(Schiff-base)vanadium(v) complex-catalyzed oxidations of substituted bis(homoallylic) alcohols - Stereoselective synthesis of functionalized tetrahydrofurans

FULL PAPER

(Schiff-base)vanadium( ) Complex-Catalyzed Oxidations of Substituted

V

Bis(homoallylic) Alcohols ؊ Stereoselective Synthesis of Functionalized

Tetrahydrofurans

Jens Hartung,*^[a]Simone Drees,^[a]Marco Greb,^[a]Philipp Schmidt,^[a]Ingrid Svoboda,^[b]

Hartmut Fuess,^[b]Alexander Murso,^[c]and Dietmar Stalke^[c]

Dedicated to Prof. Dr. K. Barry Sharpless

Keywords: Oxidation / Tetrahydrofuran / Catalysis / Asymmetric synthesis / Vanadium

Vanadium(V) complexes 4 have been prepared from tridentate

sults from ⁵¹V NMR spectroscopy and competition kinetics, it

Schiff-base ligands 3 and VO(OEt)₃. All vanadium(

V

) com- proceeds by a transition metal−peroxy pathway. In an initial

pounds were characterized (IR, UV/Vis, and ⁵¹V NMR spectro-

scopy, and in selected examples by X-ray diffraction analysis)

and were applied as oxidation catalysts for the stereoselective

synthesis of functionalized tetrahydrofurans 2 starting from

step, TBHP coordinates to, for example, N-(2-oxidophenyl)sal-

icylideniminato-derived vanadium complex 4a. Subsequent

alkenol binding gives rise to a ‘‘loaded’’ vanadium(

V) peroxy

complex (e.g. 60) which facilitates diastereoselective oxygen

substituted bis(homoallylic) alcohols 1 (mono- or trisubstituted transfer, presumably onto a coordinated substrate. This step

C−C double bonds). Oxidation of secondary or tertiary leads to the formation of functionalized tetrahydrofurans as

1-alkyl-, 1-vinyl-, or 1-phenyl-substituted 5,5-dimethyl-4-

major products. TBHP binding to the remaining vanadium(V)

penten-1-ols under optimized conditions [TBHP as primary complex then allows a regeneration of the active oxidant, for

oxidant and 1,2-(amino)indanol-derived vanadium(

V

) reagent

example peroxy complex 57. The origin of the observed dia-

stereoselectivity in this oxidation has been studied in an inde-

pendent stereochemical analysis. Thus, diastereomerically en-

riched epoxy alcohol (1R,4R)-10 was prepared. Its treatment

with 1,2-(amino)indanol-derived vanadium complex 4g af-

fords a 91:9 mixture of cis-2-(1-hydroxy-1-methylethyl)-5-

4g as catalyst] provided 2,5-cis-configured tetrahydrofurans in

synthetically useful yields and diastereoselectivities (22−96%

de). On the other hand, trans-disubstituted oxolanes (62%−96

de) were obtained from oxidations of 2- or 3-alkyl- and 2- or

3-phenyl-substituted 5,5-dimethyl-4-penten-1-ols bis(homo-

allylic) alcohols. Treatment of 4-penten-1-ols (i.e. substrates (phenyl)tetrahydrofuran (cis-6) and cis-2,2-dimethyl-6-

with monosubstituted olefinic π-bonds) with TBHP and cata- (phenyl)tetrahydropyran-3-ol (cis-7). Similarly, a 39:61 mixture

lytic amounts of vanadium( ) complex 4g furnished trans-di- of heterocycles trans-6 and trans-7 was obtained from epoxy

V

substituted tetrahydrofurans as major products (20−96% de),

no matter whether an alkyl or a phenyl substituent was loc-

ated in position 1, 2, or 3 of the alkenol chain. The mechanism

of this reaction has been investigated in detail. Based on re-

alcohol (1S,4R)-10, if treated with Lewis acid 4g.

( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,

Germany, 2003)

Introduction

and marine organisms.^[1Ϫ4]A number of these compounds

exhibit remarkable antibiotic or cytotoxic effects, which

have opened perspectives for selected clinical applications.^[2]

This circumstance has brought about a growing demand for

cyclic ethers in general and tetrahydrofuran-derived natural

products in particular.^[3Ϫ5]Since their supply cannot be co-

vered from natural sources alone, the invention of methods

for stereoselectively constructing the tetrahydrofuran nu-

cleus from δ,ε-unsaturated alcohols, e.g. 1 (Figure 1), has

received considerable attention.^[6,7]In the last few years, the

most significant progress in this field of research has orig-

inated from transition metal catalyzed oxidations^[8]Ϫ trans-

formations which utilize active oxygen compounds, such as

hydrogen peroxide,^[9,10]peroxo compounds,^[10,11]or molecu-

lar oxygen^[12]as primary oxidants. In spite of their high

oxidation potentials, these reagents, if used alone, are sur-

Functionalized substituted tetrahydrofurans (i.e. oxol-

anes) occur widely in nature as constituents of terrestrial

[a]

Institut für Organische Chemie, Universität Würzburg,

Am Hubland, 97074 Würzburg, Germany

Fax: (internat.) ϩ 49-931/888-4606

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

[b]

Institut für Materialwissenschaft, Technische Universität

Darmstadt,

Petersenstraße 23, 64287 Darmstadt, Germany

Fax: (internat.) ϩ 49-6151/166023

E-mail: deOs@hrzpub.tu-darmstadt.de

[c]

Institut für Anorganische Chemie, Universität Würzburg

Am Hubland, 97074 Würzburg, Germany

Fax: (internat.) ϩ 49-931/888-4606

E-mail: dstalke@chemie.uni-wuerzburg.de

Supporting information for this article is available on the

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

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DOI: 10.1002/ejoc.200200644

Eur. J. Org. Chem. 2003, 2388Ϫ2408

Stereoselective Synthesis of Functionalized Tetrahydrofurans

FULL PAPER

tetrahydrofurans were assessed. (ii) The mechanism of the

tetrahydrofuran synthesis from δ,ε-unsaturated alcohols

was investigated in detail. (iii) A structure-selectivity study

was performed in order to derive guidelines for predicting

diastereoselectivities for any future application of this

method.

Figure 1. Mechanisms for diastereoselective syntheses of func-

tionalized tetrahydrofurans 2 from bis(homoallylic) alcohols 1;

R^Sϭ small substituent, R^Lϭ large substituent, R^Zϭ alkyl sub-

stituent in (Z) arrangement, R^Eϭ alkyl substituent in (E) arrange-

ment, R ϭ C(CH₃)₃, C(CH₃)₂C₆H₅

Results

1. Preparation and Characterization of Vanadium(

Complexes with Tridentate Schiff-Base Ligands

V)

Dark-red to black vanadium() complexes^[27]4aϪk were

prepared in quantitative yields by treating equimolar

amounts of tris(ethoxy)- or tris(isopropoxy)vanadate^[28]and

dibasic tridentate Schiff-bases^[29]3aϪk in anhydrous EtOH

(Figure 2, Table 1).^[30]Vanadium() compounds 4 were re-

adily soluble in DMF and CH₃CN, soluble in CHCl₃and

EtOH, and sparingly soluble in C₆H₆or in hydrocarbons.

Complexes 4aϪk were characterized by ⁵¹V NMR, IR, and

UV/Vis spectroscopy (Table 1). ⁵¹V NMR spectra of va-

nadium() complexes 4a, 4cϪk were, unless otherwise

noted, recorded in EtOH and were referenced to VOCl₃

(δ ϵ 0 ppm) as external standard. For reasons which are

unclear at the moment, no ⁵¹V NMR signal was observed

for o-anthranilic acid derived vanadium complex 4b.^[27b]In

all other instances ⁵¹V NMR signals were identified be-

tween δ ϭ Ϫ518 ppm (3-aminoisoborneol-based complex

4h, see also Figure 3) and δ ϭ Ϫ557 ppm [(S)-methioninol

derivative 4k]. On standing at room temperature, dark-

prisingly inert towards organic substrates. Activation by

transition metal reagents, however, is attainable, and often

provides powerful but selective oxidants.^[8]Two major stra-

tegies have evolved for this purpose. The first route follows

a transition metalϪperoxo (H₂O₂as primary oxidant) or

Ϫperoxy pathway (alkyl hydroperoxides as active oxygen

source, Figure 1, left).^[13,14]The second mechanism pro-

ceeds via high-valent transition metalϪoxo compounds

(Figure 1, right).^[14]Both mechanisms open perspectives for

diastereoselective tetrahydrofuran syntheses, since their fa-

cial selectivities for π-bond oxygenation may, depending on

the substrate, be complementary.^[8,15]

From a historical point of view, the reagent combination

of [VO(acac)₂] [acac ϭ acetylacetonato(Ϫ1)] and TBHP was

the first and in the following years most frequently applied

oxidant for converting bis(homoallylic) alcohols, by a tran-

sition metal catalyzed oxidation, into functionalized tetra-

hydrofurans.^[2,16]This procedure has been successfully ap-

plied for the synthesis of tetrahydrofuran subunits of poly-

ether-derived natural products such as lasalocid A,^[17]iono-

mycin,^[18]teurilene,^[19]ferensimycin B,^[20]glabrescol,^[21]

venustatriol,^[22]or thyrsiferol.^[23]Surprisingly, until now this

method has not been further explored, either (i) by con-

ducting a concise structure-selectivity survey or (ii) by ap-

plication of auxiliaries other than exclusively diketonate li-

gands, in order to improve the reactivity and stereoselectiv-

ity of the active oxidant. Such achievements could have

contributed to the development of reagents that were able

to inhibit transformations which frequently interfere with

selective tetrahydrofuran formation, for instance epoxida-

tions of allylic π-bonds^[24]or electron transfer and suc-

ceeding radical reactions.^[25]Guided by these deficits of the

[VO(acac)₂]/TBHP sytem on one side and the synthetic po-

tential of transition metalϪperoxy compounds in organic

synthesis on the other, a promising new approach for con-

structing functionalized cyclic ethers has been developed re-

cently.^[26]Major improvements originated from the use of

vanadium() catalysts with tridentate auxiliaries. Such re-

agents increase the diastereoselectivity and the efficiency for

tetrahydrofuran formation from substituted bis(homoal-

lylic) alcohols, and inhibited the above-mentioned side reac-

tions to a significant degree. Based on these perspectives,

we have extended our preliminary investigation^[26]to ad-

dress three major areas. (i) Alternative (Schiff-base)vanadi-

um() complexes 4 were prepared and their catalytic

Figure 2. Structural formulae of Schiff-base auxiliaries 3aϪk for

properties for diastereoselective syntheses of functionalized the synthesis of derived vanadium() complexes 4aϪk (see Table 1)

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Table 1. Preparation of Schiff-base complexes 4 from tris(alkoxy)-

vanadate() and auxiliaries 3^[a]

Figure 3. Solid-state structures of (Schiff-base)vanadium() com-

plexes 4e, 4g, and 4h (anisotropic displacement parameters drawn

at the 50% probability level) showing labeling of selected non-H

atoms; selected hydrogen atoms are depicted as circles of an arbi-

trary radius

[a]

The graphic is valid for formation of vanadium compounds 4a,

4b, and 4dϪk from amino alcohol derived ligands 3a, 3b, and 3dϪk

but not for the synthesis of histamine-derived complex 4c from

[b]

auxiliary 3c.

Recorded in EtOH as solvent and referenced

[c]

[d]

[e]

against VOCl₃(ϵ 0 ppm).

KBr disk.

In EtOH.

Not de-

[f]

tected. δ ϭ Ϫ526 and Ϫ534 ppm (peak ratio: 1.5:1) in CD₃OD.

^[g]Peak ratio: 1.9:1. ^[h]Peak ratio: 1:2.6. ^[i]δ ϭ Ϫ534 and Ϫ538 ppm

mation. These absorptions fall, with the exception of com-

plex 4i (966 cm^Ϫ1), into a narrow spectral range of 979Ϫ997

cm^Ϫ1(Table 1).

[j]

(peak ratio: 1:1.2) in CD₃OD. δ ϭ Ϫ550 and Ϫ553 ppm (peak

ratio: 1:3) in CDCl₃. Peak ratio: 1.5:1. Peak ratio: 1.7:1.

[k]

[l]

(Schiff-base)vanadium() complexes 4aϪk exhibited rela-

tively featureless UV/Vis spectra, if dissolved in EtOH

brown block-shaped crystals precipitated from a solution of (Table 1). An intense band was located for all compounds

Schiff-base complex 4a in CHCl₃which consisted, accord- at λ ϭ 310Ϫ373 nm. With the exception of three complexes

ing to data from an X-ray analysis, of an oxygen-bridged [4a (o-aminophenol-derived ligand), 4b (o-anthranilic acid

dimer [(VOL¹)₂O, see Supporting Information; for Support- based auxiliary), and 4c (histamine-derived chelate)], a se-

ing Information see also the footnote on the first page of cond less-intense absorption was noted at λ ഠ 440 nm. A

this article]. If dissolved in EtOH or in CD₃OD, this mate- third but weak band was present in UV/Vis spectra of

rial gave rise to a single ⁵¹V NMR signal at δ ϭ Ϫ529 ppm Schiff-base complexes 4cϪk at λ ഠ 655 nm.

which was identical to the chemical shift observed for par-

Analytical data for characterization of (Schiff-base)vana-

ent vanadium complex 4a.^{[26,27a] 51}V NMR spectra of com- dium() complexes 4aϪk (Table 1) were supplemented by

plexes with chiral auxiliaries, such as (S)-valinol-, (S)-tert- results from single-crystal X-ray diffraction analyses of

leucinol-, and (S)-methioninol-derived coordination com- compounds 4e, 4g, and 4h (Figure 3, Table 2, and Support-

pounds consisted in most instances of two slightly separated ing Information). Suitable crystals were grown from satu-

lines [∆δ ϭ 8 ppm (4e), 16 (4f), 7 (4j), 12 (4k)]. In other rated solutions of vanadium complexes in 2-propanol (4e)

cases, a change from EtOH to CD₃OD [∆δ ϭ 8 ppm (4d), or ethanol (4g, 4h). Whereas the data collection for (S)-

4 (4g)] or to CDCl₃as solvent [∆δ ϭ 3 ppm (4h)] led to a valinol-derived complex 4e and (1R,2S)-(amino)indanol-

modification of the spectra from single lines to two signals based vanadium() compound 4g at room temperature af-

with approximate peak ratios of 1:1.2 to 1:2.6 (Table 1).

forded satisfactory information for unambiguously solving

IR analysis was performed on samples of vanadium() and refining these structures (Figure 3, top and center), the

complexes 4aϪk that were embedded in KBr disks. The data obtained for aminoisoborneol-derived complex 4h un-

spectral information given in Table 1 was restricted to diag- der these conditions were not of sufficient quality to solve

nostic absorptions of VϭO stretching modes^[30]because the the structure. Therefore, the latter experiment was repeated

ligands were adequately characterized prior to complex for- at Ϫ130 °C (Supporting Information). Structure solution

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Stereoselective Synthesis of Functionalized Tetrahydrofurans

˚

FULL PAPER

Table 2. Selected bond lengths [A] and angles [°] for (Schiff-base)vanadium() complexes 4g, 4e, endo-4h, and exo-4h (see also Support-

ing Information)

Entry

Parameter

(C)-4e

(C)-4g

exo-(C)-4h

endo-(A)-4h

1

2

3

4

5

6

7

8

V1ϪO1

V1ϪO2

V1ϪO3

V1ϪO4

1.562(7)

1.864(6)

1.846(6)

1.773(6)

2.165(6)

80.2(2)

76.6(2)

95.9(3)

94.2(3)

Ϫ44.4(9)

10(1)

1.586(2)

1.855(2)

1.815(3)

1.777(2)

2.106(3)

82.7(1)

77.0(1)

94.0(1)

91.8(1)

22.7(4)

9.8(6)

1.582(4)

1.860(5)

1.820(4)

1.787(4)

2.106(5)

83.0(2)

76.6(2)

94.1(2)

90.0(2)

6.1(7)

Ϫ7.3(10)

C

P1

0.54

(1R,2S,3R,4S)

1.578(4)

1.860(5)

1.818(5)

1.773(4)

2.100(5)

83.1(2)

77.5(2)

94.4(2)

89.7(2)

Ϫ7.4(7)

7.7(10)

A

V1ϪN1

N1ϪV1ϪO2

N1ϪV1ϪO3

O2ϪV1ϪO4

O3ϪV1ϪO4

N1ϪC8ϪC9ϪO3

C3ϪC2ϪC1ϪN1

Config. at V1^[a]

Point group

9

10

11

12

13

14

15

C

A

P2₁2₁2₁

0.51

(1S)

P2₁2₁2₁

0.52

(1S,2R)

P1

0.52

(1R,2R,3S,4S)

[b]

˚

Offset of V1 [A]

Configuration (amino alcohol part)

[a]

The stereochemical descriptor C refers to a clockwise and A to an anticlockwise configuration at the vanadium center.^{[31] [b]}With

respect to the best N1ϪO2ϪO4ϪO3 plane.

and refinement in the triclinic space group P1 indicated that hexen-1-ol (5)^[32]in the presence of o-aminophenol-derived

the sample consisted of stereoisomeric complexes exo- vanadium() complex 4a.^[26]The latter complex lacks ad-

4h and endo-4h in a 1:1 ratio (Figure 3, bottom). Despite ditional stereochemical information in its auxiliary and

the fact that enantiopure exo-configured aminoisoborneol therefore allows us to uncover the basic reactivity of the

3h had been applied for the synthesis of Schiff-base com- system. To begin with, substrate 5 was stirred with 1.5

plex 4h, diastereomers in regard of the configuration at C2, equiv. of TBHP in CHCl₃at 20 °C. In the absence of cata-

C3, and V1 were observed in the solid state. Samples of lyst 4a, no conversion of alkenol 5 was observed (Table 3,

compounds 4e and 4g crystallized diastereomerically pure Entry 1). Addition of 0.1Ϫ5 mol % of catalyst 4a afforded

and exhibited in one case C configuration (4e) and in the at 20 °C within 48 h 79Ϫ77% of 2-(1-hydroxy-1-methyl-

other A configuration at the vanadium center (4g). In gen- ethyl)-5-phenyltetrahydrofuran (6)^[33]besides 13Ϫ16% of

eral, short bonds were found for V1ϪO1 [1.562(7) A (4e), the corresponding tetrahydropyran 7^[33](GC yields; Sup-

˚

1.586(2) A (4g), 1.582(4) (exo-4h), and 1.578(4) A (endo- porting Information). An increase to 10 mol % of catalyst

4h)]. The remaining vanadium oxygen distances decreased 4a improved the efficiency for the synthesis of tetrahydrofu-

˚

in the series from V1ϪO2 (ca. 1.86 A) to V1ϪO3 (ca. 1.82 ran 6 marginally (81%, cis/trans ϭ 98:2). On the other hand,

A) to V1ϪO4 (ca. 1.78 A). In all complexes, relatively long formation of tetrahydropyran 7 was slightly reduced (11%,

V1ϪN1 contacts were observed (2.10Ϫ2.17 A). Bond cis/trans ϭ 46:54), but more importantly, the synthesis of

˚

angles decreased from O2ϪV1ϪO4 [phenolato to etha- further oxidation products (see below) was almost com-

nolato or 2-propanolato oxygen atom; 94.0(1)Ϫ95.9(3) °] to pletely prevented. These facts caused us to use 10 mol % of

O3ϪV1ϪO4 [amino alcoholato to ethanolato or 2-propa- catalyst 4 for all subsequent transformations. The efficiency

nolato oxygen atom; 89.7(2)Ϫ94.2(3) °] to N1ϪV1ϪO2 [im- of the synthesis of disubstituted tetrahydrofuran 6 decreases

ine nitrogen atom to phenolato oxygen atom; upon changing the solvent from CHCl₃(81%), to CH₂Cl₂

80.2(2)Ϫ83.1(2) °] to N1ϪV1ϪO3 [imine nitrogen atom to (79%), CH₃CN (33%), (H₃CO)₂CO (30%), and C₆H₅CF₃

amino alcoholato oxygen atom; 76.6(2)Ϫ77.5(2) °]. The tor- (24%; Supporting Information). Lowering of the reaction

sion angle C3ϪC2ϪC1ϪN1 deviates from the expected 0° temperature was paralleled by a reduced turnover of alkenol

by ca. Ϯ10°.

5, which provided in this case at Ϫ20 °C within 48 h only

21% of tetrahydrofuran 6. At that temperature, however,

the selectivity for the formation of tetrahydrofuran 6 versus

tetrahydropyran 7 improved from 85:15 (20 °C) to 95:5

(Ϫ20 °C; for details see Supporting Information). A change

in primary oxidant from TBHP to cumene hydroperoxide

(CHP), iodosobenzene (PhIO), or urea hydrogenperoxide

(UHP) caused a drop in yield of target compound 6. A

variation of catalysts from 4a to 4bϪk under otherwise op-

timized conditions (i.e. TBHP, CHCl₃, 20 °C, 48 h) led in

all instances to tetrahydrofuran cis-6 as the major product

(29Ϫ84%, GC analysis). The observed diastereoselectivity

2. Vanadium(

Alcohols

V)-Catalyzed Oxidations of Bis(homoallylic)

In order to identify suitable conditions for an efficient

conversion of substituted bis(homoallylic) alcohols into

functionalized tetrahydrofurans, five variables were con-

sidered for modification: (i) amount of catalyst, (ii) solvent,

(iii) reaction temperature, (iv) primary oxidant, and (v) the

auxiliary (i.e. Schiff-base ligand 3). Four of these param-

eters were optimized by oxidizing 5-methyl-1-phenyl-4-

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J. Hartung et al.

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for the synthesis of oxolane 6 remained close to cis/trans ϭ tyrolactone 8 along with additional, as yet unidentified,

98:2 (Table 3, Entries 5Ϫ15). Tetrahydropyran 7 was products.

formed in all runs as a minor product (1Ϫ15%, GC analy-

sis).

Table 3. Survey of the efficiency of primary oxidants and va-

nadium() catalysts 4 for the stereoselective synthesis of tetrahydro-

furan 6 from methyl-phenylhexenol 5

Scheme 1. Control experiments for investigating the stability of oxi-

dation products; reagents and conditions: (a) 1.5 equiv. TBHP, 10

mol % VOL¹(OEt)(EtOH) (4a)

To obtain additional information on product formation

starting from 5-methyl-1-phenyl-4-hexenol (5) and TBHP in

the presence of 10 mol % of catalyst 4g, the reaction was

monitored in two time-dependent studies. Data from GC

analyses showed that the ratio of tetrahydrofuran 6 versus

tetrahydropyran 7 (6/7 ϭ 86:14) and the cis/trans ratios of

both cyclic ethers (for 6: cis/trans ϭ 97:3; for 7: cis/trans ϭ

46:54) remained constant throughout the conversion of 5.

This observation was noteworthy, since oxidation of a ra-

cemic mixture of alkenol 5 in the presence of vanadium()

complex 4g (prepared from enantiomerically pure auxiliary

3g) might have given rise to a kinetic resolution^[34](see also

Section 3). In the second time-dependent study, H NMR

spectra were recorded at reaction times of 5, 10, 30, 60, 120,

[a]

Yields and cis/trans ratios of compounds 6 and 7 were deter-

1

mined, unless otherwise noted, by GC with n-C₁₄H₃₀as internal

standard. The experimental uncertainty for similarly determined

and 480 min. A stacking plot of a selected spectral region

is depicted in Figure 4 and illustrates that alkenol 5 was

transformed into heterocycles 6 and 7 without a buildup of

an additional intermediate, such as the expected epoxy

alcohol 10. The latter compound was prepared indepen-

yields was estimated to be Ϯ5% and for diastereoselectivities Ϯ1 in

[b]

[c]

absolute values. Not detected (GC). Isolated yields: 74% of 6

[d]

(cis/trans ϭ 97:3) and 12% of 7 (cis/trans ϭ 46:54).

mixture of exo-4h and endo-4h (see Figure 3).

Used as

In order to improve the mass balance in oxidations of

substrate 5 which had been catalyzed by the most efficient

vanadium compounds, i.e. 4a (81% of 6), 4d (81% of 6),

and especially 4g (83% of 6), the reaction mixtures in ques-

tion were further analyzed by GC. These investigations

pointed to the formation of 5-methyl-1-phenylhex-4-en-1-

one (9)^[33](4a: 4%; 4d and 4g: 1%) and in one example

lactone 8 (only 4d: 3%) in minor amounts. Based on this

additional information, the stability of oxidation products

under standard reaction conditions was studied. Thus, ke-

tone 9, tetrahydrofuran derivative 6 (cis/trans ϭ 98:2), tetra-

hydropyran derivative trans-7 (cis/trans ϭ Ͻ 2:Ͼ 98) were

treated with TBHP and vanadium complex 4a in CHCl₃at

20 °C for 7 d. Tetrahydropyran derivative trans-7 was stable

under these conditions, whereas 5-methyl-1-phenylhex-4-en-

1-one (9) and tetrahydrofuran derivative 6 were both con-

verted into further oxidation products (¹H NMR spec-

troscopy). Butyrolactone 8 is the only compound isolated

from these mixtures in sufficient quantity to allow an un-

ambiguous characterization so far (Scheme 1). It should be

added that disubstituted tetrahydrofuran 6 itself is prone

to autoxidation and on standing for several weeks in the

Figure 4. Stacking plot from a time-dependent ¹H NMR investi-

gation of the oxidation of methyl-phenylhexenol 5 with TBHP in

the presence of (Schiff-base)vanadium() complex 4g; the selected

spectral region depicts resonances of the olefinic and the benzylic

proton in substrate 5 (t ϭ 0 min) and benzylic protons of cyclic

ethers 6 and 7 (see t ϭ 4 h); for illustration purposes, ¹H NMR

spectra of a 1:1 mixture of like- and unlike-configured dia-

stereomers of epoxy alcohol 10 and a crude reaction mixture, which

had been obtained from an mCPBA-mediated oxidation of bis-

laboratory atmosphere afforded approximately 34% of bu- (homoallylic) alcohol 5, have been added to this plot

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Eur. J. Org. Chem. 2003, 2388Ϫ2408

Stereoselective Synthesis of Functionalized Tetrahydrofurans

FULL PAPER

dently in 99% yield by treatment of methyl-phenylhexenol

5 with dimethyldioxirane.^[35]For illustration purposes, its

¹H NMR resonances have been added to the stacking plot

in Figure 4.

Oxidations of 1-, 2-, and 3-substituted bis(homoallylic)

alcohols 5 and 11Ϫ15 on a preparative scale were conduc-

ted in the presence of 1-amino-2-indanol-derived catalyst

4g (Table 3, footnote^[c], Table 4). Conversion of 1-tert-butyl-

substituted alkenol 11 under these conditions provided 71%

of 5-tert-butyl-2-(1-hydroxy-1-methylethyl)tetrahydrofuran

(16) (cis/trans ϭ 91:9) and 4% of diastereomerically pure

tetrahydropyran trans-21 (¹H NMR spectroscopy). Treat-

ment of 2-phenyl- and 2-isopropyl-substituted substrates 12

and 13^[36]with TBHP and vanadium reagent 4g furnished

2,4-disubstituted tetrahydrofuran 17 (55%, cis/trans ϭ 9:91)

and 18 (90%, cis/trans ϭ 19:81) as major products. In ad-

Scheme 2. Stereoselective synthesis of functionalized cyclic ethers

28 and 29; reagents and conditions: (a) 1.5 equiv. TBHP, 10 mol %

VOL⁷(OEt) (4g), CHCl₃, 20 °C, 48 h

Oxidation of 2-allyl-substituted cyclohexanol trans-30^[38]

with TBHP and vanadium() catalyst 4g yielded 92% of

diastereomerically pure bicyclic tetrahydrofuran 6,8-cis-31

(Scheme 3). If cyclohexanol derivative cis-30^[38]was sub-

jected to these conditions, a mixture of 78% of bicyclic

tetrahydrofuran 32 (6,8-cis/6,8-trans ϭ 77:23) and 5% of

dition,

trans-2,2-dimethyl-5-phenyltetrahydropyran-3-ol

(trans-22) was obtained in 4% yield from the oxidation of

alkenol 12, whereas formation of 5-isopropyl-substituted

tetrahydropyran 23 from substrate 13 was not observed in

our experiments. Oxidation of 3-phenyl- and 3-isopropyl-

substituted bis(homoallylic) alcohols 14 and 15 with TBHP

in the presence of catalyst 4g afforded diastereomerically

pure (¹H NMR spectroscopy) 2,3-trans-configured tetra-

hydrofurans trans-19 (76%) and trans-20 (54%). 16% of

trans-configured tetrahydropyran trans-25 was obtained

from isopropyl-substituted alkenol 15, but no tetrahydropy-

ran 24 from the oxidation of 5-methyl-3-phenylhex-4-enol

(14).

Treatment of 4-methyl-1-phenylpentenol 26 (lower

homologue of 5) with TBHP and Schiff-base complex 4g

afforded 62% of 3-hydroxy-5-phenyl-substituted tetrahydro-

furan 28 (cis/trans ϭ 25:75, Scheme 2). 6-Methyl-1-phenyl-

5-hepten-1-ol (27) was oxidized under these conditions into

52% of 2-(1-hydroxy-1-methylethyl)-5-phenyltetrahydropy-

ran (29) (cis/trans ϭ 99:1) and 9% of 6-methyl-5-hepteno-

phenone^[37](not shown in Scheme 2).

Scheme 3. Formation of bicyclic compounds from both dia-

stereomers of 2-allyl-substituted cyclohexanol 30; reagents and

conditions: (a) 1.5 equiv. TBHP, 10 mol % VOL⁷(OEt) (4g), CHCl₃,

[a]

20 °C, 48 h; stereodescriptors cis and trans refer to relative con-

[b]

figurations at C6 and C8;

corresponding trans isomer was not

detected (¹H NMR spectroscopy); ^[c]stereodescriptors cis and trans

refer to relative configurations at C1 and C4; corresponding cis

[d]

isomer was not detected (¹H NMR spectroscopy)

Table 4. Vanadium()-catalyzed oxidation of 5,5-dimethyl-substituted bis(homoallylic) alcohols 11Ϫ15

[a]

[b]

The corresponding cis isomer was not detected (¹H NMR spectroscopy). Not detected (¹H NMR spectroscopy).

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diastereomerically pure tetrahydropyran derivative 1,4-

trans-33 were obtained.

Table 5. Screening for reactivity and selectivity: vanadium() cata-

lysts 4 in the diastereoselective synthesis of tetrahydrofuran 42 from

2-isopropyl-4-penten-1-ol (41)

Conversion of (R)-linalool [(R)-34] with TBHP in CHCl₃

at 20 °C furnished 65% of furanoid linalool oxide 35^[39](cis/

trans ϭ 61:39), 7% of epoxylinalool oxide 36^[39](cis/trans ϭ

54:46), and 4% of pyranoid linalool oxide 37^[39](cis/trans ϭ

38:62), if (Schiff-base)vanadium() complex 4g was applied

as catalyst. Treatment of (S,S)-bisabolol [(S,S)-38] under

these conditions led to the formation of 2,2,5-substituted

tetrahydrofuran 39^[40]in 65% yield (cis/trans ϭ 82:18) and

its epoxy derivative 40^[40]in 15% yield (cis/trans ϭ 87:13)

(Scheme 4).

[a]

[b]

[c]

GC analysis. See footnote^[a]of Table 3. Isolated yield: 74%

of 42 (cis/trans ϭ 29:71).

Table 6. Vanadium()-catalyzed oxidations of substituted 4-penten-

1-ols 43Ϫ47

Scheme 4. Vanadium()-catalyzed oxidation (R)-linalool [(R)-34]

and (S,S)-bisabolol [(S,S)-38]; reagents and conditions: (a) 1.5

equiv. TBHP, 10 mol % VOL⁷(OEt) (4g), CHCl₃, 20 °C, 48 h

Suitable conditions for diastereoselectively preparing 2-

(hydroxymethyl)-4-isopropyltetrahydrofuran (42) from 2-

isopropyl-4-penten-1-ol (41)^[41]were found by varying cata-

lysts 4aϪk (Table 5). All other parameters such as solvent,

reaction temperature, required amount of catalyst and pri-

mary oxidant TBHP were assumed to follow the same

trends as those which had been required for an efficient

conversion of methyl-phenylhexenol 5 into tetrahydrofuran

cis-6. These parameters were therefore not further modi-

[a]

The corresponding cis isomer was not detected (¹H NMR spec-

troscopy).

fied. In the absence of a vanadium reagent 4 no reaction derivative 49 (59%, cis/trans ϭ 39:61) (Table 6, Entries 1

between isopropylpentenol 41 and TBHP was noted over and 2). If 2-phenyl-substituted pentenol 45^[44]was treated

48 h (Table , Entry 1). Upon addition of 10 mol % of a va- under these conditions, 43% of 2-(hydroxymethyl)-4-phenyl-

nadium() catalyst to the reaction mixture, oxidation of tetrahydrofuran (50) was obtained (cis/trans ϭ 36:64,

substrate 41 into 2-(hydroxymethyl)-4-isopropyltetrahydro- Table 6, Entry 3). Treatment of 3-phenyl- and 3-tert-butyl-

furan (42) took place (Table 5, Entries 2Ϫ12). The yields of substituted bis(homoallylic) alcohols 46^[43]and 47^[45]with

product 42 (GC) varied between 9 and 94%. The observed TBHP and vanadium reagent 4g provided 43% of 2-

diastereoselectivities ranged from 41:59 (Table 5, Entry 4) (hydroxymethyl)-3-phenyltetrahydrofuran (51) (cis/trans ϭ

to 29:71 (Table 5, Entry 8). Based on the results, which are 40:60) and diastereomerically pure (¹H NMR spectroscopy)

collected in Table 5, we restricted ourselves to the use of 1- 3-tert-butyl-2-(hydroxymethyl)tetrahydrofuran (52) (61%,

amino-2-indanol-derived catalyst 4g for continuing the pro- Table 6, Entries 4 and 5).

ject (Table 6, Scheme 5).

Finally, 4-substituted 4-penten-1-ols 53^[46]and 54 were

Oxidation of 1-phenyl- and 1-tert-butyl-4-penten-1-ol treated with TBHP and catalyst 4g (Scheme 5). Oxidation

(43^[42]and 44^[43]) with TBHP in the presence of 10 mol % of prostereogenic substrate 53 under such conditions fur-

of catalyst 4g afforded 2-(hydroxymethyl)-5-phenyltetra- nished 82% of racemic 2-(hydroxymethyl)-2-phenyltetra-

hydrofuran (48) (47%, cis/trans ϭ 39:61) and its 5-tert-butyl hydrofuran (55). 4-Methyl-1-phenyl-4-penten-1-ol (54) was

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converted into 82% of 2,2,5-trisubstituted tetrahydrofuran

derivative 56 (cis/trans ϭ 25:75) under standard conditions.

Scheme 5. Conversion of 4-substituted bis(homoallylic) alcohols 53

and 54 into cyclic ethers 55 and 56; reagents and conditions: (a)

1.5 equiv. TBHP, 10 mol % VOL⁷(OEt) (4g), CHCl₃, 20 °C, 48 h

3. Competition Kinetics and Stereochemical Studies

The oxidation of 5-methyl-1-phenylhex-4-enol (5) with

TBHP in the presence of o-aminophenol-derived catalyst 4a

afforded 2-(1-hydroxy-1-methylethyl)-5-phenyltetrahydrofu-

ran (6) and 2,2-dimethyl-6-phenyltetrahydropyran-3-ol (7)

as major products (Table 3). Treatment of 2-methyl-6-phen-

yl-2-hexene (58)^[47]under these conditions furnished 87% of

epoxide 59. Subsequently, a vanadium()-catalyzed oxi-

dation of a mixture of substrates 5 and 58 was investigated.

This reaction led to the formation of three products: tetra-

hydrofuran 6 as a mixture of cis/trans isomers, a dia-

stereomeric mixture of tetrahydropyran cis-7 and trans-7,

and epoxide 59 (Scheme 6). Based on this information, a

set of competition experiments was devised. Thus, defined

molar ratios of substrates 5 and 58 were treated with peroxy

complex 57 under pseudo-first-order conditions at 20 °C.

Reaction products 6, 7, and 59 were quantified by GC

analysis. Similarly obtained ratios of ([6] ϩ [7])/[59] were

plotted against the corresponding ratio of [5]/[58] to provide

a linear correlation (Supporting Information). Based on a

kinetic model which requires direct irreversible oxygen

transfer from peroxy complex 57 to both substrates 5 and

58 under pseudo-first-order conditions, the slope of this lin-

ear correlation corresponds to the relative rate constant

k^relϭ k²/k¹ϭ 120 Ϯ 20 (20 °C).^[48]The large experimental

error was estimated on the basis that our experiments were

restricted, for analytical reasons, to an at least fivefold mo-

lar excess of fastest reacting substrate, i.e. alkenol 5, instead

of the desirable tenfold molar excess.

Scheme 6. Formation of peroxy complex 57 (top) and its use in

competition kinetic investigations (bottom)

(TsOH) led quantitatively to the formation of 2,5-cis-con-

figured tetrahydrofuran (2S,5R)-6 and 3,6-cis-configured

tetrahydropyran (3R,6R)-7 in a ratio of 91:9. Furthermore,

vanadium()- or acid-catalyzed rearrangement of epoxy al-

cohol (1S,4R)-10 furnished 2,5-trans-disubstituted tetra-

hydrofuran derivative (2S,5S)-6 and 3,6-trans-substituted

tetrahydropyran derivative (3R,6S)-7 in a ratio of 39:61.

Since the major component in one sample [e.g. (1R,4R)-10]

constituted the enantiomer of the minor in the second

sample [e.g. (1S,4S)-10], such by-products from each epox-

ide isomerization were readily identified.

For a stereochemical analysis of product formation from

bis(homoallylic) alcohols, a racemic mixture of methyl-phe-

nylhexenol 5 was separated into both enantiomers (R)-5

and (S)-5 (HPLC, Chiracel OD column, both Ͼ 99% ee). Scheme 7. Diastereoselective conversion of alkenols (R)-5 and (S)-

Both samples were epoxidized under Shi conditions^[49]in

5 into corresponding cyclic ethers 6 and 7; reagents and conditions:

[a]

(a) Shi epoxidation;^[49](b) TsOH (1 equiv.) or 4g (0.1 equiv.);

order to provide (1R,4R)-10 in 94% yield (76% de, ¹H NMR

yields: 80% of (2S,5R)-6, 8% of (3R,6R)-7, and 12% of a 39:61

[b]

spectroscopy) from alkenol (R)-5^[50]and (1S,4R)-10 in 96%

mixture of trans-6 and trans-7; yields: 32% of (2S,5S)-6, 50% of

(3R,6S)-7, and 18% of a 91:9 mixture of cis-6 and cis-7

1

yield (64% de, H NMR spectroscopy) from (S)-5. Assign-

ment of the (R) configuration at the stereocenter which was

Discussion

constructed in the Shi epoxidation was based on (i) the gen-

eral face-selection rule for this well-established method^[49]

and (ii) a correlation of epoxy alcohol configurations with

the geometry of rearranged products 6 and 7 (see below).

Treatment of epoxy alcohol (1R,4R)-10 with 10 mol % of

1. Characterization of (Schiff-base)vanadium(V) Complexes

4 and Their Conversion into Peroxy Derivatives

In a previous study, (Schiff-base)vanadium() complexes

vanadium() complex 4g or with p-toluenesulfonic acid had been prepared by an in situ mixing of [VO(acac)₂] and

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imine ligands 3a, 3d, and 3g. Similarly prepared vanadium which are formed by the corresponding Schiff-base func-

reagents served as catalysts for converting selected bis(ho- tions and the additional alcoholato oxygen atom (4e: 0.51

˚

moallylic) alcohols 1 into functionalized tetrahydrofurans A; 4g: 0.52 A; exo-4h: 0.54 A; endo-4h: 0.52 A; Table 2).

2. TBHP had served in all instances as primary oxidant.^[26]Connectivities of V1 to O decreased in the series V1ϪO2

In the present report, complexes 4 were synthesized in a (ca. 1.86 A, phenolato oxygen atom, part of a six-membered

separate step. All vanadium reagents 4 were characterized chelate ring) Ͼ V1ϪO3 (ca. 1.82 A, alcoholato oxygen

˚

by means of spectroscopy and elemental analysis. These re- atom, part of a five-membered chelate ring) Ͼ V1ϪO4 (ca.

˚

sults were supplemented by data from selected X-ray dif- 1.78 A, ethanolato or 2-propanolato oxygen atom) Ͼ

˚

fraction analyses. Similarly characterized coordination V1ϪO1 (1.56Ϫ1.58 A). In analogy to investigations of

compounds 4 were applied as oxidation catalysts.

structurally related complexes, the latter connectivity was

interpreted as a vanadiumϪoxygen double bond.^[30]Ob-

˚

(i) IR Analysis and UV/Vis Spectra

served long V1ϪN1 distances of 2.10Ϫ2.17 A were attri-

buted to the well-known low affinity of neutral imino nitro-

gen atoms for vanadium() centers.^[54]Bite angles in triden-

tate chelates decrease from N1ϪV1ϪO2 (ca. 82°) to

N1ϪV1ϪO3 (ca. 77°), which is reasonable since the former

describes a corner of an almost planar distorted hexagon

while the latter originates from a saturated five-membered

heterocyclic ring.

In regard to their general constitution, the vanadium()

complexes 4e, 4g, and 4h may be subdivided into two hemi-

spheres. The first hosts ligands that are considered to be

spectators in the oxidation catalysis (ligands that coordinate

via O1ϪO3 and N1 to V1). This part of the compound is

dominated by steric effects from the amino alcohol entity

(O3, N1). The second hemisphere is more open. It consists

of the vacant coordination site in trans position to O1 and

the monovalent alcoholato ligand (connected via O4 to V1).

Alkoxide ligands, however, may be displaced in solutions,

e.g. by TBHP.^[55]Further, neutral donor ligands, such as

EtOH and 1,4-dioxane, have been found to bind in trans-

position to VϪO double bonds.^[27b,56]Therefore, the second

hemisphere of complexes 4 is considered to play a major

role in catalysis, since it should allow peroxide and bis(ho-

moallylic) alcohol binding (see below).

The coordination compounds 4aϪk exhibited single Vϭ

O stretching bands in the region of 966Ϫ997 cm^Ϫ1. These

absorptions were indicative of monomeric vanadium()

compounds.^[30]Up to three characteristic electronic tran-

sitions were observed in the UV/Vis spectra of the d⁰va-

nadium() compounds 4 (in EtOH). Strong absorptions in

the region between 310Ϫ373 nm were assigned to intrali-

gand πǞπ* transitions. Two less intense lower energy tran-

sitions were observed at ca. 440 nm and at ca. 655 nm (ex-

cept for 4aϪc). Both transitions were, in extension to pre-

vious assignments in structurally related vanadium() com-

pounds, attributed to ligand-to-metal charge transfer of the

type phenolato oxygen atom Ǟ d and alcoholato oxygen

atom Ǟ d [where d represents a vacant d orbital at the va-

nadium() center].^[51]

(ii) ⁵¹V NMR Shifts

The coordination compounds 4a, 4cϪk displayed ⁵¹V

NMR signals in the range of δ ϭ Ϫ518 to Ϫ557 ppm which

were characteristic for pentavalent vanadium() complexes

with a coordination sphere that was dominated by O func-

tionalities.^[52]Two ⁵¹V signals were observed for vanadium

compounds 4d (CD₃OD), 4e and 4f (both in EtOH), 4g

(CD₃OD), 4h (CDCl₃), and 4j,k (both in EtOH). These fin-

dings implied that at least two structurally different com-

plexes existed in those cases. The exact origin of this obser-

vation remained unclear in the present study. In principle,

it may have originated from configurational desintegrity of

imine ligands, which had occurred during complex forma-

tion, or the presence of diastereomers, caused by different

configurations at the vanadium center (see below), or by

ligand-exchange reactions and therefore a dynamic be-

havior of complexes 4. The latter reasoning was based on

the well-known propensity of alkoxide ligands to be re-

placed by nucleophiles with higher affinity for vanadium(),

such as water or TBHP.^[53]We are not able to present evi-

dence for the former two arguments in general. However,

the results from X-ray crystallographic studies of the va-

nadium complexes 4e, 4g, and 4h provided valuable infor-

mation in view of such considerations.

The central ion in oxovanadium() compounds with tri-

dentate imine ligands of the type used in this study consti-

tutes a stereogenic center (see Figure 5). (S)-Valinol-derived

vanadium complex 4e exhibits

C configuration and

(1R,2S)-aminoindanol-based compound 4g A configuration

at the vanadium center.^[31]The absolute configuration of

stereocenters in the auxiliaries of both coordination com-

pounds is identical to that of the free ligands H₂L⁵(3e) and

H₂L⁷(3g). Structure solution and refinement of complex 4h

showed that the sample, which was prepared from enanti-

omerically pure exo-configured ligand H₂L⁸(3h; Figure 2),

consisted of two compounds: exo-4h with C configuration

at the vanadium center and A-configured endo-4h. This un-

(iii) X-ray Crystallography

In the complexes 4e, 4g, and 4h, the pentacoordinate va-

nadium() atoms are located in distorted tetragonal pyra-

Figure 5. Geometry of (Schiff-base)vanadium() complex (A)-4a

mids. The central ions are displaced from the best planes (left) and its enantiomer (C)-4a (right)^[31]

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expected inversion of two stereocenters in a Schiff-base

auxiliary, due to its reaction with VO(OEt)₃, is under inves-

tigation.

(iv) Reaction with TBHP

Vanadium complexes 4 reacted with TBHP.^[26,27a]For ex-

ample, conversion of VOL¹(OEt)(EtOH) (4a) with a 1.5

molar excess of TBHP in CDCl₃at 61 °C provided a brown

solution which was characterized by a ⁵¹V NMR signal

shifted to high field at δ ϭ Ϫ571. In view of additional

analytical data from previous studies^[26,27a]and more recent

results from an ESI-MS investigation of a derivative of

4a,^[57]the resonance at δ ϭ Ϫ571 ppm was assigned to per-

oxyvanadium() complex 57. This interpretation was sup-

ported by the fact that a similarly prepared solution of 57

in CH₂Cl₂converted 5-methyl-1-phenylhex-4-en-1-ol (5) in

a stoichiometric reaction, at 20 °C within 48 h, into 65% of

2,5-disubstituted tetrahydrofuran 6 (cis/trans ϭ 95:5) and

5% of 2,2-dimethyl-6-phenyltetrahydropyran-3-ol (7, cis/

trans ϭ 45:55).^[26]In analogy to this cumulative evidence

for the existence of peroxy complex 57, ⁵¹V NMR spectral

changes upon addition of 1.5 equiv. of TBHP in hot CDCl₃

(61 °C) to phenylglycine-derived vanadium complex 4d (⁵¹V

NMR: δ ϭ Ϫ575 and Ϫ580 ppm; 1.5:1 signal ratio) and to

aminoindanol-derived complex 4h (⁵¹V NMR: δ ϭ Ϫ574

and Ϫ578 ppm; 1:1.2 signal ratio) were interpreted as for-

mation of corresponding peroxy complexes.

Scheme 8. Proposed catalytic cycle for the synthesis of cyclic ethers

6 and 7 in a (Schiff-base)vanadium() complex catalyzed oxidation

of methyl-phenylhexenol 5

investigation that olefin coordination to the vanadium()

center in peroxy complex 57 was a prerequisite for selective

epoxidation of nonfunctionalized alkenes,^[27a]it was more

likely that the origin of the observed difference in rate con-

stants k¹and k²in the present work originated from an

acceleration of a rate-determining step in the alkenol oxi-

dation. The molecular basis for this kinetic effect was con-

sidered to be associated with substrate binding via the

hydroxy group to the oxophilic vanadium() ion,^[60]which

set the stage for an intramolecular π-bond oxygenation

(step iii).

2. Vanadium(V)-Catalyzed Oxidation of 5-Methyl-1-

phenylhex-4-en-1-ol (5) and Structurally Related Derivatives

The mechanism of the tetrahydrofuran formation from

bis(homoallylic) alcohol 5 and TBHP in the presence of

(Schiff-base)vanadium() complex 4a was investigated in

detail. According to the results given above, the reaction

followed a transition metalϪperoxy pathway and proceeded

in four major steps:^[8](i) formation of peroxyvanadium()

complex 57, and hence activation of TBHP, (ii) alkenol

binding to intermediate 57, (iii) stereoselective intramolecu-

lar oxygen transfer, and (iv) subsequent regeneration of per-

oxy complex 57 from proposed tert-butoxy complex 61

(Scheme 8).

(iii) Stereoselective Oxygen Transfer in ‘‘Loaded’’

Vanadium(V) Complex 60

Coordination of TBHP and bis(homoallylic) alcohol 5 to

vanadium() compound 4a provided ‘‘loaded’’ complex 60.

Intramolecular oxygen transfer from the coordinated per-

oxide to the alkenol ligand in 60 proceeded stereoselectively

and furnished 81% of 2,5-disubstituted tetrahydrofuran 6

(cis/trans ϭ 98:2) and 14% of corresponding tetrahydropy-

ran 7 (cis/trans ϭ 46:54). The preferred trajectory for oxy-

gen atom delivery to one of the prostereogenic faces of the

(Schiff-base)vanadium() complex bound alkenol was re-

constructed using the results from the stereochemical analy-

sis of product formation from diastereomerically enriched

epoxy alcohols 10 (Scheme 7). These studies had indicated

that (1R,4R)-configured substrate 10 rearranged upon

treatment with (Schiff-base)vanadium() complex 4g or

TsOH into a 91:9 mixture of cis-2,5-disubstituted tetra-

hydrofuran (2S,5R)-6 and 3,6-cis-configured tetrahydropy-

ran (3R,6R)-7. The unlike isomer (1S,4R)-10 provided un-

der the same conditions a mixture of trans-configured het-

(i) Formation of Peroxy Complex 57 from Vanadium

Reagent 4a

TBHP is a comparatively strong oxidant^[58]which, how-

ever, did not react with bis(homoallylic) alcohol 5 alone.

The hydroperoxide had to be activated for this purpose e.g.

by N-(2-oxidophenyl)salicylideniminato-derived vanadium

complex 4a. This step was associated with the formation of

peroxyvanadium() complex 57 (see above).

(ii) Alkenol Coordination to Peroxy Complex 57

Evidence for alkenol binding to intermediate 57 was erocycles (2S,5S)-6 and (3R,6S)-7, which was surprisingly

taken from results of competition kinetic experiments in favor of the tetrahydropyran derivative 7 [(2S,5S)-6/

(Scheme 6). Thus, bis(homoallylic) alcohol 5 was oxidized (3R,6S)-7 ϭ 39:61]. These results showed that the relative

120 times faster than structurally related olefin 58 (T ϭ 20 configuration of epoxy alcohol 10 dictated the preference

°C; Scheme 6).^[59]Although it was proposed in an earlier for tetrahydrofuran synthesis [from (1R,4R)-10] or tetra-

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hydropyran formation [from (1S,4R)-10]. In order to trans-

late these findings into selectivity data for the vanadium()-

catalyzed oxidation of bis(homoallylic) alcohol 5, the struc-

ture of intermediate 60 was modeled using assumptions that

related to the configuration at the vanadium center and the

mode of peroxide and alkenol binding. Since compounds

4a^[61]and 5 were both applied as racemates, the following

stereochemical discussion is restricted to the reaction of an

arbitrarily selected enantiomer of methyl-phenylhexenol 5

[i.e. (R)-5] with a peroxyvanadium() complex 57 not

further defined stereochemically. The mode of TBHP-bind-

ing in peroxy complex 57 was constructed by taking meri-

dional ligation of η²-coordinated tert-butylperoxy ligand in

a structurally well-defined (2,6-pyridinedicarboxylato)vana-

dium() complex^[62]as archetype for alkylperoxy coordi-

nation in (Schiff-base)vanadium() complexes in general. In

regard to bis(homoallylic) alcohol coordination to peroxy

complex 57, it seems reasonable to assume that this interac-

tion takes place in trans position to the VϪO double bond,

since neutral oxygen donor ligands such as EtOH or 1,4-

dioxane have been reported to bind to that site (X-ray crys-

tallographic studies).^[27b,56,61]The geometry of a thus

modeled ‘‘loaded’’ complex 60 did not significantly restrict

the conformational space of methyl-phenylhexenol 5 unless

the reacting entities, i.e. the olefinic π-bond and the trans-

ferable oxygen atom, approached. In this case, the chair-like

arrangement of the ligand in chair-60 was considered to be

one of the more significantly populated conformers (Fig-

ures 6 and 7). Intramolecular oxygen transfer in chair-60

provided vanadium() complex like-62. If oxygenation oc-

curred from the opposite diastereotopic face of the π-bond,

e.g. via gauche-60, complex unlike-62 was formed. However,

intermediates like-62 and unlike-62, if they existed at all,

should be very short-lived, because they have so far not

been detected by ¹H NMR spectroscopic monitoring of

(Schiff-base)vanadium() complex-catalyzed oxidations of

substrate 5 (Figure 4). Rearrangement of primary oxygen-

ation products like-62 and unlike-62 into tetrahydrofurans

required a stereocontrolled backside attack of the hydroxy

oxygen atom onto the C4ϪO bond of the epoxide entity.

This step was probably paralleled by elimination of tert-

Figure 6. Proposed binding modes of the tert-butylperoxy ligand

and 5-methyl-1-phenylhex-4-en-1-ol (5) in vanadium() complex

60; R^Eϭ R^Zϭ methyl

Figure 7. Stereochemical model for correlating the facial selectivity

of π-bond oxygenation from ‘‘loaded’’ peroxy complex 60 with the

geometry of similarly prepared cyclic ethers 6 and 7

cyclohexanol derivative trans-30 was oxidized under these

conditions to afford diastereomerically pure bicyclic 6,8-cis-

substituted tetrahydrofuran 31. This notable diastereoselec-

tivity was attributed to a more profound preference for ad-

opting a chair-like conformer in the transition state of the

oxygenation reaction. In this sense, it was reasonable that

formation of bicyclic tetrahydrofuran 32 proceeded with

significantly lower diastereoselectivity and was associated

with the additional formation of 5% of trans-configured

tetrahydropyran 33.

(iv) Regeneration of Peroxy Complex 57 ؊ Closing the

Catalytic Cycle

The proposed tert-butoxyvanadium() complex 61 was

butoxy complex 61. Rearrangement of like-configured ep- considered to react with TBHP in order to regenerate per-

oxy alcohol derivative like-62 provided in this model cis- oxy complex 57 for selective oxygen atom transfer in an-

substituted heterocycles (2S,5R)-6 and (3R,6R)-7. Similarly, other catalytic cycle. Highest selectivities for the formation

trans-substituted cyclic ethers (2S,5S)-6 and (3R,6S)-7 were of target compound 6 were achieved at 20 °C using TBHP

obtained from unlike-62. In view of the inherent selectivity as primary oxidant, preferentially in a solvent with low

for formation of 2,5-cis-configured tetrahydrofuran cis-6 in donicity (D_N) and a high dielectric constant (ε) such as

(peroxy)(Schiff-base)vanadium() complex mediated oxi- CHCl₃.^[63]Since 0.1 mol % of vanadium complex 4a suf-

dation of bis(homoallylic) alcohol 5, product formation ficed to convert bis(homoallylic) alcohol 5 in a total yield

from this reaction should mainly proceed via like-62. How- of 82% into heterocycles 6 and 7, an estimated turnover of

ever, since the experiment provided trans-configured prod- peroxy complex 57 in 820 catalytic cycles was achieved. For

ucts trans-6 and trans-7 in each case as side products, both practical reasons, 10 mol % of reagent 4a were applied in

stereochemical pathways for π-bond oxygenation should ex- order to reduce formation of side products (see above). The

ist.

efficiency of peroxide utilization with respect to formation

This stereochemical interpretation of the vanadium()- of heterocycles 6 and 7 under these conditions was 63%.

catalyzed oxidation of substrate 5 was supported by results The catalytic activity of the vanadium complexes faded at

from experiments with conformationally restricted bis(ho- the end of the oxidation reaction. The exact origin of this

moallylic) alcohols 30 (Scheme 3). Thus, trans-configured deactivation step was not known, but it is under investi-

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Eur. J. Org. Chem. 2003, 2388Ϫ2408

Stereoselective Synthesis of Functionalized Tetrahydrofurans

FULL PAPER

(i) Oxidation of 5,5-Dimethyl-Substituted Bis(homoallylic)

Alcohols

gation in order to develop catalysts with improved charac-

teristics for future projects.

1-Substituted secondary or tertiary bis(homoallylic) alk-

enols upon treatment with TBHP and catalyst 4g afforded

2,5-cis-configured tetrahydrofuran derivatives as major

compounds. Therefore, these substrates were considered to

follow the same stereochemical pathway for oxygenation of

the bis(homoallylic) π-bond as outlined for 5-methyl-1-phe-

nylhex-4-en-1-ol (5) in Figure 7. The observed diastereosel-

ectivities decreased from methyl-1-phenylhexenol 5 (96%

de), to 1-tert-butyl derivative 11 (82% de), 1-methyl-1-cyclo-

hexenyl-substituted alkenol (S,S)-38 (64% de) to (R)-lin-

alool (34, 22% de). It is noteworthy, that (R)-linalool [(R)-

34] was oxidized at the bis(homoallylic) rather than at the

allylic π-bond. This finding, however, may be rationalized

by considering the reluctance of Schiff-base complex 4a to

catalyze the epoxidation of allylic alcohol itself which re-

stricts the oxygen atom acceptor to the bis(homoallylic) π-

bond. The fact that (S,S)-bisabolol [(S,S)-38] is preferen-

tially oxidized at the bis(homoallylic) double bond that is

embedded in the flexible hydrocarbon chain rather than at

a more rigid cyclohexene substructure opens further useful

perspectives for applications of this new method in stereose-

lective synthesis (Scheme 4).^[70]

Finally, it is instructive to compare results from va-

nadium()-catalyzed oxidations of 4-methyl-1-phenyl-3-

buten-1-ol (26, lower homologue of 5) and 6-methyl-1-phe-

nyl-5-hepten-1-ol (27, higher homologue of 5) with respect

to the observed diastereoselectivity. The fact that trans-con-

figured tetrahydrofuran trans-28 was obtained as the major

product from substrate 26 was interpreted with a change

in facial selectivity for π-bond oxygenation, if compared to

substrate 5. Again it is worth mentioning that epoxy alcohol

intermediates were not observed in this reaction (TLC).

Formation of 2,6-cis-disubstituted tetrahydropyran cis-29

from alkenol 27 pointed to the fact that the same face-selec-

tion rule in peroxyvanadium() complex mediated oxygen-

ation applied for this substrate as for its lower homologue 5.

5,5-Dimethyl-substituted bis(homoallylic) alcohols with

substituents at positions 2 and 3 were selectively oxidized

in the presence of TBHP and catalyst 4g to provide trans-

configured tetrahydrofurans (Table 4). In extension to the

stereochemical model which is outlined in Figure 6, forma-

tion of trans-2,4-substituted tetrahydrofurans should there-

fore preferably proceed via a chair-like arranged alkenol li-

gand in a ‘‘loaded’’ complex, similar to chair-60 (see Fig-

ures 6 and 7). On the other hand a reversal of this facial

selectivity in the oxygen-transfer step had to be assumed in

order to explain the synthesis of diastereomerically pure

2,3-trans-disubstituted tetrahydrofuran derivatives, e.g. 19

and 20 (Figure 7).

Auxiliary Control in Product Formation

The observed yields of tetrahydrofuran derivative 6 were

dependent on the structure of the catalyst 4. Thus, appli-

cation of vanadium() complexes 4a, 4d, 4g, 4h, and 4j al-

lowed formation of tetrahydrofuran derivative 6 in more

than 80% yield (Table 3). This group of catalysts shared two

common structural motifs: (a) no tert-butyl substituents in

the o-hydroxybenzaldehyde entity and (b) a nonpolar amino

alcohol substructure in the chelate ligand. The remaining

catalysts either were prepared from 4,6-di-tert-butylsalicyl-

aldehyde (4e, 4f, 4i, and 4k) or from polar amines (i.e. 4c,

4i) and furnished lower yields of tetrahydrofuran 6 in the

same reaction period. In spite of the observed distinct dif-

ferences in reactivities, the catalysts had no significant effect

on the observed diastereoselectivity for formation of target

compound 6.^[64,65]

3. Structure-Selectivity Relationship in

(Schiff-base)vanadium(

V) Complex Catalyzed Oxidations of

Bis(homoallylic) Alcohols

TBHP served as efficient primary oxidant for converting

5,5-dimethyl-substituted bis(homoallylic) alcohols (Fig-

ure 8, left) and substituted 4-penten-1-ols (Figure 8, right)

into functionalized tetrahydrofurans. The reaction was cata-

lytic in vanadium(). The use of 1-amino-2-indanol-derived

complex 4g for this purpose is recommended since it was

an efficient reagent for both peroxide activation and dia-

stereoselective oxygen transfer to δ,ε-unsaturated alcohols

(Tables 3 and 5). This reagent was superior to alternative

methods which required, for example, [VO(acac)₂],^[2,26]

molybdenum() complexes,^[66]and more recently

[Cp₂TiCl₂],^[67]as catalysts. No direct comparison of the per-

oxyvanadium() complex based tetrahydrofuran formation

with highly diastereoselective oxidations using stoichio-

metric amounts of acylrhenates()^[14]or oxidations which

require the reagent combination of cobalt() diketonate

complexes, molecular oxygen and TBHP^[68]can be made at

this point because the sets of substrates in these studies did

not match. Finally, it is worth mentioning that mCPBA is

a reliable but poorly selective oxidant for converting bis(ho-

moallylic) alcohols into functionalized tetrahydrofurans

(Supporting Information).^[69]

(ii) Oxidation of Substituted 4-Penten-1-ols

(Schiff-base)vanadium()-catalyzed oxidations of 4-

penten-1-ols with alkyl or phenyl groups at position 1, 2,

and 3 (e.g. 41, 43Ϫ47, refer to Tables 5 and 6) proceeded in

all cases more slowly and less diastereoselectively than

Figure 8. Guidelines for the stereoselective synthesis of func-

tionalized tetrahydrofurans from substituted bis(homoallylic) al-

cohols

Eur. J. Org. Chem. 2003, 2388Ϫ2408

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2399

J. Hartung et al.

FULL PAPER

MATCH 7 spectrometer (EI, 70 eV). C,H,N,S analyses: Microana-

lytisches Laboratorium, Universität Würzburg, Carlo Erba 1106 or

LECO CHNS-932. Solvents were purified according to standard

procedures. (R)-Linalool [(R)-(34)], tert-butyl hydroperoxide (5.5

 in nonane), and VO(Et)₃were obtained from Fluka or Aldrich

and were used as received. Petroleum ether was distilled prior to

use (b.p. 40Ϫ55 °C).

those outlined for their 5,5-dimethyl-substituted derivatives.

trans-Disubstituted tetrahydrofurans were obtained as

major products in all experiments. Formation of corre-

sponding tetrahydropyrans was not observed. The same

trends were noted for the reaction of TBHP and 4-methyl-

1-phenyl-4-penten-1-ol (54) which furnished trans-2,5-sub-

stituted tetrahydrofuran as the major product (Scheme 5).

The fact that oxidation of 1-phenyl- and 1-tert-butyl-substi-

tuted 4-penten-1-ols 43 and 44 were favored the trans iso-

mer instead of the expected cis isomer (see above) pointed

to a change in facial selectivity for π-bond oxygenation,

which is caused by the substitution pattern at the double

bond. This issue is under investigation.

1. Preparation of Schiff Bases 3. General Procedure: Schiff bases 3

were prepared by condensation of salicylaldehydes (2 mmol, 1

equiv.) and amino alcohols (2 mmol, 1 equiv.) in refluxing ethanol

(15 mL, 3Ϫ4 h). Subsequent evaporation of the solvent furnished,

after extensive drying at 20 °C/10^Ϫ2mbar, analytically pure Schiff

bases 3 in quantitative yields [exception: 3h was purified by column

chromatography (SiO₂) and obtained in 61% yield].

2,4-Di-tert-butyl-6-({[(1S)-1-(hydroxymethyl)-2-methylpropyl]-

imino}methyl)phenol (3e): Yield: 0.64 g (quant.), yellow solid, m.p.

104Ϫ105 °C. [α]²_D⁵ϭ Ϫ32.5 (c ϭ 1.0, CHCl₃). ¹H NMR (250 MHz):

δ ϭ 0.96 (d, J ϭ 6.7 Hz, 3 H), 0.97 (d, J ϭ 7.0 Hz, 3 H), 1.31 (s,

9 H), 1.45 (s, 9 H), 1.90Ϫ2.03 (m, 1 H), 3.07 (m_c, 1 H), 3.67Ϫ3.87

(m, 2 H), 7.18 (d, J ϭ 2.4 Hz, 1 H), 7.44 (d, J ϭ 2.4 Hz, 1 H), 8.40

(s, 1 H) ppm. ¹³C NMR (63 MHz): δ ϭ 18.8, 19.8, 29.4, 31.5, 30.1,

34.1, 35.0, 64.7, 77.9, 117.7, 126.1, 127.1, 136.7, 140.2, 158.1, 167.1

ppm. IR (KBr): ν˜ ϭ 3298 cm^Ϫ1, 3223, 2953, 2871, 1624, 1468,

1435, 1275, 1250, 1025, 851. MS (70 eV, EI): m/z (%) ϭ 319 (62)

[M^ϩ], 304 (100) [C₁₉H₃₀NO₂^ϩ], 276 (50) [C₁₇H₂₆NO₂^ϩ], 219 (19)

[C₁₃H₁₇NO₂^ϩ], 162 (11) [C₉H₈NO₂^ϩ], 57 (53) [C₄H₉^ϩ], 41 (28)

[C₃H₅^ϩ]. HRMS (C₂₀H₃₃NO₂, 319.49): calcd. 319.2511, found

319.2510.

Conclusion

Vanadium() complexes 4 with tridentate Schiff-base

auxiliaries served as efficient oxidation catalysts for a

chemo- and diastereoselective conversion of bis(homoal-

lylic) alcohols into the corresponding tetrahydrofurans. The

reaction follows a transition metalϪperoxy mechanism.

Thus, coordination of TBHP to a vanadium() complex

was followed by alkenol binding to provide a ‘‘loaded’’ per-

oxy complex, e.g. 60. Subsequent intramolecular stereose-

lective oxygen transfer affords disubstituted functionalized

tetrahydrofurans. Important elementary reactions such as

the formation of tert-butylperoxy complexes (⁵¹V NMR 2,4-Di-tert-butyl-6-({[(1S)-1-(hydroxymethyl)-2,2-dimethylpropyl]-

imino}methyl)phenol (3f): Yield: 0.67 g (quant.), viscous yellow oil.

[α]²_D⁵ϭ Ϫ36.6 (c ϭ 1.0, CHCl₃). ¹H NMR (250 MHz): δ ϭ 0.98 (s,

9 H), 1.31 (s, 9 H), 1.45 (s, 9 H), 2.94 (dd, J ϭ 9.4, 2.9 Hz, 1 H),

3.74 (dd, J ϭ 11.3, 2.9 Hz, 1 H), 3.93 (dd, J ϭ 11.3, 9.5 Hz, 1 H),

7.14 (d, J ϭ 2.4 Hz, 1 H), 7.41 (d, J ϭ 2.4 Hz, 1 H), 8.38 (s, 1 H)

ppm. ¹³C NMR (63 MHz): δ ϭ 27.1, 29.4, 31.5, 33.2, 34.2, 35.1,

62.5, 81.4, 117.7, 126.2, 127.2, 136.8, 140.2, 158.2, 167.2 ppm. IR

(KBr): ν˜ ϭ 3387 cm^Ϫ1, 2960, 2907, 2869, 1631, 1474, 1440, 1172,

spectroscopy), alkenol binding (competition kinetics), and

stereoselective π-bond oxygenation (stereochemical analysis

using diastereomerically enriched epoxy alcohols 10) were

investigated in separate experiments. Guidelines for stereo-

selective synthesis, which may be derived at the present state

of our investigation, predict formation of trans-configured

tetrahydrofurans from 5,5-dimethyl-substituted bis(homo-

allylic) alcohols with alkyl and aryl groups at position 2 or

3 as well as from 1-, 2-, and 3-alkyl- or phenyl-substituted

1062. MS (70 eV, EI): m/z (%) ϭ 333 (90) [M^ϩ], 318 (100) [M^ϩ

CH₃], 290 (44) [C₁₉H₃₁NO^ϩ], 276 (48) [M^ϩϪ CH(CH₃)₃], 219 (31)

Ϫ

4-penten-1-ols. On the other hand, the vanadium()-cata- [C₁₅H₂₂O^ϩ], 162 (6) [C₁₁H₁₃^ϩ], 57 (35) [C₄H₉^ϩ]. HRMS

(C₂₁H₃₅NO₂, 333.5): calcd. 333.2668, found 333.2667.

lyzed oxidation of secondary or tertiary 5,5-dimethyl-sub-

stituted δ,ε-unsaturated alkenols proceeded 2,5-cis-selec-

tively. Formation of furanoid cis-linalool oxide (cis-35) as

the major product from (R)-linalool [(R)-34], instead of the

expected corresponding 1,2-epoxy alcohol was noteworthy

and has opened new perspectives for stereoselective syn-

thesis, e.g. for the formation of tetrahydrofuran-derived β-

carboline alkaloids.^[71]

(1R,2S,3R,4S)-3-[(2-Hydroxybenzylidene)amino]isoborneol

(3h): Yield: 0.33 g (61%), R_fϭ 0.80 (Et₂O), yellow solid, m.p.

119 °C (EtOH). [α]²_D⁵ϭ 32.7 (c ϭ 1.0, MeOH). ¹H NMR

(250 MHz): δ ϭ 0.86 (s, 3 H), 1.01 (s, 3 H), 1.26 (s, 3 H), 0.91Ϫ1.22

(m, 5 H), 3.61 (d, J ϭ 7.3 Hz, 1 H), 3.85 (d, J ϭ 7.3 Hz, 1 H), 6.91

(m_c, 2 H), 7.27 (m_c, 2 H), 8.36 (s, 1 H) ppm. ¹³C NMR (63 MHz):

δ ϭ 11.3, 21.5, 21.6, 26.5, 33.5, 47.2, 49.3, 53.3, 68.2, 81.6, 117.5,

118.3, 119.8, 131.7, 133.7, 137.0, 165.8 ppm. IR (KBr): ν˜ ϭ 3448

cm^Ϫ1, 2953, 2935, 2868, 1627, 1527, 1484, 1461, 1389, 1280, 1223,

1052, 847. MS (70 eV, EI): m/z (%) ϭ 273 (100) [M^ϩ], 230.1 (40)

[C₁₄H₁₆NO₂^ϩ], 161 (65) [C₁₀H₁₁NO^ϩ], 122 (90) [C₇H₈NO^ϩ], 41

(35) [C₃H₅^ϩ]. C₁₇H₂₃NO₂(273.4) calcd. C 74.69, H 8.48, N 5.12

found C 75.13, H 7.97, N 4.85.

Experimental Section

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

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

solution (⁵¹V NMR: EtOH) unless otherwise noted. Residual pro-

tons of deuterated solvents [δ_Hϭ 7.26 (CDCl₃)] and the corre-

3-{[(3,5-Di-tert-butyl-2-hydroxyphenyl)methylene]amino}propane-

1,2-diol (3i): Yield: 0.61 g (quant.), viscous yellow oil. ¹H NMR

sponding carbon resonances in ¹³C NMR spectra [δ_Cϭ 77.0 (250 MHz): δ ϭ 1.30 (s, 9 H), 1.44 (s, 9 H), 3.56Ϫ3.81 (m, 4 H),

(CDCl₃)] were taken as internal standards. ⁵¹V NMR: VOCl₃was

taken as external standard [δ_Vϭ 0.00 (VOCl₃)]. IR: KBr pellets,

PerkinϪElmer 1600 FT-IR spectrometer. UV/Vis: 1-cm quartz cu-

vettes, PerkinϪElmer 330 spectrophotometer. MS: Varian

3.99Ϫ4.05 (m, 1 H, 2-H), 7.10 (d, J ϭ 2.4 Hz, 1 H), 7.40 (d, J ϭ

2.4 Hz, 1 H), 8.41 (s, 1 H) ppm. ¹³C NMR (63 MHz): δ ϭ 29.4,

31.4, 34.1, 35.0, 61.9, 64.6, 71.6, 117.6, 126.1, 127.3, 136.7, 140.3,

158.0, 168.3 ppm. IR (KBr): ν ϭ 3385 cm^Ϫ1, 2959, 1636, 1458,

˜

2400

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Eur. J. Org. Chem. 2003, 2388Ϫ2408

Stereoselective Synthesis of Functionalized Tetrahydrofurans

FULL PAPER

1440, 1362, 1273, 1252, 1043. MS (70 eV, EI): m/z (%) ϭ 307 (51) δ ϭ Ϫ541 (EtOH); Ϫ534/Ϫ538 (1:1.2 in CD₃OD); Ϫ542/Ϫ545

[M^ϩ], 292 (100) [C₁₇H₂₆NO₃^ϩ], 250 (24) [C₁₄H₂₀NO₃^ϩ], 219 (33) (1:1.2 in CDCl₃) ppm. VOL⁷(OH)·(H₂O): C₁₆H₁₆NO₅V (353.3):

[C₁₃H₁₇NO^ϩ], 74 (51) [C₃H₆O₂^ϩ], 57 (56) [C₄H₉^ϩ]. HRMS

(C₁₈H₂₉NO₃, 307.4): calcd. 307.2147, found 307.2148.

calcd. C 54.40, H 4.57, N 3.97; found C 54.35, H 3.98, N 3.93.

VOL⁸(OEt) (4h): Yield: 0.38 g (quant.), red crystalline solid. IR

(KBr): ν˜ ϭ 986 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max(lg ε) ϭ 234

(4.27), 310 (3.61), 444 (2.38), 652 (2.74) nm. ⁵¹V NMR (105 MHz):

2,4-Di-tert-butyl-6-({[(1S)-1-(hydroxymethyl)-3-(methylthio)propyl]-

imino}methyl)phenol (3k): Yield: 0.70 g (quant.), viscous yellow oil.

¹H NMR (250 MHz): δ ϭ 1.32 (s, 9 H), 1.45 (s, 9 H), 1.81Ϫ1.96

(m, 2 H), 2.09 (s, 3 H), 2.08Ϫ3.63 (m, 2 H), 3.48 (m_c, 1 H),

3.65Ϫ3.79 (m, 2 H), 7.14 (d, J ϭ 2.4 Hz, 1 H), 7.41 (d, J ϭ 2.4 Hz,

1 H), 8.44 (s, 1 H) ppm. ¹³C NMR (63 MHz): δ ϭ 15.3, 29.4, 31.4,

30.7, 31.0, 34.1, 35.0, 66.1, 70.3, 117.6, 126.2, 127.3, 136.7, 140.3,

157.9, 167.6 ppm. IR (KBr): ν˜ ϭ 3420 cm^Ϫ1, 2957, 2903, 2862,

1624, 1476, 1249, 1173, 1045, 880, 826. MS (70 eV, EI): m/z (%) ϭ

351 (100) [M^ϩ], 336 (94) [C₁₉H₃₀NO₂^ϩ], 277 (34) [C₁₇H₂₇NO₂^ϩ],

203 (26) [C₁₃H₁₇NO₂^ϩ], 118 (34) [C₅H₁₁OS^ϩ], 57 (61) [C₄H₉^ϩ], 41

(30) [C₃H₅^ϩ]. HRMS (C₂₀H₃₃NO₂S, 351.6): calcd. 351.2232,

found 351.2233.

δ

ϭ

Ϫ518 (EtOH); 550/Ϫ553 (1:3 in CDCl₃) ppm.

VOL⁸(OH)·(H₂O): C₁₇H₂₄NO₅V (373.3): calcd. C 54.69, H 6.48, N

3.75; found C 54.89, H 6.28, N 3.73.

VOL⁹(OEt) (4i): Yield: 0.42 g (quant.), dark brown-black solid. IR

(KBr): ν˜ ϭ 966 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max(lg ε) ϭ 231

(4.44), 324 (3.88), 448 (2.46), 659 (2.36), 659 (2.35) nm. ⁵¹V NMR:

δ ϭ Ϫ548 (EtOH); Ϫ520 (CDCl₃) ppm. C₂₀H₃₂NO₅V (417.4):

calcd. C 57.55, H 7.73, N 3.36; found C 55.98, H 7.09, N 3.48.

VOL¹⁰(OEt) (4j): Yield: 0.35 g (quant.), brown solid. IR (KBr):

ν˜ ϭ 979 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max(lg ε) ϭ 256 (4.32),

320 (3.79), 447 (2.30), 659 (2.48) nm. ⁵¹V NMR (105 MHz): δ ϭ

Ϫ535/Ϫ542 (1.5:1 in EtOH) ppm. VOL¹⁰(OH)·2(H₂O):

C₁₂H₂₀NO₆SV (357.3): calcd. C 40.34, H 5.64, N 3.92, S 8.97;

found C 39.51, H 4.55, N 3.90, S 8.94.

2. (Schiff-base)vanadium(V) Complexes 4. General Procedure: A

solution of Schiff-base ligand 3 (1 mmol) in dry ethanol (10 mL)

was added under nitrogen to a solution of VO(OEt)₃(1 mmol) in

dry ethanol (5 mL). The reaction mixture was stirred at 20 °C for

1 h. Afterwards, the solvent was removed under reduced pressure

to provide vanadium() complexes 4 in quantitative yields.

VOL¹¹(OEt) (4k): Yield: 0.46 g (quant.), black microcrystalline

solid. IR (KBr): ν˜ ϭ 983 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max(lg

ε) ϭ 251 (4.25), 350 (3.69), 437 (1.91), 652 (2.06) nm. ⁵¹V NMR:

δ ϭ Ϫ545/Ϫ557 (1.7:1 in EtOH); Ϫ562/Ϫ573 ppm (in CDCl₃).

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.

VOL¹(OEt)(EtOH) (4a): Yield: 0.37 g (quant.), dark brown-green

microcrystalline solid. IR (KBr): ν˜ ϭ 990 cm^Ϫ1(VϭO). UV/Vis

(EtOH): λ_max(lg ε) ϭ 242 (4.16), 341 (3.78), 361 (3.80), 659 (2.40)

nm. ⁵¹V NMR (105 MHz): δ ϭ Ϫ529 (EtOH), Ϫ529; (CD₃OD);

Ϫ529 (CDCl₃) ppm.

3. Synthesis of Alkenols. General Procedure: Bis(homoallylic) al-

cohols were prepared from the corresponding carbonyl com-

pounds.^[73]Thus, a solution of a ketone or an aldehyde (1 equiv.)

in anhydrous Et₂O (1 mL/mmol) was added dropwise at 0 °C to a

suspension of LiAlH₄(0.5 equiv.) in anhydrous Et₂O (5 mL/mmol).

The reaction mixture was refluxed for 2 h and was subsequently

cooled to 0 °C, hydrolyzed (5 mL of H₂O/mmol) and neutralized by

treatment with aq. satd. NH₄Cl solution (2 mL/mmol). The organic

phase was separated and the aqueous phase was extracted with

Et₂O (2 ϫ 2 mL/mmol). The combined organic layers were washed

with brine (3 mL/mmol) and H₂O (2 ϫ 3 mL/mmol) and dried

(Na₂SO₄). The solvent was removed under reduced pressure

(950 mbar/40 °C) to provide a residue, which was purified by distil-

lation and in selected instances (see below) by column chromatog-

raphy (SiO₂).

VOL²(OEt) (4b): Yield: 0.35 g (quant.), dark-brown solid. IR

(KBr): ν˜ ϭ 996 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max(lg ε) ϭ 255

(4.16), 348 (3.69), 352 (3.69) nm. ⁵¹V NMR (105 MHz): no signal

detected (EtOH). C₁₇H₁₈NO₅V (367.3): calcd. C 55.60, H 4.94, N

3.81; found C 53.64, H 4.62, N 3.13.

VOL³(OEt) (4c): Yield: 0.33 g (quant.), black solid. IR (KBr): ν˜ ϭ

976 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max(lg ε) ϭ 247 (sh), 316

(3.28), 373 (2.99), 659 (2.43) nm. ⁵¹V NMR (105 MHz): δ ϭ Ϫ523

(EtOH) ppm.

VOL⁴(OEt) (4d): Yield: 0.35 g (quant.), brown crystals. IR (KBr):

ν˜ ϭ 997 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max(lg ε) ϭ 256 (4.36),

362 (3.15), 443 (1.88), 652 (2.20) nm. ⁵¹V NMR (105 MHz): δ ϭ

Ϫ538 (EtOH); Ϫ526/Ϫ534 (1.5:1 in CD₃OD) ppm.

VOL⁴(OH)·(H₂O): C₁₅H₁₆NO₅V (341.2): calcd. C 52.80, H 4.73, N

4.10; found C 53.66, H 4.80, N 2.62.

2,2,7-Trimethyl-6-octen-3-ol (11): 2,2,7-Trimethyl-6-octen-3-one^[73a]

(10.0 g, 59.4 mmol) was reduced with LiAlH₄(0.5 equiv.) as de-

scribed above to provide 9.47 g (94%) of alkenol 11 as a colorless

VOL⁵(OEt) (4e): Yield: 0.43 g (quant.), black microcrystalline

solid. IR (KBr): ν˜ ϭ 994 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max

(lg ε) ϭ 248 (4.36), 321 (3.78), 440 (2.53), 652 (2.50) nm. ⁵¹V NMR

(105 MHz): δ ϭ Ϫ543/Ϫ551 (1.9:1 in EtOH); Ϫ560/Ϫ562 ppm

(CDCl₃). C₂₂H₃₆NO₄V (429.5): calcd. C 61.53, H 8.45, N 3.26;

found C 61.12, H 7.85, N 3.50.

1

liquid; b.p. 92 °C/11 mbar. H NMR (250 MHz): δ ϭ 0.88 [s, 9 H,

C(CH₃)₃], 1.29 (m_c, 1 H, CH₂), 1.56 (m_c, 1 H, CH₂), 1.63 (s, 3 H,

CH₃), 1.70 (s, 3 H, CH₃), 2.13 (m_c, 2 H, CH₂), 3.20 (dd, J ϭ 10.4,

1.9 Hz, 1 H, CH), 5.15 (tquint, J_tϭ 7.2, J_quintϭ 1.5 Hz, 1 H, CH)

ppm. ¹³C NMR (63 MHz): δ ϭ 17.7, 25.6, 25.7, 25.8, 31.5, 34.9,

79.8, 124.4, 123.1 ppm. MS (70 eV, EI): m/z (%) ϭ 170 (4) [M^ϩ],

113 (17) [M^ϩϪ C(CH₃)₃], 95 (67) [M^ϩϪ C(CH₃)₃Ϫ H₂O], 82

(67) [C₆H₁₀^ϩ], 69 (100) [C₅H₉^ϩ]. C₁₁H₂₂O (170.3): calcd. C 77.58,

H 13.02; found C 78.13, H 12.86.

VOL⁶(OEt) (4f): Yield: 0.44 g (quant.), black microcrystalline

solid. IR (KBr): ν˜ ϭ 979 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max

(lg ε) ϭ 259 (4.33), 318 (3.80), 362 (3.19), 423 (2.33), 658 (1.94)

nm. ⁵¹V NMR (105 MHz): δ ϭ Ϫ533/Ϫ549 (1:2.6 in EtOH); Ϫ562/

Ϫ571 (CDCl₃) ppm. C₂₃H₃₈NO₄V (443.5): calcd. C 62.29, H 8.64,

N 3.16; found C 61.37, H 7.98, N 3.19.

5-Methyl-3-phenyl-4-hexen-1-ol

(14):

Hg(OAc)₂

(0.505 g,

1.58 mmol) was added to a solution of 2-methyl-4-phenyl-3-buten-

2-ol^[73c](4.00 g, 31.7 mmol) in ethyl vinyl ether (20 mL). The reac-

tion mixture was stirred at an oil-bath temperature of 50 °C for

VOL⁷(OEt) (4g): Yield: 0.36 g (quant.), red crystalline solid. IR

(KBr): ν˜ ϭ 997 cm^Ϫ1(VϭO). UV/Vis (EtOH): λ_max(lg ε) ϭ 272 24 h. K₂CO₃(0.5 g) was added and the volatiles were removed un-

(4.22), 345 (3.74), 435 (2.44), 652 (2.39) nm. ⁵¹V NMR (105 MHz):

der reduced pressure (600 mbar/40 °C) to afford a residue which

2401

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www.eurjoc.org

 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Hartung et al.

FULL PAPER

was purified by column chromatography [SiO₂; petroleum ether/

acetone, 9:1 (v/v)] to provide 5-methyl-3-phenyl-4-hexen-1-al

130.4, 133.3, 146.5. MS (70 eV, EI): m/z (%) ϭ 204 (1) [M^ϩ], 171

(14) [C₁₃H₁₆^ϩ], 133 (19) [C₁₀H₁₂^ϩ], 120 (100) [C₈H₉O^ϩ], 107 (39)

[C₇H₇O^ϩ], 82 (100) [C₆H₁₁^ϩ], 41 (40) [C₃H₆^ϩ]. C₁₄H₂₀O (204.3):

(2.56 g, 43%) as a colorless liquid: R_fϭ 0.70 [petroleum ether/ace-

1

tone, 9:1 (v/v)]. H NMR (250 MHz): δ ϭ 1.72 (s, 6 H, CH₃), 2.76 calcd. C 82.30, H 9.87; found C 82.23, H 9.81.

(m_c, 2 H, CH₂), 4.13 (dt, J_dϭ 6.7, J_tϭ 9.3 Hz,1 H, CH), 5.29

2,2-Dimethyl-6-hepten-3-ol (44): 2,2-Dimethyl-6-hepten-3-one^[43]

(dquint, J_dϭ 9.3, J_quintϭ 1.5 Hz, 1 H, CH), 7.15Ϫ7.36 (m, 5 H,

Ar H) 9.70 (t, J_tϭ 2.2 Hz, 1 H, CH) ppm. ¹³C NMR (63 MHz):

δ ϭ 18.7, 26.5, 39.4, 42.0, 126.7, 127.2, 128.4, 133.6, 139.8, 200.2

(4.0 g, 27.7 mmol) was treated with LiAlH₄(0.5 equiv.) as outlined

in the General Procedure. The crude material was purified by col-

umn chromatography [SiO₂; petroleum ether/Et₂O/CH₂Cl₂, 1:1:1

(v/v/v)] to afford product 44 (2.9 g, 74%) as a colorless liquid: R_fϭ

0.65 [petroleum ether/acetone, 3:1 (v/v)]. ¹H NMR (250 MHz): δ ϭ

0.88 [s, 9 H, C(CH₃)₃], 1.37 (m_c, 1 H, CH₂), 1.62 (m_c, 1 H, CH₂),

2.10 (m_c, 2 H, CH₂), 2.30 (m_c, 2 H, CH₂), 2.39Ϫ2.52 (m, 1 H, CH),

3.21 (dd, J ϭ 8.5, 1.8 Hz, 1 H, CH), 5.00 (m_c, 2 H, CH₂), 5.84

(ddt, J_dϭ 17.4, 10.4, J_tϭ 7.0 Hz, 1 H, CH) ppm. ¹³C NMR

(63 MHz): δ ϭ 11.0, 25.6, 31.2, 34.9, 79.4, 114.7, 138.8 ppm. MS

(70 eV, EI): m/z (%) ϭ 142.2 (0.3) [M^ϩ], 85 (38) [C₅H₉O^ϩ], 71 (13)

[C₄H₇O^ϩ], 67 (62) [C₅H₈^ϩ], 57 (100) [C₄H₉^ϩ], 41 (88) [C₃H₅^ϩ].

C₉H₁₈O (142.2): calcd. C 76.00, H 12.76; found C 76.10, H 12.77.

ppm. MS (70 eV, EI): m/z (%) ϭ 188 (21) [M^ϩ], 173 (45) [M^ϩ

Ϫ

CH₃], 145 (100) [C₁₁H₁₃^ϩ], 117 (62) [C₉H₉^ϩ]. C₁₃H₁₆O (188.3):

calcd. C 82.94, H 8.57; found C 83.16, H 8.51. According to the

General Procedure, 5-methyl-3-phenyl-4-hexen-1-al (2.48 g,

13.2 mmol) was treated with LiAlH₄(0.5 equiv.). The crude prod-

uct was purified by distillation to furnish 2.00 g (80%) of alcohol

14 as a colorless liquid; b.p. 140 °C/10^Ϫ2mbar. ¹H NMR

(250 MHz): ϭ 1.69 (d, J_dϭ 1.4 Hz, 3 H, CH₃), 1.71 (d, J_d

ϭ

1.4 Hz, 3 H, CH₃), 1.81Ϫ2.03 (m, 2 H, CH₂), 3.62 (t, J_tϭ 6.4 Hz,

2 H, CH₂), 3.67 (dt, J_dϭ 6.4, J_tϭ 9.3 Hz, 1 H, CH), 5.30 (dquint,

J_dϭ 9.3, J_quintϭ 1.4 Hz, 1 H, CH), 7.16Ϫ7.33 (m, 5 H, Ar H)

ppm. ¹³C NMR (63 MHz): δ ϭ 18.6, 26.4, 35.8, 43.6, 65.8, 126.4,

127.8, 128.6, 134.1, 143.5 ppm. MS (70 eV, EI): m/z (%) ϭ 190

(10) [M^ϩ], 145 (100) [C₁₁H₁₃^ϩ], 117 (32) [C₉H₉^ϩ]. C₁₃H₁₈O (190.3):

calcd. C 82.06, H 9.53; found C 81.73, H 9.21.

4-Methyl-1-phenyl-4-penten-1-ol (54): 4-Methyl-1-phenyl-4-penten-

1-one (4.0 g, 23.0 mmol) was obtained from ethyl benzoylacetate

and 3-chloro-2-methyl-1-propene in extension to a published pro-

cedure^[33]to afford 4-methyl-1-phenylpent-4-en-1-one. This ketone

was reduced with LiAlH₄(0.5 equiv.) to provide a crude product.

This material was purified by column chromatography [SiO₂; petro-

leum ether/Et₂O/CH₂Cl₂, 1:1:1 (v/v/v)] to afford alkenol 54 (3.3 g,

81%) as a colorless liquid: R_fϭ 0.45 [petroleum ether/Et₂O/

CH₂Cl₂, 1:1:1 (v/v/v)]. ¹H NMR (250 MHz): δ ϭ 1.66 (s, 3 H,

CH₃), 1.71Ϫ1.89 (m, 2 H, CH₂), 1.90Ϫ2.08 (m, 2 H, CH₂), 2.05

(br. s, 1 H, OH), 4.57 (dd, J ϭ 5.7, 7.3 Hz, 1 H, CH), 4.64 (m_c, 1

H, CH₂), 4.67 (m_c, 1 H, CH₂), 7.18Ϫ7.32 (5 H, Ar H) ppm. ¹³C

NMR (63 MHz): δ ϭ 22.5, 33.9, 36.8, 74.2, 110.1, 125.9, 127.5,

128.4, 144.6, 145.4 ppm. MS (70 eV, EI): m/z (%) ϭ 176 (5) [M^ϩ],

161 (21) [C₁₁H₁₃O^ϩ], 145 (26) [C₁₁H₁₃^ϩ], 104 (100) [C₈H₈^ϩ], 77 (95)

[C₆H₅^ϩ]. C₁₂H₁₆O (176.3): calcd. C 81.77, H 9.15; found C 81.56,

H 9.04.

5-Methyl-3-(1-methylethyl)-4-hexen-1-ol (15): Ethyl 5-methyl-3-(1-

methylethyl)-4-hexenoate^[73b](1.73 g, 8.70 mmol) was treated with

LiAlH₄(1.0 equiv.) as outlined above. The crude product was puri-

fied by column chromatography [SiO₂; petroleum ether/Et₂O/

CH₂Cl₂, 4:1:1 (v/v/v)] to furnish 1.17 g (86%) of alkenol 15 as col-

orless liquid: R_fϭ 0.60 [petroleum ether/Et₂O/CH₂Cl₂, 4:1:1 (v/v/

v)]. ¹H NMR (250 MHz): δ ϭ 0.82 (d, J ϭ 6.7 Hz, 3 H, CH₃), 0.87

(d, J ϭ 6.7 Hz, 3 H, CH₃), 1.34Ϫ1.46 (m, 1 H, CH₂), 1.53 (m_c, 1

H, CH), 1.62 (s, 3 H, CH₃), 1.72 (s, 3 H, CH₃), 1.66Ϫ1.78 (m, 1

H, CH₂), 2.17 (m_c, 1 H, CH), 3.56 (m_c, 2 H, CH₂), 4.93 (dquint,

J_dϭ 10.2, J_quintϭ 1.4 Hz, 1 H, CH) ppm. ¹³C NMR (63 MHz):

δ ϭ 19.3, 19.8, 20.5, 26.2, 33.3, 36.4, 42.0, 62.7, 114.4, 127.7 ppm.

MS (70 eV, EI): m/z (%) ϭ 156 (16) [M^ϩ], 113 (42) [C₇H₁₃O^ϩ], 95

(83) [C₇H₁₂^ϩ], 69 (100) [C₅H₈^ϩ], 55 (53) [C₄H₇^ϩ]. C₁₀H₂₀O (156.3):

calcd. C 76.86, H 12.90; found C 76.94, H 12.63.

4. Vanadium(V)-Catalyzed Oxidations of Bis(homoallylic) Alcohols.

General Procedure: Vanadium() complex 4 (0.1 equiv.) was added

at 25 °C to a solution of alkenol (1.00 mmol) in CHCl₃(5 mL/

mmol). Addition of tert-butyl hydroperoxide (5.5  in nonane, 1.5

equiv.) led to a change in color of the reaction mixture from brown

to dark red. The solution was stirred for an additional 48 h at 25

°C. After removal of the solvent under reduced pressure (250 mbar/

40 °C), the crude product was filtered through a short pad of

Al₂O₃. The product was washed from the column with Et₂O. The

combined organic phases were concentrated under reduced press-

ure to provide an oil which was purified by kugelrohr distillation

and subsequent column chromatography (SiO₂). For product

analysis by GC on an analytical level (Յ 0.1 mmol of alkenol), n-

C₁₄H₃₀(0.01 mmol) was added as an internal standard after separ-

ating the oxidation products from vanadium compounds by extrac-

tion [CHCl₃/satd. aqueous Na₂S₂O₃solution (2 mL/2 mL)].

4-Methyl-1-phenyl-3-penten-1-ol (26): 4-Methyl-1-phenyl-3-penten-

1-one^[73d](2.0 g, 11.5 mmol) was treated with LiAlH₄(0.5 equiv.)

as outlined above. The crude product was purified by column chro-

matography [SiO₂; petroleum ether/Et₂O/CH₂Cl₂, 1:1:1 (v/v/v)] to

furnish compound 26 (1.6 g, 78%) as a colorless liquid: R_fϭ 0.68

[petroleum ether/acetone, 3:1 (v/v)]. ¹H NMR (250 MHz): δ ϭ 1.61

(s, 3 H, CH₃), 1.73 (s, 3 H, CH₃), 1.78 (br. s, 1 H, OH), 2.32Ϫ2.58

(m, 2 H, CH₂), 4.69 (dd, J ϭ 7.7, 5.5 Hz, 1 H, CH), 5.18 (t, J ϭ

8.1 Hz, 1 H, CH), 7.25Ϫ7.43 (m, 5 H, Ar H) ppm. ¹³C NMR

(63 MHz): δ ϭ 18.0, 25.9, 38.3, 74.0, 119.7, 125.8, 127.4, 128.3,

135.2, 144.2 ppm. MS (70 eV, EI): m/z (%) ϭ 176 (3) [M^ϩ], 158

(10) [C₁₂H₁₅^ϩ], 143 (26) [C₁₁H₁₃^ϩ], 107 (78) [C₇H₇O^ϩ], 77 (48)

[C₆H₅^ϩ], 70 (100) [C₅H₉^ϩ]. C₁₂H₁₆O (176.3): calcd. C 81.77, H

9.15; found C 81.56, H 9.04.

Oxidation of 5-Methyl-1-phenyl-4-hexen-1-ol (5)

6-Methyl-1-phenyl-5-hepten-1-ol (27): 6-Methyl-1-phenyl-5-hepten-

1-one,^[37](3.2 g, 16.0 mmol) was treated with LiAlH₄(0.5 equiv.) 2-(1-Hydroxy-1-methylethyl)-5-phenyltetrahydrofuran (6):^[33]Yield:

as described above. The crude product was purified by column

chromatography [SiO₂; petroleum ether/acetone, 3:1 (v/v)] to pro-

vide alkenol 27 (2.9 g, 89%) as a colorless liquid: R_fϭ 0.79 [petro-

140 mg (74%), colorless liquid, b.p. 140 °C/10^Ϫ2mbar (ref.^[33]no

data given), cis/trans ϭ 98:2. cis-6: R_fϭ 0.40 [petroleum ether/

1

acetone, 4:1 (v/v)]. H NMR (250 MHz): δ ϭ 1.15 (s, 3 H, CH₃),

1

leum ether/acetone, 3:1 (v/v)]. H NMR (250 MHz): δ ϭ 1.42 (s, 3

1.23 (s, 3 H, CH₃), 1.66Ϫ1.80 (m, 1 H, CH₂), 1.85Ϫ1.95 (m, 2 H,

H, CH₃), 1.51 (s, 3 H, CH₃), 1.67Ϫ2.00 (m, 6 H, CH₂), 2.20 (br. s, CH₂), 2.05 (br. s, 1 H, OH), 2.17Ϫ2.29 (m, 1 H, CH₂), 3.80 (t, J ϭ

1 H, OH), 4.48 (dd, J ϭ 6.1, 5.2 Hz, 1 H, CH), 4.92 (t, J ϭ 7.0 Hz, 7.3 Hz, 1 H, CH), 4.80 (dd, J ϭ 8.2, 6.7 Hz,, 1 H, CH), 7.19Ϫ7.35

1 H, CH), 7.17Ϫ7.20 (m, 5 H, Ar H) ppm. ¹³C NMR (63 MHz):

δ ϭ 16.9, 26.8, 27.3, 29.4, 40.3, 72.0, 125.9, 127.5, 129.0, 135.2, 4:1 (v/v)]. H NMR (250 MHz): δ ϭ 1.23 (s, 3 H, CH₃), 1.74Ϫ1.96

(m, 5 H, Ar H) ppm. trans-6: R_fϭ 0.42 [petroleum ether/acetone,

1

2402  2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org

Eur. J. Org. Chem. 2003, 2388Ϫ2408

Stereoselective Synthesis of Functionalized Tetrahydrofurans

FULL PAPER

(m, 3 H, CH₂), 2.05 (br. s, 1 H, OH), 2.24Ϫ2.36 (m, 1 H, CH₂), 85 (38) [C₅H₉O], 59 (100) [C₃H₇O^ϩ], 57 (89) [C₄H₉^ϩ]. C₁₁H₂₂O₂

3.97 (dd, J ϭ 7.5, 6.7 Hz, 1 H, CH), 4.92 (dd, J ϭ 8.2, 5.9 Hz, 1 (186.3): calcd. C 70.92, H 11.90; found C 70.80, H 11.82.

H, CH), 7.19Ϫ7.35 (m, 5 H, Ar H) ppm.

Oxidation of 5-Methyl-2-phenyl-4-hexen-1-ol (12)

2,2-Dimethyl-6-phenyltetrahydropyran-3-ol (7):^[33]Yield: 24 mg

(12%), colorless crystals, m.p. 141 °C (subl.), ref.^[33]142Ϫ143 °C,

2-(1-Hydroxy-1-methylethyl)-4-phenyltetrahydrofuran (17): Yield:

114 mg (55%), colorless liquid, b.p. 130 °C/10^Ϫ2mbar (kugelrohr),

cis/trans ϭ 46:54. cis-7: R_fϭ 0.17 [petroleum ether/acetone, 4:1 (v/

cis/trans ϭ 9:91. MS (70 eV, EI): m/z (%) ϭ 206 (2) [M^ϩ], 148 (100)

[M^ϩϪ C₃H₆O], 147 (37) [C₁₀H₁₁O^ϩ], 129 (32) [C₁₀H₉^ϩ], 118 (70)

[C₉H₁₀^ϩ], 117 (40) [C₉H₉^ϩ], 104 (60) [C₈H₈^ϩ], 91 (76) [C₇H₇^ϩ], 59

(89) [C₃H₇O^ϩ], 41 (12) [C₃H₅^ϩ]. C₁₃H₁₈O₂(206.3) calcd. C 75.69

H 8.80; found C 75.29 H 8.62. cis-17: R_fϭ 0.29 [petroleum ether/

v)]. ¹H NMR (250 MHz): δ ϭ 1.33 (s, 3 H, CH₃), 1.38 (s, 3 H,

CH₃), 1.58 (br. s, 1 H, OH), 1.60Ϫ1.97 (m, 4 H, CH₂), 3.48 (t, J ϭ

2.9 Hz, 1 H, CH), 4.70 (dd, J ϭ 11.7, 2.9 Hz, 1 CH), 7.16Ϫ7.28

(m, 5 H, Ar H) ppm. trans-7: R_fϭ 0.15 [petroleum ether/acetone,

1

4:1 (v/v)]. H NMR (250 MHz): δ ϭ 1.30 (s, 3 H, CH₃), 1.37 (s, 3

1

acetone, 3:1 (v/v)]. H NMR (250 MHz): δ ϭ 1.20 (s, 3 H, CH₃),

H, CH₃), 1.56 (br. s, 1 H, OH), 1.61Ϫ1.78 (m, 2 H, CH₂),

1.90Ϫ1.97 (m, 2 H, CH₂), 3.56 (dd, J ϭ 11.4, 4.4 Hz, 1 H, CH),

4.57 (dd, J ϭ 11.4, 2.0 Hz, 1 H, CH), 7.19Ϫ7.32 (m, 5 H, Ar H)

ppm.

1.30 (s, 3 H, CH₃), 1.80Ϫ2.00 (m, 1 H, CH₂), 2.27Ϫ2.39 (m, 1 H,

CH₂), 3.48Ϫ3.66 (m, 1 H, CH), 3.77 (dd, J ϭ 9.6, 7.8 Hz, 1 H,

CH₂), 3.93 (dd, J ϭ 9.5, 5.5 Hz, 1 H, CH), 4.26 (dd, J ϭ 8.9,

7.9 Hz, 1 H, CH₂), 7.23Ϫ7.36 (m, 5 H, Ar H) ppm. trans-17: R_fϭ

0.31 [petroleum ether/acetone, 3:1 (v/v)]. ¹H NMR (250 MHz): δ ϭ

1.17 (s, 3 H, CH₃), 1.29 (s, 3 H, CH₃), 1.91Ϫ2.02 (m, 1 H, CH₂),

1.97 (br. s, 1 H, OH), 2.27Ϫ2.39 (m, 1 H, CH₂), 3.37Ϫ3.49 (ddd,

J ϭ 13.7, 9.0, 6.9 Hz, 1 H, CH), 3.84 (dd, J ϭ 8.5, 7.0 Hz, 1 H,

CH), 3.97 (t, J ϭ 7.5 Hz, 1 H, CH), 4.25 (dd, J ϭ 8.6, 7.0 Hz, 1

H, CH₂), 7.23Ϫ7.36 (m, 5 H, Ar H) ppm.

3-Benzoyloxy-2,2-dimethyl-5-γ-butyrolactone (8): A solution of 2-

(1-hydroxy-1-methylethyl)-5-phenyltetrahydrofuran (6, 84 mg,

0.40 mmol) in CHCl₃(2 mL) was treated with TBHP (110 µL, 5.5

 in nonane, 0.60 mmol) and VOL¹(OEt)(EtOH) (4a) (14.8 mg,

0.04 mmol). The reaction mixture was stirred at 25 °C for 7 d and

subsequently filtered through a short column of aluminum oxide.

The product was eluted (Et₂O). The combined organic phases were

concentrated under reduced pressure and the remaining residue

purified by column chromatography [SiO₂; petroleum ether/ace-

tone, 4:1 (v/v)]. Yield: 17.2 mg (18%), colorless crystals, m.p. 89 °C,

b.p. 140 °C/10^Ϫ2mbar (kugelrohr). R_fϭ 0.35 [petroleum ether/

trans-2,2-Dimethyl-5-phenyltetrahydropyran-3-ol (trans-22): Yield:

8.0 mg (4%), colorless liquid, b.p. 130 °C/10^Ϫ2mbar (kugelrohr).

R_f

ϭ

0.25 [petroleum ether/acetone, 3:1 (v/v)]. ¹H NMR

(250 MHz): δ ϭ 1.31 (s, 3 H, CH₃), 1.37 (s, 3 H, CH₃), 1.84 (s, 1

H, OH), 1.98Ϫ2.08 (m, 1 H, CH₂), 2.16Ϫ2.27 (m, 1 H, CH₂), 3.20

(m_c, 1 H, CH), 3.61 (dd, J ϭ 3.7, 3.4 Hz, 1 H, CH₂), 3.73 (dd, J ϭ

11.9, 10.4 Hz, 1 H, CH), 3.81 (ddd, J ϭ 11.6, 5.5, 1.5 Hz, 1 H,

CH₂), 7.20Ϫ7.36 (m, 5 H, Ar H) ppm. MS (70 eV, EI): m/z (%) ϭ

206 (2) [M^ϩ], 188 (6) [C₁₃H₁₆O^ϩ], 148 (14) [C₁₀H₁₂O^ϩ], 104 (100)

[C₈H₈^ϩ], 91 (19) [C₇H₇^ϩ], 77 (11) [C₆H₅^ϩ], 59 (34) [C₃H₇O^ϩ], 41

(10) [C₃H₅^ϩ]. C₁₃H₁₈O₂(206.3): calcd. C 75.69, H 8.80; found C

75.33, H 8.99.

1

acetone, 4:1 (v/v)]. H NMR (400 MHz): δ ϭ 1.51 (s, 3 H, CH₃),

1.52 (s, 3 H, CH₃), 2.71 (dd, J ϭ 18.4, 2.2 Hz, 1 H, CH₂), 3.18 (dd,

J ϭ 18.4, 6.8 Hz,, 1 H, CH₂), 5.46 (dd, J ϭ 6.8, 2.2 Hz,, 1 H, CH),

7.46Ϫ7.64 (m, 3 H, Ar H), 8.03Ϫ8.05 (m, 2 H, Ar H) ppm. ¹³C

NMR (63 MHz): δ ϭ 21.8, 26.4, 36.1, 75.1, 86.5, 128.6, 128.8,

129.7, 133.7, 165.6, 173.5 ppm. MS (70 eV, EI): m/z (%) ϭ 161

(30) [C₁₀H₉O₂^ϩ], 147 (40) [C₉H₇O₂^ϩ], 129 (30) [C₆H₉O₃^ϩ], 91 (97)

[C₇H₇^ϩ], 43 (100) [C₂H₃O^ϩ]. C₁₃H₁₄O₄(234.3): calcd. C 66.66, H

6.02; found C 67.13, H 5.88.

Oxidation of 2-Isopropyl-5-methylhex-4-en-1-ol (13)

Oxidation of 2,2,7-Trimethyl-6-octen-3-ol (11)

2-(1-Hydroxy-1-methylethyl)-4-isopropyltetrahydrofuran (18): Yield:

149 mg (90%), colorless liquid, b.p. 120 °C/10 mbar (kugelrohr),

cis/trans ϭ 19:81. MS (70 eV, EI): m/z (%) ϭ 172 (1) [M^ϩ], 113 (54)

[C₇H₁₃O^ϩ], 95 (50) [C₇H₁₁^ϩ] 59 (100) [C₃H₇O^ϩ]. C₁₀H₂₀O₂(172.3):

calcd. C 69.72, H 11.70; found C 69.62, H 11.58. cis-18: R_fϭ 0.75

[petroleum ether/Et₂O/CH₂Cl₂, 2:1:1 (v/v/v)]. ¹H NMR (250 MHz):

δ ϭ 0.87 (d, J ϭ 6.7 Hz, 3 H, CH₃), 0.92 (d, J ϭ 6.7 Hz, 3 H,

CH₃), 1.11 (s, 3 H, CH₃), 1.24 (s, 3 H, CH₃), 1.44 (sept, J ϭ 6.7 Hz,

1 H, CH), 1.36Ϫ1.60 (m, 1 H, CH₂), 1.76Ϫ2.05 (m, 1 CH₂), 3.45

(dd, J ϭ 9.1, 8.1 Hz, 1 H, CH), 3.75 (dd, J ϭ 8.0, 5.3 Hz, 1 H,

CH), 3.99 (t, J ϭ 8.1 Hz, 1 H, CH) ppm. ¹³C NMR (63 MHz): δ ϭ

21.3, 21.6, 24.1, 27.3, 29.7, 31.8, 47.9, 71.3, 73.0, 86.6 ppm. trans-

18: R_fϭ 0.75 [petroleum ether/Et₂O/CH₂Cl₂, 2:1:1 (v/v/v)]. ¹H

NMR (250 MHz): δ ϭ 0.87 (d, J ϭ 6.6 Hz, 3 H, CH₃), 0.91 (d,

J ϭ 6.6 Hz, 3 H, CH₃), 1.11 (s, 3 H, CH₃)_,1.20 (s, 3 H, CH₃), 1.48

(sept, J ϭ 6.6 Hz, 1 H, CH), 1.37Ϫ1.59 (m, 1 H, CH₂), 1.78Ϫ1.98

(m, 1 H, CH₂), 3.38 (t, J ϭ 8.6 Hz, 1 H, CH₂), 3.73 (dd, J ϭ 8.6,

5.8 Hz, 1 H, CH), 4.04 (dd, J ϭ 8.6, 5.9 Hz, 1 H, CH₂) ppm. ¹³C

NMR (63 MHz): δ ϭ 21.3, 21.5, 24.4, 26.8, 31.2, 31.7, 47.2, 71.7,

73.0, 85.7 ppm.

5-tert-Butyl-2-(1-hydroxy-1-methylethyl)tetrahydrofuran (16): Yield:

133 mg (71%), colorless liquid, b.p. 140 °C/10 mbar (kugelrohr),

cis/trans ϭ 91:9. MS (70 eV, EI): m/z (%) ϭ 186 (1) [M^ϩ], 129 (5)

[M^ϩϪ C₄H₉], 85 (32) [C₅H₉O^ϩ] 59 (100) [C₃H₇O^ϩ], 57 (62)

[C₄H₉^ϩ], 39 (31) [C₃H₃^ϩ]. C₁₁H₂₂O₂(186.3): calcd. C 70.92, H

11.90; found C 70.37, H 11.89. cis-16: R_fϭ 0.78 [petroleum ether/

Et₂O/CH₂Cl₂, 4:1:1 (v/v/v)]. ¹H NMR (250 MHz): δ ϭ 0.90 [s, 9

H, C(CH₃)₃], 1.13 (s, 3 H, CH₃), 1.23 (s, 3 H, CH₃), 1.52Ϫ1.83 (m,

4 H, CH₂), 3.54 (dd, J ϭ 8.2, 6.4 Hz, 1 H, CH), 3.65 (dd, J ϭ 7.5,

6.9 Hz, 1 H, CH) ppm. ¹³C NMR (63 MHz): δ ϭ 24.6, 26.3, 26.4,

27.7, 29.2, 34.6, 71.9, 85.5, 87.6 ppm. trans-16: R_fϭ 0.75 [petro-

1

leum ether/Et₂O/CH₂Cl₂, 4:1:1 (v/v/v)]. H NMR (250 MHz): δ ϭ

0.87 [s, 9 H, C(CH₃)₃], 1.10 (s, 3 H, CH₃), 1.21 (s, 3 H, CH₃),

1.60Ϫ1.90 (m, 4 H, CH₂), 3.63 (dd, J ϭ 10.7, 6.0 Hz, 1 H, CH),

3.67 (dd, J ϭ 9.1, 5.6 Hz, 1 H, CH) ppm. ¹³C NMR (63 MHz):

δ ϭ 24.3, 26.1, 26.4, 27.6, 28.8, 33.9, 72.0, 86.4, 88.5 ppm.

trans-6-tert-Butyl-2,2-dimethyltetrahydropyran-3-ol

(trans-21):

Yield: 7 mg (4%), colorless crystals, m.p. 43 °C, b.p. 140 °C/10 mbar

(kugelrohr). R_fϭ 0.65 [petroleum ether/Et₂O/CH₂Cl₂, 4:1:1 (v/v/

1

v)]. H NMR (250 MHz): δ ϭ 0.77 [s, 9 H, C(CH₃)₃], 1.05 (s, 3 H,

Oxidation of 5-Methyl-3-phenyl-4-hexen-1-ol (14)

CH₃), 1.14 (s, 3 H, CH₃), 1.45Ϫ1.92 (m, 4 H, CH₂), 3.04 (dd, J ϭ

11.2, 2.4 Hz, 1 H, CH), 3.35 (dd, J ϭ 11.0, 4.8 Hz, 1 H, CH) ppm. trans-2-(1-Hydroxy-1-methylethyl)-3-phenyltetrahydrofuran (trans-

¹³C NMR (63 MHz): δ ϭ 24.1, 25.6, 25.9, 27.3, 28.4, 33.5, 74.3, 19): Yield: 156 mg (76%), colorless liquid, b.p. 140 °C/10 mbar (ku-

74.6, 76.6 ppm. MS (70 eV, EI): m/z (%) ϭ 186 (1) [M^ϩ], 169 (16)

gelrohr). R_fϭ 0.45 [petroleum ether/CH₂Cl₂/acetone, 2:1:1 (v/v/v)].

[M^ϩϪ OH], 129 (30) [M^ϩϪ C₄H₉], 111 (27) [M^ϩϪ C₄H₉Ϫ H₂O], ¹H NMR (250 MHz): δ ϭ 1.26 (s, 3 H, CH₃), 1.29 (s, 3 H, CH₃),

Eur. J. Org. Chem. 2003, 2388Ϫ2408

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2403

J. Hartung et al.

FULL PAPER

2.18 (br. s, 1 H, OH), 1.96Ϫ2.20 (m, 2 H, CH₂), 2.69 (dt, J_dϭ 9.5, 7.25Ϫ7.30 (m, 1 H, Ar H), 7.33Ϫ36 (m, 4 H, Ar H) ppm. ¹³C

J_tϭ 7.5 Hz, 1 H, CH), 2.97 (d, J ϭ 9.5 Hz, 1 H, CH), 3.62 (dt, NMR (63 MHz): δ ϭ 23.9, 24.0, 25.4, 25.9, 33.9, 72.1, 79.9, 84.7,

J_dϭ 11.3, J_tϭ 6.4 Hz, 1 H, CH₂), 3.76 (ddd, J ϭ 11.1, 6.4, 5.8 Hz, 125.7, 127.2, 128.2, 143.43 ppm. MS (70 eV, EI): m/z (%) ϭ 220

1 H, 5 CH₂), 7.18Ϫ7.36 (m, 5 H, Ar H) ppm. ¹³C NMR (63 MHz): (1) [M^ϩ], 162 (100) [C₁₁H₁₃O^ϩ], 156 (43) [C₉H₁₅O₂^ϩ], 129 (100)

δ ϭ 19.0, 24.8, 38.1, 42.4, 59.7, 60.8, 68.0, 126.8, 127.4, 128.8, 141.5

[C₇H₁₂O₂^ϩ], 105 (66) [C₈H₈^ϩ], 91 (84) [C₇H₆^ϩ], 77 (41) [C₆H₅^ϩ].

C₁₄H₂₀O₂(220.3): calcd. C 76.33, H 9.15; found C 76.27, H 9.18.

ppm. MS (70 eV, EI): m/z (%) ϭ 206 (1) [M^ϩ], 148 (25) [M^ϩ

Ϫ

C₃H₈O], 119 (40) [C₉H₁₁^ϩ], 117 (100) [M^ϩϪ C₇H₅], 103 (44)

[C₈H₇^ϩ], 91 (73) [C₇H₇^ϩ], 77 (39) [C₆H₅^ϩ], 59 (20) [C₃H₇O^ϩ], 51

(29) [C₄H₃^ϩ], 39 (31) [C₃H₃^ϩ]. C₁₃H₁₈O₂(206.3): calcd. C 75.69, H

8.80; found C 75.32, H 8.68.

Oxidation of trans-2-(3-Methyl-2-butenyl)cyclohexanol (trans-30)

1,6-trans-6,8-cis-8-(1-Hydroxy-1-methylethyl)-7-oxabicyclo-

[4.3.0]nonane (31): Yield: 154 mg (92%), colorless liquid, b.p. 145

°C/10 mbar (kugelrohr). R_fϭ 0.37 [petroleum ether/Et₂O, 1:1 (v/

v)]. ¹H NMR (250 MHz): δ ϭ 1.13 (s, 3 H, CH₃), 1.21 (s, 3 H,

CH₃), 1.18Ϫ1.28 (m, 1 H, CH), 1.01Ϫ1.36 (m, 4 H, CH₂), 1.49 (dt,

J_dϭ 9.6, J_tϭ 11.3 Hz, 1 H, CH₂), 1.65Ϫ1.72 (m, 1 H, CH₂),

1.77Ϫ1.82 (m, 1 H, CH₂), 1.89 (ddd, J ϭ 11.3, 8.2, 3.6 Hz, 1 H,

Oxidation of 3-Isopropyl-5-methyl-4-hexen-1-ol (15)

trans-2-(1-Hydroxy-1-methylethyl)-3-isopropyltetrahydrofuran

trans-(20): Yield: 93.6 mg (54%), colorless liquid, b.p. 120 °C/

10 mbar (kugelrohr). R_fϭ 0.70 [petroleum ether/Et₂O/CH₂Cl₂,

1

2:1:1 (v/v/v)]. H NMR (250 MHz): δ ϭ 0.90 (d, J ϭ 6.7 Hz, 3 H, CH), 1.87Ϫ1.93 (m, 1 H, CH₂), 2.02 (br. s, 1 H, OH), 2.07Ϫ2.14

CH₃), 0.93 (d, J ϭ 6.7 Hz, 3 H, CH₃), 1.20Ϫ1.32 (m, 1 H, CH), (m, 1 H, CH₂), 3.05 (dt, J_dϭ 3.4, J_tϭ 10.2 Hz, 1 H, CH), 3.77

1.30 (s, 3 H, CH₃), 1.33 (s, 3 H, CH₃), 1.55Ϫ1.69 (m, 1 H, CH₂),

(dd, J ϭ 9.6, 3.6 Hz, 1 H, CH) ppm. ¹³C NMR (63 MHz): δ ϭ

1.67 (dq, J_dϭ 7.3, J_qϭ 6.7 Hz, 1 H, CH), 1.78Ϫ1.92 (m, 1 H, 24.3, 24.5, 25.8, 26.7, 29.3, 31.2, 32.0, 45.3, 71.9, 83.7, 84.3 ppm.

CH₂), 2.62 (d, J ϭ 9.9 Hz, 1 H, CH₂), 3.67 (dt, J_dϭ 11.0, J_tϭ MS (70 eV, EI): m/z (%) ϭ 184 (3) [M^ϩ], 102 (23) [C₁₀H₅O₂^ϩ], 82

6.1 Hz, 1 H, CH₂), 3.75Ϫ3.82 (m, 1 H, CH₂) ppm. ¹³C NMR (22) [C₆H₁₀^ϩ], 67 (58) [C₅H₇^ϩ], 59 (100) [C₃H₇O^ϩ], 41 (30) [C₃H₆^ϩ].

(63 MHz): δ ϭ 20.0, 20.4, 20.5, 25.2, 30.9, 33.9, 41.8, 60.0, 61.9,

C₁₁H₂₀O₂(184.3): calcd. C 71.70, H 10.80; found C 75.32, H 8.68

68.2 ppm. MS (70 eV, EI): m/z (%) ϭ 172 (2) [M^ϩ], 129 (18) [M^ϩ(Supporting Information).

Ϫ C₃H₇], 113 (24) [C₇H₁₃O^ϩ], 83 (42) [C₅H₇O^ϩ], 71 (97) [C₄H₇O^ϩ],

Oxidation of cis-2-(3-Methyl-2-butenyl)cyclohexanol (cis-30)

59 (100) [C₃H₇O^ϩ]. C₁₀H₂₀O₂(172.3): calcd. C 69.72, H 11.70;

found C 69.33, H 11.45.

1,6-cis-8-(1-Hydroxy-1-methylethyl)-7-oxabicyclo[4.3.0]nonane (32):

Yield: 143 mg (78%), colorless liquid, b.p. 145 °C/10 mbar

(kugelrohr), cis/trans ϭ 77:23. MS (70 eV, EI): m/z (%) ϭ 184 (1)

[M^ϩ], 125 (44) [C₈H₁₃O^ϩ], 102 (39) [C₁₀H₅O₂^ϩ], 81 (93) [C₆H₉^ϩ],

59 (100) [C₃H₇O^ϩ]. C₁₁H₂₀O₂(184.3): calcd. C 71.70, H 10.80;

found C 75.32, H 8.68 (Supporting Information). 1,6-cis-6,8-cis-32:

trans-4-Isopropyl-2,2-dimethyltetrahydropyran-3-ol

(trans-25):

Yield: 27.3 mg (16%), colorless liquid, b.p. 120 °C/10 mbar (kugel-

1

rohr). R_fϭ 0.65 [petroleum ether/Et₂O/CH₂Cl₂, 2:1:1 (v/v/v)]. H

NMR (250 MHz): δ ϭ 1.20 (s, 3 H, CH₃), 1.24 (s, 3 H, CH₃),

1.67Ϫ1.74 (m, 1 H, CH₂), 1.82Ϫ1.95 (m, 1 H, CH), 1.97Ϫ2.06 (m,

1 H, CH), 2.07Ϫ2.15 (m, 1 H, CH₂), 3.65 (d, J ϭ 11.2 Hz, 1 H,

CH), 3.76Ϫ3.84 (m, 1 H, CH₂), 3.88Ϫ3.96 (m, 1 H, CH₂) ppm.

1

R_fϭ 0.38 [petroleum ether/Et₂O, 1:1 (v/v)]. H NMR (250 MHz):

δ ϭ 1.14 (s, 3 H, CH₃), 1.24 (s, 3 H CH₃), 1.21Ϫ1.92 (m, 8 H, CH,

CH₂), 1.56Ϫ1.84 (m, 2 H, CH₂), 2.12Ϫ2.23 (m, 1 H, CH₂), 3.69

(dd, J ϭ 9.0, 7.3 Hz, 1 H, CH₂), 3.85 (dt, J_dϭ 5.8, J_tϭ 5.6 Hz, 1

H, CH₂) ppm. ¹³C NMR (63 MHz): δ ϭ 21.9, 23.0, 24.4, 27.8, 27.9,

29.3, 31.7, 37.4, 70.5, 77.4, 85.6 ppm. 1,6-cis-6,8-trans-32: R_fϭ 0.38

[petroleum ether/Et₂O, 1:1 (v/v)]. ¹H NMR (250 MHz): δ ϭ 1.10

(s, 3 H, CH₃), 1.20 (s, 3 H, CH₃), 1.12Ϫ1.64 (m, CH, CH₂),

1.81Ϫ1.94 (m, 2 H, CH₂), 1.98Ϫ2.11 (m, 1 H, CH), 3.93 (dd, J ϭ

9.1, 7.0 Hz, 1 H, CH₂), 3.95 (dd, J ϭ 6.9, 4.3 Hz, 1 H, CH₂) ppm.

¹³C NMR (63 MHz): δ ϭ 20.5, 23.7, 24.0, 27.0, 27.5, 28.3, 33.5,

38.5, 72.5, 78.0, 84.0 ppm.

Oxidation of 4-Methyl-1-phenyl-3-penten-1-ol (26)

cis- and trans-3-Hydroxy-2,2-dimethyl-5-phenyltetrahydrofuran (28):

Yield: 120 mg (62%), colorless liquid, b.p. 137 °C/10 mbar

(kugelrohr), cis/trans ϭ 2:98. MS (70 eV, EI): m/z (%) ϭ 192 (1)

[M^ϩ], 134 (73) [C₉H₁₀O^ϩ], 116 (14) [C₆H₁₁O₂^ϩ], 105 (27) [C₈H₈^ϩ],

91 (30) [C₇H₆^ϩ], 77 (22) [C₆H₅^ϩ], 59 (100) [C₃H₆O^ϩ]. C₁₂H₁₆O₂

(192.3): calcd. C 74.97, H 8.39; found C 75.03, H 8.44. cis-28: R_fϭ

0.57 [petroleum ether/acetone, 2:1 (v/v)]. ¹H NMR (250 MHz): δ ϭ

1.25 (s, 3 H, CH₃), 1.27 (s, 3 H, CH₃), 1.94 (m_c, 1 H, CH₂), 2.17

(br. s, 1 H, OH), 2.77 (m_c, 1 H, CH₂), 4.10 (dd, J ϭ 7.1, 2.6 Hz, 1

1,6-cis-1,4-trans-3,3-Dimethyl-2-oxabicyclo[4.4.0]decan-4-ol

(33):

H, CH), 5.00 (t, J ϭ 7.4 Hz, 1 H, CH), 7.26Ϫ7.38 (m, 5 H, Ar H) Yield: 8.9 mg (5%), colorless liquid, b.p. 145 °C/10 mbar (kugel-

ppm. ¹³C NMR (63 MHz): δ ϭ 22.51, 25.8, 41.5, 76.5, 78.5, 83.5,

125.8, 127.5, 128.7, 143.1 ppm. trans-28: R_fϭ 0.57 [petroleum

ether/acetone, 2:1 (v/v)]. ¹H NMR (250 MHz): δ ϭ 1.35 (s, 3 H,

rohr). R_fϭ 0.38 [petroleum ether/Et₂O, 1:1 (v/v)]. ¹H NMR

(250 MHz): δ ϭ 1.16 (s, 3 H, CH₃), 1.28 (s, 3 H, CH₃), 1.16Ϫ1.95

(m, 11 H, CH, CH₂), 3.40 (dd, J ϭ 3.1, 2.9 Hz, 1 H, CH),

CH₃), 1.37 (s, 3 H, CH₃), 2.18 (br. s, 1 H, OH), 2.21 (dd, J ϭ 5.2, 3.75Ϫ3.78 (m, 1 H, CH) ppm (Supporting Information).

1.8 Hz, 1 H, CH₂), 2.27 (dd, J ϭ 3.0, 3.7 Hz, 1 H, CH₂), 4.13 (dd,

Oxidation of (R)-Linalool [(R)-34]

J ϭ 2.7, 2.8 Hz, 1 H, CH), 5.20 (dd, J ϭ 6.4, 2.8 Hz, 1 H, CH),

7.27Ϫ7.36 (m, 5 H, Ar H) ppm. ¹³C NMR (63 MHz): δ ϭ 25.9,

2-(1-Hydroxy-1-methylethyl)-5-methyl-5-vinyltetrahydrofuran

28.5, 43.4, 76.6, 78.6, 84.0, 125.7, 127.5, 128.7, 143.4 ppm.

(35):^[39]Yield: 111 mg (65%), colorless liquid, b.p. 80 °C/10 mbar

(kugelrohr). cis-35: [α]²_D⁵ϭ ϩ29.1 (c ϭ 1.1, CHCl₃), ref.^[39][α]²_D⁵

ϭ

Oxidation of 6-Methyl-1-phenyl-5-hepten-1-ol (27)

ϩ11.7 (c ϭ 0.1, MeOH). R_fϭ 0.48 [petroleum ether/Et₂O/acetone,

1

cis-2-(1-Hydroxy-1-methylethyl)-6-phenyltetrahydropyran (cis-29):

Yield: 105 mg (52%), colorless liquid, b.p. 149 °C/10^Ϫ2mbar (kug-

elrohr). R_fϭ 0.66 [petroleum ether/acetone, 3:1 (v/v)]. ¹H NMR

5:2:1 (v/v/v)]. H NMR (250 MHz): δ ϭ 1.11 (s, 3 H, CH₃), 1.20

(s, 3 H, CH₃), 1.29 (s, 3 H, CH₃), 1.75Ϫ1.89 (m, 4 H, CH₂), 2.05

(br. s, 1 H, OH), 3.84 (dd, J ϭ 7.6, 6.6 Hz, 1 H, CH), 4.97 (dd,

(250 MHz): δ ϭ 1.21 (s, 3 H, CH₃), 1.23 (s, 3 H, CH₃), 1.44Ϫ1.54 J ϭ 10.6, 1.8 Hz, 1 H, CH₂), 5.17 (dd, J ϭ 17.4, 1.8 Hz, 1 H, CH₂),

(m, 1 H, CH₂), 1.765Ϫ1.72 (m, 2 H, CH₂), 1.81Ϫ1.83 (m, 1 H, 5.96 (dd, J ϭ 17.4, 10.6 Hz, 1 H, CH) ppm. trans-35: [α]²_D⁵ϭ Ϫ13.1

CH₂), 1.98 (m_c, 2 H, CH₂), 2.32 (br. s, 1 H, OH), 3.35 (dd, J ϭ (c ϭ 1.0, CHCl₃), ref.^[39][α]²_D⁵ϭ Ϫ10.1 (c ϭ 0.1, MeOH). R_fϭ

9.5, 1.8 Hz, 1 H, CH), 4.42 (dd, J ϭ 8.9, 2.1 Hz, 1 H, CH),

0.45 [petroleum ether/Et₂O/acetone, 5:2:1 (v/v/v)]. ¹H NMR

2404

 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjoc.org

Eur. J. Org. Chem. 2003, 2388Ϫ2408

Stereoselective Synthesis of Functionalized Tetrahydrofurans

FULL PAPER

(250 MHz): δ ϭ 1.10 (s, 3 H, CH₃), 1.21 (s, 3 H, CH₃), 1.29 (s, 3 given), cis:trans ϭ 39:61. MS (70 eV, EI): m/z (%) ϭ 178 (10) [M^ϩ],

H CH₃), 1.66Ϫ1.74 (m, 1 H, CH₂), 1.75Ϫ1.93 (m, 3 H, CH₂), 2.05 160 (19) [C₁₁H₁₂O^ϩ], 147 (100) [C₁₀H₁₁O^ϩ], 129 (49) [C₁₀H₉^ϩ], 91

(br. s, 1 H, OH), 3.78 (t, J ϭ 7.1 Hz, 1 H, CH), 4.98 (dd, J ϭ 10.6, (75) [C₇H₇^ϩ], 77 (18) [C₆H₅^ϩ], 41 (17) [C₃H₅^ϩ]. C₁₁H₁₄O₂(178.2)

1.8 Hz, 1 H, CH₂), 5.18 (dd, J ϭ 17.4, 1.8 Hz, 1 H, CH₂), 5.85 (dd,

J ϭ 17.4, 10.6 Hz, 1 H, CH) ppm.

calcd. C 74.13, H 7.92; found C 73.54, H 7.90. cis-48: R_fϭ 0.19

[petroleum ether/acetone, 2:1 (v/v)]. ¹H NMR (250 MHz): δ ϭ

1.74Ϫ1.87 (m, 2 H, CH₂), 1.91Ϫ2.09 (m, 1 H, CH₂), 2.04 (s, 1 H,

OH), 2.20Ϫ2.37 (m, 1 H, CH₂), 3.67 (ddd, J ϭ 17.1, 11.5, 6.1 Hz,

2 H, CH₂), 4.13 (m, 1 H, CH), 4.84 (dd, J ϭ 7.8, 6.6 Hz, 1 H, CH),

7.17Ϫ7.29 (m, 5 H, Ar H) ppm. trans-48: R_fϭ 0.21 [petroleum

2-(1-Hydroxy-1-methylethyl)-5-methyl-5-(oxiran-2-yl)tetrahydro-

furan (36):^[39]Yield: 13.0 mg (7%), colorless liquid, b.p. 80 °C/

10 mbar (kugelrohr, ref.^[39]no data available), cis/trans ϭ 54:46.

1

2,2,6-Trimethyl-6-vinyltetrahydropyran-3-ol (37):^[39]Yield: 7.4 mg

(4%), colorless liquid, b.p. 80 °C/10 mbar (kugelrohr, ref.^[39]no data

given), cis/trans ϭ 38:62.

ether/acetone, 2:1 (v/v)]. H NMR (250 MHz): δ ϭ 1.74Ϫ1.87 (m,

2 H, CH₂), 1.91Ϫ2.09 (m, 1 H, CH₂), 2.04 (s, 1 H, OH), 2.20Ϫ2.37

(m, 1 H, CH₂), 3.67 (ddd, J ϭ 15.0, 11.6, 3.4 Hz, 2 H, CH₂), 4.29

(m_c, 1 H, CH), 4.92 (dd, J ϭ 7.8, 6.3 Hz, 1 H, CH), 7.17Ϫ7.29 (m,

5 H, Ar H) ppm.

Oxidation of (S,S)-Bisabolol [(S,S)-38]

2-(1-Hydroxy-1-methylethyl)-5-methyl-5-(1-methylcyclohex-1-en-4-

yl)tetrahydrofuran (39):^[40]Yield: 155 mg (0.65 mmol, 65%), color-

less liquid, b.p. 125 °C/10^Ϫ2mbar (kugelrohr, ref.^[40]no data

available), cis/trans ϭ 82:18. cis-(2R,5S,1ЈS)-39: [α]²_D⁵ϭ Ϫ32.8 (c ϭ

1.0, CHCl₃), ref.^[40][α]²_D⁵ϭ Ϫ64.1 (c ϭ 0.5, MeOH). R_fϭ 0.65

[petroleum ether/Et₂O/acetone, 5:1:1 (v/v/v)]. ¹H NMR (250 MHz):

δ ϭ 1.10 (s, 3 H, CH₃), 1.11 (s, 3 H, CH₃), 1.19 (s, 3 H, CH₃), 1.62

(s, 3 H, CH₃), 1.51Ϫ2.01 (m, 11 H, CH, CH₂), 2.05 (br. s, 1 H,

OH), 3.76 (dd, J ϭ 7.3, 7.0 Hz, 1 H, CH), 5.34Ϫ5.37 (m, 1 H,

CH) ppm. trans-(2S,5S,1ЈS)-39: R_fϭ 0.62 [petroleum ether/Et₂O/

acetone, 5:1/1 (v/v/v)]. ¹H NMR (250 MHz): δ ϭ 1.06 (s, 3 H,

CH₃), 1.09 (s, 3 H, CH₃), 1.18 (s, 3 H, CH₃), 1.62 (s, 3 H, CH₃),

1.51Ϫ2.01 (m, 11 H, CH, CH₂), 2.05 (br. s, 1 H, OH), 3.75 (dd,

J ϭ 10.8, 6.6 Hz, 1 H, CH), 5.34Ϫ5.37 (m, 1 H, CH) ppm.

Oxidation of 2,2-Dimethyl-6-hepten-3-ol (44)

5-tert-Butyl-2-(hydroxymethyl)tetrahydrofuran (49):^[74a,74b]Yield:

94 mg (59%), colorless liquid, b.p. 100 °C/10^Ϫ2mbar (kugelrohr),

cis/trans ϭ 39:61. cis-49: R_fϭ 0.66 [petroleum ether/Et₂O/CH₂Cl₂,

4:1:1 (v/v/v)]. ¹H NMR (250 MHz): δ ϭ 0.89 [s, 9 H, C(CH₃)₃],

1.62Ϫ1.89 (m, 4 H, CH₂), 3.46 (dd, J ϭ 11.2, 6.1 Hz, 1 H, CH₂),

3.65 (dd, J ϭ 11.2, 8.4 Hz, 1 H, CH₂), 3.61 (m_c, 1 H, CH), 4.00

(m_c, 1 H, CH) ppm. trans-49: R_fϭ 0.64 [petroleum ether/Et₂O/

CH₂Cl₂, 4:1:1 (v/v/v)]. ¹H NMR (250 MHz): δ ϭ 0.88 [s, 9 H,

C(CH₃)₃], 1.55Ϫ1.96 (m, 4 H, CH₂), 3.48 (dd, J ϭ 11.4, 6.3 Hz, 1

H, CH₂), 3.65 (dd, J ϭ 11.4, 9.6 Hz, 1 H, CH₂), 3.66 (m_c, 1 H,

CH), 4.01 (m_c, 1 H, CH) ppm.

Oxidation of 2-Phenyl-4-penten-1-ol (45)

2-(1-Hydroxy-1-methylethyl)-5-methyl-5-(6-methyl-7-oxabicyclo-

[4.1.0]hept-3-yl)tetrahydrofuran (40):^[40]Yield: 37.8 mg (15%), col-

orless liquid, b.p. 125 °C/10^Ϫ2mbar (kugelrohr, ref.^[40]no data

available), cis/trans ϭ 87:13. cis-40: R_fϭ 0.55 [petroleum ether/

Et₂O/acetone, 5:1:1 (v/v/v)]. ¹H NMR (250 MHz): δ ϭ 1.11 (s, 3

H, CH₃), 1.19 (s, 6 H, CH₃), 1.29 (s, 3 H, CH₃), 1.51Ϫ2.01 (m, 11

H, CH, CH₂), 2.05 (br. s, 1 H, OH), 2.97 (dd, J ϭ 6.1, 5.4 Hz, 1

H, CH), 3.65 (dd, J ϭ 9.0, 6.1 Hz, 1 H, CH) ppm. trans-40: R_fϭ

0.55 [petroleum ether/Et₂O/acetone, 5:1:1 (v/v/v)]. ¹H NMR

(250 MHz): δ ϭ 1.05 (s, 3 H, CH₃), 1.08 (s, 3 H, CH₃), 1.18 (s, 3

H, CH₃), 1.29 (s, 3 H, CH₃), 1.51Ϫ2.01 (m, 11 H, CH, CH₂), 2.05

(br. s, 1 H, OH), 2.96Ϫ2.99 (m, 1 H, CH), 3.64 (dd, J ϭ 11.5,

4.6 Hz, 1 H, CH) ppm.

2-(Hydroxymethyl)-4-phenyltetrahydrofuran (50): Yield: 77.1 mg

(43%), colorless liquid, b.p. 145 °C/10^Ϫ2mbar (kugelrohr), cis/

trans ϭ 36:64. MS (70 eV, EI): m/z (%) ϭ 178 (3) [M^ϩ], 147 (82)

[C₁₀H₁₁O^ϩ], 129 (41) [C₁₀H₉^ϩ], 119 (50) [C₉H₁₁^ϩ], 91 (100)

[C₇H₇^ϩ], 77 (14) [C₆H₅^ϩ], 41 (34) [C₃H₅^ϩ]. C₁₁H₁₄O₂(178.2) calcd.

C 74.13, H 7.92; found C 72.61, H 8.00 (Supporting Information).

cis-50: R_fϭ 0.60 [petroleum ether/acetone, 2:1 (v/v)]. ¹H NMR

(250 MHz): δ ϭ 1.86 (dt, J_dϭ 12.3, J_tϭ 10.5 Hz, 1 H, CH₂), 2.28

(ddd, J ϭ 12.3, 7.4, 6.3 Hz, 1 H, CH₂), 2.34 (br. s, 1 H, OH), 3.47

(m_c, 1 H, CH₂), 3.61 (dd, J ϭ 11.6, 5.8 Hz, 1 H, CH₂), 3.75 (m_c, 1

H, CH₂), 3.76 (dd, J ϭ 11.0, 8.6 Hz, 1 H, CH), 4.22 (dd, J ϭ 8.6,

7.0 Hz, 1 H, CH₂), 4.33 (m_c, 1 H, CH), 7.16Ϫ7.32 (m, 5 H, Ar H)

ppm. ¹³C NMR (63 MHz): δ ϭ 35.7, 45.0, 64.7, 74.3, 80.5, 126.6,

127.2, 128.6, 141.2 ppm. trans-50: R_fϭ 0.60 [petroleum ether/ace-

tone, 2:1 (v/v)]. ¹H NMR (250 MHz): δ ϭ 2.08 (dt, J_dϭ 12.9, J_tϭ

7.9 Hz, 1 H, CH₂), 2.18 (ddd, J ϭ 12.9, 8.8, 5.8 Hz, 1 H, CH₂),

2.34 (br. s, 1 H, OH), 3.42 (quint, J ϭ 7.9 Hz, 1 H, CH), 3.55 (dd,

J ϭ 11.6, 5.8 Hz, 1 H, CH₂), 3.71 (dd, J ϭ 11.6, 8.5 Hz, 1 H, CH₂),

3.73 (t, J ϭ 8.6 Hz, 1 H, CH₂), 4.24 (dd, J ϭ 8.6, 7.0 Hz, 1 H,

CH₂), 4.30 (m_c, 1 H, CH), 7.16Ϫ7.32 (m, 5 H, Ar H) ppm. ¹³C

NMR (63 MHz): δ ϭ 35.6, 45.4, 65.1, 74.8, 79.9, 126.7, 127.2,

128.6, 141.9 ppm.

Oxidation of 3-(Hydroxymethyl)-2-methyl-5-hexene (41)

2-(Hydroxymethyl)-4-isopropyltetrahydrofuran

(42):^[41]

Yield:

77.1 mg (74%), colorless liquid, b.p. 95 °C/10 mbar (kugelrohr), cis/

trans ϭ 29:71. cis-42: R_fϭ 0.48 [petroleum ether/acetone, 4:1 (v/

v)]. ¹H NMR (600 MHz): δ ϭ 0.87 (d, J ϭ 6.6 Hz, 3 H, CH₃), 0.93

(d, J ϭ 6.6 Hz, 3 H, CH₃), 1.34 (m_c, 1 H, CH₂), 1.47 (sept, J ϭ

6.6 Hz, 1 H, CH), 1.98 (m_c, 1 H, CH), 2.00 (m_c, 1 H, CH₂), 3.45

(t, J ϭ 7.9 Hz, 1 H, CH₂), 3.51 (dd, J ϭ 11.6, 5.9 Hz, 1 H, CH₂),

3.69 (dd, J ϭ 11.6, 3.1 Hz, 1 H, CH₂), 3.96 (t, J ϭ 7.9 Hz, 1 H,

CH₂), 4.05 (m_c, 1 H, CH) ppm. trans-42: R_fϭ 0.47 [petroleum

ether/acetone, 4:1 (v/v)]. ¹H NMR (250 MHz): δ ϭ 0.87 (d, J ϭ

6.6 Hz, 3 H, CH₃), 0.93 (d, J ϭ 6.6 Hz, 3 H, CH₃), 1.47 (sept, J ϭ

6.6 Hz, 1 H, CH), 1.64 (dt, J_dϭ 12.5, J_tϭ 8.5 Hz, 1 H, CH₂), 1.82

(ddd, J ϭ 12.7, 8.5, 4.8 Hz, 1 H, CH₂), 1.93 (m_c, 1 H, CH), 3.40

(t, J ϭ 8.8 Hz, 1 H, CH₂), 3.47 (dd, J ϭ 11.5, 6.2 Hz, 1 H, CH₂),

3.62 (dd, J ϭ 11.5, 3.5 Hz, 1 H, CH₂), 4.02 (dd, J ϭ 8.2, 7.5 Hz, 1

H, CH₂), 4.08 (m_c, 1 H, CH) ppm.

Oxidation of 3-Phenyl-4-penten-1-ol (46)

2-(Hydroxymethyl)-3-phenyltetrahydrofuran (51): Yield: 77.1 mg

(43%), colorless liquid, b.p. 125 °C/10^Ϫ2mbar (kugelrohr), cis/

trans ϭ 40:60. MS (70 eV, EI): m/z (%) ϭ 178 (4) [M^ϩ], 160 (13)

[C₁₁H₁₂O^ϩ], 147 (100) [C₁₀H₁₁O^ϩ], 118 (16) [C₉H₁₀^ϩ], 117 (56)

[C₉H₉^ϩ], 91 (81) [C₇H₇^ϩ], 77 (10) [C₆H₅^ϩ], 41 (10) [C₃H₅^ϩ].

C₁₁H₁₄O₂(178.2) calcd. C 74.13, H 7.92; found C 73.12, H 8.28.

cis-51: R_fϭ 0.39 [petroleum ether/acetone, 3:1 (v/v)]. ¹H NMR

(250 MHz): δ ϭ 2.17Ϫ2.40 (m, 2 H, CH₂), 3.19 (dd, J ϭ 6.4,

Oxidation of 1-Phenyl-4-penten-1-ol (43)

2-(Hydroxymethyl)-5-phenyltetrahydrofuran (48):^[74a]Yield: 84 mg 5.2 Hz, 2 H, CH₂), 3.54 (t, J ϭ 7.6 Hz, 1 H, CH), 3.94 (td, J_tϭ

(47%), colorless liquid, b.p. 135 °C/10^Ϫ2mbar (ref.^[74a]no data

8.5, J_dϭ 7.6 Hz, 1 H, CH₂), 4.16 (m_c, 1 H, CH), 4.21 (m_c, 1 H,

Eur. J. Org. Chem. 2003, 2388Ϫ2408

www.eurjoc.org

 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

2405

J. Hartung et al.

CH₂), 7.23Ϫ7.36 (m, 5 H, Ar H) ppm. ¹³C NMR (63 MHz): δ ϭ 1-phenyl-4-hexen-1-ol (5) (100 mg, 0.526 mmol) in acetone

FULL PAPER

32.1, 46.4, 63.2, 67.6, 82.0, 126.8, 127.6, 128.7, 140.8 ppm. trans-

(10 mL). The reaction mixture was allowed to warm to 25 °C

within 30 min. After complete consumption of alkenol 5 and di-

51: R_fϭ 0.41 [petroleum ether/acetone, 2:1 (v/v)]. ¹H NMR

(250 MHz): δ ϭ 2.12Ϫ2.39 (m, 2 H, CH₂), 3.19 (q, J ϭ 8.6 Hz, 1 methyldioxirane (KI/starch test), the solvent was removed under

H, CH), 3.52 (t, J ϭ 7.6 Hz, 1 H, CH₂), 3.75 (dd, J ϭ 11.8, 2.9 Hz,

1 H, CH), 3.93 (m_c, 1 H, CH), 4.00 (td, J_tϭ 8.2, J_dϭ 7.0 Hz, 1

reduced pressure (650 mbar/40 °C) to provide epoxy alcohol 10

(108 mg, 99%) as an analytically pure colorless liquid (50:50 mix-

H, CH₂), 4.11 (td, J_tϭ 8.2, J_dϭ 4.6 Hz, 1 H, CH₂), 7.23Ϫ7.36 ture of diastereomers): b.p. 140 °C/10 mbar (kugelrohr). MS (70 eV,

(m, 5 H, Ar H) ppm. ¹³C NMR (63 MHz): δ ϭ 35.3, 46.0, 62.7, EI): m/z (%) ϭ 206 (1) [M^ϩ], 148 (14) [C₁₀H₁₂O^ϩ], 104 (100)

68.2, 86.3, 126.7, 127.5, 128.4, 141.1 ppm.

Oxidation of 3-tert-Butyl-4-penten-1-ol (47)

trans-3-tert-Butyl-2-(hydroxymethyl)tetrahydrofuran

[C₈H₈^ϩ], 77 (47) [C₆H₅^ϩ], 59 (36) [C₃H₇O^ϩ]. C₁₃H₁₈O₂(206.3):

calcd. C 75.69, H 8.80; found C 75.79, H 8.89. like-10: R_fϭ 0.40

[petroleum ether/acetone, 4:1 (v/v)]. ¹H NMR (400 MHz): δ ϭ 1.26

(s, 3 H, CH₃), 1.31 (s, 3 H, CH₃), 1.51Ϫ1.69 (m, 2 H, CH₂),

1.71Ϫ1.89 (m, 1 H, CH₂), 1.88Ϫ1.96 (m, 1 H, CH₂), 2.70 (dd, J ϭ

7.6, 4.8 Hz, 1 H, CH), 4.80 (dd, J ϭ 7.4, 5.7 Hz,, 1 H, CH),

7.23Ϫ7.36 (m, 5 H, Ar H) ppm. ¹³C NMR (63 MHz): δ ϭ 18.6,

25.2, 35.9, 58.8, 64.2, 74.1, 125.9, 127.6, 128.6, 144.5 ppm. unlike-

10: R_fϭ 0.40 [petroleum ether/acetone, 4:1 (v/v)]. ¹H NMR

(400 MHz): δ ϭ 1.24 (s, 3 H, CH₃), 1.30 (s, 3 H, CH₃), 1.58Ϫ1.64

(m, 2 H, CH₂), 1.82Ϫ1.92 (m, 1 H, CH₂), 1.95Ϫ2.04 (m, 1 H, CH₂),

2.75 (t, J ϭ 6.3 Hz, 1 H, CH), 4.73 (dd, J ϭ 5.7, 7.7 Hz, 1 H, CH),

7.19Ϫ7.35 (m, 5 H, Ar H) ppm. ¹³C NMR (63 MHz): δ ϭ 18.7,

24.8, 25.4, 35.9, 58.6, 64.3, 73.7, 125.7, 127.5, 128.4, 144.5 ppm.

(trans-52):

Yield: 97.1 mg (61%), colorless liquid, b.p. 110 °C/10^Ϫ2mbar (kug-

elrohr). R_fϭ 0.60 [petroleum ether/acetone, 4:1 (v/v)]. ¹H NMR

(250 MHz): δ ϭ 0.96 [s, 9 H, C(CH₃)₃], 0.87Ϫ0.96 (m, 1 H, CH),

1.56Ϫ1.70 (m_c, 1 H, CH₂), 1.85Ϫ1.97 (m_c, 1 H, CH₂), 2.62 (dd,

J ϭ 4.7, 2.9 Hz, 1 H, CH₂), 2.82 (ddd, J ϭ 9.3, 3.8, 2.9 Hz, 1 H,

CH), 2.91 (dd, J ϭ 4.7, 3.8 Hz, 1 H, CH₂), 3.68 (m, 1 H, CH₂),

3.78 (m, 1 H, CH₂) ppm. ¹³C NMR (63 MHz): δ ϭ 27.9, 32.1, 33.3,

49.3, 54.6, 62.0, 80.8 ppm. MS (70 eV, EI): m/z (%) ϭ 158 (1) [M^ϩ],

141 (8) [C₉H₁₇O^ϩ], 127 (14) [C₈H₁₅O^ϩ] 69 (18) [C₄H₆O^ϩ], 57 (100)

[C₄H₉^ϩ], 41 (34) [C₃H₆^ϩ]. C₉H₁₈O₂(158.2): calcd. C 68.31, H

11.47; found C 68.77, H 11.18.

(1R,4R)-4,5-Epoxy-5-methyl-1-phenyl-1-hexanol [(1R,4R)-10] and

(1S,4R)-4,5-Epoxy-5-methyl-1-phenyl-1-hexanol [(1S,4R)-10]: A ra-

cemic mixture of 5-methyl-1-phenyl-4-hexen-1-ol (5) was separated

into (S)-5 and (R)-5 (both Ͼ 99% ee) by HPLC [Chiralcel OD (21

ϫ 250 mm); iPrOH/nC₆H₁₄, 1:99 (v/v)]. (R)-5: [α]²_D⁵ϭ ϩ13.4 (c ϭ

Oxidation of 4-Phenyl-4-penten-1-ol (53)

2-(Hydroxymethyl)-2-phenyltetrahydrofuran (55): Yield: 146 mg

(82%), colorless liquid, b.p. 155 °C/10^Ϫ2mbar (kugelrohr), (S)/

(R) ϭ 50:50. R_fϭ 0.40 [petroleum ether/acetone, 2:1 (v/v)]. ¹H

NMR (250 MHz): δ ϭ 1.78Ϫ1.91 (m_c, 1 H, CH₂), 1.92Ϫ2.04 (m_c,

1 H, CH₂), 2.12 (ddd, J ϭ 15.7, 12.1, 7.1 Hz, 1 H, CH₂), 2.37 (dt,

J_dϭ 12.1, J_tϭ 8.2 Hz, 1 H, CH₂), 2.75 (br. s, 1 H, OH), 3.66 (dd,

J ϭ 12.8, 11.8 Hz, 2 H, CH₂), 3.99 (ddt, J_dϭ 15.7, 8.2, J_tϭ 7.1 Hz,

2 H, CH₂), 7.22Ϫ7.41 (m, 5 H, Ar H) ppm. ¹³C NMR (63 MHz):

δ ϭ 26.1, 33.9, 68.4, 68.9, 87.4, 125.3, 127.0, 128.2, 144.2 ppm. MS

(70 eV, EI): m/z (%) ϭ 178 (0.1) [M^ϩ], 147 (100) [C₁₀H₁₁O^ϩ], 105

(95) [C₇H₅O^ϩ], 77 (36) [C₆H₅^ϩ] 51 (10) [C₄H₃^ϩ]. C₁₁H₁₄O₂(178.2):

calcd. C 74.13, H 7.92; found C 74.46, H 8.74 (Supporting Infor-

mation).

1.24, CHCl₃). (S)-5: [α]²_D⁵ϭ Ϫ11.2 (c ϭ 1.24, CHCl₃) {ref.^[50a]

:

[α]²_D⁵ϭ Ϫ10.7 (c ϭ 1.60, CHCl₃)}. A solution of (R)- or (S)-5-

methyl-1-phenyl-4-hexen-1-ol (5, 19.0 mg, 0.526 mmol) in dimeth-

oxymethane/CH₃CN/aq. Na₂B₄O₇buffer (0.05 )/4 ϫ 10^Ϫ4 aq.

Na₂EDTA buffer, 2:1:1:1 (v/v/v/v, total volume of 2.5 mL), 1,2-4,5-

di-O-isopropylidene-β--erythro-2,3-hexodiulo-2,6-pyranose^[49]

(7.74 mg, 0.03 mmol), and nBu₄HSO₄(1.5 mg, 0.004 mmol) was

treated at Ϫ10 °C over a period of 2 h with a solution of Oxone^

(85 mg, 0.138 mmol) and K₂CO₃(80 mg, 5.8 mmol) in aq.

Na₂EDTA buffer (4 ϫ 10^Ϫ4, 0.65 mL) and H₂O (0.65 mL) using

a syringe pump. After addition was complete, the reaction mixture

was diluted with petroleum ether (10 mL) and H₂O (10 mL). Epoxy

alcohols 10 were extracted from this mixture with petroleum ether

(2 ϫ 10 mL). The combined organic phases were washed with brine

(10 mL), dried (MgSO₄), and concentrated under reduced pressure

to afford products 10 as colorless liquids. (1R,4R)-10: Yield:

19.4 mg (0.094 mmol, 94%), like/unlike ϭ 88:12 (according to ¹H

NMR spectroscopy). (1S,4R)-10: Yield: 19.8 mg (0.096 mmol,

Oxidation of 1-Phenyl-4-methyl-4-penten-1-ol (54)

2-(Hydroxymethyl)-2-methyl-5-phenyltetrahydrofuran (56): Yield:

114 mg (0.82 mmol, 82%), colorless liquid, b.p. 145 °C/10^Ϫ2mbar

(kugelrohr), cis/trans ϭ 25:75. MS (70 eV, EI): m/z (%) ϭ 161 (32)

[C₁₁H₁₃O^ϩ], 117 (5) [C₉H₁₀^ϩ], 77 (7) [C₆H₅^ϩ] 43 (100) [C₂H₃O^ϩ].

C₁₂H₁₆O₂(192.3): calcd. C 74.97, H 8.39; found C 74.68, H 8.49.

cis-56: R_fϭ 0.50 [petroleum ether/Et₂O/CH₂Cl₂ϭ 1:1:1 (v/v/v)].

¹H NMR (250 MHz): δ ϭ 1.32 (s, 3 H, CH₃), 1.75Ϫ2.00 (m, 2 H,

CH, CH₂), 2.07Ϫ2.16 (m, 1 H, CH₂), 2.18 (br. s, 1 H, OH),

2.27Ϫ2.39 (m, 1 H, CH), 3.55 (dd, J ϭ 18.4, 11.2 Hz, 2 H, CH₂),

5.00 (dd, J ϭ 9.0, 6.0 Hz, 1 H, CH), 7.25Ϫ7.33 (m, 5 H, Ar H)

ppm. ¹³C NMR (63 MHz): δ ϭ 24.0, 35.0, 35.7, 69.7, 80.9, 84.1,

126.4, 128.0, 128.9, 142.7 ppm. trans-56: R_fϭ 0.45 [petroleum

ether/Et₂O/CH₂Cl₂ϭ 1:1:1 (v/v/v)]. ¹H NMR (250 MHz): δ ϭ 1.34

(s, 3 H, CH₃), 1.74Ϫ1.85 (m, 1 H, CH₂), 1.87Ϫ2.00 (m, 1 H, CH₂),

2.04Ϫ2.17 (m, 1 H, CH₂), 2.25Ϫ2.36 (m, 1 H, CH), 2.48 (br. s, 1

H, OH), 3.54 (s, 2 H, CH₂), 4.93 (dd, J ϭ 9.3, 5.5 Hz, 1 H, CH₂),

7.19Ϫ7.35 (m, 5 H, Ar H) ppm. ¹³C NMR (63 MHz): δ ϭ 24.7,

34.4, 36.0, 69.1, 82.5, 84.3, 126.4, 128.0, 128.9, 142.7 ppm.

1

96%), colorless liquid, like/unlike ϭ 82:18 (according to H NMR

spectroscopy). Both samples were immediately used in the suc-

ceeding two experiments.

Formation of Tetrahydrofuran Derivative (2S,5R)-6 and Tetrahydro-

pyran Derivative (3R,6R)-7: A solution of (1R,4R)-10 (19.4 mg,

0.094 mmol) in CDCl₃(0.7 mL) was treated with p-toluenesulfonic

acid (34.4 mg, 0.20 mmol) or with VOL⁷(OEt) (4g, 3.7 mg,

0.01 mmol) and stirred at 25 °C for 2 h. After removal of the sol-

vent under reduced pressure (250 mbar/40 °C), the products were

filtered through a short pad of Al₂O₃using Et₂O as eluent. The

combined organic phases were concentrated under reduced press-

ure to provide an oil, which was purified by column chromatogra-

phy [SiO₂; petroleum ether/acetone, 4:1 (v/v)]. Yield: 19.0 mg

(98%), colorless liquid, (2S,5R)-6/(3R,6R)-7 ϭ 91:9 (¹H NMR spec-

troscopy). (2S,5R)-6: [α]²_D⁵ϭ Ϫ21.0 (c ϭ 0.50, CHCl₃). R_fϭ 0.40

[petroleum ether/acetone, 4:1 (v/v)]. (3R,6R)-7: [α]²_D⁵ϭ Ϫ2.6 (c ϭ

0.50, CHCl₃). R_fϭ 0.17 [petroleum ether/acetone, 4:1 (v/v)].

5. Epoxidation of 5-Methyl-1-phenyl-4-hexen-1-ol (5)

rac-4,5-Epoxy-5-methyl-1-phenyl-1-hexanol (10): Dimethyldioxirane

(11.56 mL of a 0.05  solution in acetone, 0.578 mmol) was added

dropwise at 0 °C over a period of 15 min to a solution of 5-methyl-

2406

 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjoc.org

Eur. J. Org. Chem. 2003, 2388Ϫ2408

Stereoselective Synthesis of Functionalized Tetrahydrofurans

FULL PAPER

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

Cambridge, 1999.

Formation of Tetrahydrofuran Derivative (2S,5S)-6 and Tetrahydro-

pyran Derivative (3R,6S)-7: A solution of (1S,4R)-10 (19.8 mg,

0.096 mmol) in CDCl₃(0.7 mL) was treated with p-toluenesulfonic

acid (34.4 mg, 0.20 mmol) or with VOL⁷(OEt) (4g, 3.7 mg,

0.01 mmol) and was stirred at 25 °C for 2 h. After removal of the

solvent under reduced pressure (250 mbar/40 °C) the products were

filtered through a short pad of aluminum oxide using Et₂O as elu-

ent. The combined organic phases were concentrated under re-

duced pressure to provide an oil, which was purified by column

chromatography [SiO₂; petroleum ether/acetone, 4:1 (v/v)]. Yield:

18.9 mg (97%), colorless liquid, (2S,5S)-6/(3R,6S)-7 ϭ 39:61 (¹H

NMR spectroscopy). (2S,5S)-6: [α]²_D⁵ϭ ϩ49.7 (c ϭ 0.50, CHCl₃).

^{[11] [11a]}R. A. Sheldon, Syntheses and Uses of Alkyl Hydroperoxides

and Dialkylperoxides in The Chemistry of Functional Groups,

Peroxides (Ed.: S. Patai), Wiley, Chichester, 1983, pp. 161Ϫ199.

^[11b]K. B. Sharpless, T. R. Verhoeven, Aldrichim. Acta 1979,

12, 63Ϫ74.

[12] [12a]

D. T. Sawyer, Oxygen Chemistry, Oxford University Press,

[12b]

´ ´

G. Henrici-Olive, S. Olive, Angew. Chem.

New York, 1991.

1974, 86, 1Ϫ12; Angew. Chem. Int. Ed. Engl. 1974, 13, 29Ϫ41.

[13]

`

H. E. B. Lempers, A. Ripolles i Garcia, R. A. Sheldon, J. Org.

Chem. 1998, 63, 1408Ϫ1413.

[14] [14a]

F. E. McDonald, C. C. Schultz, Tetrahedron 1997, 53,

16435Ϫ16448. ^[14b]T. B. Towne, F. E. McDonald, J. Am. Chem.

Soc. 1997, 119, 6022Ϫ6028.

R_fϭ 0.42 [petroleum ether/acetone, 4:1 (v/v)]. (3R,6S)-7: [α]²_D⁵

ϭ

ϩ27.0 (c ϭ 0.50, CHCl₃). R_fϭ 0.15 [petroleum ether/acetone, 4:1

(v/v)].

[15] [15a]

S. Tang, R. M. Kennedy, Tetrahedron Lett. 1992, 33,

[15b]

5299Ϫ5302.

S. Tang, R. M. Kennedy, Tetrahedron Lett.

1992, 33, 5303Ϫ5306.

6. X-ray Crystallographic Study: Suitable crystals of vanadium()

complexes 4e, 4g, and 4h were grown by slowly concentrating satu-

rated solutions in EtOH at room temperature. CCDC-197917

(4h), -197918 [(VOL¹)₂O, see Supporting Information], -197919

(4g), and -197920 (4e) contain the supplementary crystallographic

data for this paper. These data can be obtained free of charge at

www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge

Crystallographic Data Center, 12 Union Road, Cambridge

[16] [16a]

V. Conte, F. Di Furia, G. Licini, J. Mol. Catal. A. 1997,

[16b]

157, 335Ϫ361.

C. K. Sams, K. A. Jørgensen, Acta Chim.

Scand. 1995, 49, 839Ϫ847.

[17]

[18]

T. Nakata, G. Schmid, B. Vranesic, M. Okigawa, T. Smith-

Palmer, Y. Kishi, J. Am. Chem. Soc. 1978, 100, 2933Ϫ2935.

S. Hanessian, N. G. Cooke, B. DeHoff, Y. Sakito, J. Am. Chem.

Soc. 1990, 112, 5276Ϫ5290.

[19] [19a]

Y. Morimoto, T. Iwai, T. Yoshimura, T. Kinoshita, Bioorg.

[19b]

CB2 1EZ, UK; Fax: (internat.)

ϩ

44-1223/336-033; E-mail:

Med. Chem. Lett. 1998, 8, 2003Ϫ2004.

M. Hashimoto, H.

Harigaya, M. Yanagiya, H. Shirahama, J. Org. Chem. 1991,

deposit@ccdc.cam.ac.uk]. For details on crystallographic

investigations see Supporting Information.

56, 2299Ϫ2311.

[20]

D. A. Evans, R. P. Polniaszek, K. M. DeVries, D. E. Guinn,

D. J. Mathre, J. Am. Chem. Soc. 1991, 113, 7613Ϫ7630.

^{[21] [21a]}H. Hioki, C. Kanehara, Y. Ohnishi, Y. Umemori, H. Sakai,

S. Yoshio, M. Matsushita, M. Kodama, Angew. Chem. 2000,

122, 2652Ϫ2655. ^[21b]Z. Xiong, E. J. Corey, J. Am. Chem. Soc.

2000, 122, 4831Ϫ4832.

Acknowledgments

This work was generously supported by the Fonds der Chemischen

Industrie and the Deutsche Forschungsgemeinschaft (Sonder-

forschungsbereich 347, ‘‘Selektive Reaktionen Metall-aktivierter

Moleküle’’, Schwerpunktprogramm ‘‘Peroxidchemie: Präparative

und mechanistische Aspekte des Sauerstofftransfers’’, grants Ha

1705/6-1 and 8-1, and Graduiertenkolleg 690 ‘‘Elektronendichte Ϫ

Theorie und Experiment‘‘).

[22]

E. J. Corey, D.-C. Ha, Tetrahedron Lett. 1988, 29, 3171Ϫ3174.

M. Hashimoto, T. Kan, K. Nozaki, M. Yanagiya, H. Shirah-

ama, T. Matsumoto, J. Org. Chem. 1990, 55, 5088Ϫ5107.

G. Ohloff, W. Giersch, K. H. Schulte-Elte, P. Enggist, E. De-

[23]

[24]

mol, Helv. Chim. Acta 1980, 63, 1582Ϫ1588.

[25] [25a]

R. A. Sheldon, Metal-Catalyzed Epoxidation of Olefins

with Hydroperoxides, in Aspects of Homogeneous Catalysis

[1]

(Ed.: R. Ugo), Reidel Publishing, Dordrecht, 1981, vol. 4, pp.

The following abbreviations have been used: acac ϭ acetyl-

[25b]

3Ϫ70.

F. Freeman, Oxidation by Vanadium Compounds, in

acetone monoanion, CHP ϭ cumene hydroperoxide, DMD ϭ

dimethyl dioxirane, TBHP ϭ tert-butyl hydroperoxide, UHP ϭ

urea hydrogen peroxide. Unless otherwise noted by a proper

stereodescriptor, all graphics refer to racemic.

Organic Synthesis by Oxidations with Metal Compounds (Eds.:

W. J. Mijs, C. R. H. De Jonge), Plenum Press, New York, 1986,

pp. 1Ϫ39.

[26]

[27]

[2]

J. Hartung, P. Schmidt, Synlett 2000, 367Ϫ370.

M. M. Faul, B. E. Huff, Chem. Rev. 2000, 100, 2407Ϫ2473.

Preparation of (Schiff-base)vanadium() complexes: 4a: ^[27a]H.

[3]

^[3a]R. Hoppe, H.-D. Scharf, Synthesis 1995, 1447Ϫ1464. ^[3b]G.

W. Gribble, J. Nat. Prod. 1992, 55, 1353Ϫ1395. ^[3c]G. W. Grib-

Mimoun, M. Mignard, P. Brechot, L. Saussine, J. Am. Chem.

[27b]

[3d]

Soc. 1986, 108, 3711Ϫ3718. 4a,b:

M. J. Clague, N. L.

ble, Acc. Chem. Res. 1998, 31, 141Ϫ152.

S. Schulz, G.

Keder, A. Butler, Inorg. Chem. 1993, 32, 4754Ϫ4761.

Beccaloni, R. Nishida, Y. Roisin, R. I. Vane-Wright, J. N.

[28]

[29]

[3e]

W. Prandtl, L. Hess, Z. Anorg. Chem. 1913, 82, 103Ϫ129.

Synthesis of Schiff-base ligands 3: 3a: A. D. Westland, M. T.

H. Tarafder, Inorg. Chem. 1981, 20, 3992Ϫ3995. 3b: A. G. J.

Ligtenbarg, R. Hage, A. Meetsma, B. L. Feringa, J. Chem.

Soc., Perkin Trans. 2 1999, 807Ϫ812. 3c: C. R. Cornman, J.

Kampf, M. S. Lah, V. L. Pecoraro, Inorg. Chem. 1992, 31,

2035Ϫ2043. 3d: G. Desimoni, P. Quadrelli, P. P. Righetti, Tetra-

McNeil, Z. Naturforsch., Teil C 1998, 53, 107Ϫ116.

E.-J.

Kim, F. Tian, M.-H. Woo, J. Nat. Prod. 2000, 63, 1503Ϫ1506.

[4] [4a]

H. Avedissian, S. C. Sinha, A. Yazbak, A. Sinha, P. Neogi,

S. C. Sinha, E. Keinan, J. Org. Chem. 2000, 65, 6035Ϫ6051.

[4b]

Z.-M. Wang, S.-K. Tian, M. Shi, Eur. J. Org. Chem. 2000,

349Ϫ356.

[5]

[6]

M. Cueto, J. Darias, Tetrahedron 1996, 52, 5899Ϫ5906, and

´

hedron 1990, 46, 2927Ϫ2934. 3g: L. Z. Flores-Lopez, M. Parra-

references cited therein.

J.-C. Harmange, B. Figadere, Tetrahedron: Asymmetry 1993,

4, 1711Ϫ1754.

M. H. D. Postema, Tetrahedron 1992, 48, 8545Ϫ8599.

T. L. B. Boivin, Tetrahedron 1987, 43, 3309Ϫ3363.

Hake. R. Somanathan, P. J. Walsh, Organometallics 2000, 19,

2153Ϫ2160. 3j: G. Desimoni, G. Dusi, G. Faita, P. Quadrelli,

P. P. Righetti, Tetrahedron 1995, 51, 4131Ϫ4144.

`

[7] [7a]

[7b]

[30]

For further work on syntheses and characterization of (Schiff-

base)vanadium() complexes with tridentate auxiliaries see:

[8]

[9]

J. Hartung, M. Greb, J. Organomet. Chem. 2002, 661, 67Ϫ84.

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

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

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

berg, 1978.

^[30a]M. Bashirpoor, H. Schmidt, C. Schulzke, D. Rehder, Chem.

[30b]

Ber./Recueil 1997, 130, 651Ϫ657.

V. Vergopoulos, W. Pri-

ebsch, M. Fritzsche, D. Rehder, Inorg. Chem. 1993, 32,

1844Ϫ1849. ^[30c]L. J. Theriot, G. O. Carlisle, H. J. Hu, J. Inorg.

[10]

[30d]

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

Nucl. Chem. 1969, 31, 2841Ϫ2844.

C. P. Rao, A. Sreed-

Eur. J. Org. Chem. 2003, 2388Ϫ2408

www.eurjoc.org

 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2407

J. Hartung et al.

FULL PAPER

[52c]

hara, P. V. Rao, M. B. Verghese, K. Rissanen, E. Kolehmainen,

73Ϫ80.

A. T. Harrison, O. W. Howarth, J. Chem. Soc.,

N. K. Lokanath, M. A. Sridhar, J. S. Prasad, J. Chem. Soc.,

[30e]

[53]

[54]

[55]

[56]

[57]

[58]

[59]

Dalton Trans. 1998, 2383Ϫ2393.

G. Asgedom, A. Sreed-

hara, J. Kivikoski, J. Valkonen, E. Kolehmainen, C. P. Rao,

Inorg. Chem. 1996, 35, 5674Ϫ5683.

[31]

The stereochemical descriptor C denotes a clockwise arrange-

ment of donor atoms in the order of declining CIP priority

1Ϫ2Ϫ3 (view on top of the VϭO bond). The mirror image of

a C-configured complex has A configuration (A is an abbrevi-

ation for anticlockwise). For a more detailed treatise on the

chirality of coordination compounds: L. H. Gade, Koordina-

tionschemie, Wiley-VCH, Weinheim, 1998, pp. 73Ϫ86.

J. Hartung, M. Hiller, P. Schmidt, Liebigs Ann. 1996,

1425Ϫ1436.

ˇ

[32]

[33]

[34]

[35]

J. P. Michael, M. M. Nkwelo, Tetrahedron 1990, 46,

2549Ϫ2560.

T. O. Lukas, C. Girard, D. R. Fenwick, H. B. Kagan, J. Am.

Chem. Soc. 1999, 121, 9299Ϫ9306 and references cited therein.

W. Adam, C. R. Saha-Möller, P. A. Ganeshpure, Chem. Rev.

2001, 101, 3499Ϫ3548.

[60]

[61]

[62]

[36] [36a]

L. A. Paquette, J. P. Gilday, J. Am. Chem. Soc. 1988, 53,

4972Ϫ4978. ^[36b]M. Chastrette, E. Rallet, Flavour Fragrance J.

1998, 53, 4972Ϫ4978.

[37]

[38]

I. Keiji, N. Saburo, O. Yoshio, J. Organomet. Chem. 1994,

473, 215Ϫ224.

[63]

[64]

P. A. Bartlett, P. C. Ting, J. Org. Chem. 1986, 51, 2230Ϫ2240.

^{[39] [39a]}M. Castrette, G. P. Axiotis, J. Organomet. Chem. 1981, 206,

139Ϫ147. ^[39b]G. Ohloff, Helv. Chim. Acta 1964, 47, 602Ϫ626.

[39c]

R. Amouroux, G. Folefoc, F. Chastrette, M. Chastrette,

[39d]

Tetrahedron Lett. 1981, 22, 2259Ϫ2262.

chambre, Tetrahedron Lett. 1984, 25, 543Ϫ546.

L. David, H. Ves-

[39e]

W. W.

Epstein, L. A. Gaudioso, Phytochemistry 1984, 23, 2257Ϫ2262.

^[39f]A. Meou, N. Bouanah, A. Archelas, X. M. Zhang, R. Gug-

[39g]

lielmetti, R. Furstoss, Synthesis 1990, 9, 752Ϫ753.

Wang, K. Ando, K. Morita, K. Kubota, A. Kobayashi, Biosci.

Biotechnol. Biochem. 1994, 58, 2050Ϫ2053.

D.

[39h]

J. G. Urones,

VO(salen)(OEt): green-black

D. Diez, I. S. Marcos, P. Basabe, A. M. Lithgow, Tetrahedron

1995, 51, 3691Ϫ3704.

[40]

E. Flaskamp, G. Nonnenmacher, G. Zimmermann, O. Isaac,

Z. Naturforsch., Teil B 1981, 36, 1023Ϫ1030.

[41] [41a]

G. Descotes, B. Giroud-Abel, J.-C. Martin, Bull. Soc.

[66]

[67]

[68]

[41b]

Chim. Fr. 1967, 7, 2466Ϫ2472.

D. M. Hodgson, A. M.

Foley, L. T. Boulton, P. J. Lovell, G. N. Maw, J. Chem. Soc.,

Perkin Trans. 1 1999, 2911Ϫ2922.

J. Hartung, M. Hiller, P. Schmidt, Chem. Eur. J. 1996, 2,

1014Ϫ1023.

J. Hartung, F. Gallou, J. Org. Chem. 1995, 60, 6706Ϫ6716.

J. Iqbal, R. R. Srivastava, Tetrahedron 1991, 47, 3155Ϫ3170.

Prepared in extension to: E. Vogel, G. H. Büchi, Org. Synth.,

Coll. Vol. 1993, 8, 536Ϫ539.

Y. Taura, M. Tanaka, X. M. Wu, K. Funakoshi, K. Sakai,

Tetrahedron 1991, 47, 4879Ϫ4888.

J. Yin, W. M. Jones, Tetrahedron 1995, 51, 4395Ϫ4406.

J. Moore, R. G. Pearson, Kinetics and Mechanism, 3rd ed., John

Wiley & Sons, New York, 1981, pp. 284Ϫ333.

[42]

[43]

[44]

[45]

[69c]

M. Lj. Mihailovic, D.

[46]

[47]

[48]

[71]

[72]

[49] [49a]

Z.-X. Wang, Y. Tu, M. Frohn, J.-R. Zhang, Y. Shi, J. Am.

[49b]

Chem. Soc. 1997, 119, 11224Ϫ11235.

Z.-X. Wang, Y. Shi,

J. Org. Chem. 1998, 63, 3099Ϫ3104.

[50] [50a]

J. L. Von dem Bussche-Huennefeld, D. Seebach, Tetra-

[50b]

[73c]

hedron 1992, 48, 5719Ϫ5730.

J. Yun, S. L. Buchwald, J.

J. G.

Am. Chem. Soc. 1999, 121, 5640Ϫ5644.

[51] [51a]

S. Battacharya, T. Gosh, Trans. Met. Chem. 2002, 27,

[51b]

89Ϫ94.

D. C. Crans, P. K. Shin, J. Am. Chem. Soc. 1994,

116, 1305Ϫ1315.

[52] [52a]

[74b]

D. Rehder, Biological Applications of ⁵¹V NMR Spec-

J.

troscopy in Vanadium in Biological Systems (Ed.: D. N. Chas-

teen), Kluwer Academic Publishers, Dordrecht, 1990, pp.

[52b]

173Ϫ197.

K. P. Bryliakov, N. N. Karpyshev, S. A. Fomin-

sky, A. G. Tolstikov, E. P. Talsi, J. Mol. Catal. A 2001, 171,

Received November 20, 2002

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Article Doi

(Schiff-base)vanadium(v) complex-catalyzed oxidations of substituted bis(homoallylic) alcohols - Stereoselective synthesis of functionalized tetrahydrofurans

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