The (Schiff base)vanadium(v) complex catalyzed oxidation of bromide - A new method for the in situ generation of bromine and its application in the synthesis of functionalized cyclic ethers

FULL PAPER

The (Schiff base)vanadium(

V

) Complex Catalyzed Oxidation of Bromide ؊ A

New Method for the in situ Generation of Bromine and Its Application in the

Synthesis of Functionalized Cyclic Ethers

[a]

[a][‡]

Marco Greb,^[a]Jens Hartung,*^[a][‡]Franz Köhler, Kristina Spehar,

Ralph Kluge,^[b]and

ˇ

[b]

´

Rene Csuk

Keywords: Bromide / tert-Butyl hydroperoxide / Catalysis / Oxidation / Peroxy complexes / Tetrahydrofuran / Vanadium

(Schiff base)vanadium(

V

) complexes 5 with tridentate imine

ated that the mechanism of the new bromination reaction

consists of vanadium-dependent and vanadium-independent

steps. A (Schiff base)vanadium(V) compound 5 is required for

auxiliaries served as catalysts for the oxidation of Br⁻with

tert-butyl hydroperoxide (TBHP) in nonaqueous solvents.

This reaction has been applied for the conversion of substi-

activation of TBHP via in situ formation of the corresponding

tuted 4-penten-1-ols into 5-exo-bromo-cyclized products, in- tert-butylperoxy complex. This reagent oxidizes Br⁻, which

cluding a diastereomerically pure heterocyclic precursor under the reaction conditions provides Br₂as the active bro-

used in a synthesis of the all-trans-configured 2,3,4,5-substi-

tuted tetrahydrofuran 2-epi-magnosalicin. Treatment of ω- released into the solution at a steady rate and serves as a

substituted bis(homoallylic) alcohols with the reagent com- reagent for the synthesis of β-brominated cyclic ethers from

bination of pyHBr, TBHP, and a vanadium( ) catalyst 5 af- bis(homoallylic) alcohols in a second, vanadium-independ-

forded 6-endo-cyclized products, i.e. brominated tetrahy- ent step.

dropyrans, as major compounds. The results from ⁵¹V NMR, ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,

minating reagent. The molecular bromine generated thus is

V

ESI-MS, and supporting reactivity-selectivity studies indic-

Germany, 2004)

Introduction

The on-site generation of molecular bromine,^[1]either in

a separate ex situ free halogen reactor^[2]or in solution (i.e.

in situ),^[3]avoids the necessity to store Br₂in larger quantit-

ies in a laboratory or at a production site. This strategy also

circumvents the need to dispose of the waste HBr formed

in the course of most substitution-based electrophilic bro-

minations of organic substrates, because the hydrobromic

acid is almost instantly oxidized to Br₂in a succeeding step

of the reaction cycle (Figure 1).^[4]This concept has been

successfully applied in, for example, the CAB/H₂O₂process

(i.e. the side-chain oxidation of toluenes)^[5]and in the for-

mation of aryl halide based disinfectants from electron-rich

aromatic compounds.^[6]

Figure 1. Principle for the in situ generation of Br₂and its appli-

cation in the synthesis of organobromine compounds;^[1Ϫ4,7]R¹ϭ

e.g. aryl; R²ϭ H, alkyl

The generation of Br₂from HBr and H₂O₂was disco-

vered and investigated in depth by Maas and Hiebert in

1924.^[8]The fact that this reaction requires a comparatively

low pH in order to proceed with a satisfactory rate has pre-

cluded its application in the synthesis of acid-labile fine

chemicals for a long time.^[9]This situation changed con-

siderably in the last decades because vanadium()-depen-

dent haloperoxidases have been isolated from various al-

gae^[10]and fungi.^[11]These enzymes are able to catalyze the

oxidation of, for example, Br^Ϫwith H₂O₂under physiologi-

cal conditions.^[12]In particular, a vanadium()-dependent

bromoperoxidase (VBPO) from the brown algae Ascophyllum

nodosum has attracted attention,^[10a]since its turnover of

Br^Ϫat pH ϭ 6.5 in the presence of the primary oxidant

[a]

Institut für Organische Chemie, Universität Würzburg,

Am Hubland, 97074 Würzburg, Germany

[b]

Institut für Organische Chemie, Universität Halle-Wittenberg,

Kurt-Mothes-Straße 2, 06120 Halle (Saale), Germany

Fax: (internat.) ϩ 49-345-5527030

E-mail: kluge@chemie.uni-halle.de

csuk@chemie.uni-halle.de

[‡]

New address: Fachbereich Chemie, Organische Chemie,

Technische Universität Kaiserslautern,

Erwin-Schrödinger-Straße, 67663 Kaiserslautern, Germany

Fax: (internat.) ϩ 49-631-205-3921

E-mail: hartung@chemie.uni-kl.de

Supporting information for this article is available on the

WWW under http://ww w .eurjoc.org or from the author.

Ϫ

H₂O₂exceeds that of the powerful reagent VO(O₂)₂at

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DOI: 10.1002/ejoc.200400071

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FULL PAPER

pH ϭ 1.^[13]Although the exact nature of the electrophilic ino alcohol side chain (4cϪ4e), or in the steric demand of

halogenating reagent in such transformations remains the the hydrocarbon substituent (4f, 4g) (Figure 3), were chosen

subject of ongoing discussions,^[14]the fundamentals of this in order to screen for selectivity and catalytic reactivity of

chemistry are of notable synthetic interest, since they com- the derived vanadium() reagents 5 for the oxidation of

bine the benefits of on-site generation of Br₂with that of bromide under different conditions.^[16,19]Auxiliaries

transition metal based catalysis. In view of this background, H₂L¹ϪH₂L⁷(4aϪg) were prepared from appropriate o-

we have started to explore the vanadium()-catalyzed oxi- hydroxyarenecarbaldehydes and selected amino alcohols in

dation of Br^Ϫwith the aim of developing a method that EtOH at reflux. Chiral amino alcohols were obtained

is applicable for the conversion of a given bis(homoallylic) through NaBH₄/I₂-mediated reductions of the correspond-

alcohol 1 into β-brominated cyclic ethers, i.e. a tetrahydro- ing amino acids.^[20]Treatment of methylsulfanyl-func-

furan 2 or a tetrahydropyran 3, (Figure 2).^[7]A major ob- tionalized ligand 4c with TBHP furnished sulfoxide 4d in

jective of this study was associated with the search for an 47% yield as a mixture of like/unlike-configured dia-

adequate combination of bromide source and primary oxi- stereomers.

dant that would reduce the inherent propensity of (Schiff

Dark brown to black (Schiff base)vanadium() com-

base)vanadium() complexes in the presence of tert-butyl plexes 5 were prepared in excellent yields (Ͼ 95%) by mix-

hydroperoxide (TBHP) to convert alkenols 1 directly into ing of equimolar amounts of VO(OEt)₃and one of the

hydroxy-functionalized tetrahydrofurans.^[15,16]Thus, reac- auxiliaries 4aϪg in hot EtOH (Table 1).^[21]Compounds

tivity-selectivity studies on the vanadium()-catalyzed oxi- 5aϪg are soluble in CH₃CN, CHCl₃, CH₂Cl₂, or EtOH.

dation of bromide were conducted. The results were sup- Dilute solutions of, for example, methioninol-derived va-

plemented by information obtained from spectroscopic and nadium() compound 5c in CHCl₃typically exhibit a red-

spectrometric investigations in order to interpret crucial dish color, which darkens to brown with increasing concen-

steps in the process such as peroxide activation and the gen- tration. If dissolved in EtOH, complexes 5 show ⁵¹V NMR

eration of an active brominating reagent.^[17,18]

signals that are located in the spectral range between δ ϭ

Ϫ529 ppm (5a) and Ϫ551 ppm (5f). Single ⁵¹V NMR reson-

ances were observed for complexes 5a, 5b, 5d, and 5e,

whereas compounds 5c, 5f, and 5g were each characterized

by two slightly separated signals (∆δ ϭ 3 for 5c, 8 for 5f,

and 16 for 5g). IR spectra (KBr) of all complexes 5 were

recorded. The spectral information given in Table 1 is re-

stricted to the diagnostic VϭO stretching mode because the

ligands had been characterized independently. Except for

the sulfoxide-derived complex 5d (ν˜ ϭ 961 cm^Ϫ1) and the

pyridoxal-based compound 5e (ν˜ ϭ 945 cm^Ϫ1), all absorp-

tions are grouped around 989 Ϯ 10 cm^Ϫ1. Solutions of va-

nadium() complexes 5 displayed featureless UV/Vis spec-

tra consisting of up to three bands. The energetically lowest

band for each compound was located in the λ ϭ 625 (5b)

and 673 nm (5d) range. Except for the pyridoxal-derived co-

ordination compound 5e, each vanadium() complex dis-

played a second electronic transition in the near UV region

[361 (5a) to 318 nm (5g)]. A third band was present in the

spectra of the methioninol-derived complex 5c (437 nm),

the valinol derivative 5f (444 nm), and the tert-leucinol-

based vanadium() compound 5g (423 nm).

Figure 2. Strategy for the conversion of alkenols 1 in the presence

of Br^Ϫ, ROOH, and V^5ϩinto bromo-cyclized target products 2

and/or 3; R ϭ H, C(CH₃)₃; R¹ϭ CH₃, C₆H₅, aryl; R^Eϭ H, CH₃,

C₆H₅; R^Zϭ H, CH₃; V^ϩ5ϭ (Schiff base)vanadium() complex,

e.g. 5 (see Table 1)

Results

1. Preparation and Characterization of (Schiff

base)vanadium(V) Complexes

Tridentate Schiff base auxiliaries, which differ in solu-

bility (4a, 4b), in the heteroatom functionalities on the am-

2. The Oxidation of Bromide in the Presence of 1-Phenyl-4-

penten-1-ol (6)

Suitable reaction conditions for the synthesis of bromin-

ated cyclic ethers (Figure 1) were identified by varying: (i)

the primary oxidant, (ii) the bromide source, (iii) the sol-

vent, and (iv) the vanadium() reagent 5. In all instances,

the conversion of 1-phenyl-4-penten-1-ol (6)^[22]into 2-

(bromomethyl)-5-phenyltetrahydrofuran (7) served as re-

porter reaction. Initial efforts were directed towards an ap-

plication of H₂O₂as reactive oxygen source (Supporting In-

formation, see also the footnote on the first page of this

article).^[23]For this purpose, solutions of Bu₄NBr (c₀ϭ 0.1

) and alkenol 6 (c₀ϭ 2 ϫ 10^Ϫ2) in DMF were treated

Figure 3. Structures of Schiff bases H₂L¹ϪH₂L⁷(4aϪg) intended

to serve as ligands for the syntheses of vandium() complexes 5aϪg

(see Table 1)^[16,19]

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The (Schiff base)vanadium(V) Complex Catalyzed Oxidation of Bromide

FULL PAPER

In an initial run, TBHP (1.1 equiv.), pyHBr (1.5 equiv.),

and 1-phenyl-4-penten-1-ol (6) were stirred at 20 °C for 48 h

in the absence of vanadium() complex 5a to furnish a 29%

yield (GC) of 2-(bromomethyl)-5-phenyltetrahydrofuran

(7). This reactivity is referred to from now on as background

bromination. The molar ratio of reagents used in this trans-

formation was established in a separate series of experi-

ments. The formation of target product 7 was improved to

72% (GC) upon addition of 1 mol % of VOL¹(EtO)(EtOH)

(5a) (Table 2, Entry 4). An increase in the molar ratio of

catalyst 5a under otherwise identical conditions provided

73% (GC; 5 and 10 mol % of 5a, Supporting Information

and Table 2, Entries 1 and 3), 45% (GC, 50 mol % of 5a,

Supporting Information), and 44% yields (GC) of product

7 (100 mol % of 5a, Supporting Information). A change of

the solvent from CH₃CN to CHCl₃(10 mol % of 5a) was

associated with a slight decrease in the diastereoselectivity

for formation of disubstituted tetrahydrofuran 7, from cis/

trans ϭ 28:72 (CH₃CN) to 34:66 (Table 2, Entries 1 and 2).

Application of di-tert-butyl-substituted vanadium() com-

plex VOL²(OEt) (5b) in this reaction indicated comparable

reactivity but improved solubility in CH₃CN and CHCl₃

relative to compound 5a (Table 2, Entry 5). The use of 1

mol % of methylsulfanyl-substituted catalyst 5c in CHCl₃

Table 1. Preparation of vanadium() complexes 5aϪg from

VO(OEt)₃and auxiliaries 4aϪg (see Figure 3)

^[a]In EtOH, referenced versus VOCl₃as internal standard (δ ϭ

0 ppm). ^[b]In KBr pellets. ^[c]In EtOH. ^[d]Broad.

with different concentrations of H₂O₂(c₀ϭ 4 ϫ 10^Ϫ3 to was sufficient to convert substrate 6 into product 7 in 61%

2 ϫ 10^Ϫ2) and VOL¹(OEt)(EtOH) (5a) (c₀ϭ 4 ϫ 10^Ϫ3 yield in 8 h (GC, cis/trans ϭ 34:66). If this reaction is per-

to 2 ϫ 10^Ϫ2). Since the oxidation of Br^Ϫconsumes 1 formed on a larger scale, it is advisable to increase the

equiv. of H^ϩper equiv. of H₂O₂(see Figure 1 for R²ϭ H), amount of catalyst VOL³(OEt) (5c) to 5 mol % (66% yield

aqueous HCl (c₀ϭ 1 ϫ 10^Ϫ3 to 2 ϫ 10^Ϫ2) was added of 7 after 10 h, Table 2, Entry 7). The synthesis of tetra-

to the reaction mixture in order not to limit the oxidation hydrofuran 7 from alkenol 6 took considerably longer to

in acid.^[23]These experiments, however, provided only traces reach completion if vanadium() complex VOL⁴(OEt) (5d)

(Ͻ 2%, GC) of 2-(bromomethyl)-5-phenyltetrahydrofuran with the sulfoxide-functionalized chelate ligand was used as

(7).^[22]No target compound 7 was obtained if the reactions catalyst (73%, cis/trans ϭ 34:66, Table 2, Entry 9). The use

were conducted in the absence of aqueous HCl, or if equim- of either the pyridoxal-derived complex VOL⁵(OEt) (5e),

olar ratios of H₂O₂and 5a were added to the reaction mix- the leucinol-based coordination compound VOL⁶(OEt)

ture. In additional experiments, the HCl concentration was (5f), or the tert-butylaminoethanol derivative VOL⁷(OEt)

increased to 2.2 ϫ 10^Ϫ2, which was associated with an (5g) provided 70Ϫ71% yields of product 7 (cis/trans ϭ

improvement in the yield of product 7 (26%, at 20 °C for 28:72, Table 2, Entries 10Ϫ12) after 48 h. Pursuit of further

48 h). Addition of 5 mol % of complex 5a to a similarly optimization studies was refrained from in the latter three

prepared solution of H₂O₂, aq. HCl, and substrate 6 did instances, since catalysts 5eϪg offered a similar selectivity

not raise the yield of heterocycle 7 (27%). The use of 100 profile to that of o-aminophenol-derived vanadium() com-

mol % of complex 5a under such conditions completely in- plex 5a.

hibited the formation of tetrahydrofuran 7 (Supporting In-

Additional information concerning the rate of product

formation).

formation from bis(homoallylic) alcohol 6, TBHP, pyHBr,

In view of the observed complications, the primary oxi- and selected (Schiff base)vanadium() complexes 5 was ob-

dant H₂O₂was replaced by tert-butyl hydroperoxide tained by monitoring of the yield of bromocyclization prod-

(TBHP). Attempts to apply aqueous TBHP for the syn- uct 7 as a function of the reaction time. The information

thesis of bromomethyl-substituted tetrahydrofuran 7 fol- outlined in Figure 4 indicates that the rate of (bromometh-

lowed the same trends that had been noted in (Schiff base)- yl)phenyltetrahydrofuran formation in CHCl₃increased

vanadium() complex catalyzed oxidations of Br^Ϫin the over the sequence of catalysts 5c (10 mol %) Ͼ 5d (10

presence of aqueous H₂O₂. We therefore restricted ourselves mol %) Ͼ 5c (1 mol %) Ͼ 5a (10 mol %) Ͼ 5a (1 mol %) Ͼ

to the use of anhydrous TBHP and dry solvents. Further, no catalyst (Supporting Information). In detail, the use of

Bu₄NBr was replaced by pyridinium hydrobromide 1 mol % of methioninol-derived vanadium() complex 5c

(pyHBr). This reagent is adequately soluble in CH₃CN, led to a 3.8-fold increase in the rate of product formation,

CHCl₃, and CH₂Cl₂, media that are commonly applied in which was improved to a factor of 4.5 in relation to the

preparative-scale bromocyclizations.^[24]Further, this modi- uncatalyzed reaction if 10 mol % of 5c was used as catalyst.

fication helped to maintain the ratio of H^ϩto oxidizable It is worth mentioning that 1 mol % of VO(acac)₂, if applied

Br^Ϫconstant throughout the reaction.

as catalyst under such conditions, led to the formation of a

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mixture of like/unlike isomers). The ratio of products cis-7/

trans-7 to the two diastereomers of 8 remained constant

during the course of this reaction. In a separate experiment,

diastereomerically pure heterocycles cis-7 and trans-7^[22]

were each treated with 1 equiv. of pyHBr in CDCl₃at 20

°C for 48 h. In both instances, resonances of the opposite

diastereomer or of the dibromide 8 were not observed.

Table 2. Screening for reactivity: application of vanadium() cata-

lysts 5aϪg for the oxidation of bromide in the presence of 1-phenyl-

4-penten-1-ol (6)

[a]

Preparative scale (0.5 mmol). All other yields were determined

by GC with n-C₁₄H₃₀as internal standard. An experimental error

of Ϯ5% was estimated for similarly determined yields.

Figure 5. Stacking plot: time-dependent ¹H NMR study on the

conversion of 1-phenyl-4-penten-1-ol (6) in the presence of TBHP

(1.1 equiv.), pyHBr (1.5 equiv.), and methioninol-derived va-

nadium()-catalyst 5c (20 °C, CDCl₃); the selected spectral region

depicts the resonances of olefinic protons, benzylic protons, and

protons located in the vicinity of oxy or bromo substituents; for

illustrative purposes the spectra of neat alkenol 6 and of purified

dibromide 8 (equimolar mixture of like/unlike isomers) have been

added to this plot

31% yield of product 7 after 5 h and a 61% yield after 48 h

from alkenol 6, TBHP, and pyHBr (Supporting Infor-

mation).

3. The Formation of Bromocyclization Products from

Bis(homoallylic) Alcohols

The scope of the (Schiff base)vanadium()-catalyzed oxi-

dation of bromide in the synthesis of bromocyclization

products was explored in bromination reactions of 1-, 2-, 3-,

and 4-substituted bis(homoallylic) alcohols 9Ϫ13.^[22]All

transformations were conducted under previously optim-

ized conditions (Table 2) on a preparative scale with 5

mol % of methioninol-derived (Schiff base)vanadium()

complex 5c as catalyst, TBHP as primary oxidant, and

pyHBr as bromide source (Table 3). This setup is referred

to from now on as the standard conditions. Treatment of 1-

Figure 4. Time dependence of 2-(bromomethyl)-5-phenyltetra-

hydrofuran formation from 1-phenyl-4-penten-1-ol (6), TBHP, and

pyHBr in the presence of vanadium() catalysts 5a, 5c, and 5d

(CHCl₃, 20 °C, GC)

In addition to the reactivity studies, the conversion of 1- (p-methoxyphenyl)-4-penten-1-ol (9) in CH₂Cl₂under these

phenyl-4-penten-1-ol (6) into bromocyclized product 7 was conditions afforded a 69% yield of 5-(p-anisyl)-2-(bromo-

1

monitored by H NMR spectroscopy with the aim of de- methyl)tetrahydrofuran (14) (cis/trans ϭ 33:67). Bromo-

tecting additional products that had escaped the chromato- cyclization of 4-methyl-1-phenyl-4-penten-1-ol (10) in

graphic workup procedure, thus improving the mass bal- CH₂Cl₂furnished a 64% yield of 2,2,5-substituted oxolane

ance of this reaction (Figure 5). Spectra were recorded prior 15 (cis/trans ϭ 26:74). An 82% yield of 2-(bromomethyl)-4-

to addition of pyHBr and catalyst 5c (ϵ 0 min), after 15, phenyltetrahydropyran (16) (cis/trans ϭ 74:26) was ob-

30, 60, 240, and 360 min, and after 6 d (CDCl₃, 20 °C). The tained from 2-phenylpentenol (11) in CH₃CN^[25]and an

stacking plot of two selected spectral regions, at δ ϭ 88% yield (cis/trans ϭ 72:28) in CH₂Cl₂. 3-Phenyl-4-pen-

4.0Ϫ5.2 and 5.7Ϫ6.0 ppm, illustrates that alkenol 6 is trans- tenol (12) was converted under standard conditions into 2-

formed into heterocycle 7 and a new product that has been (bromomethyl)-3-phenyltetrahydrofuran (17) in 55% yield

identified as 4,5-dibromo-1-phenylpentan-1-ol (8) (50:50 (cis/trans ϭ 21:79, in CH₃CN) and in 56% yield (cis/trans ϭ

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The (Schiff base)vanadium(V) Complex Catalyzed Oxidation of Bromide

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30:70, in CH₂Cl₂).^[25]A 66% yield of 2-(bromomethyl)-2- relative configuration (Scheme 2). Product 23 is predomi-

phenyltetrahydrofuran (18) was obtained upon treatment of nantly formed from the diastereomer like-22 (6,8-cis/6,8-

4-phenylpentenol (13) with TBHP, pyHBr, and 5 mol % of trans ϭ 93:7),^[33]whereas dibromide 24, for reasons of mass

5c in CH₂Cl₂.^[26]

balance, is considered to originate mainly from unlike-22.

Table 3. Application of the vanadium()-catalyzed oxidation of

Br^Ϫ: bromocyclizations of substituted bis(homoallylic) alcohols

9Ϫ13

Scheme 2. Formation of bromination products from 5-substituted

bis(homoallylic) alcohols 22 and 25

The reaction between pyHBr, TBHP, and VOL³(OEt)

(5c) (5 mol %) in the presence of (E)-6-phenyl-5-hexen-2-ol

(25)^[22]provided brominated tetrahydropyran 26 as the

major (58%, 2,6-cis/2,6-trans ϭ 86:14) and 2-[bromo(phe-

nyl)methyl]-5-methyltetrahydrofuran (27) as a minor prod-

uct (5%, cis/trans ϭ 42:58).^[26]

Bromocyclization of 4-methyl-1-phenyl-4-penten-1-ol

(28) under standard conditions exclusively afforded 5-endo-

cyclized product 29 (31%, cis/trans ϭ 84:16) after chroma-

tographic workup.^[16]The higher homologue, 5-methyl-1-

phenyl-5-hexen-1-ol (30), was converted into a mixture of

tetrahydropyran 31 (61%, cis/trans ϭ 9:91),^[25]disubstituted

tetrahydrofuran 32 (13%, cis/trans ϭ 46:54),^[25]and di-

bromo alcohol 33 (17%, 50:50 mixture of like/unlike dia-

stereomers), if treated similarly.^[34]Treatment of 6-methyl-

1-phenyl-5-hepten-1-ol (34) with the reagent combination

of TBHP, pyHBr, and catalyst 5c (5 mol %) afforded 5,6-

dibromo-6-methyl-1-phenylheptan-1-ol (35) (72%, 50:50

mixture of diastereomers) as sole product (Scheme 3).

The conversion of (1S*,2S*,3R*)-2-methyl-1,3-bis(2,4,5-

trimethoxyphenyl)-4-penten-1-ol (19)^[27]in the presence of

pyHBr, TBHP, and catalyst 5c provided diastereomerically

pure (¹H NMR) all-trans-configured tetrasubstituted tetra-

hydrofuran 20 (70%, Scheme 1). Side products originating

either from arene bromination^[28]or from methyl ether

cleavage were not detected (¹H NMR spectroscopy).^[29]Re-

duction (LiAlH₄/LiH)^[30]of the bromocyclization product

20 provided tetrahydrofuran 21, the 2-epimer of the neolig-

nan-derived natural product (Ϯ)-magnosalicin.^[31]

4. Mechanistic Studies: The Search for Intermediates

In order to clarify the role of (Schiff base)vanadium()

complexes 5 in the bromination reaction of organic sub-

strates starting from Br^Ϫ, TBHP, and an alkenol, ⁵¹V NMR

spectroscopic, ESI mass spectrometric, and reactivity-selec-

tivity studies were conducted. In all instances the properties

and the reactivity of o-aminophenol-derived vanadium()

complex 5a served as benchmark, because its chemistry has

previously been explored in some detail.^[15,16,35]Upon ad-

Scheme 1. Formation of 2-epi-magnosalicin (21) from 2-methyl-1,3-

bis(2,4,5-trimethoxyphenyl)-4-penten-1-ol (19)

[a]

The 2-cis-configured diastereomer of bromocyclization product dition of TBHP to a sample of 5a in CDCl₃(δ ϭ Ϫ529

20 was not detected (¹H NMR spectroscopy)

ppm, referenced to VOCl₃), a new sharp signal appeared at

δ ϭ Ϫ569 ppm, which was assigned, on the basis of refer-

Treatment of 2-(cyclohex-2-en-1-yl)-1-phenylethanol (22, ence data from the literature, to the corresponding tert-bu-

50:50 mixture of like/unlike stereoisomers)^[32]with the re- tylperoxy complex (not shown).^[35Ϫ37]Further, an intense

agent combination of TBHP, pyHBr, and vanadium() resonance at δ ϭ Ϫ434 ppm appeared 1 min after mixing

catalyst 5c (5 mol %) furnished a 33% yield of bicyclic tetra- of the reagents. A spectrum that was recorded 10 min after

hydrofuran 23^[33]and a 30% yield of a 77:23 diastereomeric addition of 1-phenyl-4-penten-1-ol (6) and pyHBr to this

mixture of two dibromohydrins 24 of hitherto unknown solution showed resonances at δ ϭ Ϫ434, Ϫ529, Ϫ539,

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(m/z ϭ 1100) were also detected. The fragmentation process

(collision-induced dissociation, CID) of the isolated parent

ion at m/z ϭ 366 (MS³experiment) pointed to the forma-

tion of one main product ion at m/z ϭ 322 that probably

originated from the loss of H₃CCHO (∆m ϭ 44 amu). In a

second experiment, a 10-fold excess of TBHP was added to

a solution of (Schiff base)vanadium() complex 5h in

CH₂Cl₂. The reaction mixture was allowed to stand for

30 min and was afterwards diluted with CH₃CN. The ESI

mass spectrum of this sample exhibited a molecular ion

peak at m/z ϭ 410, which was assigned to the signal

[VOL⁸(tBuOO) Ϫ H]^Ϫ, relating to peroxy complex 38 (Fig-

ure 6). The zoom scan spectrum of this ion showed an

m/z value of 409.9 (calcd. 410.04) and the expected isotopic

envelope (Figure 6, insets b and c). In addition to the latter

signal, other peaks were present in this spectrum, which

were interpreted as decomposition products of peroxy com-

plex 38 {e.g. [VOL⁸(OH) Ϫ H]^Ϫ(m/z ϭ 338), [VOL⁸(OCH₃)

Ϫ H]^Ϫ(m/z ϭ 352), [VOL⁸(OtBu) (39) Ϫ H]^Ϫ(m/z ϭ 394)}

and the corresponding mixed clusters of the type [M_A(M_B

Ϫ H)]^Ϫat m/z ϭ 691, 705, 733, 749, and 763. The identity

of peroxy complex 38 was confirmed by investigating its

fragmentation pattern (CID). The CID spectrum of the iso-

lated parent ion showed two main product ions at m/z ϭ

354 (∆m ϭ 56 amu) and m/z ϭ 336 (∆m ϭ 74 amu), prob-

ably formed by the loss of isobutene in the former case and

Scheme 3. The conversion of ω,ω-dimethyl-1-phenyl-substituted al-

kenols 28, 30, and 34 into brominated compounds

Ϫ543, and Ϫ569 ppm. After 24 h, the ⁵¹V NMR spectrum a C₃H₆O₂or C₄H₁₀O fragment in the latter (Figure 6, inset

of this reaction mixture was characterized by a strong sharp d). In succeeding experiments, a marked propensity of

resonance at δ ϭ Ϫ569 ppm. The remaining signals had (Schiff base)vanadium() complex 5h to undergo ligand ex-

either faded completely (δ ϭ Ϫ434 ppm) or had become change reactions through replacement of the C₂H₅O^Ϫwith

very small (δ ϭ Ϫ542, Ϫ539 ppm). In order to further ver- an OH^Ϫligand (e.g. from the reaction of 5h with water,

ify formation of (peroxy)(Schiff base)vanadium() com- formation of complex 36) was noted. Similarly, treatment

plexes from the reaction between coordination compounds of 5h with a 10-fold excess of 5-methyl-1-phenyl-4-hexen-1-

5 and TBHP, solutions containing both reagents were ana- ol (30) furnished vanadium complex 37, which was ident-

lyzed by ESI-MS.^[38Ϫ41]Attempts to detect neutral va- ified by the molecular ion peak at m/z ϭ 510 [VOL⁸(-

nadium() complex 5a by ESI-MS failed in both negative- OC₁₃H₁₇) Ϫ H]^Ϫ(zoom scan m/z ϭ 510.2, calcd. 510.11).

and positive-ion polarity modes. In order to overcome this

problem, carboxy-substituted coordination compound VO-

L⁸(OEt) (5h) was prepared. This compound allows more

facile anion formation under ESI-MS conditions through

deprotonation of its carboxylic acid functionality. Va-

nadium complex 5h, dissolved in CDCl₃, exhibited a single

sharp ⁵¹V NMR resonance at δ ϭ Ϫ538 ppm. Addition of

TBHP to a solution of 5h led to the appearance of two new

resonances: a stronger one at δ ϭ Ϫ438 ppm and a weaker

one at δ ϭ Ϫ578 ppm. In combination with the information

obtained from previous investigations,^{[15,16,35Ϫ37]}the signal

at δ ϭ Ϫ578 ppm was assigned to (peroxy)(Schiff base)van-

adium() complex 38 (Scheme 4). Subsequently, a solution

of 5h in CH₂Cl₂/CH₃CN was injected into an ESI mass

spectrometer operating in the negative ion polarity mode.

An intense signal at m/z ϭ 366 (zoom scan 366.0, calcd.

366.02) was recorded that originated from the molecular

ion [VOL⁸(OEt) Ϫ H]^Ϫ(Figure 6, inset a). The observed

isotopic envelope of this ion was in good agreement with

Scheme 4. Ligand exchange in the (Schiff base)vanadium() com-

the calculated values. Further, signals originating from the

plex 5h: (i) formation of tert-butylperoxy complex 38 (⁵¹V NMR

complex [VOL⁸(OH) Ϫ H]^Ϫ(m/z ϭ 338) and clusters of the

spectroscopy and ESI-MS) and its reactivity towards bromide, and

type [M[M Ϫ H]]^Ϫ(m/z ϭ 733) and [M₂[M Ϫ H]]^Ϫ(ii) generation of complexes 36 and 37

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The (Schiff base)vanadium(V) Complex Catalyzed Oxidation of Bromide

FULL PAPER

Discussion

The oxidation of bromide in nonaqueous solvents is a

synthetically useful transformation for the in situ genera-

tion of Br₂. This reagent is in turn applicable for selectively

converting unsaturated alcohols into bromocyclized prod-

ucts with an N-bromosuccinimide (NBS)-^[25,43]or 2,4,4,6-

tetrabromocyclohexa-2,5-dienone

(TBCD)-like

selec-

tivity,^[43,44]but with improved efficiency in selected in-

stances (Scheme 6).^[7a]This new alkenol bromination reac-

tion applies the principles of transition metal catalyzed oxi-

dations for the activation of an environmentally benign and

powerful but safe to handle primary oxidant.^[15]In this

study, coordination compounds of the type VOL(OEt) 5

(L ϭ dibasic tridentate imine auxiliary) in combination

with tert-butyl hydroperoxide have been applied for this

purpose. The choice of this system originated from the ex-

perimentally determined Adam parameter of x_SOϭ 0.2 for

the reagent combination of VOL¹(OEt)(EtOH) (5a) and

TBHP, which points to electrophilic properties of the active

oxidant generated in situ, such as required for the oxidation

of Br^Ϫ(reference values: x_SOϭ 1.0 for NaOH/H₂O₂; x_SOϭ

0.0 for TBHP/HClO₄).^[45Ϫ47]

Figure 6. Identification of (Schiff base)vanadium() peroxy com-

plex [38 Ϫ H]^Ϫby ESI-MS; insets: (a) full-scan spectrum of com-

plex 5h (negative ions; solvent: CH₂Cl₂/CH₃CN); (b) full-scan spec-

trum 30 min after treatment of complex 5h with TBHP; (c) zoom-

scan spectrum showing the molecular ion [M Ϫ H]^Ϫof peroxy

complex 38; (d) fragmentation (CID spectrum) of the isolated par-

ent ion at m/z ϭ 410

The reactivity of tert-butylperoxy complex 38 was ex-

plored by ESI-MS analysis of solutions that were obtained

by mixing (Schiff base)vanadium() complex 5h in CH₂Cl₂/

CH₃CN with TBHP and pyHBr. An intense signal at m/z ϭ

237 was observed in this case (negative ion polarity mode).

Due to its fingerprint isotopic envelope of m/z ϭ 237, 239,

241 and 243 in an intensity ratio of 1:3:3:1, this signal was

Ϫ

assigned to the Br₃ion. Further ions detected in this

experiments originated from [VOL⁸(OH) Ϫ H]^Ϫ(m/z ϭ

338), [VOL⁸(Br)₂]^Ϫ(m/z ϭ 480), and [V₂O₃(L⁸)₂Br]^Ϫ(m/

z ϭ 739). A positive-ion polarity mode ESI spectrum of this

sample pointed to the formation of the following cations:

[Py₂H₂Br]^ϩ(m/z

ϭ ϭ 401),

239), [VOL⁸py]^ϩ(m/z

[V₂O₃(L⁸)₂H]^ϩ(m/z ϭ 661), and [V₂O₃(L⁸)₂pyH]^ϩ(m/z ϭ

740). It should, however, be noted that these cations were

also detected from a solution of 5h and pyHBr in CH₂Cl₂/

CH₃CN without TBHP.

Scheme 6. Schematic presentation of reaction cycles leading to the

formation of 2-(bromomethyl)-5-phenyltetrahydrofuran (7) from

TBHP, pyHBr, 1-phenyl-4-penten-1-ol (6), and vanadium() com-

pounds 38 and 39 (data refer to reaction in CHCl₃); Oϭ[V]^ϩrefers

to the fragment VOL^ϩ, where H₂L represents a tridentate dibasic

Schiff base auxiliary such as 4

The formation of Br₂and hence Br₃^Ϫ, which exists in

equilibrium with Br₂and Br^Ϫunder the reaction con-

ditions,^[42]has been confirmed in further experiments, such

as in the formation of a 75% yield of dibromide 41 upon

treatment of O-acetyl-protected alkenol 40 with TBHP,

pyHBr, and catalyst 5c under standard conditions

(Scheme 5).

In earlier work, (Schiff base)vanadium() complexes 5

have been reported to catalyze the diastereoselective oxy-

genation of substituted bis(homoallylic) alcohols 1 with

TBHP as primary oxidant.^[16,35]The fact that addition of

pyHBr changes the reactivity of this system entirely from

direct π-bond oxygenation towards electrophilic bromin-

ation is one of the major results of the present study. The

overall sequence proceeds through: (i) TBHP activation [i.e.

formation of (peroxy)(Schiff base)vanadium() complexes,

e.g. 38 from 39], (ii) Br₂generation in situ, and (iii) bromo-

cyclization of alkenols in a non-vanadium-dependent step

(Scheme 6).

Scheme 5. Formation of dibromide 41 from olefin 40

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FULL PAPER

1. The Reactivity of (Schiff base)vanadium(

towards TBHP

V) Complexes 5

Bu₄NBr in the absence of an additional proton source (e.g.

the formation of an 11% yield of bromocyclization product

7 from substrate 6).

(Schiff base)vanadium() complexes 5 have been pre-

pared and characterized according to previously disclosed

guidelines.^[16,21,47]The reaction of coordination compounds

5a and 5h with TBHP provides at least two new va-

nadium() complexes, one of them is characterized by an

about 40 ppm high-field shift in relation to the resonance

of the starting vanadium() reagent (⁵¹V NMR spec-

troscopy). The magnitude and the sign of the shift is con-

sistent with the formation of the corresponding η²-tert-bu-

tylperoxy complex (Scheme 4).^[35Ϫ37]It should be noted

that additional ⁵¹V NMR resonances at δ ϭ Ϫ434 ppm

(from 5a) and δ ϭ Ϫ438 ppm (from 5h) were observed after

TBHP addition. These signals of yet unidentified va-

nadium() complexes were conserved upon addition of 1

equiv. of pyHBr, but faded within 24 h. Treatment of coor-

dination compounds 5a or 5h with TBHP and pyHBr pro-

vided two additional signals in both instances. On the basis

of reference values from the literature, one of these reson-

ances was assigned in both cases to the corresponding

(hydroxo)vanadium() complex (e.g. δ ϭ Ϫ543 ppm from

5a).^[23]

Support for the interpretation that (tert-butylperoxy)van-

adium() complexes (e.g. 38) are formed from the reaction

between a vanadium() compound VOL(EtO) (5) and

TBHP was obtained from the results of ESI-MS investi-

gations (Scheme 4 and Figure 6). The choice of a carboxy-

substituted ligand in complex 5h for this purpose was gu-

ided by the necessity to allow facile anion generation under

ESI conditions in order to record spectra in the negative ion

mode. This technique has been applied to identify (Schiff

base)vanadium() complex 5h and its tert-butylperoxy de-

rivative 38 by their molecular ions [M Ϫ H]^Ϫand sub-

sequent CID fragmentations of the trapped ions.

Scheme 7. Intermediates from the (Schiff base)vanadium() com-

plex catalyzed oxidation of pyHBr with TBHP

(ii) The product of bromide oxidation was trapped with

1-phenyl-4-penten-1-ol (6) to afford 2-(bromomethyl)-5-

phenyltetrahydrofuran (7) as the major product and 4,5-

dibromo-1-phenylpentan-1-ol (8) as a minor compound

(Figures 4 and 5). Products of identical chemo-, regio-, and

diastereoselectivities have been obtained upon treatment of

a solution of 1-phenyl-4-penten-1-ol (6) in Et₂O with Br₂.

An application of TBCD in CH₂Cl₂for this purpose af-

forded an 88% yield of bromocyclized product 7 (cis/

trans ϭ 31:69), without providing dibromide 8.

(iii) A stereochemical analysis of compounds obtained

from the (Schiff base)vanadium()-catalyzed oxidation of

Br^Ϫwith TBHP points to products that are characteristic

of a bromonium ion pathway, for example, the formation

of trans-1,2-dibromocyclohexane (74%, Supporting Infor-

mation) from cyclohexene and 5,6-like-configured bromo-

cyclization products 26 and 27 from (E)-6-phenyl-5-hexen-

2-ol (25) (Scheme 8). The latter observation points to a dia-

stereoselective conversion of, for example, the arbitrarily

selected enantiomer (S*)-25 into bromonium ion (2S*,5S*,

6S*)-42, which for stereoelectronic reasons rearranges

through a backside approach of the oxygen nucleophile

onto the positively polarized carbonϪbromine bonds (i.e.,

C5ϪBr or C6ϪBr) to furnish 5,6-like-configured tetra-

hydropyran 26 as the major product and 5,6-like-arranged

tetrahydrofuran 27 as a minor product (Scheme 8).

2. Evidence for the Formation of Molecular Bromine

The oxidation of Br^Ϫwith TBHP in anhydrous media

requires peroxide activation through coordination to (Schiff

base)vanadium() complex 5 (fast reaction) or protonation

(e.g. from pyH^ϩ, slow reaction).^[49]Both processes are con-

sidered to afford Br₂as active bromination reagent for the

following reasons:

(i) The oxidation potential of TBHP (E° ϭ 1.20 V versus

NHE in CH₃OH/C₆H₆)^[50]exceeds the value required for

the conversion of Br^Ϫinto Br₂or into the tribromide anion

[E°(Br₂/Br^Ϫ) ϭ 0.73 V, E°(Br₃^Ϫ/Br^Ϫ) ϭ 1.13 V, both versus

NHE in CH₃CN].^[42]The latter intermediate has been

identified in ESI-MS studies of authentic reaction mixtures

{K ϭ ([Br₂][Br^Ϫ])/[Br₃^Ϫ] ϭ 6.8Ϫ7.0 in CH₃CN at 25 °C}.^[42]

Scheme 8. Stereochemical model for the selective conversion of alk-

enol (S*)-25 into products (2R*,3S*,6S*)-26 and (2R*,5S*,6S*)-

27; [Br₂] ϭ TBHP, pyHBr, 5c

Application of (Schiff base)vanadium() catalyst 5a for

On the basis of additional experiments that have not been initiation of bromocylizations was not compatible with the

disclosed in this report, the conversion of Br^Ϫinto Br₂with use of aqueous solvents or of H₂O₂as primary oxidant.

the peroxidic reagent TBHP is the rate-determining step in The conversion of 1-phenyl-4-penten-1-ol (6) into 2-

the synthesis of heterocycle 7 from alkenol 6. This reaction (bromomethyl)-5-phenyltetrahydrofuran (7) with the re-

consumes 1 equiv. of H^ϩper equiv. of oxidized Br^Ϫagent combination of TBHP and pyHBr in anhydrous me-

(Scheme 7).^[23]It is therefore limited in acid, as noted in dia was complete (GC) after 8Ϫ48 h in the case of va-

transformations of substrate 6 with TBHP, catalyst 5a, and nadium()-catalyzed reactions, whereas 14Ϫ21 d were re-

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The (Schiff base)vanadium(V) Complex Catalyzed Oxidation of Bromide

FULL PAPER

quired for the same transformation in the absence of a cata- mary oxidant. This transformation leads to an efficient in

lyst 5. The most active catalyst in the present study was the situ generation of Br₂, which is applicable for selectively

methioninol-derived complex 5c, if applied in chlorinated converting bis(homoallylic) alcohols into bromocyclized

solvents. Since the marked reactivity of reagent 5c could, in products with an NBS- or TBCD-like selectivity under mild

principle, have been associated with its conversion into the conditions. The reaction profits from the phenomenon of

sulfoxide derivative 5d in an early phase of the reaction, the catalysis, which is desirable for larger scale state-of-the-art

latter reagent was independently prepared and its catalytic applications and provides products of notable synthetic util-

activity checked.^[51]Comparison of rates for formation ity, as in the synthesis of the 2-epimer 21 of natural product

from alkenol 6 points to differences in the catalytic activity (Ϯ)-magnosalicin.

of vanadium reagents 5c and 5d (Figure 4).

The mechanism of the new method for bromocyclization

The diastereoselectivity of product formation from sub- of alkenols proceeds in three decisive steps. In the first step,

strate 6 was independent of the auxiliary L^2Ϫin VOL(OEt) TBHP binds to a vanadium()-based catalyst to furnish the

(5) but was improved slightly upon an increase in solvent corresponding (tert-butylperoxy)(Schiff base)vanadium()

polarity. The catalytic activity of reagents 5 was most pro- complex (e.g. 38). The activated peroxide is considered to

nounced within the first 120 min and leveled off after ap- be the oxidant for the conversion of Br^Ϫinto Br₂, which

proximately 4 h. Thereafter, the rate of product formation then serves as a brominating reagent for the subsequent

in the presence of either of the selected complexes 5a؊g bromocyclization of alkenols in a third, vanadium()-inde-

was similar to that of the background bromination. It was pendent step. The results from transformations of mono-

not possible to resume effective catalysis in this late phase substituted bis(homoallylic) alcohols [e.g. 1-phenyl-4-

by adding further amounts of catalyst 5.

penten-1-ol (6)] suggest that the efficiency of TBCD, which

is the reagent most frequently applied today for conducting

bromocyclizations in multistep natural product syntheses, is

competitive with, to slightly superior to, the new method.

The fact, however, that the oxidative procedure has been

successfully applied in instances in which TBCD failed to

provide useful yields, such as in the synthesis of the strained

hexasubstituted core of the marine natural product aplysia-

pyranoid A and its 5-epi isomer, shows that it is worth con-

sideration, especially in nontrivial cases in which slow but

steady release of the electrophilic brominating reagent is re-

quired.^[7a]

3. Application of the (Schiff base)vanadium(V)-Catalyzed

Oxidation of Bromide ؊ Bromocyclization of Alkenols

Bromocyclizations of 1-, 2-, and 3-substituted bis(ho-

moallylic) alcohols provided 2,5-trans-, 2,4-cis-, and 2,3-

trans-disubstituted tetrahydrofurans (i.e. 5-exo-bromo-

cyclized compounds) as major products (Table 3,

Schemes 1Ϫ3). The magnitudes and the degrees of stereo-

chemical preferences for product formation in such ring-

closure reactions resembled those observed in I₂- or NBS-

mediated halocyclizations with these or structurally related

substrates.^[22,25,30]This information has been applied in the

present study in order to develop a concise synthesis of the

2-epimer 21 of the naturally occurring tetrasubstituted

tetrahydrofuran (Ϯ)-magnosalicin Ϫ an antiallergic com-

pound that has been isolated from the buds of the far east-

ern plant Magnolia salicifolia.^[31]The ease and the efficiency

of this transformation are noteworthy. In spite of the poten-

Experimental Section

1

1. General Remarks: H, ¹³C and ⁵¹V NMR spectra were recorded

with Bruker AC 250 and WM 400 instruments (20 °C) in CDCl₃

solution unless otherwise noted. Residual protons of deuterated

tial of pyHBr to cleave aromatic methyl ether entities^[31]or solvents [δ_Hϭ 7.26 (CDCl₃)] and the corresponding carbon reson-

ances in ¹³C NMR spectra [δ_Cϭ 77.0 ppm (CDCl₃)] were taken as

to furnish products of arene bromination if treated with 5c

internal standards. ⁵¹V NMR resonances were referenced against

and TBHP (Supporting Information), no such side prod-

ucts were identified (¹H NMR spectroscopy).

VOCl₃as external standard (VOCl₃; δ ϭ 0 ppm). IR spectra were

recorded as KBr pellets with a PerkinϪElmer 1600 FT-IR spec-

Products of 5-endo- or 6-endo-selective ring closures were

trometer. UV/Vis: EtOH solutions in 1-cm quartz cuvettes with a

prepared from bis(homoallylic) alcohols with ω-substituted

PerkinϪElmer 330 spectrophotometer. MS: Varian MATCH 7

spectrometer [EI 70 eV]. ESI-MS: mass spectra were obtained with

an ESI mass spectrometer LCQ (Finnigan Mat) under the follow-

ing conditions: solvent flow, 8 µL/min, ESI spray voltage 3.3 kV,

π-bonds. In those instances, polar contributions in tran-

sition states of CϪO bond formation are more important

than stereoelectronic effects.^[7]The fact that the attempted

bromocyclization of 6-methyl-1-phenyl-5-hepten-1-ol (34)

capillary temperature 150 °C, capillary voltage Ϫ34 or ϩ34 V, tube

by the new procedure exclusively furnished dibromide 35 lens-offset Ϫ10 or ϩ10 V, sheath gas N₂, damping gas He. The

(¹H NMR) points to a comparatively slow 7-endo ring clos-

ure, which obviously is not able to compete with a direct π-

CID experiments were carried out in the mass analyzer region with

use of He as the collision gas and by applying a resonance exci-

tation RF voltage (varying from 0 to 5 V, peak-to-peak). The

bond bromination of this substrate in terms of the associ-

masses, charge states, and isotopic envelopes of the parent ions and

ated rate.

the fragment ions (CID) were established by applying the zoom-

scan mode (high-resolution scan, resolution Ͻ 0.2 amu, 10 amu

width). The solutions for the ESI measurements were prepared in

CH₂Cl₂, simulating the typical oxidation conditions. Immediately

Conclusion

(Schiff base)vanadium() complexes catalyze the oxi-

before the measurements, the solutions were diluted with CH₃CN

dation of Br^Ϫin nonaqueous solvents with TBHP as pri- to a final concentration of approx. 10^Ϫ3. After filtration through

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FULL PAPER

a 0.2-µm filter, the solutions were directly injected into the API 3. Preparation of (Schiff base)vanadium(V) Complexes

source of the mass spectrometer by syringe pump. GC: Carlo Erba

General Procedure: A solution of a Schiff base 4 (1 mmol) in dry

EtOH (10 mL) was added under nitrogen to a solution of

VO(OEt)₃(202 mg, 1 mmol) in dry EtOH (5 mL). The reaction

mixture was stirred at 20 °C for 1 h to furnish a dark brown solu-

tion. The solvent was removed under reduced pressure to provide,

after drying at 5 ϫ 10^Ϫ2mbar (20 °C), the corresponding (Schiff

base)vanadium() complex 5 in quantitative yield.

GC 6000 (Vega Series 2), FID, Spectra Physics Integrator 4290,

DB-5 column (30 m ϫ 0.32 mm, 0.25 µm film, J&W Scientific),

split 10:1, helium as carrier gas with a flow of 3 mL/min (80 kPa),

220 °C injector and detector temperature, temperature program: 70

°C (5 min), 10 °C min^Ϫ1to 150 °C, 25 °C min^Ϫ1to 220 °C, 220 °C

(15 min), reference values for retention times: 2-(bromomethyl)-5-

phenyltetrahydrofuran (7): R_tϭ 11.90 min for cis-7 and 12.10 min

for trans-7. C,H,N,S analyses: Microanalytical Laboratory, Univer-

sität Würzburg and Technische Universität Kaiserslautern, Carlo

Erba 1106 or LECO CHNS-932. Solvents were purified according

to standard procedures.^[52]tert-Butyl hydroperoxide (5.5  in

nonane) and triethyl vanadate() were obtained from Fluka and

Aldrich and were used as received. Pyridinium hydrobromide was

obtained from Aldrich and was dried with P₂O₅and stored under

nitrogen. Petroleum ether was distilled prior to use (b.p. 35Ϫ45 °C).

VOL¹(OEt)(EtOH) (5a): Yield: 360 mg (quant.) from 213 mg 4a;

dark brown, microcrystalline solid. ⁵¹V NMR (105 MHz): δ ϭ

Ϫ529 ppm (EtOH); Ϫ529 (CD₃OD); Ϫ529 (CDCl₃). IR (KBr): ν˜ ϭ

990 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max.(lg ε) ϭ 242 nm (4.16),

341 (3.78), 361 (3.80), 659 (2.40).

VOL²(OEt) (5b): Yield: 440 mg (quant.) from 325 mg 4b; dark

brown to black solid. ⁵¹V NMR (105 MHz): δ ϭ Ϫ539 ppm

(EtOH). IR (KBr): ν˜ ϭ 999 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max.

(lg ε) ϭ 257 nm (4.15), 349 (3.90), 485 (2.98), 526 (2.53), 625 (2.34).

C₂₃H₃₀NO₄V (435.4): calcd. C 63.44, H 6.94, N 3.22; found C

63.48, H 6.89, N 3.18.

2. Preparation of Schiff-Base Ligands H₂L (4)

3,5-Di-tert-butyl-N-(2-hydroxyphenyl)salicylidenimine (4b) (H₂L²):

3,5-Di-(tert-butyl)-2-hydroxybenzaldehyde (469 mg, 2 mmol) and

o-aminophenol (218 mg, 2 mmol) were dissolved in dry EtOH

(15 mL) and heated under reflux for 3Ϫ4 h. The solvent was re-

moved in vacuo and the residue was dried at 5 ϫ 10^Ϫ2mbar (20

°C) to afford Schiff base 4b (645 mg, 99%) as a pale yellow solid;

m.p. 128 °C. ¹H NMR (CDCl_3,250 MHz): δ ϭ 1.40 [s, 9 H,

C(CH₃)₃], 1.53 [s, 9 H, C(CH₃)₃], 6.98Ϫ7.10 (m, 2 H, ArϪH),

7.19Ϫ7.30 (m, 2 H, ArϪH), 7.32 (m_c, 1 H, ArϪH), 7.55 (m_c, 1 H,

ArϪH), 8.76 (s, 1 H, CH) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ ϭ

29.4, 31.4, 34.1, 35.1, 115.7, 118.2, 118.5, 121.0, 127.3, 128.4, 128.7,

136.0, 137.1, 141.2, 149.9, 157.7, 165.2 ppm. MS (70 eV, EI): m/z

VOL³(OEt) (5c): Yield: 466 mg (quant.) from 352 mg 4c; black,

microcrystalline solid. ⁵¹V NMR (105 MHz): δ ϭ Ϫ534, Ϫ557 ppm

(EtOH); Ϫ562 /Ϫ573 (br.) ppm, (CDCl₃). IR (KBr): ν˜ ϭ 987 cm^Ϫ1

(VϭO). UV/Vis (EtOH): λ_max.(lg ε) ϭ 251 nm (4.25), 350 (3.69),

437 (1.91), 652 (2.06). C₂₂H₃₆NO₄SV (461.5): calcd. C 57.25, H

7.86, N 3.03, S 6.95; found C 56.13, H 7.22, N 3.24, S 7.00.

VOL⁴(OH)(H₂O) (5d): Yield: 471 mg (quant.) from 368 mg 4d;

dark brown solid. ⁵¹V NMR (105 MHz): δ ϭ Ϫ544 ppm (EtOH);

Ϫ439, Ϫ433, Ϫ558 ppm (in CDCl₃). IR (KBr): ν˜ ϭ 961 cm^Ϫ1. UV/

Vis (EtOH): λ_max.(lg ε) ϭ 260 (4.33), 334 (3.76), 518 (3.01), 673

(2.88). C₂₂H₃₂NO₅SV·H₂O (467.5): calcd. C 51.38, H 7.33, N 3.00,

S 6.86; found C 49.56, H 7.33, N 2.04, S 5.06.

(%) ϭ 325 (48) [M^ϩ], 310 (100) [M^ϩϪ CH₃], 268 (24) [M^ϩ

Ϫ

C(CH₃)₃], 282 (43) [C₁₈H₂₀NO₂^ϩ], 254 (13) [C₁₆H₁₆NO₂^ϩ], 120 (31)

[C₇H₆NO₂^ϩ], 57 (61) [C₄H₉^ϩ]. IR (KBr): ν˜ ϭ 3544 cm^Ϫ1, 3484,

2953, 2903, 2870, 1615, 1583, 1489, 1168, 756. HRMS

(C₂₁H₂₇NO₂, 325.5): calcd. 325.2042, found 325.2038.

VOL⁵(OEt) (5e): Yield: 360 mg (quant.) from 258 mg 4e; black,

microcrystalline solid. ⁵¹V NMR (105 MHz): δ ϭ Ϫ531 ppm (in

EtOH). IR (KBr): ν˜ ϭ 945 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max.(lg

ε) ϭ 549 nm (2.87), 556 (2.81), 652 (2.66).

(2S)-3,5-Di-tert-butyl-N-[1-hydroxy-4-(methylsulfinyl)butyl]-

salicylidenimine (4d) (H₂L⁴): A solution of Schiff base 4c^[16]

(100 mg, 0.29 mmol) in dry CH₂Cl₂(4 mL) was treated with TBHP

(56 µL of a 5.5  solution in nonane, 0.31 mmol). The reaction

mixture was stirred at 20 °C for 5 d. The solution was filtered

through a short pad of SiO₂, and the yellow band of starting mate-

rial 4c was eluted with petroleum ether/Et₂O (1:1, v/v). The sulfox-

ide 4d was then eluted from this column with CH₃OH to provide

a yellow solution, which was concentrated in vacuo to furnish after

drying 50.1 mg (47%) of ligand 4d: viscous yellow oil, mixture of

like/unlike diastereomers. ¹H NMR (CDCl_3,250 MHz): δ ϭ 1.31

[s, 9 H, C(CH₃)₃], 1.43 [s, 9 H, C(CH₃)₃], 1.60Ϫ2.30 (br. s, OH),

2.09Ϫ2.29 (m, 2 H, CH₂), 2.58 (s, 3 H, CH₃), 2.67Ϫ2.81 (m, 2 H,

CH₂), 3.43Ϫ3.63 (m, 1 H, CH), 3.69Ϫ3.96 (m, 2 H, CH₂), 7.17

(m_c, 1 H, ArϪH), 7.43 (m_c, 1 H, ArϪH), 8.48 (s, 1 H, CH) ppm.

¹³C NMR (CDCl₃, 101 MHz): δ ϭ 24.8, 25.9, 29.3, 29.4, 31.3, 31.5,

34.2, 35.0, 38.4, 38.8, 50.5, 51.2, 65.8, 65.9, 70.1, 70.8, 117.5, 126.4

(2C), 127.6, 136.8, 136.9, 140.6, 157.9, 168.0, 168.1 (2 C’s not de-

tected) ppm. IR (KBr): ν˜ ϭ 3387 cm^Ϫ1, 3318, 2956, 2910, 2866,

1630, 1467, 1440, 1032. MS (70 eV, EI): m/z (%) ϭ 367 (100) [M^ϩ],

VOL⁸(OEt) (5h): A solution of 3-amino-4-hydroxybenzoic acid

(306 mg, 2.0 mmol) and 2-hydroxybenzaldehyde (244 mg,

2.0 mmol) in dry EtOH (15 mL) was heated at reflux for 4 h. The

solvent was removed under reduced pressure to furnish a yellow

residue, which was recrystallized twice from CH₃OH to afford a

crude product (412 mg). A fraction of this material (206 mg) was

treated with VO[OCH(CH₃)₂]₃(286 mg) in dry EtOH (10 mL).The

reaction mixture was heated at reflux for 30 min. Afterwards, the

amount of solvent was concentrated to half of its volume to provide

a dark solution that was allowed to stand at 20 °C for 24 h. (Schiff

base)vanadium() complex 5h separated as a black, microcrystal-

line solid from this solution to provide pure 5h (120 mg, 33%) after

filtration and drying. ⁵¹V NMR (105 MHz): δ ϭ Ϫ534 ppm (in

EtOH); Ϫ538 ppm (in CDCl₃). IR (KBr): ν˜ ϭ 991 cm^Ϫ1(VϭO).

UV/Vis (EtOH): λ_max.(lg ε) ϭ 267 (4.51), 363 (4.26), 564 (4.18),

661 (4.38). C₁₆H₁₄NO₆V (367.2): calcd. C 52.33, H 3.84, N 3.81;

found C 52.40, H 3.87, N 4.01.

4. Vanadium(V)-Catalyzed Oxidation of Bromide in the Presence of

Alkenols

351 (11) [M^ϩ

Ϫ

O], 336 (10) [C₁₉H₃₀NO₂S^ϩ], 303 (61)

[C₁₉H₃₀NO₂^ϩ], 288 (93) [C₁₉H₂₉NO^ϩ], 272 (23) [C₁₈H₂₉NO^ϩ], 232 General Procedure: In a typical run, catalyst VOL³(OEt) (5c,

(29) [C₁₅H₂₂NO^ϩ], 71 (13) [C₄H₈O^ϩ], 57 (50) [C₄H₉^ϩ], 41 (18)

11.5 mg, 25.0 µmol, 5 mol %) was dissolved in a dry solvent

[C₃H₅^ϩ]. HRMS (C₂₀H₃₃NO₃S, 367.6): calcd. 367.2181, found [CH₃CN, CHCl₃or CH₂Cl₂(2 mL)]. TBHP (100 µL of a 5.5 

367.2182.

solution in nonane, 0.55 mmol) was added, and the solution was

3808

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The (Schiff base)vanadium(V) Complex Catalyzed Oxidation of Bromide

FULL PAPER

heated at 40 °C for 2 min. Stirring was continued at 20 °C for Bromocyclization of 4-Methyl-1-phenyl-4-penten-1-ol (10)

5 min. Afterwards, this solution was added portionwise to a solu-

tion of alkenol (0.50 mmol) and pyHBr (120 mg, 0.75 mmol) in a

dry solvent (CH₃CN, CHCl₃or CH₂Cl₂, 3 mL). The reaction mix-

ture was stirred at 20 °C for 48 h. Afterwards, the solvent was re-

2-(Bromomethyl)-2-methyl-5-phenyltetrahydrofuran (15): Yield:

81.7 mg (64%), cis/trans ϭ 26:74, colorless liquid. C₁₂H₁₅BrO

(255.2): calcd. C 56.45, H 5.93; found C 56.47, H 5.81. MS (70 eV,

EI): m/z (%) ϭ 256/254 (3) [M^ϩ], 161 (50) [M^ϩϪ Br], 105 (100)

moved under reduced pressure to provide a brown, viscous, oily

[C₈H₉^ϩ], 77 (49) [C₆H₅^ϩ], 43 (56) [C₂H₃O^ϩ]. cis-15: R_fϭ 0.77

residue that was purified by column chromatography [SiO₂; typical

[SiO₂; petroleum ether/Et₂O (13:1, v/v)]. ¹H NMR (CDCl₃,

eluent: petroleum ether/Et₂O (10:1, v/v)].

250 MHz): δ ϭ 1.50 (s, 3 H, CH₃), 1.86Ϫ2.02 (m, 2 H, CH₂),

2.16Ϫ2.41 (m, 2 H, CH₂), 3.50 (m_c, 2 H, CH₂), 5.04 (m_c, 1 H, CH),

Bromocyclization of 1-Phenyl-4-penten-1-ol (6)

7.23Ϫ7.46 (m, 5 H, PhϪH) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ ϭ

2-(Bromomethyl)-5-phenyltetrahydrofuran (7):^[25]Yield: 79.6 mg

(66%), cis/trans ϭ 34:66, colorless liquid. cis-7: R_fϭ 0.73 [SiO₂;

25.2, 35.5, 36.4, 41.1, 81.3, 82.4, 125.9, 127.4, 128.3, 142.1 ppm.

trans-15: R_fϭ 0.77 [SiO₂; petroleum ether/Et₂O (13:1, v/v)]. ¹H

NMR (CDCl₃, 250 MHz): δ ϭ 1.53 (s, 3 H, CH₃), 1.86Ϫ2.02 (m,

2 H, CH₂), 2.16Ϫ2.41 (m, 2 H, CH₂), 3.51 (m_c, 2 H, CH₂), 5.05

(dd, J ϭ 9.0, 5.7 Hz, 1 H, CH), 7.23Ϫ7.42 (m, 5 H, PhϪH) ppm.

¹³C NMR (CDCl₃, 63 MHz): δ ϭ 25.9, 35.5, 36.4, 41.6, 82.0, 82.6,

125.7, 127.4, 128.3, 142.2 ppm.

petroleum ether/Et₂O (10:1, v/v)]. ¹H NMR (CDCl₃, 250 MHz):

δ ϭ 1.86Ϫ2.01 (m, 2 H, CH₂), 2.17Ϫ2.35 (m, 2 H, CH₂), 3.50 (dd,

J ϭ 10.1, 5.4 Hz, 1 H, CH₂), 3.58 (dd, J ϭ 10.1, 5.4 Hz, 1 H, CH₂),

4.35 (m_c, 1 H, CH), 4.95 (dd, J ϭ 8.1, 5.9 Hz,,1 H, CH), 7.23Ϫ7.41

(m, 5 H, PhϪH) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ ϭ 30.4, 34.3,

35.8, 78.5, 82.1, 125.8, 127.5, 128.7, 142.2 ppm. trans-7: R_fϭ 0.80

[SiO₂; petroleum ether/Et₂O (10:1, v/v)]. ¹H NMR (CDCl₃,

Bromocyclization of 2-Phenyl-4-penten-1-ol (11)

250 MHz): δ ϭ 1.86Ϫ2.01 (m, 2 H, CH₂), 2.17Ϫ2.35 (m, 1 H, 2-(Bromomethyl)-4-phenyltetrahydrofuran (16): Yield: 106 mg

CH₂), 2.38Ϫ 2.56 (m, 1 H, CH₂), 3.46 (dd, J ϭ 10.1, 7.2 Hz, 1 H,

CH₂), 3.55 (dd, J ϭ 10.1, 3.8 Hz, 1 H, CH₂), 4.48 (m_c, 1 H, CH),

5.10 (dd, J ϭ 8.3, 6.1 Hz, 1 H, CH), 7.23Ϫ 7.41 (m, 5 H, PhϪH)

ppm. ¹³C NMR (CDCl₃, 63 MHz): δ ϭ 31.1, 35.2, 36.0, 78.7, 81.5,

125.6, 127.4, 128.6, 142.6 ppm.

(88%), cis/trans ϭ 72:28, colorless liquid.^[25]

Bromocyclization of 3-phenyl-4-penten-1-ol (12)

2-(Bromomethyl)-3-phenyltetrahydrofuran (17): Yield: 67.5 mg

(56%), cis/trans ϭ 30:70, colorless liquid.^[25]

Bromocyclization of 4-Phenyl-4-penten-1-ol (13)

4,5-Dibromo-1-phenylpentan-1-ol (8): Yield 33.8 mg (21%), 50:50

mixture of diastereomers, colorless liquid. R_fϭ 0.26 [SiO₂; petro-

leum ether/Et₂O (10:1, v/v)]. ¹H NMR (CDCl₃, 400 MHz): δ ϭ

1.58Ϫ1.72 (br. s, 2 H, OH), 1.75Ϫ2.10 (m, 6 H, CH₂), 2.18Ϫ2.28

(m, 1 H, CH₂), 2.33Ϫ2.42 (m, 1 H, CH₂), 3.61 (dd, J ϭ 9.9, 4.4 Hz,

2 H, CH₂), 3.84 (2 t, J ϭ 9.9 Hz, 2 H, CH₂), 4.20 (m_c, 2 H, CH),

4.74 (m_c, 2 H, CH), 7.28Ϫ7.39 (m, 10 H, ArϪH) ppm. ¹³C NMR

(CDCl₃, 101 MHz): δ ϭ 32.4, 32.8, 36.0, 36.1, 36.2 (2 C), 52.5,

52.9, 73.6, 74.2, 125.7, 125.8, 127.8, 127.9, 128.6, 128.7, 144.1,

144.2 ppm. MS (70 eV, EI): m/z (%) ϭ 304 (12) [M^ϩϪ OH], 242/

240 (12) [M^ϩϪ Br], 147 (29) [C₁₀H₁₁O^ϩ], 129/128 (29) [C₁₀H₉^ϩ],

117 (100) [C₉H₉^ϩ], 104 (22) [C₈H₉^ϩ], 91 (22) [C₇H₇^ϩ], 77 (13)

[C₆H₅^ϩ], 41 (13) [C₂H₂^ϩ]. C₁₁H₁₄Br₂O (322.0): calcd. C 41.03, H

4.38; found C 41.07, H 4.08.

2-(Bromomethyl)-2-phenyltetrahydrofuran (18): Yield: 79.6 mg

(66%), colorless liquid. R_fϭ 0.52 [SiO₂; petroleum ether/Et₂O

1

(10:1, v/v)]. H NMR (CDCl₃, 250 MHz): δ ϭ 1.79Ϫ1.93 (m, 1 H,

CH₂), 1.98Ϫ2.14 (m, 1 H, CH₂), 2.26 (ddd, J ϭ 12.3, 7.9, 5.2 Hz,

1 H, CH₂), 2.43 (dt, J ϭ 12.3, 8.2 Hz, 1 H), 3.65 (s, 2 H, CH₂),

3.94 (dt, J ϭ 8.2, 5.8 Hz, 1 H, CH₂), 4.09 (dt, J ϭ 8.2, 7.0 Hz, 1

H, CH₂), 7.24Ϫ7.44 (m, 5 H, PhϪH) ppm. ¹³C NMR (CDCl₃,

63 MHz): δ ϭ 26.1, 36.4, 42.2, 68.6, 85.3, 125.6, 127.4, 128.3, 144.0

ppm. MS (70 eV, EI): m/z (%) ϭ 160 (78) [M^ϩϪ HBr], 147 (100)

[C₁₀H₁₁O^ϩ], 118 (42) [C₈H₇O^ϩ], 105 (57) [C₇H₅O^ϩ], 91 (29)

[C₇H₇^ϩ], 77 (24) [C₆H₅^ϩ], 51 (12) [C₄H₃^ϩ]. C₁₁H₁₃BrO (241.1):

calcd. C 54.79, H 5.43; found C 54.03, H 5.45.

Bromocyclization of (1S*,2S*,3R*)-2-Methyl-1,3-bis(2Ј,4Ј,5Ј-tri-

methoxyphenyl)-4-penten-1-ol (19)

Bromocyclization of 1-(4-Methoxyphenyl)-4-penten-1-ol (9)

2-(Bromomethyl)-5-(4-methoxyphenyl)tetrahydrofuran (14): Yield:

(2R*,3R*,4S*,5S*)-2-(Bromomethyl)-4-methyl-1,3-bis(2Ј,4Ј,5Ј-tri

93.5 mg (69%), cis/trans ϭ 33:67, colorless liquid. C₁₂H₁₅BrO₂methoxyphenyl)-tetrahydrofuran (20): A solution of VOL³(OEt) (5c;

(271.2): calcd. C 53.16, H 5.58; found C 52.25, H 5.49. MS (70 eV,

11.6 mg, 5 mol %) in CH₂Cl₂(2 mL) was treated with TBHP (100

µL of a 5.5  solution in nonane, 0.55 mmol) as outlined in the

EI): m/z (%) ϭ 270/272 (23) [M^ϩ], 239/241 (15) [M^ϩϪ OCH₃], 191

(21) [M^ϩϪ Br], 135 (100) [C₉H₁₀O^ϩ], 83 (21) [C₅H₈^ϩ], 55 (36) General Procedure. This mixture was added dropwise to a solution

[C₃H₃O^ϩ]. cis-14: R_fϭ 0.44 [SiO₂; petroleum ether/Et₂O (6:1, v/

of 2-methyl-1,3-bis(2Ј,4Ј,5Ј-trimethoxyphenyl)-4-penten-1-ol (19;

1

v)]. H NMR (CDCl₃, 250 MHz): δ ϭ 1.83Ϫ2.05 (m, 2 H, CH₂), 216 mg, 0.50 mmol) and pyHBr (120 mg, 0.75 mmol) in CH₂Cl₂

2.14Ϫ2.35 (m, 2 H, CH₂), 3.47 (dd, J ϭ 10.1, 6.1 Hz, 1 H, CH₂),

3.56 (dd, J ϭ 10.1, 2.7 Hz, 1 H, CH₂), 3.80 (s, 3 H, OCH₃), 4.31

(3 mL). The reaction mixture was stirred at 20 °C for 48 h. The

solvent was removed under reduced pressure to provide a residue,

(m_c, 1 H, CH), 4.89 (dd, J ϭ 8.2, 5.8 Hz, 1 H, CH), 6.88 (m_c, 2 H, which was purified by column chromatography [SiO₂; petroleum

ArϪH), 7.30 (m_c, 2 H, ArϪH) ppm. ¹³C NMR (CDCl₃, 63 MHz):

ether/Et₂O (1:1, v/v)]. Yield: 178 mg (70%), colorless solid. m.p.

δ ϭ 30.5, 34.2, 35.9, 55.3, 78.3, 81.8, 113.8, 127.2, 134.2, 159.1 44Ϫ46 °C. R_fϭ 0.30 [SiO₂; petroleum ether/Et₂O (1:1, v/v)]. ¹H

ppm. trans-14: R_fϭ 0.45 [SiO₂; petroleum ether/Et₂O (6:1, v/v)]. NMR (CDCl₃, 400 MHz): δ ϭ 0.90 (d, J ϭ 6.4 Hz, 3 H, CH₃),

¹H NMR (CDCl₃, 250 MHz): δ ϭ 1.82Ϫ2.10 (m, 2 H, CH₂), 2.52 (ddq, J ϭ 11.2, 9.6, 6.4 Hz, 1 H, CH), 3.36 (dd, J ϭ 11.2,

2.20Ϫ2.40 (m, 2 H, CH₂), 3.44 (dd, J ϭ 10.1, 6.7 Hz, 1 H, CH₂),

3.54 (dd, J ϭ 10.1, 4.9 Hz, 1 H, CH₂), 3.80 (s, 3 H, OCH₃), 4.46

8.8 Hz, 1 H, CH), 3.48 (dd, J ϭ 10.6, 5.2 Hz, 1 H, CH₂Br), 3.62

(dd, J ϭ 10.6, 3.9 Hz, 1 H, CH₂Br), 3.82 (s, 3 H, OCH₃), 3.83 (s,

(m_c, 1 H, CH), 5.03 (dd, J ϭ 7.9, 5.4 Hz, 1 H, CH), 6.87 (m_c, 2 H, 3 H, OCH₃), 3.84 (s, 3 H, OCH₃), 3.89 (s, 9 H, 3ϫOCH₃), 4.46

ArϪH), 7.25 (m_c, 2 H, ArϪH) ppm. ¹³C NMR (CDCl₃, 63 MHz):

(ddd, J ϭ 8.9, 5.2, 3.9 Hz, 1 H, CH), 5.03 (d, J ϭ 9.6 Hz, 1 H,

δ ϭ 31.3, 35.1, 36.1, 55.3, 78.5, 81.3, 113.8, 127.0, 134.5, 159.0 CH), 6.53 (s, 1 H, ArϪH), 6.54 (s, 1 H, ArϪH), 6.76 (s, 1 H,

ppm.

ArϪH), 7.06 (s, 1 H, ArϪH) ppm. ¹³C NMR (101 MHz): δ ϭ 14.6,

Eur. J. Org. Chem. 2004, 3799Ϫ3812

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M. Greb, J. Hartung, F. Köhler, K. Spehar, R. Kluge, R. Csuk

FULL PAPER

36.8, 49.4, 52.2, 56.3, 56.5 (2C), 57.0, 57.2, 57.3, 82.6, 83.4, 98.3,

98.5, 112.0, 113.2, 118.8, 121.6, 143.7, 143.8, 149.1, 149.5, 152.2,

C₁₂H₁₅BrO (255.2): calcd. C 56.49, H 5.93; found C 56.19, H 5.87.

MS (70 eV): m/z (%) ϭ 256/254 (1) [M^ϩ], 174 (95) [M^ϩϪ Br], 118

152.9 ppm. MS (70 eV, EI): m/z (%) ϭ 510/512 (36) [M^ϩ], 430 (2) (100) [C₈H₆O^ϩ], 90 (49) [C₇H₆^ϩ], 55 (14) [C₄H₈^ϩ], 43 (10) [C₃H₆^ϩ].

[M^ϩϪ Br], 223 (100) [C₁₂H₁₃O₄^ϩ]. C₂₄H₃₁BrO₇(511.4): calcd. C 2,6-cis-26: R_fϭ 0.64 [SiO₂; petroleum ether/Et₂O (10:1, v/v)]. ¹H

56.37, H 6.11; found C 55.94, H 6.13.

NMR (CDCl₃, 250 MHz): δ ϭ 1.23 (d, J ϭ 6.4 Hz, 3 H, CH₃),

1.60 (ddt, J ϭ 10.7, 4.0, 13.1 Hz, 1 H, CH₂), 1.79 (m_c, 1 H, CH₂),

2.16 (ddt, J ϭ, 11.9, 4.5, 13.1 Hz, 1 H, CH₂), 2.55 (m, 1 H, CH₂),

3.74 (ddq, J ϭ 13.1, 2.1, 6.4 Hz, 1 H, CH), 4.00 (ddd, J ϭ 11.9,

10.1, 4.5 Hz, 1 H, CH), 4.39 (d, J ϭ 10.1 Hz, 1 H, CH), 7.29Ϫ7.43

(m, 5 H, PhϪH) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ ϭ 21.6, 35.5,

36.2, 52.6, 74.6, 85.2, 127.8, 128.2, 128.4, 139.8 ppm. 2,6-trans-26:

R_fϭ 0.45 [SiO₂; petroleum ether/Et₂O (10:1, v/v)]. ¹H NMR

(CDCl₃, 250 MHz): δ ϭ 1.38 (d, J ϭ 6.7 Hz, 3 H, CH₃), 1.72 (m_c,

2 H, CH₂), 2.25Ϫ2.36 (m, 2 H, CH₂), 4.22 (m_c, 1 H, CH), 4.28 (dt,

J ϭ 5.8, 8.3 Hz, 1 H, CH), 4.79 (d, J ϭ 8.3 Hz, 1 H, CH) 7.26Ϫ7.43

(m, 5 H, PhϪH) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ ϭ 17.5, 30.1,

30.8, 52.6, 68.8, 81.6, 127.3, 128.2, 128.4, 139.4 ppm.

(2R*,3R*,4S*,5S*)-2,4-Dimethyl-1,3-bis(2Ј,4Ј,5Ј-trimeth-

oxyphenyl)tetrahydrofuran (21): A solution of 2-(bromomethyl)-4-

methyl-1,3-bis(2Ј,4Ј,5Ј-trimethoxyphenyl)tetrahydrofuran

(20;

124 mg, 240 µmol) in dry Et₂O (5 mL) was added dropwise to a

stirred mixture of LiH (10.1 mg, 1.44 mmol) and LiAlH₄(29.0 mg,

720 µmol) in dry Et₂O (10 mL), under argon. The mixture was

stirred at 20 °C for 12 h and cooled to 0 °C, and H₂O was added

until no further hydrogen was evolved. The salts were dissolved

with aq. HCl (10%, w/w), the organic phase was separated, and the

aqueous phase was extracted with Et₂O (2 ϫ 10 mL). The com-

bined organic phases were concentrated in vacuo to afford crude

product (126 mg), which was purified by column chromatography

[SiO₂; petroleum ether/Et₂O (1:1, v/v)]. Yield: 81.0 mg (78%), color-

less solid. R_fϭ 0.35 [SiO₂; petroleum ether/Et₂O (1:1, v/v)]. ¹H

NMR (400 MHz): δ ϭ 0.90 (d, J ϭ 6.6 Hz, 3 H, CH₃), 1.26 (d,

J ϭ 6.1 Hz, 3 H, CH₃), 2.44 (ddq, J ϭ 10.9, 9.1, 6.4 Hz, 1 H, CH),

3.11 (dd, J ϭ 10.9, 9.3 Hz, 1 H, CH), 3.80 (s, 3 H, OCH₃), 3.82 (s,

3 H, OCH₃), 3.83 (s, 3 H, OCH₃), 3.88 (s, 3 H, OCH₃), 3.89 (s, 6

H, 2 ϫ OCH₃), 4.34 (dq, J ϭ 9.3, 6.1 Hz, 1 H, CH), 5.01 (d, J ϭ

9.3 Hz, 1 H, CH), 6.53 (s, 1 H, ArϪH), 6.55 (s, 1 H, ArϪH), 6.75

(s, 1 H, ArϪH), 7.07 (s, 1 H, ArϪH) ppm.

2,6-unlike-2-(6-Bromo-6-phenylmethyl)-5-methyltetrahydrofuran

(27): Yield: 6.5 mg (5%), cis/trans ϭ 58:42, colorless liquid. 2,6-

1

unlike-2,5-cis-27: H NMR (CDCl₃, 600 MHz): δ ϭ 1.27 (d, J ϭ

6.1 Hz, CH₃), 1.45Ϫ1.53 (m, 1 H, CH₂), 2.00Ϫ2.08 (m, 2 H, CH₂),

2.18 (m_c, 1 H, CH₂), 4.10Ϫ4.18 (m, 1 H, CH), 4.41 (dt, J ϭ 7.4,

6.2 Hz, 1 H, CH), 4.87 (d, J ϭ 7.4 Hz, 1 H, CH), 7.26Ϫ7.35 (m,

3 H, PhϪH), 7.41Ϫ7.45 (m, 2 H, PhϪH) ppm. ¹³C NMR (CDCl₃,

151 MHz): δ ϭ 21.4, 30.8, 34.0, 57.8, 76.0, 81.9, 128.3, 128.4, 128.5,

139.5 ppm. 2,6-unlike-2,5-trans-27: ¹H NMR (CDCl₃, 600 MHz):

δ ϭ 1.18 (d, J ϭ 6.1 Hz, CH₃), 1.45Ϫ1.55 (m, 1 H, CH₂),

2.02Ϫ2.10 (m, 2 H, CH₂), 2.26 (m_c, 1 H, CH₂), 4.17 (m_c, 1 H, CH),

4.53 (q, J ϭ 7.0 Hz, 1 H, CH), 4.93 (d, J ϭ 7.0 Hz, 1 H, CH),

7.26Ϫ7.35 (m, 3 H, PhϪH), 7.41Ϫ7.45 (m, 2 H, PhϪH) ppm. ¹³C

NMR (CDCl₃, 151 MHz): δ ϭ 21.1, 31.3, 33.9, 58.5, 76.3, 81.6,

128.3, 128.4, 128.5, 139.5 ppm.

Bromocyclization of 2-Cyclohex-2-en-1-yl-1-phenylethanol (22)

6,8-trans-5-Bromo-8-phenyl-7-oxabicyclo[4.3.0]nonane (23): Yield:

46.6 mg (33%), 6,8-cis/6,8-trans ϭ 7:93. R_fϭ 0.82 [SiO₂; petroleum

ether/Et₂O (10:1, v/v)]. ¹H NMR (CDCl₃, 250 MHz):

δ ϭ

1.23Ϫ1.81 (m, 4 H, CH₂), 1.82Ϫ1.88 (m, 1 H, CH₂), 1.94 (ddd,

J ϭ 12.5, 7.6, 6.4 Hz, 1 H, CH₂), 2.10 (m_c, 1 H, CH₂), 2.21 (ddd,

J ϭ 12.4, 7.3, 6, 5 Hz, 1 H, CH₂), 2.53Ϫ2.65 (m, 1 H, CH), 4.40

(t, J ϭ 4.3 Hz, 1 H, CH), 4.44 (m_c, 1 H, CH), 5.22 (dd, J ϭ 7.6,

7.3 Hz, 1 H, CH), 7.22Ϫ7.37 (m, 5 H, PhϪH) ppm. ¹³C NMR

(CDCl₃, 63 MHz): δ ϭ 19.8, 26.3, 30.5, 36.2, 40.5, 52.1, 79.6, 82.6,

125.3, 127.2, 128.4, 144.2 ppm. MS (70 eV): m/z (%) ϭ 282/280

(43) [M^ϩ], 211 (1) [M^ϩϪ Br], 189 (4) [C₁₂H₁₄O₂^ϩ], 129 (80), 120

(15) [C₃H₆Br^ϩ], 105 (86) [C₇H₅O^ϩ], 59 (1) [C₂H₃O^ϩ], 43 (100)

[C₂H₃O^ϩ]. HRMS (C₁₄H₁₇BrO, 281.2): calcd. 280.0463; found

280.0462.

Bromocyclization of 4-Methyl-1-phenyl-3-penten-1-ol (28)

3-Bromo-2,2-dimethyl-5-phenyltetrahydrofuran (29): Yield: 39.6 mg

(31%, cis/trans ϭ 84:16, colorless liquid. C₁₂H₁₅BrO (255.2): calcd.

C 56.49, H 5.93; found C 56.18, H 5.73. MS (70 eV): m/z (%) ϭ

254/256 (1) [M^ϩ], 174 [M^ϩϪ HBr], 131 (96) [C₉H₇O^ϩ], 69 (100)

[C₄H₅O^ϩ], 77 (30) [C₆H₅^ϩ], 69 (44) [C₅H₉^ϩ], 43 (69) [C₂H₃O^ϩ]. cis-

29: R_fϭ 0.52 [SiO₂; petroleum ether/Et₂O (10:1, v/v)]. ¹H NMR

(CDCl₃, 400 MHz): δ ϭ 1.43 (s, 3 H, CH₃), 1.46 (s, 3 H, CH₃),

2.38 (dt, J ϭ 13.0, 6.5 Hz, 1 H, CH₂), 2.90 (dt, J ϭ 13.0, 9.8 Hz,

1 H, CH₂), 4.21 (dd, J ϭ 9.8, 6.5 Hz, 1 H, CH), 4.98 (dd, J ϭ 9.8,

6.5 Hz, 1 H, CH), 7.24Ϫ7.38 (m, 5 H, PhϪH) ppm. ¹³C NMR

(CDCl₃, 101 MHz): δ ϭ 26.3, 26.8, 44.8, 54.4, 77.9, 82.7, 125.7,

127.6, 128.4, 142.0 ppm. trans-29: R_fϭ 0.67 [SiO₂; petroleum ether/

2-(2,3-Dibromocyclohexyl)-1-phenylethanol (24): Yield: 53.9 mg

(30%), diastereomer I/diastereomer II ϭ 23:77, colorless oil.

C₁₄H₁₈Br₂O (362.1): calcd. C 46.44, H 5.01; found C 46.82, H 5.08.

MS (70 eV, EI): m/z (%) ϭ 364/362 (1) [M^ϩ], 280 (1) [M^ϩϪ HBr],

205 (4) [C₈H₁₂OBr^ϩ], 184 (26) [C₂H₂Br₂^؉], 107 (100) [C₇H₇O^ϩ],

81 (18) [HBr^ϩ], 79 (57) [Br^ϩ], 77 (25) [C₆H₅^؉], 41 (13) [C₃H₅^؉].

Diastereomer I: R_fϭ 0.21 [SiO₂; petroleum ether/Et₂O (10:1, v/v)].

¹H NMR (CDCl₃, 400 MHz): δ ϭ 1.50 (m_c, 2 H) 1.58Ϫ1.79 (m, 3

H), 1.83Ϫ1.97 (m, 2 H), 2.37Ϫ2.51 (m, 2 H), 4.75Ϫ4.82 (m, 3 H),

7.27Ϫ7.37 (m, 5 H, PhϪH) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ ϭ

20.2, 26.0, 28.0, 32.5, 44.9, 54.2, 62.0, 71.8, 125.7, 127.7, 128.6,

144.5 ppm. Diastereomer II: R_fϭ 0.28 [SiO₂; petroleum ether/Et₂O

(10:1, v/v)]. ¹H NMR (CDCl₃, 400 MHz): δ ϭ 1.43Ϫ1.54 (m, 1

H) 1.60Ϫ1.70 (m, 3 H), 1.82Ϫ1.93 (m, 3 H), 2.38Ϫ2.48 (m, 2 H),

4.70Ϫ4.79 (m, 3 H), 7.27Ϫ7.37 (m, 5 H, PhϪH) ppm. ¹³C NMR

(CDCl₃, 63 MHz): δ ϭ 20.4, 27.3, 28.2, 31.9, 44.4, 54.0, 60.3, 71.1,

125.5, 127.7, 128.6, 144.8 ppm.

1

Et₂O (10:1, v/v)]. H NMR (CDCl₃, 400 MHz): δ ϭ 1.48 (s, 3 H,

CH₃), 1.49 (s, 3 H, CH₃), 2.54 (dt, J ϭ 13.4, 7.0 Hz, 1 H, CH₂),

2.73 (dt, J ϭ 13.4, 7.0 Hz, 1 H, CH₂), 4.21 (t, J ϭ 7.0 Hz, 1 H,

CH), 5.22 (t, J ϭ 7.0 Hz, 1 H, CH), 7.24Ϫ7.37 (m, 5 H, PhϪH)

ppm. ¹³C NMR (CDCl₃, 101 MHz): δ ϭ 25.0, 27.3, 44.8, 55.6,

77.8, 83.4, 125.7, 127.5, 128.5, 142.6 ppm.

Bromocyclization of 5-Methyl-1-phenyl-4-hexen-1-ol (30)

3-Bromo-2,2-dimethyl-6-phenyltetrahydropyran (31): Yield: 164 mg

(61%), cis/trans ϭ 9:91 colorless liquid.

2-(1-Bromo-1-methylethyl)-5-phenyltetrahydrofuran (32): Yield:

35.1 mg (13%), cis/trans ϭ 46:54, colorless liquid.

Bromocyclization of (E)-6-Phenyl-5-hexen-2-ol (25)

4,5-Dibromo-5-methyl-1-phenylhexan-1-ol (33): Yield: 59.5 mg

(17%), like/unlike ϭ 50:50, colorless liquid. R_fϭ 0.26 [SiO₂; petro-

2,3-trans-3-Bromo-6-methyl-2-phenyltetrahydropyran (26): Yield:

73.9 mg (58%), 2,6-cis/2,6-trans

ϭ

86:14, colorless liquid. leum ether/Et₂O (5:1, v/v)]. C₁₃H₁₈Br₂O (350.1): calcd. C 44.60, H

3810

 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjoc.org

Eur. J. Org. Chem. 2004, 3799Ϫ3812

The (Schiff base)vanadium(V) Complex Catalyzed Oxidation of Bromide

FULL PAPER

5.18; found C 44.46, H 5.17. MS (70 eV, EI): m/z (%) ϭ 269 (6) chemie Ϫ Mechanistische und Präparative Aspekte des Sauer-

[M^ϩϪ HBr], 251 (4) [M^ϩϪ H₂O Ϫ HBr], 189 (2) [M^ϩϪ 2 HBr], stofftransfers).

147 (5) [C₁₀H₁₁O^ϩ], 107 (100) [C₇H₇O^ϩ], 79 (22) [Br^ϩ], 41 (8)

[C₃H₅^ϩ]. ¹H NMR (CDCl₃, 600 MHz): δ ϭ 1.79 (s, 3 H, CH₃),

[1]

1.81 (s, 3 H, CH₃), 1.80Ϫ1.95 (m, 3 H, 2 CH₂), 1.97 (s, 3 H, CH₃),

1.98 (s, 3 H, CH₃), 1.99Ϫ2.05 (m, 1 H, CH₂), 2.13Ϫ2.24 (m, 2 H,

CH₂), 2.51Ϫ2.57 (m, 1 H, CH₂), 2.63Ϫ2.68 (m, 1 H, CH₂), 4.23

(dd, J ϭ 11.1, 1.7 Hz, 1 H, CH), 4.25 (dd, J ϭ 10.8, 1.7 Hz, 1 H,

CH), 4.73 (dd, J ϭ 7.9, 5.2 Hz, 1 H, CH), 4.77 (dd, J ϭ 8.6, 4.5 Hz,

1 H, CH), 7.28Ϫ7.39 (m, 10 H, PhϪH) ppm. ¹³C NMR (CDCl₃,

151 MHz): δ ϭ 28.3, 28.4, 32.2, 32.8, 35.2, 35.3, 37.6, 37.9, 66.4,

67.0, 68.5, 68.6, 73.3, 74.3, 125.7, 125.9, 127.7, 127.8, 128.5, 128.6,

144.3, 144.4 ppm.

The following abbreviations have been used: acac ϭ acetyl-

acetone monoanion, BPO ϭ bromoperoxidase, CAB ϭ co-

balt() acetate/acetic acid/bromide, NBS ϭ N-bromosuccinim-

ide, TBCD

ϭ 2,4,4,6-tetrabromocyclohexa-2,5-dien-1-one,

TBHP ϭ tert-butyl hydroperoxide. Unless otherwise noted by

an appropriate stereodescriptor, all graphics refer to racemic

compounds.

W. M. Weigert, W. Merck, H. Offermanns, G. Prescher, G.

Schreyer, O. Weiberg, in Wasserstoffperoxide und seine Derivate,

Chemie und Anwendung (Ed.: W. M. Weigert), Hüthig, Heidel-

berg, 1978.

C. W. Jones, Applications of Hydrogen Peroxide and Derivatives

(Series Ed.: J. H. Clark), RSC Clean Technology Monographs,

Cambridge, 1999.

[2]

[3]

Bromocyclization of 6-Methyl-1-phenyl-5-hepten-1-ol (34)

5,6-Dibromo-6-methyl-1-phenylheptan-1-ol (35): Yield: 131 mg

(72%), like/unlike ϭ 50:50. R_fϭ 0.43 [SiO₂; petroleum ether/Et₂O

1

[4] [4a]

(5:1, v/v)]. H NMR (CDCl₃, 250 MHz): δ ϭ 1.68Ϫ1.96 (m, 6 H,

B. M. Choudary, T. Someshwar, C. V. Reddy, M. L. Kan-

tam, K. J. Ratnam, L. V. Sivaji, Appl. Catal. A 2003, 251,

CH₂), 1.79 (s, 6 H, CH₃), 1.97 (s, 6 H, CH₃), 2.35Ϫ2.50 (m, 4 H,

CH₂), 4.15 (dd, J ϭ 6.1, 1.5 Hz, 1 H, CH), 4.19 (dd, J ϭ 5.9,

1.4 Hz, 1 H, CH), 4.67Ϫ4.75 (m, 2 H, CH), 7.27Ϫ7.38 (m, 10 H,

PhϪH) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ ϭ 24.6, 24.7, 25.2,

28.1 (2C), 35.3, 35.4, 35.5, 35.6, 38.0, 66.5, 66.6, 68.7, 70.4, 74.3,

74.5, 125.8, 125.9, 127.5, 127.6, 128.5, 128.6, 144.6, 144.7 ppm. IR

(neat): ν˜ ϭ 3415 cm^Ϫ1, 3484, 3062, 3021, 2932, 2845, 1709, 1492,

1454, 1370, 1096, 760, 700. MS (70 eV): m/z (%) ϭ 266/264 (4) [M^ϩ

Ϫ HOBr], 202 (26) [M^ϩϪ 2 HBr], 184 (46) [M^ϩϪ HBr Ϫ HOBr],

128 (41) [C₈H₁₆O^ϩ], 117 (100) [C₉H₉^ϩ], 77 (28) [C₆H₅^ϩ], 51 (15)

[C₄H₃^ϩ], 39 (15) [C₃H₃^ϩ]. C₁₄H₂₀Br₂O (364.1): calcd. C 46.18, H

5.54; found C 47.15, H 5.66.

[4b]

397Ϫ409.

Chem. 2000, 36, 1758Ϫ1759.

I. M. Lazarev, N. A. Nedolya, Russ. J. Org.

[4c]

S. Mukhopadhyay, S. Anan-

thakrishnan, S. B. Chandalia, Org. Proc. Res. Dev. 1999, 3,

451Ϫ454.

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[5b]

W. Partenheimer, J. Mol. Catal. A 2003, 206, 105Ϫ119.

[5c]

W. Partenheimer, J. Mol. Catal. A 2001, 174, 29Ϫ33.

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Partenheimer, Catal. Today 1995, 23, 69Ϫ158.

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S. Mukhopadhay, J. K. Mukhopadhyaya, D. E. Ponde, S.

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509Ϫ512.

H. Bubbecke, P. Boldt, Angew. Chem. 1976, 88,

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641Ϫ642; Angew. Chem. Int. Ed. Engl. 1976, 15, 608.

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A.

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J. Hartung, M. Greb, Tetrahedron Lett. 2003, 44,

Bromination of 1-Phenylpent-4-en-1-yl Acetate (40)

[7b]

6091Ϫ6063.

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M. E. Jung, B. T. Fahr, D. C. D’Amico, J.

[7c]

1-Phenylpent-4-en-1-yl Acetate (40):^[34]5-Methyl-1-phenyl-4-hexen-

1-ol (4.00 g, 21.0 mmol) was dissolved in pyridine (16 mL). Acetic

anhydride (254 mmol) was added portionwise, and the solution was

stirred at 20 °C for 18 h. After removal of the volatiles under re-

duced pressure (80 °C, 10 mbar), the resulting residue was purified

by distillation (110Ϫ140 °C/10 mbar), followed by column filtration

(SiO₂; petroleum ether) to afford a colorless liquid (3.45 g, 71%

E. J. Corey, D.-C. Ha,

[7d]

´

A. G. Gonzalez, J.

´

D. Martın, C. Perez, M. A. Ramırez, F. Ravelo, Tetrahedron

Lett. 1981, 22, 5071Ϫ5072.

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O. Maas, P. G. Hiebert, J. Am. Chem. Soc. 1924, 46, 290Ϫ308.

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[10b]

H. Vilter, Phytochemistry 1984, 23, 1387Ϫ1390.

Vilter, Bot. Mar. 1983, 26, 451Ϫ455.

H.

1

yield). H NMR (CDCl₃, 250 MHz): δ ϭ 1. 54 (s, 3 H, CH₃), 1.68

[11] [11a]

(s, 3 H, CH₃), 1.73Ϫ1.87 (m, 1 H, CH₂), 1.90Ϫ2.02 (m, 3 H, CH₂),

2.07 (s, 3 H, CH₃), 5.10 (m_c, 1 H, CH), 5.71 (dd, J ϭ 7.3, 6.0 Hz,

1 H, CH), 7.23Ϫ7.38 (m, 5 H, PhϪH) ppm. ¹³C NMR (CDCl₃,

63 MHz): δ ϭ 17.6, 21.2, 24.1, 25.7, 36.3, 75.6, 123.1, 126.5, 127.8,

128.4, 132.4, 140.7, 170.3 ppm.

E. G. M. Vollenbroek, L. H. Simons, J. W. M. P. van

Schijndel, P. Barnett, M. Balzar, H. L. Dekker, C. van der Lin-

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A. Siegel), Marcel Dekker, New York, 1995, vol. 31, p.

325Ϫ362.

[12]

[13]

4,5-Dibromo-1-phenylpent-1-yl Acetate (41): Yield: 147 mg (75%),

like/unlike ϭ 50:50, colorless liquid. R_fϭ 0.67 [SiO₂; petroleum

ether/Et₂O (5:1, v/v)]. ¹H NMR (CDCl₃, 250 MHz): δ ϭ 1.73, 1.76

(2 s, 6 H, CH₃), 1.79Ϫ2.08 (m, 4 H, CH₂) 1.96 (2 s, 6 H, CH₃),

2.09, 2.10 (2 s, 6 H, CH₃), 2.19Ϫ2.38 (m, 2 H, CH₂), 2.43Ϫ2.57

(m, 2 H, CH₂), 4.21 (2 dd, J ϭ 11.0, 1.8 Hz, 2 H, CH), 5.78 (dd,

J ϭ 7.6, 5.8 Hz, 1 H, CH), 5.84 (dd, J ϭ 8.2, 3.9 Hz, 1 H, CH),

7.26Ϫ7.37 (m, 10 H, PhϪH) ppm. ¹³C NMR (CDCl₃, 63 MHz):

δ ϭ 21.3 (2 C), 28.0, 28.2, 31.7, 32.3, 35.0, 35.2, 35.3, 35.4, 65.6,

66.3, 68.3 (2 C), 74.3, 75.5, 126.3, 126.6, 128.0, 128.1, 128.5, 140.0,

140.3, 170.3 (2 C) (1 C not detected) ppm. MS (70 eV): m/z (%) ϭ

394/390 (1) [M^ϩ], 313/311 (1) [M^ϩϪ Br], 122 (22) [M^ϩϪ C₃H₆Br],

107 (68) [C₇H₆O^ϩ], 79 (24) [Br^ϩ], 51 (10) [C₄H₃^ϩ], 43 (100)

[C₂H₃O^ϩ]. C₁₅H₂₀Br₂O₂(392.1): calcd. C 45.95, H 5.54; found C

47.11, H 5.14.

A. Butler, J. V. Walker, Chem. Rev. 1993, 93, 1937Ϫ1944.

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M. Weynand, H.-J. Hecht, M. Kieß, M.-F.

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187, 17Ϫ35.

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595Ϫ611.

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O. Bortolini, C. Chiappe, V. Conte, M. Carraro, Eur. J.

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Acknowledgments

Financial support was provided by the Deutsche Forschungsgeme-

inschaft (Grant Ha 1705/8-1 and Schwerpunktprogramm: Peroxid-

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www.eurjoc.org

 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

3811

ˇ

M. Greb, J. Hartung, F. Köhler, K. Spehar, R. Kluge, R. Csuk

FULL PAPER

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The (Schiff base)vanadium(v) complex catalyzed oxidation of bromide - A new method for the in situ generation of bromine and its application in the synthesis of functionalized cyclic ethers

DOI: 10.1002/ejoc.200400071

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