Baeckvall J.-E. (ed.) Modern Oxidation Methods

Подождите немного. Документ загружается.

Enantioselective Alkene Epoxidation Although ascorbic acid is chiral and plays a key

role in boosting the activity of 6, enantioselective epoxidation was not observed [94a].

By contrast, Beller, Bolm, and coworkers reported that enantiomerically enriched

epoxides were obtained with manganese complexes based on chiral analogs of the

tmtacn ligand (Figure 11.8) [94f,103,104]. The ﬁrst asymmetric epoxidation reactions

were catalyzed by in situ prepared Mn catalysts from N-substituted chiral tacn ligands

[103a]. The chirality was introduced via alkylation of the secondary amine moieties

to generate the C

-symmetric ligands depicted in Figure 11.8.

Styrene was converted to the corresponding epoxide with an ee of 43%, albeit in

only 15% yield after 5 h using H

and the Mn complex based on ligand 25. Using

longer reaction times, higher temperatures and higher catalyst loadings, the yield

was increased but at the price of a decrease in enantioselectivity [103a]. With the

sterically more demanding ligand 26, enantioselectivities in the range 13–38% were

observed for styrene and chromene. Higher enantioselectivity was achieved with

cis-b-methylstyrene as substrate. The trans-epoxide was found as the major product in

55% ee whereas the cis-epoxide was formed as the minor product with an ee of 13%

(Scheme 11.12).

The enantiopure C

-symmetric tris-pyrrolidine-1,4,7-triazacyclononane ligand 27

has been reported by Bolm and coworkers (Figure 11.9) [94f]. The tacn derivative

was obtained by reduction of an

L-proline-derived cyclotripeptide, and the corre-

sponding dinuclear manganese complex was applied in the catalytic enantioselective

epoxidation of vinylarenes with H

as oxidant. For the epoxidation of styrene,

3-nitrostyrene, and 4-chlorostyrene excellent conversions (up to 88%) and ees of up to

30% were obtained [94f]. In addition to the chiral C

- and C

-symmetric ligands,

iPr

iPr iP

HO OH

eMeM

HO OH

Figure 11.8 C

-symmetric chiral ligands [103a].

HHO

3 mol% Mn(OAc)

.4H

4.5 mol% ligand

2 equiv. H

(aq. 30%)

MeOH, 0

55% e.e.

Scheme 11.12 Asymmetric epoxidation with Mn complex of ligand 26 [103a].

11.4 Epoxidation and cis-Dihydroxylation of Alkenes

393

-symmetric tacn analogs have been tested (Figure 11.9) [103]. Thus far, modest

enantioselectivity has been obtained, but the potential of these tmtacn analogs by

further ﬁne-tuning of the chiral ligand structure is evident.

Recently S

€

uss-Fink, Schulpin and coworkers have reported two tmtacn detivatives

where one of the methyl groups has been replaced by a 2-methyl-butyl or 2-hydro-

xybutyl group [105]. The catalytic activity was examined in the oxidation of indene

and phenylethanol (racemic) in the presence of ascorbic acid [94] or oxalate [97].

Although moderate activity was observed (up to 300 t.o.n.), unfortunately only very

low levels of enantioselectivity were achieved (<17%).

Kilic et al. have reported an alternative approach to controlling the stereochemical

outcome of the epoxidation catalyzed by Mn-tmtacn complexes using substrate

control via the hydroxyl group of allylic alcohols and by varying the steric nature of the

substituents on the alkene [106].

Manganese-tacn Derivatives on Solid Supports Several successful attempts to im-

prove catalyst selectivity have been made by encapsulation of the Mn-tmtacn complex

in zeolites [107]. Immobilization of the triazacyclononane ligand on an inorganic

support provided a new class of heterogeneous manganese catalysts with increased

epoxidation selectivity [108]. A novel approach to immobilizing Mn-tmacn-based

catalysts has been taken by Veghini et al. who employed tungstosilicic acid (as a large

anion) to render the catalyst insoluble but still allowing it to be dispersed in

solution [109]. However, as is often the case with immobilized homogenous catalysts,

the conversions were lower than those obtained with the analogous homogenous

catalysts [108].

A notable exception to this is found in the seminal work of De Vos and Jacobs on

immobilization of the tmtacn catalyst onto silica. The heterogenization procedure of

the tacn ligand started with the conversion of dimethyl tacn (dmtacn, 30, Figure 11.10)

to the silylated compound 31 with 3-(glycidyloxy)propyltrimethoxysilane followed

by immobilization on an SiO

surface and subsequently metalation of the hetero-

genized ligand with MnSO

O [99]. Not only was this system highly effective, but

serendipitously it led to the discovery of a previously unexplored ﬁeld of oxidation

catalysis for the tmtacn family of catalysts, that of cis-dihydroxylation of alkenes.

This will be discussed in more depth in the following section. A similar approach to

= R

= Me

= R

28 29

Figure 11.9 Chiral tmtacn based ligands.

394

11 Manganese-Catalyzed Oxidation with Hydrogen Peroxide

immobilizing manganese polypyridyl catalysts has been taken by Stack and

coworkers recently, which may be of relevance to the tmtacn-based systems [110].

By using a copper templating approach, the immobilization of the ligands in

sufﬁcient proximity to allow for two ligands to bind each manganese ion was found

to be essential to achieve full catalytic activity. Although the system employed

peracetic acid as the oxidant, it nevertheless is of direct relevance to the future

design of immobilized manganese-based oxidation catalysts. For example, where a

binuclear catalyst is the active species under homogenous conditions, low surface

coverage of the ligand will limit the ability to form such catalysts in a heterogenized

form. The templating approach allows for two ligands to be immobilized in proximity

to each other and thereby overcomes this problem.

cis-Dihydroxylation of Alkenes cis-Dihydroxylation is an important synthetic trans-

formation, and several reagents can be used for the addition of two hydroxyl groups to

an alkene. Both OsO

and alkaline KMnO

are suitable for cis-dihydroxylation [1, 14],

but the catalytic versions of the OsO

method using O

[111], H

[112], or other

oxidants [113] is the method of choice for this transformation [114]. The introduction

of the highly enantioselective OsO

-catalyzed dihydroxylation by Sharpless and its

extensive use in synthetic chemistry in recent years have provided ample demon-

stration of the key role of this oxidation reaction [115]. The toxicity of OsO

and the

stoichiometric nature of the KMnO

cis-dihydroxylation, which usually provides only

modest yields of diols, are strong incentives to develop catalytic cis-dihydroxylation

reactions with H

such as those based on Fe [116] and Mn (see below).

When using the heterogenized Mn-tmtacn system for the oxidation of alkenes (see

above), De Vos, Jacobs and coworker noted that substantial amounts of cis-diol were

formed in addition to the expected epoxide [99]. In oxidation reactions with 32, with

as oxidant and CH

CN as solvent, alkenes were converted to the corresponding

cis-diols albeit with the catalyst activity with respect to cis-diol formation being modest

(10–60 mol cis-diol/mol Mn) and epoxides being the major products. For internal

alkenes, for example, 2-hexene, retention of conﬁguration was found for both

epoxide and cis-diol. Control experiments with dmtacn 30 showed severe peroxide

decomposition, and no oxidation products were obtained. A sufﬁciently long-lived

MnN

SiO

Si(OCH

)

30 31

Figure 11.10 Structures of dmtacn (30), heterogenizable ligand 31, and the proposed active

complex 32 (X ¼ activated O to be transferred) [99].

11.4 Epoxidation and cis-Dihydroxylation of Alkenes

395

mononuclear complex (32) was postulated as the active species for both epoxidation

and cis-dihydroxylation. This complex contains cis coordination sites for labile

ligands (e.g., H

O and X), and both oxygen atoms from H

O and X (the activated

oxygen) are proposed to be transferred to the alkene to produce the cis-diol [99].

Although the proposed structure was speculative, it did correspond with the results

obtained experimentally.

Prompted by the use of oxalate and other additives and by the observation of cis-diol

formation in the hetereogenized system of De Vos and coworkers, a wider search

for effective additives both to suppress the catalase type activity of the Mn-tmtacn

complexes and to promote cis-dihydroxylation was initiated. An early success was the

strongly enhanced cis-dihydroxylation activity observed using [Mn

(tmtacn)

]

(PF

)

(6) (Figure 11.2) in the combination with aldehydes such as glyoxylic acid

methylester methyl hemiacetal (gmha (33), Scheme 11.13) [94k].

This mixed Mn-tmtacn/activated carbonyl system provided for a highly active and

efﬁcient catalyst for the epoxidation of alkenes as well as the ﬁrst homogeneous

Mn-based catalytic cis-dihydroxylation system using H

. Catalytic oxidations were

performed by slow addition of aqueous 50% H

(1.3 equiv. with respect to the

substrate) to a mixture of alkene, the Mn-tmtacn catalyst (0.1 mol%), and gmha

(25 mol%) in CH

CN at 0



C. Under these reaction conditions high conversions are

reached, whereas only 30% excess of oxidant with respect to substrate was required

(Table 11.8). The H

efﬁciency represented a dramatic improvement compared to

previous Mn-based systems [132]. In most cases the conversions were also signif-

icantly higher than those obtained with oxalate as co-catalyst using 1.3 equiv. of H

Substantial amounts of cis-diols were formed with the cis-diol/epoxide ratio depend-

ing heavily on the alkene structure. The highest selectivity for cis-dihydroxylation was

obtained with cyclooctene (Scheme 11.13), which afforded the cis-diol as the main

product (42%, 420 t.o.n.). Minor amounts of 2-hydroxycyclooctanone were observed

due to overoxidation of the diol. The ring size of cycloalkenes had a profound

inﬂuence on the cis-diol/epoxide product ratio. For cyclic alkenes, almost no trans-diol

could be detected (ratio cis-diol/trans-diol >99.5/0.5). cis-Diol formation is also

observed for aliphatic acyclic alkenes. Yields of diol were signiﬁcantly lower for

trans-2-hexene than for cis-2-hexene, but the cis-diol/epoxide ratio was similar for both

substrates. The aryl-substituted alkenes yielded nearly exclusively epoxide under

these conditions. Importantly, diols were not formed when the substrate was replaced

by the corresponding epoxide in the reaction, excluding epoxide hydrolysis as a

source of diol.

Since cis-diol formation through Mn-catalyzed epoxide hydrolysis can be excluded

it was proposed that the cis-diols were formed by reaction of the alkene with a Mn oxo-

hydroxo species. As in the case of oxalate, activated carbonyl compounds such as

gmha

could in principle inhibit the catalase-active dinuclear Mn complex 6

(Figure 11.2) [34] through formation of mononuclear Mn species via complexation

1) Gmha is an equilibrium mixture, which also contains some hydrated methyl glyoxylate. NMR

experiments indicated that the formation peroxyhydrate from gmha and aqueous H

is established

slowly.

396

11 Manganese-Catalyzed Oxidation with Hydrogen Peroxide

Table 11.8 cis-Dihydroxylation and epoxidation of selected alkenes by H

with Mn-tmtacn/gmha

catalysts [132].

Substrate Conversion % Product Turnover number (t.o.n.)

Cyclohexene 88 Epoxide 590

cis-Diol 90

2-Cyclohexenone 80

Cyclooctene 90 Epoxide 360

cis-Diol 420

2-HO-Cyclooctanone 220

Norbornylene 95 exo Epoxide 540

exo-cis-Diol 180

trans-2-Hexene 77 trans-Epoxide 210

cis-Epoxide 50

RR/SS-Diol 150

RS/SR-Diol 0

cis-2-Hexene 93 cis-Epoxide 450

trans-Epoxide 40

SR/RS-Diol 280

RR/SS-Diol 10

cis-Stilbene 82 cis-Epoxide 260

trans-Epoxide 200

meso-Hydrobenzoin 40

Hydrobenzoin 40

Styrene 97 Epoxide 860

Ph(CH)(OH)CH

OH 60

PhC(O)CH

OH 10

a) 50% aqueous H

(1.3 equiv. with respect to substrate) was added over 6 h to a mixture of alkene

(40 mmol), Mn

(tmtacn)

(PF

)

(0.1 mol%), and GMHA (25 mol%) in MeCN (40 ml) with

internal standard (1.2-dichlorobenzene, 20 mmol) at 0



C. Analysis by GC 1 h after addition of

oxidant was completed.

0.1 mol%

25 mol% gmha

1.3 equiv. H

(aq. 50 %)

MeCN

OHHO

Cis-diol

42% 36%

gmha =

OCH

(33)

Scheme 11.13 Dihydroxylation of alkenes in the presence of glyoxylic acid methyl ester methyl

hemiacetal (33) [94k].

11.4 Epoxidation and cis-Dihydroxylation of Alkenes

397

to the Mn center. cis-Diol formation from an Mn oxo-hydroxo species with a

coordinated hydrated carbonyl ligand could be induced through a hydrogen-bonded

6- membered ring transition state (concerted pathway, Scheme 11.14). Reoxidation of

the Mn center by H

, release of the diol from Mn, and hydration of the carbonyl

compound closes the catalytic cycle. It should be noted that this mechanism was

tentative and based on general principles of manganese coordination chemistry

rather than empirical data, which, once it became available (see below), as is so often

the case, demonstrated that a thorough understanding of a system is essential to

unraveling mechanistic aspects. Nevertheless, the use of activated carbonyl com-

pounds in combination with Mn-tmtacn not only provides for a highly active (up to

860 t.o.n.) and H

-efﬁcient epoxidation system (see above), but also was the most

active Os-free homogeneous catalyst for cis-dihydroxylation (up to 420 t.o.n.),

reported at that stage. Due to competing cis-dihydroxylation and epoxidation path-

ways it was not suitable for routine application in synthesis, however. Nevertheless it

proved an important lead to develop highly selective Mn-catalyzed cis-dihydroxylation

systems employing H

Subsequent to these re ports on the activity of aldehydes in enhancing the

reactivity of Mn-tmtacn-based catalysts, Feringa and coworkers demonstrated that

carboxylic acids at co-catalytic levels wer eactuallyresponsiblefortheenhancement,

and that the aldehydes served solely as a source of these acids [117]. Indeed, in the

presence of carboxylic acids, complex 6 [M n

(m-O)

(tmtacn)

]

2 þ

proved to be

highly efﬁcient in catalyzing the oxidation of alkenes to the corresponding ci s -diol

and epoxide products using H

. The selectivity of the catal ytic syst em both in

terms of cis-dihydroxylation and epoxidation of alkenes could be tuned readily by

judicious choice of the carboxylic acid employed. High turnover numbers (t.o.n.

cis-alkene

cis

concerted pathway

Scheme 11.14 Early proposal for the mechanism of cis-dihydroxylation by 6 (L ¼ tmtacn,

X ¼ CO

Me). Note that gmha is an equilibrium mixture which also contains some hydrated methyl

glyoxylate.

398

11 Manganese-Catalyzed Oxidation with Hydrogen Peroxide

>2000) were achie ved, especially for cis-dihydroxylation, that is, with 2,6-dichloro-

benzoic acid, the highest t.o.n. reported thus far for cis-dihydroxylation of alkenes

catalyzed by an osmium free system. Furthermore, the catalyst formed (see below)

is almost completely efﬁcient in regard to the use of H

for oxidation of

substrates [118].

Recent Mechanistic Insights Until recently, most attention focused either on the

coordination chemistry of the Mn-tmtacn family of complexes or on their appli-

cation in functional group transformation, such as the oxidation of alkenes. A key

challenge faced was probing the molecular nature of the catalysts under the reaction

conditions. In part this was a consequence of their high activity and hence the low

catalyst loadings employed. The complex coordination and redox chemistry, not

least ligand exchange and disproportionation reactions, complicates unraveling the

mode of action of this versatile oxidation catalyst. By analogy with manganese

porphyrin and permanganate chemistry, the obvious candidates for the active

catalytic species are high-valent manganese-oxo species as well as radical inter-

mediates (the latter being readily excluded by the retention of stereochemistry

observed during catalysis). The ﬁrst concerted efforts to explore the mechanistic

aspects of the catalysis were reported by Hage and coworkers [119], who identiﬁed

the formation of carboxylic acid-bridged dinuclear manganese complexes upon

reduction of 6 in aqueous media and by Lindsay-Smith and coworkers in their

studies on the oxidation of cinnamates in buffered aqueous media, primarily using

mass spectrometry [94i,k, 120, 121, 122].

A key feat ure of catalysis with complex 6 was the frequent observation of an

induction period prior to initiation of su bstrate conversion. This indicated that the

original [Mn

(tmtacn)

](PF

)

complex (6)hasﬁrst to be converted to a catalyt-

ically active species. Indeed , it was found that the catalytic activity of Mn-tmtacn was

signiﬁcantly increased when it was pre-treated with excess of H

prior to the

addition of the substrate (in the case of benzyl alcohol oxidation) [94c]. From the

16-line spectrum obtained by electron paramagnetic resonance spectroscopy

(EPR) measurements it was inferred that the Mn

–Mn

dimer was reduced by

to a dinuclear Mn

III

–Mn

mixed-valent species in acetone. The intensity of

the mixed-valent species gradually diminished, with the subse quent appearance of

an Mn

species. EPR stud ies of the catalysts under comparable cat alytic oxidation

conditions using alkenes as subst rates instead of alcohols showed again the mixed-

valence Mn

III

–Mn

dimer [40a, 97]. B ased on EPR data, similar manganese species

were identiﬁed during related phenol oxidation experiments [120]. Barton et al.

proposed the formation of an Mn

¼ O intermediate during the oxidation of 2,6-di-

tert-butylphenol with Mn-tmtacn and H

[121]. In electrospray mass spectro-

metry (ESI/MS) experiments the mononuclear Mn

¼ O species could indeed be

assigned [122]. This species was also generated in oxidation reactions using a

mononuclear Mn

complex and from an in situ prepared Mn

complex using

MnSO

and free tmtacn ligand [94g]. A key question arises, however, as to th e

relevance of these species. It was subsequently shown that the features observed by

EPR spectros copy were only in part related to th e catalysis its elf but w ere mostly

11.4 Epoxidation and cis-Dihydroxylation of Alkenes

399

related to disproportionation reactions at the high catalyst concentrations em-

ployed in mechanistic studies [118]. Furthermore, it was not demonstrated that the

¼ O specie s observed by ESI-MS were active in the catalytic oxidation of

alkenes.

For the combination of 6 and alkyl and aromatic carboxylic acids, the high activity

and selectivity was found to be due to the in situ formation of bis-m-carboxylato-

bridged dinuclear manganese(III,III) complexes [117, 118]. These complexes were

formed through a series of redox processes (Scheme 11.15) in which H

acts as a

terminal reductant of the dimeric Mn

complex 6. The ability of different carboxylate

ligands to tune the activity of the catalyst was found to be dependent on both the

electron-withdrawing nature of the ligand and on steric effects; that is, bulky electron-

deﬁcient ligands gave the highest activity. By contrast, the cis-diol/epoxide selectivity

is determined primarily by steric factors; that is, more bulky carboxylic acids lead to

a higher ratio in favor of the cis-diol product. A mechanistic study of the roles played

76543210

200

400

600

800

1000

Phase II

Phase I

t.o.n.

time (h)

Phase III

0.1 mol% [Mn

(tmtacn)

](PF

)

0.1 mol% CCl

(aq. 50% aq.)

CN, 0 °C

OHHOO

Scheme 11.15 cis-Dihydroxylation and

epoxidation of alkenes by 6: the multiple roles of

carboxylic acids in forming the active catalysts

for homogenous alkene oxidation from the

catalyst 6 allow for the effect of variations in the

composition of the reaction mixture on catalytic

activity to be understood at a molecular level.

400

11 Manganese-Catalyzed Oxidation with Hydrogen Peroxide

by solvent, initial catalyst oxidation state, water, carboxylic acid concentration, and

the nature of the carboxylic acid employed in determining both the activity and the

selectivity observed was reported [118]. The resting state of the active form of the

catalyst, that is, [Mn

III

O(m-O)(m-RCO

)

(tmtacn)

]

2 þ

, was identiﬁed through a com-

bination of speciation analysis employing a range of spectroscopic techniques and

isotope-labeling studies. These [Mn

III

(m-O)(m-RCO

)

(tmtacn)

]

2 þ

complexes show

coordination chemistry dependent on redox state and solvent (Scheme 11.15), but the

available evidence indicates that redox changes or change in the dinuclear structure

do not occur during catalysis.

CCl

III III

CCl

II II

CCl

II II

H HH

CCl

III III

OMn

IV IV

CCl

II II

CCl

OMn

IV IV

OHHO O

+ H

+ 2 H

+ CCl

+ H

+ 2 CCl

= LMn

activated complex]

+ H

- H

Phase I

Scheme 11.15 (Continued).

11.4 Epoxidation and cis-Dihydroxylation of Alkenes

401

The report by de Boer et al. [118] does not exclude the possibility of the transient

formation of high-valent mononuclear species in the catalytic cycle as proposed by

several groups [94i,k, 120, 121, 122]. However, the data available up to now support

an alternative view of the role of the tmtacn-based manganese catalysts as Lewis acid

activators of H

, which holds considerable implications for the study of related

homogeneous manganese oxidation catalysts and in building a conceptual bridge

with related biological systems such as dinuclear catalase and arginase enzymes (see

above) [10].

An important question, however, is whether all systems based on the manganese-

tmtacn catalyst system operate via a similar mechanism, that is, the in situ formation

of [Mn

III

O(m-O)(m-RCO

)

(tmtacn)

]

2 þ

complexes. The recent spectroscopic iden-

tiﬁcation of carboxylate-bridged complexes as active catalysts does not necessarily

mean that the ﬁrst systems based on 6 in which oxalic acid or ascorbic acid were used

by De Vos, Berkessel, and coworkers to promote oxidation catalysis involve the same

general mechanism [94a,b,d]. Recently de Boer et al. compared the catalytic activity of

[Mn

(m-O)

(tmtacn)

]

2 þ

using salicylic acid, ascorbic acid, and oxalic acid as

additives by observing the spectroscopic changes during the course of the catalyzed

reactions [123]. In the case of salicyclic acid, the electronic absorption spectra of the

reaction mixture were quite different from what is observed using other carboxylic

acids. Furthermore, a mononuclear complex was isolated in which the salicylato

dianion is bound as a chelate. However, it was demonstrated through other

spectroscopic and electrochemical techniques that these differences were not

directly relevant to the catalysis itself. It was found that the role of the salicylic acid

in the catalysis, that is, to act as a carboxylato ligand for binuclear complexes, was the

same as that for other acids despite the presence of a potentially chelating hydroxyl

group.

In the case of ascorbic acid and oxalic acid as additives, their redox activity adds

an additional dimension to the catalysis they promote with 6 [123]. For both these

acids the most notable observation was the absence of an induction period; that is,

catalysis commenced immediately upon addition of H

. This is not surprising as

both oxalic acid and ascorbic acid are reductants. In the case of ascorbic acid, although

a [Mn

III

O(m-O)(m-RCO

)

(tmtacn)

]

2 þ

-type complex could be identiﬁed by UV-Vis

spectroscopy, EPR spectroscopy indicated that Mn

III,IV

dinuclear species are present

in the reaction mixture during catalysis also. Hence, although in principle ascorbic

acid may promote the system both by serving as a reductant of [Mn

(m-O)

(tmtacn)

]

2 þ

as well as generating [Mn

III

O(m-O)(m-RCO

)

(tmtacn)

]

2 þ

-type

complexes, it is also possible that a distinct mechanism is in operation. This is

especially the case considering the systems ability to oxidize electron-deﬁcient

alkenes.

In the case of oxalic acid an even more complex picture emerged [123]. Initially

only epoxidation is observed. However, after a certain period of time, cis-dihydrox-

ylation begins. This is in stark contrast to the other carboxylic acid-based systems

where epoxidation and cis-dihydroxylation proceed concurrently. Furthermore, the

reaction mixture does not contain EPR-active species at 77 K, and the UV-vis

absorption spectra are unstructured. Concurrently with the initiation of cis-dihy-

402

11 Manganese-Catalyzed Oxidation with Hydrogen Peroxide