+) hexafluorophosphate(1–) (8) (2.2 g,

6.0 mmol) was dissolved in dry dichloromethane (20 mL) and co-

oled to –100 °C. The solution of the nucleophile at –100 °C was

added to the salt through a cannula at –100 °C, and the mixture

was stirred for 2 h. The reaction was quenched with water (50 mL)

and diethyl ether (50 mL) at –100 °C and the mixture warmed

to room temp. The mixture was extracted with diethyl ether

(3 ϫ 50 mL). The combined organic extracts were washed with

water (3ϫ50 mL), dried (MgSO₄), and filtered. The solvent was

removed under reduced pressure to afford a brown oil. Column

chromatography (40 % diethyl ether/60 % cyclohexane) afforded

tricarbonyl{(1–4-η)-2,5β-dimethoxy-5α-[4Ј,5Ј-dimethoxy-2Ј-(meth-

oxymethyl)phenyl]-1,3-cyclohexadiene}iron(0) [9, R = Me, Ar =

4,5-(MeO)₂-2-MeOCH₂C₆H₃] as a nearly colourless oil (0.865 g,

CO), 2049 (ν_asymCO), 1171, 963, 846 cm^–1. HRMS (FAB): calcd.

for C₂₀H₂₁FeO₇429.0637; found 429.0637 [M – PF₆]⁺.

General Procedure for the Addition of Methyl 2-Cyano-2-sodioacet-

ate to (1-Arylcyclohexadienyl)iron(1+) Salts: Methyl 2-cyanoacetate

was dissolved in dry THF (5 mL) and cooled to 0 °C under nitro-

gen. NaH (60% suspension in mineral oil) was added, and methyl

2-cyano-2-sodioacetate was formed as a milky suspension by stir-

ring at 0 °C for 15 min. This was added to a suspension of the (1-

arylcyclohexadienyl)iron(1+) salt in THF (5 mL) at 0 °C, and the

mixture was stirred for 1 h. The reaction was quenched with water

(25 mL) and diethyl ether (25 mL) and the mixture extracted with

diethyl ether (3 ϫ 25 mL). The combined organic extracts were

washed with water (3ϫ25 mL), dried (MgSO₄), and filtered. The

solvent was removed under reduced pressure to afford a yellow oil

which was purified by chromatography.

Tricarbonyl{methyl 2-cyano-2-[(2–5-η)-4-methoxy-1β-phenyl-2,4-cy-

clohexadien-1α-yl]acetato}iron(0) (19): According to the general

procedure, methyl 2-cyanoacetate (300 mg, 3 mmol), NaH (60%

suspension in mineral oil) (120 mg, 3 mmol) in THF (20 mL) and

the salt 10 (135 mg, 0.29 mmol) afforded a yellow oil. Column

chromatography (hexane/ethyl acetate gradient; 5:1 to 4:1) afforded

19 as two inseparable diastereoisomers as a golden oil (100 mg,

82%).¹H NMR (270 MHz, CDCl₃) (major diastereoisomer): δ =

1

31%). H NMR (400 MHz, CDCl₃): δ = 7.07 (s, 1 H, 3Ј-H), 7.04

3

(s, 1 H, 6Ј-H), 5.28 (dd, J_H,H= 6.8, 2.4 Hz, 1 H, 3-H), 4.53 (s, 2

H, CH₂), 3.92 (s, 3 H, Ar-OMe), 3.88 (s, 3 H, Ar-OMe), 3.64 (s, 3

3

7.4–7.2 (m, 5 H, Ar-H), 5.30 (dd, J_H,H= 6.7, 2.3 Hz, 1 H, 3-H),

H, 2-OMe), 3.40 (s, 3 H, CH₂OMe), 3.31 (ddd, J_H,H= 3.9, 2.4,

2.4 Hz, 1 H, 1-H), 2.99 (d, ³J_H,H= 6.8 Hz, 1 H, 4-H), 2.93 (s, 3 H,

5-OMe), 2.31 (dd, ³J_H,H= 14.7, 3.9 Hz, 1 H, 6β-H), 2.17 (dd, ³J_H,H

= 14.7, 2.3 Hz, 1 H, 6α-H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ

= 147.8 (4Ј-C or 5Ј-C), 146.2 (4Ј-C or 5Ј-C), 140 (2-C), 134.2 (1Ј-

C or 2Ј-C), 130.8 (1Ј-C or 2Ј-C), 111.9 (2 C, 3Ј-C and 6Ј-C), 82.4

(6-C), 71.6 (CH₂), 65.0 (3-C), 58.3 (CH₂OMe), 56.1 (5Ј-OMe), 55.8

(4Ј-OMe), 54.8 (4-C), 54.6 (2-OMe), 51.5 (1-C), 49.4 (5-OMe), 42.9

3.70 (s, 3 H, Ar-OMe), 3.59 (s, 1 H, CO₂Me) 3.62 (s, 1 H, CHCN),

3

3.33 (m, 1 H, 5-H), 3.13 (d, J_H,H= 6.6 Hz, 1 H, 3-H), 2.67 (dd,

3

³J_H,H= 15.5, 2.6 Hz, 1 H, 6β-H); 2.44 (dd, J_H,H= 15.5, 3.3 Hz, 1

H, 6α-H); (minor diastereoisomer): δ = 7.4–7.2 (m, 5 H, Ar-H),

3

5.22 (dd, J_H,H= 6.6, 2.6 Hz, 1 H, 3-H), 3.66 (s, 3 H, Ar-OMe),

3.64 (s, 1 H, CHCN), 3.41 (s, 1 H, CO₂Me), 3.33 (m, 1 H, 5-H),

3

3.09 (d, J_H,H= 6.6 Hz, 1 H, 3-H), 2.79 (dd, J_H,H= 15.5, 2.6 Hz,

3

1 H, 6β-H); 2.39 (dd, J_H,H= 15.5, 3.3 Hz, 1 H, 6α-H) ppm. MS

(6-C) ppm. IR (CH Cl ): ν_max= 2048 (ν_symCO), 1979, 1968 (ν_asym

˜

2

(EI): m/z (%) = 376 (1) [M – 2 CO]⁺, 339 (12) [M – 3 CO]⁺, 240

CO), 1266, 1106, 747 cm^–1. HRMS (EI): calcd. for C₁₉H₂₄FeO₆

404.0922; found 404.0922 [M – 2 CO]⁺. Also isolated, was tricar-

bonyl[(2–5-η)-4-methoxy-2,4-cyclohexadienone]iron(0)^[47](0.279 g,

18%).

(14), 184 (100), 169 (56), 141 (50) 115 (44). IR (CH Cl ): ν =

˜

max

2

2247 (CN), 2048 (ν_symCO), 1975, 1745 (ν_asymCO), 1600,

1492 cm^–1. HRMS (CI): calcd. for C₂₀H₂₁FeN₂O₆441.0749; found

441.0749 [M + NH₄]⁺.

Tricarbonyl{(1–5-η)-1-[4Ј,5Ј-dimethoxy-2Ј-(methoxymethyl)phenyl]-

4-methoxy-2,4-cyclohexadienyl}iron(1+) Hexafluorophosphate(1–) Tricarbonyl{methyl 2-[(2–5-η)-1β-(2Ј-allyloxyphenyl)-4-methoxy-

(18): Triphenylcarbenium hexafluorophosphate (388 mg, 1 mmol)

was dissolved in freshly distilled dichloromethane (10 mL) and the

mixture stirred with potassium carbonate (100 mg, 1 mmol) at 0 °C

for 5 min. Tricarbonyl{(1–4-η)-2,5β-dimethoxy-5α-[4Ј,5Ј-dimeth-

oxy-2Ј-(methoxymethyl)phenyl]-1,3-cyclohexadiene}iron(0) [9, R =

2,4-cyclohexadien-1α-yl]-2-cyanoacetato}iron(0) (21): According to

the general procedure, methyl 2-cyanoacetate (297 mg, 3 mmol),

NaH (60% suspension in mineral oil) (120 mg, 3 mmol) and the

salt 14 (300 mg, 0.57 mmol) afforded a yellow oil. Column

chromatography (70% diethyl ether/30% petroleum ether) afforded

Me, Ar = 4Ј,5Ј-(OMe)₂-2Ј-MeOCH₂C₆H₃] (462 mg, 1 mmol) was 21 as two inseparable diastereoisomers as a pale yellow gum

1

dissolved in freshly distilled dichloromethane (2 mL) and added to

the solution at 0 °C. The reaction mixture darkened and was stirred

at 0 °C for 1 h. The reaction mixture was added dropwise to dry

diethyl ether (200 mL) at 0 °C, and an orange precipitate formed.

Reprecipitation (acetone/diethyl ether) afforded tricarbonyl{(1–5-

η)-1-[4Ј,5Ј-dimethoxy-2Ј-(methoxymethyl)phenyl]-4-methoxy-2,4-

cyclohexadienyl}iron(1+) hexafluorophosphate(1–) (18) as an

(214 mg, 79%). H NMR (270 MHz, CDCl₃): δ = 7.48–6.84 (m, 8

3

H, Ar), 6.02 (tdd, J_H,H= 17.2, 10.2, 5.0 Hz, 2 H, CH₂CH=CH₂)

5.39 (m, 4 H, CH₂CH=CH₂), 5.32 (m, 1 H, 3-H), 5.19 (dd, J = 6.6,

2.3 Hz, 1 H, 3-H), 4.88 (s, 1 H, 2Ј-H), 4.84 (s, 1 H, 2Ј-H), 4.56 (d,

³J_H,H= 5.3 Hz, 4 H, OCH₂), 3.84 (s, 3 H, 4-OMe), 3.77 (s, 3 H, 4-

OMe), 3.66 (s, 3 H, CH₂OMe), 3.39 (s, 3 H, CH₂OMe), 3.28 (m, 2

H, 5-H), 3.03 (d, ³J_H,H= 6.6 Hz, 1 H, 2-H), 2.98 (dd, ³J_H,H= 16.2,

1

3

orange solid (363 mg, 65%): H NMR (270 MHz, CD₃COCD₃): δ

2.6 Hz, 1 H, 6β-H), 2.84 (d, J_H,H= 6.6 Hz, 1 H, 2-H), 2.54 (dd,

Eur. J. Org. Chem. 2008, 196–213

www.eurjoc.org

209

C. E. Anson, A. V. Malkov, C. Roe, E. J. Sandoe, G. R. Stephenson

NaH (60% suspension in mineral oil) (45 mg, 1.13 mmol) and the

FULL PAPER

³J_H,H= 16.2, 2.3 Hz, 1 H, 6β-H), 2.20 (dd, J_H,H= 16.2, 3.3 Hz, 1

3

H, 6α-H), 2.07 (dd, J_H,H= 16.2, 3.3 Hz, 1 H, 6α-H) ppm. MS salt 24 (400 mg, 0.75 mmol) afforded a yellow oil. Column

(EI): m/z (%) = 451 (1) [M – CO]⁺, 423 (1) [M – 2 CO]⁺, 395 (18) chromatography (50% diethyl ether/50% petroleum ether) afforded

[M – 3 CO]⁺, 354 (27), 322 (23), 255 (76), 199 (100). IR (film): ν

27 as two inseparable diastereoisomers as a pale yellow gum

˜

max

= 2246 (CN), 2048 (ν_symCO), 1971 (ν_asymCO), 1743 (C=O), 1599, (40 mg, 11%). ¹H NMR (270 MHz, CDCl₃) (major diastereoiso-

1489, 1042, 752 cm^–1. C₂₃H₂₁FeNO₇(479.26): calcd. C 57.6, H 4.4,

N 2.9; found C 57.8, H 4.5, N 3.2.

mer): δ = 7.18 (t, ³J_H,H= 8.3 Hz, 1 H, Ar), 6.55 (d, ³J_H,H= 8.6 Hz,

3

2 H, Ar), 5.64 (d, J_H,H= 5.0 Hz, 1 H, 3-H), 5.51 (d, J_H,H

=

5.0 Hz, 1 H, 4-H), 3.93 (s, 3 H, Ar-OMe), 3.86 (s, 3 H, Ar-OMe),

Tricarbonyl{methyl 2-[(2–5-η)-1β-(2Ј-anisyl)-4-methoxy-2,4-cyclo-

hexadien-1α-yl]-2-cyanoacetato}iron(0) (23): According to the gene-

ral procedure, methyl cyanoacetate (495 mg, 5 mmol), NaH (60%

suspension in mineral oil) (200 mg, 5 mmol) and the salt 22^[4]

(500 mg, 1.0 mmol) afforded a yellow oil. Column chromatography

(50% diethyl ether/50% petroleum ether) afforded 23 as pale yellow

solids. Diastereoisomer 1 (168 mg, 37 %). ¹H NMR (270 MHz,

CDCl₃): δ = 7.29–7.24 (m, 2 H, Ar), 7.00–6.86 (m, 2 H, Ar), 5.39

3

3.83 (d, J_H,H= 3.3 Hz, 1 H, 1Ј-H), 3.73 (s, 3 H, 2-OMe), 3.49 (s,

3 H, CO₂Me), 3.26 (m, 1 H, 1-H), 2.29 (dd, ³J_H,H= 15.2, 11.1 Hz,

3

1 H, 6β-H), 1.62 (dd, J_H,H= 15.2, 3.3 Hz, 1 H, 6α-H) ppm. MS

(EI): m/z (%) = 244 (100) [M]⁺. IR (film): ν

= 2250 (CN), 2038

˜

max

(ν_symCO), 1968 (ν_asymCO), 1750 (C=O), 1593, 1473, 1257, 1111,

728 cm^–1. IR (CH Cl ): ν_max= 3071, 1487, 1135 cm^–1. HRMS (EI):

˜

2

calcd. for C₂₀H₂₁FeNO₆427.0718; found 427.0718 [M – 2 CO]⁺.

Also isolated, was 2,2Ј,4-trimethoxybiphenyl^[53](42 mg,

0.172 mmol, 23%). ¹H NMR (270 MHz, CDCl₃): δ = 7.27 (m, 3

3

(dd, J_H,H= 7.0, 3.0 Hz, 1 H, 3-H), 4.80 (s, 1 H, 2Ј-H), 3.85 (s, 3

H, 4-OMe), 3.77 (s, 3 H, Ar-OMe), 3.39 (s, 3 H, CO₂Me), 3.28 (m,

3

H, Ar), 6.95 (d, J_H,H= 8.9 Hz, 2 H, Ar), 6.65 (d, J_H,H= 8.3 Hz,

2 H, Ar), 3.84 (s, 3 H, OMe), 3.74 (s, 6 H, OMe, OMe) ppm.

C₁₅H₁₆O₃(244.29): calcd. C 73.8, H 6.6; found C 73.6, H 6.7.

3

1 H, 5-H), 2.84 (d, J_H,H= 6.9 Hz, 1 H, 2-H), 2.50 (dd, J_H,H

=

3

16.2, 2.6 Hz, 1 H, 6β-H), 2.15 (dd, J_H,H= 16.2, 3.3 Hz, 1 H, 6α-

H) ppm. MS (EI): m/z (%) = 369 (2) [M – 3 CO]⁺, 319 (2), 255 (2)

Tricarbonyl{methyl 2-cyano-2-[(2–5-η)-5-{[2ЈЈ-cyano-2ЈЈ-(meth-

oxycarbonyl)ethenyl]phenyl}-2-methoxy-2,4-cyclohexadien-1α-yl]-

acetato]iron(0) (28): According to the general procedure, methyl 2-

cyanoacetate (300 mg, 3 mmol), NaH (60% suspension in mineral

oil) (120 mg, 3 mmol) and the salt 12b (150 mg, 0.3 mmol) afforded

a yellow oil. Column chromatography (hexane/ethyl acetate gradi-

ent; 5:1 to 2:1) afforded 28 as a mixture of inseparable diastereoiso-

214 (40), 184 (7), 121 (19), 43 (100). IR (CH Cl ): ν_max= 2048 (ν_sym

˜

2

CO), 1972 (ν_asymCO) cm^–1. HRMS (EI): calcd. for C₁₈H₁₉FeNO₄

369.0663; found 369.0663 [M – 3 CO]⁺. Diastereoisomer 2 (195 mg,

1

43%). H NMR (270 MHz, CDCl₃): δ = 7.46–6.88 (m, 4 H, Ar),

3

5.18 (dd, J_H,H= 6.9, 2.6 Hz, 1 H, 3-H), 4.75 (s, 1 H, 2Ј-H), 3.84

(s, 3 H, C4-OMe), 3.82 (s, 3 H, Ar-OMe), 3.81 (s, 3 H, CO₂Me),

3

3.28 (m, 1 H, 5-H), 3.03 (d, J_H,H= 6.9 Hz, 1 H, 2-H), 2.94 (dd,

mers as a yellow gum (116 mg, 72%). ¹H NMR (270 MHz, CDCl₃)

3

³J_H,H= 16.2, 2.6 Hz, 1 H, 6β-H), 2.03 (dd, J_H,H= 16.2, 3.3 Hz, 1

3

H, 6α-H) ppm. MS (EI): m/z (%) = 425 (1) [M – CO]⁺, 397 (1)

[M – 2 CO]⁺, 369 (8) [M⁺– 3 CO]⁺, 313 (12) [M⁺– 3 CO – Fe]⁺,

(major diastereoisomer): δ = 8.69 (s, 1 H, 1Ј-H), 8.01 (d, J_H,H

=

3

8 Hz, 1 H, Ar-H), 7.6–7.2 (m, 3 H, Ar-H), 5.58 (dm, J_H,H

3

5.1 Hz, 1 H, 3-H or 4-H), 5.31 (d, J_H,H= 5.1 Hz, 1 H, 3-H or 4-

H), 3.91 (s, 3 H, Ar-OMe), 3.9–3.7 (m, 1 H, CHCN), 3.72 (s, 3 H,

CO₂Me), 3.44 (s, 3 H, CO₂Me), 2.70 (dd, J_H,H= 15.8, 4 Hz, 1 H,

214 (100). IR (CH Cl ): ν = 2051 (ν_symCO), 1978 (ν_asymCO)

˜

max

2

cm^–1. C₂₁H₁₉FeNO₇(453.23): calcd. C 55.7, H 4.2, N 3.1; found C

3

55.8, H 4.1, N 3.1.

3

1-H), 2.33 (dd, ³J_H,H= 15.8, 11 Hz, 1 H, 6β-H), 1.75 (dd, d, J_H,H

Tricarbonyl(methyl 2-cyano-2-{(2–5-η)-5-[2Ј-methoxy-6Ј-(meth-

oxymethyl)phenyl]-2,4-cyclohexadien-1α-yl}acetato)iron(0) (25): Ac-

cording to the general procedure, methyl 2-cyanoacetate (46 mg,

0.46 mmol), NaH (60 % suspension in mineral oil) (18 mg,

0.46 mmol) and the salt 16 (125 mg, 0.23 mmol) afforded a yellow

oil. Column chromatography (10 % diethyl ether/90 % petroleum

ether) afforded 25 as two inseparable diastereoisomers as a pale

yellow gum (96 mg, 88%). ¹H NMR (270 MHz, CDCl₃) (major

= 15.8, 3 Hz, 1 H, 6α-H); (minor diastereoisomer): δ = 8.67 (s, 1

3

H, 1Ј-H), 7.99 (d, J_H,H= 8 Hz, 1 H, Ar-H), 7.6–7.2 (m, 3 H, Ar-

3

H), 5.60 (d, J_H,H= 5.1 Hz, 1 H, 3-H or 4-H), 5.28 (d, J_H,H

=

5.1 Hz, 1 H, 3-H or 4-H), 3.92 (s, 3 H, Ar-OMe), 3.9–3.8 (m, 1 H,

CHCN), 3.81 (s, 3 H, Ar-CO₂Me), 3.42 (s, 3 H, Ar-CO₂Me), 2.65

3

(dd, J_H,H= 15.8, 4 Hz, 1 H, 1-H), 2.47 (dd, J_H,H= 15.8, 11 Hz,

3

1 H, 6β-H), 1.80 (dd, J_H,H= 15.8, 3 Hz, 1 H, 6α-H) ppm. MS

(EI): m/z (%) = 448 (14) [M – 3 CO]⁺, 349 (27), 295 (32), 234 (55),

3

195 (83), 165 (100) [M]⁺, 152 (55). IR (film): ν

= 2956, 2925,

diastereoisomer): δ = 7.25 (t, J_H,H= 7.9 Hz, 1 H, Ar), 7.07 (d,

˜

max

3

³J_H,H= 7.6 Hz, 1 H, Ar), 6.85 (d, J_H,H= 8.3 Hz, 1 H, Ar), 5.63

2849 (CN), 2048 (ν_symCO), 1968 (ν_asymCO), 1735 (C=O) cm^–1.

HRMS (CI): calcd. for C₂₅H₂₄FeN₃O₈550.0913; found 550.0910

[M + NH₄]⁺.

3

(d, J_H,H= 5.0 Hz, 1 H, 3-H), 5.59 (d, J_H,H= 5.0 Hz, 1 H, 4-H),

4.68 (d, ³J_H,H= 10.6 Hz, 1 H, CH₂OMe), 4.46 (d, ³J_H,H= 10.6 Hz,

1 H, CH₂OMe), 3.96 (s, 3 H, Ar-OMe), 3.89 (d, J_H,H= 3.3 Hz, 1

3

Tricarbonyl(methyl 2-cyano-2-{(2–5-η)-1β-[4Ј,5Ј-dimethoxy-2Ј-

(methoxymethyl)phenyl]-2,4-cyclohexadien-1α-yl}acetato)iron(0)

(29): According to the general procedure, methyl 2-cyanoacetate

(86 mg, 0.871 mmol), NaH (60% suspension in mineral oil) (35 mg,

0.871 mmol) and 18 (250 mg, 0.436 mmol) afforded a yellow oil.

Column chromatography (40% diethyl ether/60% petroleum ether)

afforded 29 as two inseparable diastereoisomers as a pale yellow

H, 1Ј-H), 3.74 (s, 3 H, 2-OMe), 3.52 (s, 3 H, CO₂Me), 3.51 (s, 3 H,

3

CH₂OMe), 3.30 (m, 1 H, 1-H), 2.42 (dd, J_H,H= 15.2, 10.9 Hz, 1

3

H, 6β-H), 1.56 (dd, J_H,H= 15.2, 3.3 Hz, 1 H, 6α-H) ppm. IR

(CH Cl ): ν = 2245 (CN), 2045 (ν_symCO), 1975 (ν_asymCO),

˜

max

2

1752 (C=O), 1630, 1384, 1266, 1079, 738 cm^–1. HRMS (EI): calcd.

for C₂₀H₂₃FeNO₅413.0926; found 413.0926 [M – 3 CO]⁺. Also

isolated, was 2,4Ј-dimethoxy-6-(methoxymethyl)biphenyl (3 mg,

0.012 mmol, 4%). ¹H NMR (270 MHz, CDCl₃): δ = 7.33 (t, J =

7.9 Hz, 1 H, Ar), 7.19–7.13 (m, 3 H, Ar), 6.98–6.89 (m, 3 H, Ar),

4.16 (s, 2 H, CH₂), 3.86 (s, 3 H, OMe), 3.72 (s, 3 H, OMe), 3.27 (s,

1

gum (139 mg, 0.264 mmol, 61%). H NMR (270 MHz, CDCl₃): δ

= 7.19 (s, 1 H, Ar), 7.03 (s, 1 H, Ar), 6.87 (s, 1 H, Ar), 6.85 (s, 1

3

H, Ar), 5.35 (dd, J_H,H= 6.6, 2.3 Hz, 1 H, 3-H), 5.20 (dd, J = 6.6,

2.3 Hz, 1 H, 3-H), 4.83 (s, 1 H, 1Ј-H), 4.75 (s, 1 H, 1Ј-H), 4.52 (dd,

3 H, CH OMe) ppm. IR (CH Cl ): ν_max= 1598, 1468, 1384, 1260,

˜

2

3

³J_H,H= 17.2, 11.2 Hz, 2 H, CH₂OMe), 4.18 (dd, J_H,H= 11.2,

1079, 740 cm^–1. HRMS (EI): calcd. for C₁₆H₁₈O₃258.1256; found

4.3 Hz, 2 H, CH₂OMe), 3.97 (s, 3 H, Ar-OMe), 3.92 (s, 3 H, Ar-

OMe), 3.89 (s, 6 H, Ar-OMe, ArOMe), 3.87 (s, 3 H, 4-OMe), 3.79

258.1256 [M]⁺.

Tricarbonyl{methyl 2-cyano-2-[(2–5-η)-5-(2Ј,6Ј-dimethoxyphenyl)-2- (s, 3 H, 4-OMe), 3.68 (s, 3 H, CO₂Me), 3.48 (s, 3 H, CO₂Me), 3.38

methoxy-2,4-cyclohexadien-1α-yl]acetato}iron(0) (27): According to

the general procedure, methyl 2-cyanoacetate (112 mg, 1.13 mmol),

(s, 3 H, CH₂OMe), 3.36 (s, 3 H, CH₂OMe), 3.32 (m, 2 H, 5-H),

3.07 (m, 2 H, 6β-H, 2-H), 2.82 (d, J_H,H= 6.6 Hz, 1 H, 2-H), 2.68

3

210

www.eurjoc.org

Eur. J. Org. Chem. 2008, 196–213

Stereomanipulation of (η⁵-1-Arylcyclohexadienyl)iron Complexes

3

2003, 44, 5393–5395; A. J. Pearson, X. Wang, J. Am. Chem.

Soc. 2003, 125, 13326–13327; H.-J. Knölker, S. Filali, Synlett

2003, 1752–1754; H.-J. Knölker, M. Wolpert, Tetrahedron 2003,

59, 5317–5322; H.-J. Knölker, W. Frohner, K. R. Reddy, Eur. J.

Org. Chem. 2003, 740–746; L. Miesch, C. Gateau, F. Morin,

M. Franck-Neumann, Tetrahedron Lett. 2002, 43, 7635–7638;

H.-J. Knölker, T. Hopfmann, Tetrahedron 2002, 58, 8937–8945;

M. Franck-Neumann, P. Geoffroy, D. Gassmann, Synlett 2002,

2054–2058; M. Franck-Neumann, P. Geoffroy, H. D. Philippe,

Tetrahedron Lett. 2002, 43, 2277–2280; M. Franck-Neumann,

P. Geoffroy, P. Bissinger, S. Adelaide, Tetrahedron Lett. 2001,

42, 6401–6404; M. Franck-Neumann, L. Miesch-Gross, C. Ga-

teau, Eur. J. Org. Chem. 2000, 3693–3702; M. Franck-Neum-

ann, P. Geoffroy, F. Gumery, Tetrahedron Lett. 2000, 41, 4219–

4222; H.-J. Knölker, W. Frohner, Synthesis 2000, 14, 2131–

2136; H.-J. Knölker, S. Cammerer, Tetrahedron Lett. 2000, 41,

5035–5038; H.-J. Knölker, W. Frohner, Tetrahedron Lett. 1999,

40, 6915–6918; H.-J. Knölker, E. Baum, T. Hopfmann, Tetrahe-

dron 1999, 55, 10391–10412; H.-J. Knölker, M. Bauermeister,

J.-B. Pannek, D. Bläser, R. Boese, Tetrahedron 1993, 49, 841–

862; H.-J. Knölker, K. Hartmann, Synlett 1991, 428–430; A. J.

Pearson, M. K. O’Brien, J. Org. Chem. 1989, 54, 4663–4673;

A. J. Pearson, Y. S. Cheng, J. Org. Chem. 1986, 51, 1939–1947;

M. Chandler, E. Mincione, P. J. Parsons, J. Chem. Soc. Chem.

Commun. 1985, 1233–1234; A. J. Pearson, G. C. Heywood, M.

Chandler, J. Chem. Soc. Perkin Trans. 1 1982, 2631–2639; A. J.

Pearson, C. W. Ong, J. Am. Chem. Soc. 1981, 103, 6686–6690.

D. A. Owen, A. V. Malkov, I. M. Palotai, C. Roe, E. J. Sandoe,

G. R. Stephenson, Chem. Eur. J. 2007, 13, 4293–4311.

A. V. Malkov, A. Auffrant, C. Renard, E. Rose, F. Rose-

Munch, D. A. Owen, E. J. Sandoe, G. R. Stephenson, Inorg.

Chim. Acta 1999, 296, 139–149.

This nomenclature has been discussed in the context of our

synthesis of O-methyl joubertiamine (see ref.^[7]), and sub-

sequently reviewed (see ref.^[1a]). All four possible patterns of

iterative reactions (1,1, 1,2, 1,3 and 1,4) are accessible with the

(η⁵-cyclohexadienyl)iron series of electrophiles: G. R. Stephen-

son, S. T. Astley, I. M. Palotai, P. W. Howard, D. A. Owen, S.

Williams, in Organic Synthesis via Organometallics (Eds.: K. H.

Dötz, R. W. Hoffmann), Vieweg, Braunschweig, 1991, pp. 169–

185.

G. R. Stephenson, H. Finch, D. A. Owen, S. Swanson, Tetrahe-

dron 1993, 49, 5649–5662.

D. A. Owen, G. R. Stephenson, H. Finch, S. Swanson, Tetrahe-

dron Lett. 1990, 31, 3401–3404.

The terms “linear” and “iterative” refer to the pattern of

changing hapticity during a sequence of nucleophile additions

to the same metal complex. The hapticity of the electrophile

decreases by one at each nucleophile addition in a linear path-

way, but alternates between hapticities in an iterative pathway;

see: G. R. Stephenson, R. P. Alexander, C. Morley, P. W. How-

ard, Philos. Trans. R. Soc. London, Ser. A 1988, 326, 545–556.

a) S. T. Astley, M. Meyer, G. R. Stephenson, Tetrahedron Lett.

1993, 34, 2035–2038; b) C. E. Anson, S. Hartmann, R. D. Kel-

sey, G. R. Stephenson, Polyhedron 2000, 19, 569–571; c) S. T.

Astley, G. R. Stephenson, J. Chem. Soc. Perkin Trans. 1 1992,

1953–1955; d) S. T. Astley, G. R. Stephenson, Synlett 1992,

507–509.

G. R. Stephenson, I. M. Palotai, W. J. Ross, D. E. Tupper, Syn-

lett 1991, 586–588.

For our formal total synthesis of lycoramine, see: a) E. J.

Sandoe, G. R. Stephenson, S. Swanson, Tetrahedron Lett. 1996,

37, 6283–6286; b) E. J. Sandoe, G. R. Stephenson, Adv. Synth.

Catal., submitted.

(dd, J_H,H= 14.8, 2.3 Hz, 1 H, 6β-H), 3.30 (dd, J_H,H= 14.8,

3

3.3 Hz, 1 H, 6α-H), 2.18 (dd, J_H,H= 14.8, 3.3 Hz, 1 H, 6α-H)

ppm. IR (film): ν

= 2254 (CN), 2048 (ν_symCO), 1972 (ν_asym

˜

max

CO), 1743 (C=O), 1496, 1228, 1123, 914, 734 cm^–1. HRMS (EI):

calcd. for C₂H₂₅FeNO₆443.1031; found 443.1031 [M – 3 CO]⁺.

Also isolated, was tricarbonyl{(2–5-η)-methyl 2-cyano-5-[4Ј,5Ј-di-

methoxy-2Ј-(methoxymethyl)phenyl]-2-methoxy-2,4-cyclohexa-

dien-1α-yl]acetato}iron(0) (30) (36 mg, 16%). ¹H NMR (270 MHz,

CDCl₃): δ = 6.93 (s, 1 H, Ar), 6.87 (s, 1 H, Ar), 5.68 (d, J_H,H

4.6 Hz, 1 H, 4-H), 5.58 (dd, J_H,H= 4.6, 1.0 Hz, 1 H, 3-H), 4.56

(d, J_H,H= 10.6 Hz, 1 H, CH₂OMe), 4.44 (dd, J_H,H= 10.6 Hz, 1

H, CH₂OMe), 3.93 (d, J_H,H= 5.3 Hz, 1 H, 1Ј-H), 3.88 (s, 6 H,

Ar-OMe), 3.76 (s, 3 H, 2-OMe), 3.52 (s, 3 H, CO₂Me), 3.51 (s, 3

H, CH₂OMe), 3.34 (m, 1 H, 1-H), 2.37 (dd, J_H,H= 16.2, 11.2 Hz,

1 H, 6β-H), 1.82 (dd, J_H,H= 16.2, 2.3 Hz, 1 H, 6α-H) ppm. IR

3

=

3

(film): ν

= 2249 (CN), 2044 (ν_symCO), 1967 (ν_asymCO), 1748

˜

max

(C=O), 1607, 1507, 1343, 1088, 1028, 737 cm^–1. HRMS (EI): calcd.

for C₂₁H₂₅FeNO₆443.1031; found 443.1042 [M – 3 CO]⁺. Also

isolated, was 2-(methoxymethyl)-4,4Ј,5-trimethoxybiphenyl (11 mg,

1

9%). H NMR (270 MHz, CDCl₃): δ = 7.30 (d, J = 8.6 Hz, 2 H,

Ar), 7.03 (s, 1 H, Ar), 6.96 (d, J = 8.6 Hz, 2 H, Ar), 6.78 (s, 1 H,

Ar), 4.27 (s, 2 H, CH₂OMe), 3.94 (s, 3 H, C4Ј-OMe), 3.88 (s, 3 H,

OMe), 3.86 (s, 3 H, OMe), 3.34 (s, 3 H, CH₂OMe) ppm. HRMS

(EI): calcd. for C₁₇H₂₀O₄288.1362; found 288.1362 [M]⁺.

[4]

[5]

Acknowledgments

The authors acknowledge the Royal Society (London), the Un-

derwood Fund, Engineering and Physical Sciences Research Coun-

cil (EPSRC), and Glaxo Smith Kline for financial support, and

the EPSRC Mass Spectrometry Centre at the University of Wales,

Swansea for high-resolution mass spectrometric measurements.

[6]

[1] a) For a review of stereocontrolled multihapto electrophilic π

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enyl)iron series is one of the most widely applied of this series

of electrophiles, that span the hapticity range η²–η⁷. b) For a

survey of organoiron complexes, see: G. R. Stephenson, “Orga-

nometallic Complexes of Iron” in “Science of Synthesis”,

Houben-Weyl Methods of Molecular Transformations, vol. 1

(Ed.: M. Lautens), Georg Thieme Verlag, Stuttgart, 2001, pp.

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[2] The chirality properties of these complexes and their use in

iterative and linear sequences of asymmetric C–C bond-forma-

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C. E. Anson, A. V. Malkov, C. Roe, E. J. Sandoe, G. R. Stephenson

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Received: September 27, 2007

Published Online: November 7, 2007

Eur. J. Org. Chem. 2008, 196–213

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213

Article Doi

Stereomanipulation of (η5-1-arylcyclohexadienyl)iron complexes

DOI: 10.1002/ejoc.200700919

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Full text of DOI:10.1002/ejoc.200700919

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