A synthesis of densely functionalized 2,3-dihydropyrans using ring-closing metathesis and base-induced rearrangements of dihydropyran oxides

FULL PAPER

A Synthesis of Densely Functionalized 2,3-Dihydropyrans Using Ring-Closing

Metathesis and Base-Induced Rearrangements of Dihydropyran Oxides

Bernd Schmidt*^[a]and Holger Wildemann^[a]

Keywords: C-Glycosides / Deprotonation / Epoxidation / Metathesis / Rearrangements

The preparation of dihydropyran and dihydrofuran oxides

and their rearrangement in the presence of lithium dial-

kylamides to functionalized 2,3-dihydropyrans or 2,3-dihy-

drofurans, respectively, is described. The regiochemical out-

come of the reaction can be influenced by the relative config-

uration of the starting epoxides and the steric demand of the

base. The 2,3-dihydropyrans obtained were converted ster-

eoselectively to difunctionalized 3,4-dihydropyrans by the

carbon-Ferrier reaction, or to fused acetals by addition of di-

medone, mediated by ceric ammonium nitrate. The stereo-

chemical results are rationalized by mechanistic proposals.

Introduction

ocycles. A recent report by Brimble et al. describes a single

example of a base-promoted rearrangement of a spiroace-

tal-derived dihydropyran oxide, leading to a 3,4-dihydropy-

ran derivative as the major product.^[32]A two-step synthesis

of glycals from carbohydrate-derived epoxides by sub-

sequent epoxide opening with iodide and elimination of li-

thium methoxide was described by Thiem et al.^[33]More

recently, the epoxides of glycosyl phosphonates were shown

to be very sensitive towards base (due to the acidifying pho-

sphonate group) and to undergo rearrangement to phos-

phonated glycals even in the presence of sodium acetate.^[34]

In this contribution, we present a novel approach to func-

tionalized 2,3-dihydropyrans, which uses the base-induced

rearrangement of dihydropyran oxides as a key step. Some

dihydrofuran oxides were also investigated as substrates for

base-induced rearrangements. Furthermore, we present

some examples for the utilization of the dihydropyrans ob-

tained in this way for the stereoselective synthesis of difunc-

tionalized dihydropyrans and fused acetals.

Densely functionalized tetrahydropyrans and -furans are

important targets in organic synthesis, as these structures

are found in a large variety of biologically active natural

products.^[1Ϫ11]The variation and structural diversity of the

target molecules in question had a strong impact on the

development of synthetic methods.^[13Ϫ16]Many syntheses

employ carbohydrates as readily available starting materials.

In particular, 1,2-unsaturated derivatives Ϫ the so-called

glycals Ϫ are starting materials in a variety of transforma-

tions.^[17,18]More recently, metal-mediated approaches to

these cyclic enolethers have been developed. The cyclization

of acetylenic alcohols at a metal template yields 2,3-dihy-

drofurans or 2,3-dihydropyrans, either directly^[19]or via a

carbene complex intermediate, which is subsequently

cleaved by action of a base.^[20]Alternatively, ring-closing

metathesis of appropriately substituted enol ethers gives

cyclic enol ethers related to glycals; however, use of the con-

veniently accessible GrubbsЈ catalyst is rather limited in

these cases.^[21Ϫ23]

In the course of our studies directed towards the cleavage

of conformationally rigid dihydropyran oxides by nucleo-

philes,^[24]we investigated the base-promoted rearrangement

of these substrates with a view towards the synthesis of 2,3-

dihydropyrans and -furans.^[25,26]The base-promoted re-

arrangement of epoxides to allylic alcohols in the presence

of lithium dialkylamides has been used in organic synthesis

for a long time.^[27Ϫ29]From early investigations into the

mechanism it became clear that the rearrangement proceeds

via a syn-selective β-elimination, with the lithium ion coor-

dinating to the epoxide oxygen and the nitrogen of the base,

thereby directing the amide to the syn-β-hydrogen.^[30,31]To

the best of our knowledge, this reaction has not been sys-

tematically investigated for the corresponding oxygen heter-

Results and Discussion

Preparation of the Dihydropyran Oxides

The dihydropyran oxides required for this study were ob-

tained by epoxidation of 3,4-dihydropyrans, which are avail-

able from homoallylic alcohols by O-allylation and sub-

sequent ring-closing metathesis (Scheme 1 and Table 1). An

influence of the relative configuration of the epoxides on

the regiochemical course of the rearrangement reaction is

to be expected; thus we attempted to make both diastere-

omeric dihydropyran oxides available. Diastereomeric dihy-

dropyran oxides can easily be separated by column chroma-

tography. In most cases, epoxidation was achieved using

MCPBA. If the 2-position of the dihydropyran is a quatern-

ary centre (3f,g), action of MCPBA leads to decomposition,

probably due to cleavage of the dihydropyran ring. In these

cases, MMPP (magnesium monoperoxophthalate) was

used. The diphenyl derivative 3j was epoxidized with

[a]

Universität Dortmund, Fachbereich Chemie, Organische

Chemie I,

44221 Dortmund, Germany

Fax: (internat.) ϩ49-231/755-5363

E-mail: bschmidt@citrin.chemie.uni-dortmund.de

Eur. J. Org. Chem. 2000, 3145Ϫ3163

WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000

1434Ϫ193X/00/0918Ϫ3145 $ 17.50ϩ.50/0

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B. Schmidt, H. Wildemann

FULL PAPER

DMDO (dimethyldioxirane) in acetone; all other agents

lead to complete and rapid decomposition of the material.

Figure 1 shows the different dihydropyran oxides 4 em-

ployed in this study. Throughout this manuscript we will

refer to a numbering scheme for the tetrahydropyran ring

system which may well deviate from systematic nomenclat-

ure in some cases. The numbering is demonstrated for 4a

in Figure 1.

Scheme 1. Synthesis of dihydropyran oxides

Reagents and conditions: i) NaH, allyl bromide, THF, 65 °C

(77Ϫ91%); ii) GrubbsЈ catalyst (2 mol-%), DCM, 20 °C (85Ϫ95%);

iii) MCPBA or MMPP or DMDO, 20 °C, then separate (65Ϫ80%).

Figure 1. Numbering scheme for dihydropyran oxides 4a؊l

Addition of vinylmagnesium chloride to ethyl lactate

gives the homoallylic alcohol (S)-1k.^[37a]The subsequent O-

allylation has to be carried out at 0 °C to avoid allylation

of the tertiary hydroxy functionality. Allyl homoallyl ether

2l was obtained in a slightly different manner, by allylating

methyl mandelate with allyl bromide and silver oxide to

give allyloxy ester 6 (action of sodium hydride leads to par-

Table 1. Designation used for the dihydropyran oxides 1Ϫ4

1؊4

R¹

R²

R³

R⁴

a

b

c

d

e

f

H

Ph

H

4-MeOC₆H₄Ϫ

c-C₆H₁₁Ϫ

H

Ϫ(S*,S*)-CH(Me)Ph

Ϫ(R*,S*)-CH(Me)Ph

Ph

H

Me

H

g

h

i

Ϫ(CH₂)₆Ϫ

H

ϪCH₂OCMe₂OCH₂Ϫ

Ϫ(CH₂)₄Ϫ

Ph

H

j

k

l

H

Ph

OH

H

Me

Ph

ϪCHϭCH₂

H

The homoallylic alcohols 1a؊g were prepared by Grig-

nard addition of allylmagnesium bromide to the corres-

ponding aldehydes or ketones. Alcohol (S)-1b was obtained

in enantiomerically enriched form (90% ee) by an enzymatic

resolution of racemic 1b, using lipase PS in vinyl acetate.^[35]

Alcohols 1h؊j were obtained by cleavage of epoxides 5h؊j

with vinylmagnesium chloride in the presence of CuI or

CuBrSMe₂(Scheme 2).^[36]

Scheme 3. Preparation of dihydropyran oxides 4k,l

Reagents and conditions: i) Ag₂O, allyl bromide, Et₂O, 20 °C (99%

of 6); ii) DIBAL, Et₂O, Ϫ90 °C, vinylmagnesium chloride, Ϫ90 °C

to 20 °C (97% of 2l); iii) GrubbsЈ catalyst (5 mol-%), DCM, 20 °C

(66Ϫ69%); iv) VO(acac)₂, tBuOOH, toluene, 110 °C; v) vinylmag-

nesium chloride (3 equiv.), Et₂O, Ϫ70 °C (86%); vi) NaH, THF, 0

°C, then allyl bromide, 0 °C (51%).

Scheme 2. Preparation of trans-disubstituted homoallylic alcohols

Reagents and conditions: i) CuI, vinylmagnesium chloride, THF,

Ϫ30 °C (40Ϫ55%)

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Eur. J. Org. Chem. 2000, 3145Ϫ3163

Synthesis of Densely Functionalized 2,3-Dihydropyrans

FULL PAPER

tial Wittig rearrangement), following a literature proced- antly from the geometries of all other dihydropyran oxides

ure.^[37b]Subsequent reduction of the ester functionality and studied in this work, as the phenyl groups adopt pseudoax-

addition of vinylmagnesium chloride in a one-pot reaction ial configurations here in order to minimize steric interac-

furnishes 2l. Ring-closing metathesis yields 3k and l with a tions which would otherwise occur. This may result in signi-

hydroxy functionality in the allylic position, allowing the ficant distortion of the oxacycle, making abstraction of

use of substrate-directed epoxidations. We used tert-butyl H6_axunfavourable. Additionally, H3 is a benzylic hydrogen

hydroperoxide and VO(acac)₂as a catalyst to achieve dia- and will therefore be more acidic than H3 protons in the

stereoselective epoxidation. In the case of 3k, epoxidation is other dihydropyran oxides (Scheme 5).

also highly regioselective, as only the endocyclic double

bond is attacked. (Scheme 3).

Three dihydrofuran oxides 10a؊c were synthesized, in

similar manner to dihydropyran oxides 4a؊g. Starting from

diallyl ethers 8a؊c (obtained from allylic alcohols 7a؊c by

allylation with allyl bromide/NaH), dihydrofurans 9a؊c

were obtained by ring-closing metathesis. Epoxidation with

MCPBA gave dihydrofuran oxides 10a؊c. In the case of

10a, varying amounts of a dihydrofuranone 10aЈ were ob-

tained (Scheme 4).

Scheme 4. Preparation of dihydrofuran oxides

Reagents and conditions: i) NaH, allyl bromide, THF (52Ϫ76%);

Scheme 5. Base-promoted rearrangement of dihydropyran oxides

Reagents and conditions: i) LDA or LiTMP, THF, 20 °C (38Ϫ89%)

ii) GrubbsЈ catalyst (2 mol-%), DCM, 20 °C (66Ϫ90%); iii)

MCPBA, DCM, 20 °C, then separate (54Ϫ81%).

Consideration of the mechanism postulated for base-pro-

moted rearrangements with lithium amides may rationalize

Base-Induced Rearrangement of Dihydropyran Oxides

Reaction of diastereomerically pure dihydropyran oxides the different selectivities observed for cis- and trans-dihy-

trans-4a؊i with one equivalent of LDA or LiTMP in THF dropyran oxides (Figure 2). In the transition state, the li-

at ambient temperature gave a clean rearrangement to the thium ion coordinates to the epoxide oxygen and directs the

corresponding 2,3-dihydropyrans. Only dihydropyran oxide amide to the syn-hydrogen. Fragmentation of this transition

trans-4f, with a quaternary centre in the 2-position, did not state is assumed to proceed in a concerted manner, because

give satisfactory selectivity with LDA, as 30% of re- there is no hint that a carbanionic intermediate (i.e. a β-

gioisomer trans-12f resulted. This problem was circum- lithiated epoxide with the lithium located at the β-carbon

vented by using LiTMP instead of LDA. If the cis isomers centre) plays a significant role during the rearrangement

were treated with LDA, inseparable mixtures of regioiso- process.^[27]In the case of the dihydropyran oxides 4a؊f, the

mers of varying composition resulted in the cases of 4a؊c. substituent in the 2-position is a molecular anchor group

Typical ratios were 3:1 to 5:1 in favour of the cyclic enol and adopts a pseudoequatorial position, indicated by the

3

ether. The ratio of regioisomers improved to Ͼ95:5 if trans-diaxial coupling constants J(H2-H3_ax) of approxim-

LiTMP was used as a base. Rearrangement of dihydropyran ately 11 Hz. In the case of 4f, a NOESY experiment was

oxide 4j was a very special case, as reaction with lithium used to show that the methyl group adopts a pseudoaxial

dialkyl amides yielded the unexpected rearrangement prod- and the phenyl group a pseudoequatorial position. If the

uct 13 exclusively. This product obviously results from ini- generally accepted mechanism for the rearrangement of ep-

tial deprotonation of H3 and subsequent isomerization of oxides to allylic alcohols is operating here, the syn-hydro-

the double bond into conjugation with both phenyl sub- gens in the 3- or the 6-position are required for abstraction.

1

stituents. The geometry of 4j (deduced from its H NMR In the case of the trans-dihydropyran oxides, the syn-hydro-

spectroscopic data: ³J(H2-H3) ϭ 2.8 Hz) differs signific- gens are pseudoequatorially oriented in the 3- and pseudo-

Eur. J. Org. Chem. 2000, 3145Ϫ3163

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B. Schmidt, H. Wildemann

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axially oriented in the 6-position. For the cis-dihydropyran

One may argue that it is not primarily the stereochem-

oxides the situation is reversed: the syn-proton in the 3- istry of the dihydropyran oxide starting materials that influ-

position is pseudoaxially oriented and the syn-proton in the ences the regioselectivity of the rearrangement (see discus-

6-position adopts a pseudoequatorial position. For the sion above) but the relative stereochemistry of the transition

trans- as well as for the cis-dihydropyran oxide, abstraction states depicted in Figure 2. Thus, it may well be that the

of a pseudoaxially oriented hydrogen may proceed via a lithium chelate transition state for the cis-dihydropyran ox-

transition state where a nearly synclinal conformation is at- ides undergoes a conformational change prior to the re-

tained (transition states A and D). Thus, in the case of cis- arrangement.

dihydropyran oxides, the products cis-12 resulting from

It would be an interesting extension, both from the syn-

transition state D should be preferred. However, this ration- thetic and from the mechanistic point of view, to employ

ale does not take into account steric interactions between dihydrofuran oxides in base-induced rearrangement reac-

the dialkylamide and the substituent in the 2-position, and tions. The expected products, 2,3-dihydrofurans with a hy-

obviously these outweigh the benefits resulting from syn- droxy function in the allylic position, are normally prepared

clinal arrangement in transition state D and so make trans- from carbohydrate-derived starting materials, using elim-

ition state C (leading to the desired 2,3-dihydropyrans cis- ination reactions,^[38]or from nucleosides.^[39]These com-

11) more favourable overall. Thus, improvement of the re- pounds are useful building blocks in the synthesis of poly-

gioselectivity when LDA is substituted by LiTMP may be ether antibiotics^[40,41]or C-nucleosides.^[42]From a mechan-

rationalized by greater steric hindrance between the base istic point of view, it is interesting to see whether good regi-

and the substituent in the 2-position. The exceptional beha- ocontrol can also be achieved for five-membered oxacycles,

viour of trans-4f may result from distortion of the molecule in which both β-positions are adjacent to the ring oxygen.

by steric interactions of the axially oriented methyl group. For substrate 10a, with a quaternary centre in the 2-posi-

For 2-phenylethyl-substituted dihydropyran oxides 4d and tion, no regioisomers are to be expected. Only the re-

e, comparatively good selectivities were obtained even with arrangement product 14a is observed in NMR spectra of

LDA, which is probably due to better shielding of the 3- the crude product. Column chromatography on silica in-

position of the dihydropyran ring. For spirocyclic derivative duces a partial rearrangement to hemiacetal 15; this is sup-

4g, the ratio of regioisomers 11 and 12 was very good (50:1) pressed if the hydroxy group in 14a is protected as a benzyl

even when LDA was used as a base, which may probably ether 16 (Scheme 6).

be explained by steric interactions between the base and the

cycloheptane ring. For dihydropyran oxides 4h, i, k and l,

with a substituent in the 3-position, no regioisomeric re-

arrangement products 12 were detected at all (Figure 2).

Scheme 6. Base induced rearrangement of 10a and subsequent

double bond migration

Reagents and conditions: i) LDA, THF, 20 °C (95%); ii) SiO₂; iii)

NaH, benzyl bromide, THF, 65 °C (78%).

Dihydrofuran oxide 10b was obtained as an inseparable

mixture of diastereomers and used directly in the rearrange-

ment reaction. A 4:3:1 mixture of isomers resulted, and was

characterized by NMR spectroscopy of the crude reaction

mixture. The two major products resulted from depro-

tonation at C5 and were diastereomers; trans-14b slightly

preferred. Assignment of relative configuration is based on

3

the value for J(H2-H3), which is approximately 2.5 Hz for

the major diastereomer and 7.0 Hz for the minor isomer.

These values are in good agreement with those reported in

the literature for similarly substituted glycals.^[39]The third

isomer Ϫ 14bЈ Ϫ was formed by abstraction of H2. The

corresponding isomers were obtained for 2-methoxyphenyl

derivatives trans- and cis-10c. Treatment of trans-10c with

LiTMP gave three products in a ratio of 9:3:1; these were

identified as 14cЈ, trans-14c and the elimination product,

furan 17c. Compound 14cЈ was identified by the character-

istic AB coupling pattern for hydrogens H5 and H5Ј. Base-

Figure 2. Transition states for the deprotonation step of base-pro-

moted rearrangements of dihydropyran oxides.

3148

Eur. J. Org. Chem. 2000, 3145Ϫ3163

Synthesis of Densely Functionalized 2,3-Dihydropyrans

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induced rearrangement of cis-10c yielded only one re- ment:^[45,46]the nucleophilic displacement of a leaving group

arrangement product, which was identified as cis-14c. It by a carbon electrophile, such as allyltrimethylsilane,^[47]me-

may be concluded that (at least for 10c) the syn elimination diated by Lewis acid. More recently, this transformation has

mechanism is also operating for dihydrofuran oxides, as been applied to a variety of syntheses.^[48Ϫ52]These reactions

product 14cЈ is only observed for the trans isomer. The pref- proceed via an oxocarbenium ion and normally yield the

erence for 14cЈ in this case may be attributed to higher acid- kinetic substitution product Ϫ the trans or α anomer Ϫ in

ity in the benzylic position and a more rigid conformation good yields and with high diastereoselectivities, explained

of 10c compared to 10b (Scheme 7).

by a kinetic anomeric effect.^[53Ϫ55]Related investigations

have also been made for nucleophilic displacement reac-

tions in tetrahydrofuran derivatives.^[56]

We have studied the reaction of cyclic enol ethers 11a؊d,

f-i (diastereomerically pure or as mixtures of trans and cis

isomers) with allyltrimethylsilane and BF₃·OEt₂. For 11a,

c, d, h and i, formation of the trans-dihydropyrans 18 pro-

ceeded with good diastereoselectivity (Ͼ95:5, determined

by ¹H NMR spectroscopy). The acetal structure in 11h was

cleaved under the reaction conditions and it was not pos-

sible to obtain the resulting diol in analytically pure form

and in good yield (Scheme 9). The stereochemical results

obtained are in agreement with those predicted on the basis

of the kinetic anomeric effect.

Scheme 9. Stereoselective allylation of 2,3-dihydropyrans

Reagents and conditions: i) Ac₂O, NEt₃, DMAP (cat.), DCM, 0

°C; ii) allyltrimethylsilane, BF₃·OEt₂, DCM, Ϫ78 °C (49Ϫ87% over

two steps).

Scheme 7. Product distribution for base-promoted rearrangements

of dihydrofuran oxides 10b,c

Reagents and conditions: i) LDA or LiTMP, THF, 20 °C

Allylation of the 4-methoxyphenyl derivative 11b under

the same conditions gave the expected kinetic product trans-

18b if the reaction was carried out at Ϫ80 °C and quenched

at this temperature after consumption of the starting mat-

erial was complete (Scheme 10). If the reaction mixture was

warmed to Ϫ10 °C and stirring was continued for 3 hours,

a rearrangement to the thermodynamically more stable cis

isomer occurred (cis/trans ϭ 7:1). We propose that this ano-

merization proceeds via a cleavage, mediated by Lewis acid,

of the C2ϪO-bond, followed by isomerization and recyc-

lization, a mechanism originally proposed by Suzuki et al.

for anomerization reactions of C-aryl glycosides.^[57]Thus,

cis-18b is the product of a sequential allylation reaction/

anomerization mediated by Lewis acid. The fact that the

first step of the sequence is fast at very low temperatures

compared to the second step allowed us to control the ste-

reochemical outcome just by controlling the temperature

and reaction time. We used enantiomerically enriched (ee ϭ

Attempts to separate individual compounds from the

mixtures were not successful, due at least in part to decom-

position upon chromatography. Therefore, the mixtures of

stereoisomeric dihydrofuran oxides 10b and c were treated

with LDA followed by tosyl chloride, inducing an elimina-

tion to the corresponding furans 17b and c. Isolated yields

of 17 were approximately 75% based on the starting epox-

ide (Scheme 8).

Scheme 8. One-pot procedure for the preparation of furans from

dihydrofuran oxides

Reagents and conditions: i) LDA, THF, then TosCl (75%).

Stereoselective Transformations of Dihydropyrans 11

The dihydropyrans obtained by base-promoted re- 90%) homoallylic alcohol (S)-(Ϫ)-1b as a starting material

arrangement are structurally related to glycals, which have for this sequence. No significant deviation from the ratio of

proven to be valuable starting materials for a large variety enantiomers in (ϩ)-cis-18b could be detected by NMR shift

of target molecules in carbohydrate chemistry.^[43]Glycals experiments (Eu(hfc)₃, 500 MHz), compared to (Ϫ)-1b.

also serve as building blocks in the synthesis of marine nat- Electronic stabilization of the intermediate seems to play an

ural products with 2,6-difunctionalized dihydropyrans em- important role, because no noticeable anomerization to the

bedded in a macrocycle.^[44]A reaction commonly used in cis isomer was observed for the phenyl derivative trans-18a.

this field is the so called carbonϪFerrier rearrange- Allylation of 11f preferentially yields the dihydropyran cis-

Eur. J. Org. Chem. 2000, 3145Ϫ3163

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B. Schmidt, H. Wildemann

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18f, with a quaternary centre at C2 (cis/trans ϭ 17:1) of our knowledge, only conformationally mobile dihydropy-

(Scheme 10). The cis arrangement of the phenyl and the ran substrates without stereogenic centres have so far been

allyl substituent was unambiguously determined by investigated. We have chosen the conformationally rigid

NOESY experiments: NOE interactions between H6 and trans-decalin analogues 11i (both diastereomers were invest-

the methyl group show that both substituents adopt a igated separately) to study the stereochemical outcome of

pseudoaxial position; thus, phenyl and allyl substituent the reaction with dimedone in the presence of CAN. Sub-

must be oriented pseudoequatorially. It is difficult to decide jecting unprotected 11i to the reaction conditions led to

what the origin of this stereochemical outcome is. The rapid and complete decomposition of the starting material.

reason may be a shielding of one face of the cyclic oxycar- We repeated the reaction with the benzyl-protected derivat-

benium ion in the transition state by the pseudoaxially ori- ives trans- and cis-19i (Scheme 11). In both cases, formation

ented methyl group, making an attack of the nucleophile of one diastereomer of the tetracyclic derivative 20i was

from the opposite side energetically more favourable. Al- strongly preferred, with diastereomeric ratios of approxim-

ternatively, an anomerization of the intermediate substitu- ately 20:1. Related compounds have been prepared from

tion product trans-18f may occur, analogously to 18b. How- glycals by rhodium-catalysed carbenoid insertion^[63]and by

ever, trans-18f could not be detected in significant amounts radical cascades of O-glycosides with acetylene func-

when the reaction was conducted and quenched at Ϫ80 tionality in their side chains.^[64,65]

°C (Scheme 10).

Scheme 11. CAN-mediated annellation of dimedone to dihydropyr-

ans

Reagents and conditions: i) CAN, NaHCO₃, acetonitrile, water, 20

°C (60%).

Elucidation of the relative configuration was achieved

both for cis- and trans-20i by analysis of the coupling con-

stants and by COSY and NOESY experiments. Orientation

of the benzyloxy group does not seem to exert any signific-

Scheme 10. cis-Stereoselective allylation reactions

ant influence on the stereochemical outcome of the addi-

tion; the five-membered oxacycle is anellated in such a way

that relative orientation of hydrogens H2, H5 and H6 is

cis, regardless of the relative configuration of the starting

Reagents and conditions: i) Ac₂O, NEt₃, DMAP (cat.), DCM, 0

°C; ii) allyltrimethylsilane, BF₃·OEt₂, DCM, Ϫ78 °C (87% over two

steps for 18b, 78% for 18f); iii) allyltrimethylsilane, BF₃·OEt₂,

DCM, Ϫ78 °C to Ϫ10 °C, 3 h (75% over two steps).

Our synthetic route to dihydropyrans 11 makes accessible material. Formation of products cis- and trans-20i may be

individual diastereomers with different relative configura- rationalized on the basis of a mechanism recently proposed

tions of substituents R^1Ϫ4. This advantage can be exploited by Linker et al. for the CAN-mediated addition of malon-

for investigations into the diastereoselectivity of addition ates to glycals;^[60]in the first step of the mechanism the

reactions across the endocyclic enol ether double bond. dimedone radical will attack at the carbon atom C5, leading

Over the past few years, addition of 1,3-dicarbonyl radicals to anomeric radical intermediate A. The rigid decalin-like

(generated by oxidation of 1,3-dicarbonyl compounds with structure of the molecule is probably the reason for the pre-

Mn^IIIor Ce^IVsalts)^[58]to enol ethers has been investigated ferred axial attack of the dimedone radical. In the next step

for CϪC bond-forming reactions.^[59-60]The reaction has of the mechanism, oxidation of the anomeric radical will

also been applied to the synthesis of fused acetals from di- occur, leading to an oxo carbeniumion intermediate B,

hydropyrans and dihydrofurans;^[61,62]however, to the best which is attacked by one of the carbonyl oxygens, thereby

3150

Eur. J. Org. Chem. 2000, 3145Ϫ3163

Synthesis of Densely Functionalized 2,3-Dihydropyrans

FULL PAPER

creating the acetal bond. Elimination of H^ϩcompletes the

mechanism.

and filtered to remove any precipitates. The organic layer was sep-

arated, and the aqueous layer was extracted with ether. The com-

bined organic extracts were dried with MgSO₄, and the crude prod-

uct was purified by flash chromatography.

Conclusion

(5 *,6 *)-2,2-Dimethyl-6-vinyl-1,3-dioxepan-5-ol (1h): Obtained

from 5h (7.20 g, 50.0 mmol) as a colourless liquid. Yield: 5.90 g

(55%). Ϫ LRMS (EI); m/z: [M^ϩ] not found, 115 (23), 59 (100). Ϫ

¹H NMR: δ ϭ 5.71 (ddd, 1 H, J ϭ 17.3, 10.5, 8.3, ϪCHϭCH₂),

5.20 (d, 1 H, J ϭ 17.3, ϭCH₂), 5.17 (d, 1 H, J ϭ 10.5, ϭCH₂),

3.72 (dd, 1 H, J ϭ 12.3, 2.3, OCHH), 3.65 (dd, 1 H, J ϭ 12.3, 3.0,

OCHH), 3.62Ϫ3.47 (3 H, OCHH, CHOH), 2.36 (d, 1 H, J ϭ 5.3,

OH), 2.23 (m, 1 H, CHϪCHϭ), 1.31 (s, 3 H, Me), 1.28 (s, 3 H,

Me). Ϫ ¹³C NMR: δ ϭ 136.5 (1), 118.1 (2), 101.2 (0), 72.2 (1), 63.2

(2), 60.9 (2), 51.2 (1), 24.6 (3), 24.5 (3). Ϫ IR (NaCl, neat): ν˜ ϭ

3454 (s), 2989 (s), 1640 (m), 1372 (s), 1220 (s), 1047 (s), 919 (s),

846 (s).

In conclusion, we have shown that dihydropyran oxides

can be converted into synthetically useful dihydropyrans in

good yields and selectivities, starting from easily accessible

homoallylic alcohols. Dihydrofurans with one quaternary

centre can be prepared analogously, while for other derivat-

ives regioselectivity is poor. However, in these cases a clean

elimination reaction leads to functionalized furans in pre-

paratively useful yields. The regiochemical results of the

base-induced rearrangement reactions are in agreement

with a syn-deprotonation mechanism. Utilization of the di-

hydropyrans obtained in this study is possible either by con-

verting the newly generated alcohol functionality into a

leaving group (stereoselective synthesis of difunctionalized

cis- or trans-dihydropyrans, depending on the reaction con-

ditions) or by addition reactions across the enol ether bond.

Application of the methodology described in this contri-

bution is currently under investigation in our laboratory.

(1 *,2 *)-1,2-Diphenylbut-3-en-1-ol (1j): Obtained from 5j (7.90 g,

40.0 mmol) as a colourless solid, m.p. 70 °C. Yield: 3.60 g (40%).

Ϫ C₁₆H₁₆O (224.3): calcd. C 85.6, H 7.2; found C 85.0, H 7.2. Ϫ

¹H NMR: δ ϭ 7.37Ϫ7.21 (10 OH, Ph), 5.89 (ddd, 1 H, J ϭ 17.1,

10.3, 8.0 Hz, ϪCHϭ), 4.99 (ddd, 1 H, J ϭ 10.3, 1.3, 1.0, ϭCH₂),

4.89 (d, 1 H, J ϭ 8.0, CHOH), 4.85 (ddd, 1 H, J ϭ 17.1, 1.5, 1.3, ϭ

CH₂), 3.63 (dd, 1 H, J ϭ 8.0, 8.0, CHϪCHϭ), 2.00 (s(br.), 1 H,

OH). Ϫ ¹³C NMR: δ ϭ 141.8 (0), 140.2 (0), 137.6 (1), 128.7 (1),

128.6 (1), 128.0 (1), 127.7 (1), 127.0 (1), 127.0 (1), 117.2 (2), 77.4

(1), 58.4 (1). Ϫ IR (NaCl, neat): ν˜ ϭ 3386 (s), 3029 (m), 1495 (m),

1454 (s), 1051 (m), 1010 (m), 754 (s), 698 (s). Ϫ

Experimental Section

Methyl 2-Allyloxy-2-phenylacetate (6): To a solution of methyl

mandelate (3.00 g, 18.0 mmol) in ether (100 mL) was added allyl

bromide (2.3 mL, 27.0 mmol) and silver oxide (8.40 g, 36.0 mmol)

under an atmosphere of argon. The mixture was refluxed for 2

hours in the dark, and then stirring was continued for 48 hours at

room temperature. The silver salts were removed by filtration,

washed with ether (100 mL) and the solvent was removed in vacuo

to give analytically pure 6 (3.70 g, 99%). Ϫ C₁₂H₁₄O₃(206.2): calcd.

General Remarks: All experiments were conducted in dry reaction

vessels under an atmosphere of dry argon. Solvents were purified

by standard procedures. Ϫ Unless otherwise stated, ¹H NMR spec-

tra were recorded at 400 MHz in CDCl₃with CHCl₃as internal

standard (δ ϭ 7.24). Signal assignment for tetrahydropyran derivat-

ives refers to the numbering scheme denoted in Figure 1 and does

not necessarily correlate to systematic nomenclature. Ϫ ¹³C NMR

spectra were recorded at 100 MHz in CDCl₃with CDCl₃as in-

ternal standard (δ ϭ 77.0). In some cases, NMR spectra were re-

corded in C₆D₆(¹H NMR: C₆D₅H as internal standard, δ ϭ 7.18;

¹³C NMR: C₆D₆as internal standard, δ ϭ 128.0). J values are

given in Hz. The number of coupled protons was analysed by

DEPT experiments and is denoted by a number in parentheses fol-

lowing the δ_Cvalue. Ϫ IR spectra were recorded as films on NaCl

plates or as KBr disks. The peak intensities are defined as very

strong (vs), strong (s), medium (m), and weak (w). Ϫ Mass spectra

were obtained at 70 eV. Ϫ Melting points are not corrected. Ϫ Al-

cohols 1a؊g were prepared by addition of allylmagnesium bromide

to the appropriate aldehyde or ketone.^[66]4,4-Dimethyl-3,5,8-triox-

abicyclo[5.1.0]octane (5h)^[67]and 2-vinyl-1-cyclohexanol (1i)^[36]

have been described in the literature. Experimental and analytical

details for compounds 2a,b and c, 3a, b and c and 4a, b and c

have been described by us previously.^[24]The ruthenium catalyst

Cl₂(PCy₃)₂RuϭCHPh was prepared following Grubbs’ proced-

ure.^[68]

C 69.9, H 6.8; found C 69.4, H 6.8. LRMS (EI ); m/z: 207 (M^ϩ

ϩ

1, Ͻ5), 147 (95), 129 (10), 121 (36), 105 (100), 91 (12), 77 (8), 51

1

(10). Ϫ H NMR δ ϭ 7.48Ϫ7.43 (2 H, Ph), 7.37Ϫ7.30 (3 H, Ph),

5.93 (dddd, 1 H, J ϭ 17.3, 10.3, 6.0, 5.5, CHϭCH₂), 5.28 (dddd, 1

H, J ϭ 17.3, 1.5, 1.5, 1.5, CH₂ϭCH), 5.21 (ddm, 1 H, J ϭ 10.3,

1.3, CH₂ϭCH), 4.94 (s, 1 H, CHϪO), 4.06Ϫ4.03 (2 H, CH₂ϪO),

3.80 (s, 3 H, CH₃). Ϫ ¹³C NMR: δ ϭ 171.0 (0), 136.1 (0), 133.6

(1), 128.5 (1), 128.4 (1), 127.1 (1), 118.0 (2), 79.5 (1), 70.2 (2), 52.0

(3). Ϫ IR (NaCl, neat): ν˜ ϭ 3032 (w), 2953 (m), 2865 (w), 1755 (s),

1554 (m), 1209 (s), 1173 (s), 1101 (s), 699 s.

( )-3-Vinylpent-4-en-2-ol (1k):^[37a]To a solution of methyllactate

(6.00 g, 51.0 mmol) in ether (200 mL) was added vinylmagnesium

chloride (1.7  solution in THF, 120 mL, 203 mmol) at Ϫ70 °C.

The mixture was allowed to warm to room temperature and stirring

was continued for 12 hours. The reaction was poured onto satur-

ated NH₄Cl solution, extracted with ether and the organic layer

was dried with MgSO₄. Filtration and removal of the solvent under

reduced pressure gave crude 1l (5.60 g, 86%), which was sufficiently

pure for preparative purposes. Ϫ C₇H₁₂O₂(128.2): calcd. C 65.6,

H 9.4; found C 65.6, H 9.4. Ϫ [α]²_D³ϭ ϩ5.1 (c ϭ 1.66, DCM). Ϫ

General Procedure for the Preparation of Alcohols 1h؊j by Cleavage

of Epoxides: CuI (5.70 g, 30.0 mmol) was suspended in dry ether

(80 mL) and the mixture cooled to Ϫ60 °C. A solution of vinylmag-

nesium chloride (70.0 mmol, 41.0 mL) in THF was added, and the LRMS (EI); m/z: 111 (M^ϩϪ OH, 10%), 83 (20), 55 (100). Ϫ

mixture was stirred at Ϫ60 °C for 30 min. A solution of the epoxide

(30.0 mmol) in ether (25 mL) was slowly added and the reaction

mixture was warmed to Ϫ30 °C. Stirring was continued until the

starting material had been fully consumed as indicated by TLC.

¹H NMR: δ ϭ 5.95 (dd, 1 H, J ϭ 17.3, 10.8, CHϭCH₂), 5.93 (dd,

1 H, J ϭ 17.3, 10.8, CHϭCH₂), 5.38 (dd, 1 H, J ϭ 17.3, 1.3, CH₂ϭ

CH), 5.35 (dd, 1 H, J ϭ 17.3, 1.3, CH₂ϭCH), 5.23 (dd, 1 H, J ϭ

10.8, 1.3, CH₂ϭCH), 5.22 (dd, 1 H, J ϭ 10.8, 1.3, CH₂ϭCH), 3.67

The reaction mixture was poured onto aqueous NH₄Cl solution (dq, 1 H, J ϭ 6.5, 4.3, CHϪCH₃), 2.45 (br. s, 1 H, HO), 2.24 (br.

Eur. J. Org. Chem. 2000, 3145Ϫ3163 3151

B. Schmidt, H. Wildemann

FULL PAPER

s, 1 H, HO), 1.12 (d, 3 H, J ϭ 6.5, CH₃ϪCH). Ϫ ¹³C NMR: δ ϭ

7.42Ϫ7.22 (5 H, Ph), 5.92 (dddd, 1 H, J ϭ 17.1, 10.3, 5.3, 5.3,

140.0 (1), 138.0 (1), 115.7 (2), 115.3 (2), 78.4 (0), 72.7 (1), 16.8 (3). OCH₂CHϭCH₂), 5.69 (dddd, 1 H, J ϭ 17.1, 10.8, 7.0, 7.0,

Ϫ IR (NaCl, neat): ν˜ ϭ 3430 (s), 2987 (m), 1424 (m), 1087 (m), CH₂CHϭCH₂), 5.30 (dddd, 1 H, J ϭ 17.1, 1.8, 1.5, 1.5, ϭCH₂),

1001 (s), 930 (s).

5.13 (dddd, 1 H, J ϭ 10.3, 1.5, 1.5, 1.5, ϭCH₂), 5.02 (dm, 1 H,

J ϭ 10.8, ϭCH₂), 5.01 (dm, 1, J ϭ 17.1, ϭCH₂), 3.79 (dddd, 1 H,

J ϭ 12.6, 5.3, 1.5, 1.5, OCHH), 3.68 (dddd, 1 H, J ϭ 12.6, 5.3, 1.8,

1.5, OCHH), 2.61 (dd, 1 H, J ϭ 14.1, 7.0, CHH), 2.54 (dd, 1 H,

J ϭ 14.1, 7.0, CHH), 1.56 (s, 3 H, CH₃). Ϫ ¹³C NMR: δ ϭ 144.9

(0), 135.5 (1), 134.1 (1), 128.1 (1), 126.9 (1), 126.1 (1), 117.6 (2),

115.6 (2), 78.8 (0), 63.8 (2), 47.6 (2), 23.3 (3). Ϫ IR (NaCl, neat):

ν˜ ϭ 3076 (m), 2980 (s), 2859 (m), 1641 (m), 1446 (s), 1069 (s), 916

(s), 701 (s).

General Procedure for the Preparation of Allyl Ethers 2a؊j and

8a؊c: NaH (2.10 g 60% dispersion in mineral oil, 53.0 mmol) was

suspended in dry THF (100 mL). A solution of the corresponding

homoallylic or allylic alcohol 1 or 7, respectively, (34.0 mmol) in

THF (35 mL) was added dropwise with stirring at ambient temper-

ature. After the addition was complete, the mixture was heated to

reflux for 30 min and then cooled to ambient temperature. Allyl

bromide (4.4 mL, 51.0 mmol) was added slowly, causing an exo-

thermic reaction and formation of a white precipitate. The mixture

was stirred for one hour, after which time the starting material had

been consumed completely, as monitored by TLC. Water (50 mL)

was carefully added with stirring and the mixture was diluted with

MTBE (150 mL). The organic layer was washed with saturated

NH₄Cl solution and dried with MgSO₄. The solvent was evapor-

ated and the residue distilled or chromatographed on silica.

1-Allyl-1-allyloxycycloheptane (2g): Obtained from 1g (2.30 g,

15.0 mmol) as a colourless liquid. Yield: 2.80 g (96%). Ϫ LRMS

1

(EI); m/z: 153 (M^ϩϪ CH₂CHϭCH₂, 100%), 41 (88). Ϫ H NMR:

δ ϭ 5.89 (ddt, 1 H, J ϭ 17.3, 10.3, 5.3, OCH₂CHϭCH₂), 5.81 (ddt,

1 H, J ϭ 17.3, 10.5, 7.0, CH₂CHϭCH₂), 5.26 (ddt, 1 H, J ϭ 17.3,

1.8, 1.8, ϭCH₂), 5.08 (ddt, 1 H, J ϭ 10.3, 1.8, 1.5, ϭCH₂), 5.03

(dm, 1 H, J ϭ 10.5, ϭCH₂), 5.01 (dm, 1 H, J ϭ 17.3, ϭCH₂), 3.86

(ddd, 1 H, J ϭ 5.3, 1.5, 1.5, OCH₂), 2.23 (ddd, 1 H, J ϭ 7.0, 1.3,

1.3, OCHH), 1.77 (dd, 1 H, J ϭ 14.1, 8.5, CHH(cycloheptane),

1.65Ϫ1.30 (10 H, cycloheptane). Ϫ ¹³C NMR: δ ϭ 136.0 (1), 134.5

(1), 117.1 (2), 115.5 (2), 79.4 (0), 62.0 (2), 43.1 (2), 37.7 (2), 29.7

(2), 22.1 (2). Ϫ IR (NaCl, neat): ν˜ ϭ 3075 (m), 2978 (s), 2924 (vs),

2857 (vs), 1461 (s), 1127 (m), 1065 (s), 995 (s).

1-(( )-1-Allyloxybut-3-enyl)-4-methoxybenzene (2b): Obtained from

(S)-1b (2.30 g, 12.8 mmol) as a colourless liquid, b.p. 120 °C

(0.1 mbar), yield: 2.86 g (100%). Ϫ [α]²_D⁰ϭ Ϫ38.2 (c ϭ 2.44,

CHCl₃).

((1 *,2 *)-2-Allyloxy-1-methylpent-4-enyl)benzene (2d): Obtained

from 1d (3.70 g, 21.0 mmol) as a colourless liquid, b.p. 120 °C

(0.5 mbar), yield: 4.10 g (90%). Ϫ C₁₅H₂₀O (216.3): calcd. C 83.2,

H 9.3; found C 82.6, H 9.4. Ϫ LRMS (EI); m/z: 175 (M^ϩϪ 41,

49), 111 (100), 41 (64). Ϫ ¹H NMR: δ ϭ 7.30Ϫ7.15 (5 H, Ph), 5.88

(dddd, 1 H, J ϭ 17.3, 10.5, 5.6, 5.6, OCH₂CHϭ), 5.82 (dddd, 1 H,

J ϭ 17.3, 10.3, 7.3, 7.0, CHCH₂CHϭ), 5.24 (ddd, 1 H, J ϭ 17.3,

3.3, 1.8, ϭCH₂), 5.12 (ddd, 1 H, J ϭ 10.5, 3.0, 1.3, ϭCH₂), 5.02

(dm, 1 H, J ϭ 10.3, ϭCH₂), 4.99 (ddd, 1 H, J ϭ 17.3, 3.3, 1.3, ϭ

CH₂), 4.03 (dddd, 1 H, J ϭ 12.6, 5.6, 1.5, 1.5, OCH₂), 3.89 (dddd,

1 H, J ϭ 12.6, 5.6, 1.5, 1.5, OCH₂), 3.44 (ddd, 1 H, J ϭ 6.8, 6.5,

5.0, CHOϪ), 2.87 (qd, 1 H, J ϭ 7.0, 6.8, CHCH₃), 2.22 (ddd, 1 H,

J ϭ 14.5, 7.0, 5.0, CHCHHCHϭ), 2.07 (ddd, 1 H, J ϭ 14.5, 7.3,

6.5, CHCHHCHϭ), 1.33 (d, 3 H, J ϭ 7.0, CH₃). Ϫ ¹³C NMR:

δ ϭ 144.7 (0), 135.1 (1), 134.9 (1), 128.2 (1), 127.8 (1), 126.1 (1),

116.8 (2), 116.4 (2), 83.3 (1), 71.3 (2), 43.4 (1), 36.4 (2), 17.0 (3). Ϫ

IR (NaCl, neat): ν˜ ϭ 3078 (m), 2930 (m), 2858 (m), 1641 (m), 1453

(m), 1085 (s), 916 (s), 701 (s).

(5 *,6 *)-5-Allyloxy-2,2-dimethyl-6-vinyl-1,3-dioxepane (2h): Ob-

tained from 1h (5.90 g, 34.0 mmol) as a colourless liquid. Yield:

5.60 g (77%). Ϫ C₁₂H₂₀O₃(212.29): C 67.9, H 9.5; found C 67.9,

H, 9.5. Ϫ LRMS (EI); m/z: 212 (M^ϩ, 1%), 124 (23), 101 (70), 55

1

(100). Ϫ H NMR: δ ϭ 5.85 (dddd, 1 H, J ϭ 17.3, 10.3, 5.8, 5.8,

OCH₂CHϭCH₂), 5.70 (ddd, 1 H, J ϭ 17.3, 10.5, 7.8, CHCHϭ

CH₂), 5.23 (dddd, 1 H, J ϭ 17.3, 1.5, 1.5, 1.5, ϭCH₂), 5.13 (dm, 1

H, J ϭ 17.3, ϭCH₂), 5.11 (dm, 1 H, J ϭ 10.5, ϭCH₂), 4.05 (dddd,

1 H, J ϭ 12.8, 5.8, 1.5, 1.5, OCHHCHϭCH₂), 3.98 (dddd, 1 H,

J ϭ 12.8, 5.8, 1.3, 1.3, OCHHCHϭCH₂), 3.67 (dd, 1 H, J ϭ 12.3.

4.3, OCHH), 3.64 (dd, 1 H, J ϭ 12.3, 7.0, OCHH), 3.60 (dd, 1 H,

J ϭ 12.6, 3.6, OCHH), 3.53 (dd, 1 H, J ϭ 12.6, 8.5, OCHH), 3.21

(ddd, 1 H, J ϭ 7.3, 7.3, 4.3), 2.34 (ddd, 1 H, J ϭ 8.5, 7.3, 3.6),

1.31 (s, 3 H), 1.28 (s, 3 H). Ϫ ¹³C NMR: δ ϭ 136.9 (1), 135.0 (1),

117.0 (2), 117.0 (2), 101.0 (0), 80.1 (1), 70.9 (2), 61.7 (2), 61.6 (2),

49.1 (1), 24.7 (3), 24.4 (3). Ϫ IR (NaCl, neat): ν˜ ϭ 2990 (s), 2941

(s), 1380 (s), 1372 (s), 1220 (s), 1161 (s), 1085 (s), 919 (s).

((1 *,2 *)-2-Allyloxy-1-methylpent-4-enyl)benzene (2e): Obtained

from 1e (2.30 g, 13.0 mmol) as a colourless liquid, b.p. 120 °C

(0.5 mbar), yield: 2.30 g (81%). Ϫ LRMS (EI); m/z: 175 (M^ϩϪ 41,

47), 111 (100), 41 (51). Ϫ ¹H NMR: δ ϭ 7.33Ϫ7.17 (5 H, Ph), 5.85

(dddd, 1 H, J ϭ 17.0, 10.5, 7.0, 7.0, CH₂CHϭCH₂), 5.73 (dddd, 1

H, J ϭ 17.0, 10.2, 5.8, 5.3, OCHCH₂CHϭCH₂), 5.17 (dm, 1 H,

J ϭ 17.0, ϭCH₂), 5.09 (dm, 1 H, J ϭ 10.5, ϭCH₂), 5.07 (dm, 1 H,

J ϭ 10.1, ϭCH₂), 5.06 (dm, 1 H, J ϭ 17.0, ϭCH₂), 3.97 (dddd, 1

H, J ϭ 12.6, 5.8, 1.5, 1.5, OCH₂), 3.83 (dddd, 1 H, J ϭ 12.6, 5.3,

1.5, 1.5, OCH₂), 3.45 (ddd, 1 H, J ϭ 6.8, 6.8, 5.8, CHOϪ), 2.98

(qd, 1 H, J ϭ 6.8, 6.8, CHCH₃), 2.28Ϫ2.15 (2, CHCHHCHϭ),

1.33 (d, 3 H, J ϭ 6.8, CH₃). Ϫ ¹³C NMR: δ ϭ 143.9 (0), 135.4 (1),

135.3 (1), 128.3 (1), 128.0 (1), 126.2 (1), 116.7 (2), 116.3 (2), 83.4

(1), 71.4 (2), 42.9 (1), 35.8 (2), 16.7 (3). Ϫ IR (NaCl, neat): ν˜ ϭ

3078 (m), 2976 (s), 2858 (m), 1641 (m), 1453 (m), 1073 (s), 916 (s),

701 (s).

(1 *,2 *)-1-Allyloxy-2-vinylcyclohexane (2i): Obtained from 1i

(1.30 g, 10.0 mmol) as a colourless liquid. Yield: 1.40 g (85%). Ϫ

1

LRMS (EI); m/z: 167 (M^ϩϩ 1, 5%), 109 (100). Ϫ H NMR: δ ϭ

5.93Ϫ5.81 (2 H, ϪCHϭCH₂), 5.23 (dddd, 1 H, J ϭ 17.3, 1.8, 1.8,

1.8, ϭCH₂), 5.09 (dddd, 1 H, J ϭ 10.3, 1.8, 1.3, 1.3, ϭCH₂), 5.03

(ddd, 1 H, J ϭ 17.6, 1.8, 1.3, ϭCH₂), 4.97 (ddd, 1 H, J ϭ 10.3,

1.8, 1.0, ϭCH₂), 4.05 (dddd, 1 H, J ϭ 12.8, 5.5, 1.5, 1.5, OCHH),

3.91 (dddd, 1 H, J ϭ 12.8, 5.5, 1.5, 1.5, OCHH), 2.98 (ddd, 1 H,

J ϭ 9.5, 9.5, 4.4, CHCHOCH₂), 2.10Ϫ1.95 (2 H, CH, CH₂),

1.80Ϫ1.68 (2 H, CH, CH₂), 1.60 (m, 1 H, CH, CH₂), 1.26Ϫ1.10 (4

H, CH, CH₂). Ϫ ¹³C NMR: δ ϭ 141.6 (1), 135.6 (1), 116.2 (2),

113.9 (2), 81.0 (1), 69.8 (2), 47.6 (1), 31.3 (2), 31.0 (2), 25.0 (2), 24.6

(2). Ϫ IR (NaCl, neat): ν˜ ϭ 3079 (m), 2926 (vs), 2856 (vs), 1640

(m), 1449 (m), 1093 (s), 912 (s), 805 (m).

(1 *,2 *)-1-Allyloxy-1,2-diphenylbut-3-ene (2j): Obtained from 1j

(1.00 g, 5.0 mmol) as a colourless liquid. Yield: 1.00 g (84%). Ϫ

(1-Allyloxy-1-methylbut-3-enyl)benzene (2f): Obtained from 1f

(3.00 g, 18.0 mmol) as a colourless liquid. Yield: 3.60 g (89%). Ϫ

LRMS (EI); m/z: 207 (M^ϩϪ OCH₂CHϭCH₂, 40%), 147 (100),

1

C₁₄H₁₈O (202.3): calcd. C 83.1, H 8.9; found C 82.9, H 9.2. Ϫ 105 (90). Ϫ H NMR: δ ϭ 7.45Ϫ7.05 (5 H, Ph), 5.95 [ddd, 1 H,

LRMS (EI); m/z: 161 (M^ϩϪ 41,), 145 (100). Ϫ ¹H NMR: δ ϭ

J ϭ 17.1, 10.0, 8.3, CH(Ph)CHϭCH₂], 5.72 (dddd, 1 H, J ϭ 16.8,

Eur. J. Org. Chem. 2000, 3145Ϫ3163

3152

Synthesis of Densely Functionalized 2,3-Dihydropyrans

FULL PAPER

10.5, 5.9, 4.8, OCH₂CHϭCH₂), 5.07 (dm, 1 H, J ϭ 16.8, ϭCH₂),

10.8, 1.5, CH₂ϭCHϪC), 5.13 (dd, 1 H, J ϭ 10.8, 1.5, CH₂ϭ

5.06 (dm, 1 H, J ϭ 10.0, ϭCH₂), 4.95 (dm, 1 H, J ϭ 10.5, ϭCH₂), CHϪC), 5.09 (dddd, 1 H, J ϭ 10.3, 3.0, 1.5, 1.5, CH₂ϭCHϪCH₂),

4.86 (dm, 1 H, J ϭ 17.1, ϭCH₂), 4.58 [d, 1 H, J ϭ 7.5, OCH(Ph)],

3.89 (dddd, 1 H, J ϭ 13.3, 4.8, 1.8, 1.5, OCHH), 3.66 (dddd, 1 H,

4.05 (dddd, 1 H, J ϭ 12.8, 5.5, 1.5, 1.5, CH₂ϪCH), 3.87 (dddd, 1

H, J ϭ 12.8, 6.0, 1.5, 1.5, CH₂ϪCH), 3.35 (q, 1 H, J ϭ 6.3,

J ϭ 13.3, 5.9, 1.3, 1.3, OCHH), 3.65 (dd, 1 H, J ϭ 8.3, 7.5, CHPh). CHϪCH₃), 2.53 (br. s, 1 H, HO), 1.07 (d, 3 H, J ϭ 6.3, CH₃ϪCH).

¹³C NMR: δ ϭ 141.1 (0), 140.2 (0), 138.4 (1), 134.8 (1), ¹³C NMR: δ ϭ 139.9 (1), 138.8 (1), 134.8 (1), 116.8 (2), 114.7

129.0Ϫ127.0 (1), 126.3 (1), 125.4 (1), 116.5 (2), 116.4 (2), 84.1 (1), (2), 114.6 (2), 80.1 (1), 77.7 (0), 70.6 (2), 14.1 (3). Ϫ IR (NaCl,

Ϫ

69.4 (2), 57.3 (1). Ϫ IR (NaCl, neat): ν˜ ϭ 3083 (m), 3028 (m), 2859

neat): ν˜ ϭ 3464 (s), 2983 (m), 2871 (m), 1411 (m), 1374 (m), 1091

(m), 1494 (m), 1452 (m), 1088 (s), 1069 (s), 919 (s), 699 (s).

(s), 995 (s), 924 (s).

1-Allyloxy-1-vinylcyclohexane (8a):^[69]Obtained from 7a (3.50 g,

28.0 mmol) as a colourless liquid. Yield: 2.40 g (52%). Ϫ ¹H NMR:

δ ϭ 5.87 (ddt, 1 H, J ϭ 17.1, 10.5, 5.5, OCH₂CHϭCH₂), 5.69 (dd,

1 H, J ϭ 17.6, 11.1, CHHCHϭCH₂), 5.23 (ddt, 1 H, J ϭ 17.1, 1.8,

(1 ,2 )-1-Allyloxy-1-phenyl-but-3-en-2-ol (2l): To a solution of

ester 6 (2.50 g, 12.0 mmol) in ether (100 mL) was added at Ϫ90 °C

DIBAL (2.6 mL, 15 mmol). After complete consumption of the es-

ter (TLC control), vinylmagnesium chloride (1.7  solution in

1.8, OCH₂CHϭCH₂), 5.11 (dd, 1 H, J ϭ 11.1, 1.3, CHϭCH₂), 5.09 THF, 10.7 mL, 18 mmol) was added and the mixture was slowly

(dd, 1 H, J ϭ 17.6, 1.5, CHϭCH₂), 5.05 (ddt, 1 H, J ϭ 10.6, 1.8, warmed to room temperature. After stirring for 12 hours, the reac-

1.5, OCH₂CHϭCH₂), 3.74 (ddd, 1 H, J ϭ 10.6, 1.8, 1.5, tion was poured into water, the precipitate was dissolved with the

OCHHCHϭCH₂), 1.77Ϫ1.15 (10 H, CH₂). Ϫ ¹³C NMR: δ ϭ 143.1 minimum amount possible of 2  HCl (aq), and the mixture was

(1), 135.9 (1), 115.3 (2), 114.4 (2), 75.8 (0), 62.6 (2), 34.3 (2), 25.7 extracted with ether. The organic extracts were dried and evapor-

(2), 21.7 (2).

ated, and the residue was purified by column chromatography on

silica (hexanes/MTBE, 3:1) to give 2k (2.40 g, 97%) as an insepar-

able mixture of diastereomers (1S*,2S*):(1S*,2R*) ϭ 5:1. Ϫ

LRMS (EI); m/z: 187 (M^ϩϪ OH, 29), 169 (18), 147 (100), 129

(65), 117 (25), 105 (100), 91 (28), 57 (10), 51 (10). Ϫ ¹H NMR: δ ϭ

7.28Ϫ7.19 (5 H, Ph), 5.81 (dddd, 1 H, J ϭ 17.3, 10.5, 6.3, 5.0,

CH₂ϪCH), 5.52 (ddd, 1 H, J ϭ 17.3, 10.5, 5.5, CHϪCHϭCH₂),

5.16 (dddd, 1 H, J ϭ 17.3, 1.5, 1.5, 1.5, CH₂ϭCHϪCH₂), 5.12

(ddd, 1 H, J ϭ 17.3, 1.5, 1.3, CH₂ϭCHϪCH), 5.09 (dddd, 1 H,

J ϭ 10.5, 1.5, 1.3, 1.3, CH₂ϭCHϪCH₂), 4.99 (ddd, 1 H, J ϭ 10.5,

1.5, 1.5, CH₂ϭCHϪCH), 4.15 (dddd, 1 H, J ϭ 8.0, 5.5, 1.5, 1.3,

CHϪOH), 4.06 (d, 1 H, J ϭ 8.0, CHϪPh), 3.89 (dddd, 1 H, J ϭ

12.6, 5.0, 1.5, 1.5, CH₂ϪCH), 3.73 (dddd, 1 H, J ϭ 12.6, 6.3, 1.5,

1.3, CH₂ϪCH), 3.07 (br. s, 1 H, HO). Ϫ ¹³C NMR: δ ϭ 137.8 (0),

135.4 (1), 134.3 (1), 128.3 (1), 128.2 (1), 127.8 (1) 117.3 (2), 116.9

(2), 85.1 (1), 76.1 (1), 69.5 (2). Ϫ IR (NaCl, neat): ν˜ ϭ 3464 (s),

3083 (m), 2866 (m), 1647 (w), 1453 (m), 1256 (m), 1083 (s), 995 (s),

926 (s), 702 s. Ϫ NMR spectroscopical data of the minor diastere-

omer (partially overlapped by the signals for the major isomer): ¹H

NMR: δ ϭ 4.34 (d, 1 H, J ϭ 5.0, CHϪPh), 3.95 (dddd, 1 H, J ϭ

12.8, 5.0, 1.5, 1.5, CH₂ϪCH). Ϫ ¹³C NMR: δ ϭ 137.8 (0), 136.3

(1), 134.4 (1), 128.3 (1), 127.9 (1), 127.6 (1), 117.1 (2), 116.5 (2),

83.9 (1), 75.7 (1), 69.9 (2).

3-Allyloxyoct-1-ene (8b):^[70]Obtained from 7b (6.50 g, 51.0 mmol)

as a colourless liquid, b.p. 100 °C (7 mbar). Yield: 6.50 g (76%). Ϫ

¹H NMR: δ ϭ 5.88 (dddd, 1 H, J ϭ 17.3, 10.3, 6.0, 5.0, OCH₂CHϭ

CH₂), 5.64 (ddd, 1 H, J ϭ 16.6, 10.8, 7.8, CHCHϭCH₂), 5.23

(dddd, 1 H, J ϭ 17.3, 1.8, 1.8, 1.8, OCH₂CHϭCH₂), 5.17Ϫ5.10 (3

H, CHHCHϭCH₂ϩ CHCHϭCH₂), 4.01 (dddd, 1 H, J ϭ 12.8,

5.0, 1.5, 1.5, OCHH), 3.80 (dddd, 1 H, J ϭ 12.8, 6.0, 1.5, 1.3,

OCHH), 3.64 (ddd, 1 H, J ϭ 7.8, 6.4, 6.4, OCHCHϭ), 1.66Ϫ1.20

(8 H, CH₂), 0.85 (t, 3 H, J ϭ 7.0, CH₃). Ϫ ¹³C NMR: δ ϭ 139.2

(1), 135.2 (1), 116.7 (2), 116.5 (2), 80.7 (1), 69.1 (2), 35.4 (2), 31.8

(2), 25.0 (2), 22.6 (2), 14.0 (3).

1-(1-Allyloxyallyl)-4-methoxybenzene (8c): Obtained from 7c

(4.50 g, 27.0 mmol) as a colourless liquid, b.p. 175 °C (0.3 mbar).

Yield: 3.50 g (63%). Ϫ LRMS (EI) m/z: 204 (M^ϩ, 25%), 163 (77),

1

147 (73), 135 (100). Ϫ H NMR: δ ϭ 7.16 (d, 2 H, J ϭ 8.3, Ar),

6.78 (d, 2 H, J ϭ 8.3, Ar), 5.89Ϫ5.77 (2 H, CHϭ), 5.17 (dddd, 1

H, J ϭ 17.3, 1.8, 1.8, 1.8, OCH₂CHϭCH₂), 5.15 (ddd, 1 H, J ϭ

17.1, 1.5, 1.5, CHCHϭCH₂), 5.07 (ddd, 1 H, J ϭ 10.3, 1.5, 1.0,

CHCHϭCH₂), 5.06 (dddd,

1 H, J ϭ 10.5, 1.8, 1.5, 1.5,

OCH2CHCH2), 4.65 (d, 1 H, J ϭ 6.5, CHO), 3.87 (dddd, 1 H,

J ϭ 12.8, 5.5, 1.5, 1.3, OCHH), 3.83 (dddd, 1 H, J ϭ 12.8, 7.0, 1.5,

1.5, OCHH), 3.67 (s, 3 H, OCH₃). Ϫ ¹³C NMR: δ ϭ 159.0 (0),

139.0 (1), 134.8 (1), 133.0 (1), 128.1 (1), 116.6 (2), 115.8 (2), 113.7

(1), 81.5 (1), 68.9 (2), 55.1 (3). Ϫ IR (KBr, neat): ν˜ ϭ 2836 (m),

1611 (s), 1512 (s), 1247 (s), 1071 (m), 1036 (m), 924 (m), 829 (m).

General Procedure for the Preparation of Dihydropyrans 3 and Dihy-

drofurans 9: The ruthenium catalyst (138 mg, 2 mol-%) was added

in one portion to a solution of the corresponding ether 2 or 8

(8.4 mmol) in DCM (40 mL). The mixture was stirred at room tem-

perature until complete conversion was indicated by TLC (approx-

imately 0.5 h). The solvent was evaporated and the residue was

purified by kugelrohr distillation or by flash chromatography as

indicated for the individual compounds.

( )-3-(1-Allyloxyethyl)-penta-1,4-dien-3-ol (2k): A solution of diol

1k ( 1.00 g, 8.0 mmol) was cooled to 0 °C. NaH (60% dispersion in

mineral oil, 0.31 g, 8.0 mmol) was added, followed by allyl bromide

(1.0 mL, 12.0 mmol). The mixture was stirred at 0 °C for 12 hours,

after which time the reaction was complete as indicated by TLC.

The reaction was diluted with MTBE, hydrolysed with saturated

NH₄Cl solution, dried with MgSO₄, filtered and the solvent was

removed in vacuo. The residue was purified by flash chromato-

graphy (hexanes/MTBE, 2:1). Yield: 0.67 g (51%). Ϫ C₁₀H₁₆O₂

(168.23): C 71.4, H 9.6; found C 71.4, H 9.6. Ϫ [α]²_D⁶ϭ ϩ19.6 (c ϭ

( )-2-(4-Methoxyphenyl)-3,6-dihydro-2 -pyran (3b): Obtained from

(S)-2b (1.10 g, 5.0 mmol) as a colourless liqid, b.p. 150 °C

(0.09 mbar), yield: 0.87 g (91%). Ϫ [α]²_D⁰ϭ Ϫ73.7 (c ϭ 2.78,

CHCl₃).

( *)-2-[( *)-1-Phenylethyl)]-3,6-dihydro-2 -pyran (3d): Obtained

1.40, CHCl₃). Ϫ LRMS (EI); m/z: 163 (M^ϩϩ 1, Ͻ 5), 151 (10), from 2d (2.10 g, 10.0 mmol) as a colourless liquid. TLC: cyclohex-

133 (10), 107 (14), 95 (90), 85 (26), 73 (16), 67 (16), 55 (100). Ϫ ane/ether 40:1. Purification by kugelrohr distillation, b.p. 130 °C

¹H NMR: δ ϭ 5.92 (dd, 1 H, J ϭ 17.3, 10.3, CϪCHϭCH₂), 5.91 (0.3 mbar). Yield: 1.70 g (90%). Ϫ LRMS (EI); m/z: 188 (M^ϩ, 4),

(dd, 1 H, J ϭ 17.3, 10.8, CϪCHϭCH₂), 5.82 (dddd, 1 H, J ϭ 17.3,

10.3, 6.0, 5.5, CH₂ϪCHϭCH₂), 5.31 (dd, 1 H, J ϭ 17.3, 1.5 CH₂ϭ

105 (85), 83 (100), 55 (81). Ϫ ¹H NMR: δ ϭ 7.32Ϫ7.25 (2, Ph),

7.23Ϫ7.18 (3 H, Ph), 5.75Ϫ5.65 (2 H, H3,4), 4.30Ϫ4.18 (2 H, H5_ax/eq),

CHϪC), 5.29 (dd, 1 H, J ϭ 17.3, 1.5, CH₂ϭCHϪC), 5.19 (dddd, 3.54 (ddd, 1 H, J ϭ 10.3, 8.5, 3.3, H2), 2.74 (dq, 1 H, J ϭ 8.5,

1 H, J ϭ 17.3, 3.0, 1.5, 1.5, CH₂ϭCHϪCH₂), 5.13 (dd, 1 H, J ϭ

Eur. J. Org. Chem. 2000, 3145Ϫ3163

6.8, CHCH₃), 1.92 (dddd, 1 H, J ϭ 17.1, 10.3, 3.5, 3.5, H3_ax), 1.63

3153

B. Schmidt, H. Wildemann

FULL PAPER

(dm, 1 H, J ϭ 17.1, H3_eq), 1.38 (d, 3 H, J ϭ 6.8, CH₃). Ϫ ¹³C (4 H, CH₂), 1.35Ϫ1.20 (3 H, CH₂), 1.00 (m, 1 H, CH, CH₂), 0.81

NMR: δ ϭ 144.2 (0), 128.3 (1), 127.8 (1), 126.3 (1), 126.0 (1), 124.4

(m, 1 H, CH, CH₂). Ϫ ¹³C NMR: δ ϭ 129.6 (1), 125.6 (1), 78.7

(1), 78.3 (1), 66.3 (2), 45.6 (1), 29.5 (2), 18.4 (3). Ϫ IR (NaCl, neat): (1), 66.3 (2), 40.8 (1), 32.0 (2), 30.5 (2), 25.9 (2), 25.1 (2). Ϫ IR

ν˜ ϭ 3061 (m), 3030 (m), 2929 (s), 2829 (s), 1494 (m), 1452 (m), (NaCl, neat): ν˜ ϭ 3076 (m), 2924 (s), 2852 (s), 1641 (m), 1449 (m),

1180 (m), 1091 (s), 701 (s).

1081 (s), 912 (m), 708 (m).

(2 *,3 *)-2,3-Diphenyl-3,6-dihydro-2 -pyran (3j): Obtained from

2j (1.00 g, 3.8 mmol) as a colourless liquid. TLC: cyclohexane/ether

20:1. Purification by flash chromatography. Yield: 0.81 g (89%). Ϫ

LRMS (EI); m/z: 235 (M^ϩϪ 1, 5%), 219 (40), 130 (100). Ϫ ¹H

NMR: δ ϭ 7.14Ϫ7.05 (6 H, Ph), 6.96Ϫ6.90 (4 H, Ph), 6.13Ϫ6.02

(2 H,H3,4), 4.97 (d, 1 H, J ϭ 3.3, H2), 4.60 (d, 1 H, J ϭ 17.0, H6),

4.51 (d, 1 H, J ϭ 17.0, H6), 3.48 (m, 1 H, H3). Ϫ ¹³C NMR: δ ϭ

140.4 (0), 138.5 (0), 129.9 (1), 128.1 (1), 127.5 (1), 127.3 (1), 126.7

(1), 126.4 (1), 126.3 (1), 125.8 (1), 79.2 (1), 67.2 (2), 47.7 (1). Ϫ IR

(NaCl, neat): ν˜ ϭ 3030 (m), 1452 (s), 1093 (s), 741 (s), 699 (s).

( *)-2-[( *)-1-Phenylethyl]-3,6-dihydro-2 -pyran (3e): Obtained

from 2e (1.10 g, 5.0 mmol) as a colourless liquid. TLC: cyclohex-

ane/ether 40:1. Purification by kugelrohr distillation, b.p. 130 °C

1

(0.3 mbar). Yield: 0.80 g (85%). Ϫ H NMR: δ ϭ 7.26Ϫ7.10 (5 H,'

Ph), 5.73 (dm, 1 H, J ϭ 10.0, H3), 5.62 (dm, 1 H, J ϭ 10.0, H4),

4.08 (dm, 1 H, J ϭ 16.5, H5), 4.01 (dm, 1 H, J ϭ 16.5, H5), 3.58

(ddd, 1 H, J ϭ 10.0, 7.3, 3.5, H2), 2.80 (dq, 1 H, J ϭ 7.3, 7.0,

CHCH₃), 2.03 (ddm, 1 H, J ϭ 17.1, 10.0, H3_ax), 1.92 (dm, 1 H,

J ϭ 17.1, H3_eq), 7.0, 6.8, H3_eq), 1.20 (d, 3 H, J ϭ 7.0, CH₃). Ϫ

¹³C NMR: δ ϭ 144.5 (0), 128.1 (1), 127.8 (1), 126.3 (1), 126.1 (1),

124.2 (1), 77.7 (1), 66.4 (2), 44.8 (1), 28.3 (2), 17.2 (3). Ϫ IR (NaCl,

neat): ν˜ ϭ 3061 (m), 3030 (m), 2929 (s), 2831 (s), 1494 (m), 1452

(m), 1180 (m), 1089 (s), 700 (s).

(2 ,3 )- and (2 ,3 )-2-Methyl-3-vinyl-3,6-dihydro-2 -pyran-3-ol

(3k): Obtained from triene 2k (1.46 g, 6.0 mmol) as a 2.5:1 mixture

of diastereomers. TLC: hexanes/MTBE, 2:1. Purification by flash

chromatography on silica. Yield: 0.55 g (66%). Ϫ [α]²_D⁶ϭ ϩ150.2

(c ϭ 1.64, CHCl₃). Ϫ LRMS (EI); m/z: 123 (M^ϩϪ OH, 84), 95

(75), 81 (100), 78 (12), 69 (18), 67 (50), 55 (36). Ϫ IR (NaCl, neat):

ν˜ ϭ 3442 (s), 2985 (m), 1376 (m), 1065 (s), 993 (s), 972 (s), 925 (m).

2-Methyl-2-phenyl-3,6-dihydro-2 -pyran (3f): Obtained from 2f

(3.40 g, 17.0 mmol) as a colourless liquid. TLC: cyclohexane/ether

40:1. Purification by kugelrohr distillation, b.p. 150 °C (0.3 mbar).

Yield: 2.80 g (95%). Ϫ C₁₂H₁₄O (174.2): calcd.C 82.7, H 8.1; found

C 82.6, H 8.4. Ϫ LRMS (EI); m/z: 174 (M^ϩ, 15%), 157 (100). Ϫ

¹H NMR: δ ϭ 7.45 (d, 2 H, J ϭ 8.0, Ph, ortho-H), 7.35 (dd, 2 H,

J ϭ 8.0, 7.3, Ph, meta-H), 7.25 (t, 1 H, J ϭ 7.3, Ph, para-H), 5.87

(dm, 1 H, J ϭ 10.3, H3,4), 5.62 (dm, 1 H, J ϭ 10.3, H3,4), 4.18

(dm, 1 H, J ϭ 16.8, H5), 3.96 (dm, 1 H, J ϭ 16.8, H5), 2.68 (dm,

1 H, J ϭ 17.6, H3), 2.39 (dm, 1 H, J ϭ 17.6, H3), 1.50 (s, 3 H,

CH₃). Ϫ ¹³C NMR: δ ϭ 145.2 (0), 128.1 (1), 126.8 (1), 125.9 (1),

125.5 (1), 123.0 (1), 73.6 (0), 61.7 (2), 34.0 (2), 29.4 (3). Ϫ IR (NaCl,

neat): ν˜ ϭ 3034 (m), 2975 (s), 2927 (s), 2833 (s), 1494 (m), 1445 (s),

1088 (m), 763 (s), 700 (s).

1

Ϫ (2 , 3 )-3k: H NMR: δ ϭ 5.92 (ddd, 1 H, J ϭ 10.0, 4.0, 3.5,

CHϭCH), 5.80 (ddd, 1 H, J ϭ 10.0, 1.5, 1.5, CHϭCH), 5.78 (dd,

1 H, J ϭ 17.6, 10.8, CHϭCH₂), 5.36 (dd, 1 H, J ϭ 17.6, 1.5, CH₂ϭ

CH), 5.20 (dd, 1 H, J ϭ 10.8, 1.5, CH₂ϭCH), 4.22 (ddd, 1 H, J ϭ

16.8, 3.5, 1.8, CH₂ϪCH), 4.16 (ddd, 1 H, J ϭ 16.8, 4.0, 1.5,

CH₂ϪCH), 3.50 (q, 1 H, J ϭ 6.3, CHϪCH₃), 2.58 (br. s, 1 H, HOϪ),

1.21 (d, 3 H, J ϭ 6.3, CH₃ϪCH). Ϫ ¹³C NMR: δ ϭ 139.5 (1), 130.7

(1),128.2 (1), 115.0 (2), 77.7 (1), 70.0 (0), 65.7 (2), 14.1 (3). ؊ (2 ,

3 )-3k: ¹H NMR: δ ϭ 5.98 (dd, 1 H, J ϭ 17.6, 10.8, CHϭCH₂),

5.27 (dd, 1 H, J ϭ 17.3, 1.5, CH₂ϭCH), 5.22 (dd, 1 H, J ϭ 10.8, 1.5,

CH₂ϭCH), 3.57 (q, 1 H, J ϭ 6.3, CHϪCH₃), 2.46 (br. s, 1 H, HOϪ),

1.17 (d, 3 H, J ϭ 6.3, CH₃ϪCH). Ϫ ¹³C NMR: δ ϭ 138.3 (1), 131.0

(1), 126.2 (1), 114.4 (2), 77.0 (1), 71.9 (0), 65.2 (2), 14.8 (3).

1-Oxaspiro[5,6]dodec-3-ene (3g):^[71]Obtained from 2g (1.46 g,

7.5 mmol) as a colourless liquid. TLC: cyclohexane/ether 20:1.

Purification by kugelrohr distillation, b.p. 150 °C (7 mbar). Yield:

(2 ,3 )-2-Phenyl-3,6-dihydro-2 -pyran-3-ol (3l): Obtained from

2l (2.10 g, 10.0 mmol) as a colourless liquid; 5:1 mixture of diaster-

eomers. TLC: hexanes/MTBE 2:1. Purification by flash chromato-

graphy on silica. Yield: 1.25 g (69%). Ϫ LRMS (EI); m/z: 177 (M^ϩ

ϩ 1, 56), 161 (10), 149 (12), 135 (100), 121 (80), 91 (50), 77 (58),

65 (20), 51 (30). Ϫ ¹H NMR: δ ϭ 7.31Ϫ7.27 (5 H, Ph), 6.03 (dddd,

1 H, J ϭ 10.0, 5.3, 3.3, 3.0, CHϭCHϪCH₂), 5.94 (ddd, 1 H, J ϭ

10.0, 3.5, 1.5, CHϪCH₂), 4.53 (d, 1 H, J ϭ 1.7, CHϪC), 4.34 (ddd,

1 H, J ϭ 17.1, 3.5, 1.8, CH₂), 4.21 (dm, 1 H, J ϭ 16.9, CH₂), 3.96

(m, 1 H, CHϪOH), 1.63 (d (br.), 1 H, J ϭ 7.3, HO). Ϫ ¹³C NMR:

δ ϭ 138.5 (0), 130.2 (1), 128.2 (1), 127.4 (1), 126.5 (1), 126.0 (1),

79.2 (1), 66.6 (2), 64.9 (1). Ϫ IR (NaCl, neat): ν˜ ϭ 3443 (s), 3034

(m), 2823 (m), 1452 (m), 1182 (m), 1092 (s), 1022 (s), 733 (s), 700

s. Spectroscopical data of the minor diastereomer (2S*, 3R*)-3l

(partially overlapped by the signals of the major isomer): ¹H NMR:

δ ϭ 7.35Ϫ7.20 (5 H, Ph), 1.92 (br. s, 1 H, HO). Ϫ ¹³C NMR: δ ϭ

139.4 (0), 128.4 (1), 128.2 (1), 128.0 (1), 127.7 (1), 127.1 (1), 81.0

(1), 68.7 (2), 65.9 (1).

1-Oxaspiro[4,5]dec-3-ene (9a):^[71]Obtained from 8a (1.20 g,

7.2 mmol) as a colourless liquid. TLC: cyclohexane/ether 30:1.

Purification by kugelrohr distillation at 125 °C (7 mbar). Yield:

0.90 g (90%). Ϫ ¹H NMR: δ ϭ 5.84 (dt, 1 H, J ϭ 6.3, 2.3, H4),

5.78 (dt, 1 H, J ϭ 6.3, 1.0, H3), 4.59 (dd, 1 H, J ϭ 2.3, 1.0, H5),

1.71Ϫ1.30 (10 H, CH₂). Ϫ ¹³C NMR: δ ϭ 133.8 (1), 125.1 (1), 89.4

(0), 73.6 (2), 37.0 (2), 25.4 (2), 23.4 (2).

1

1.12 g (90%). Ϫ H NMR: δ ϭ 5.71Ϫ5.63 (2 H, H4,5), 4.06 (m, 2

H, H6), 1.92 (m, 2 H, H3), 1.80Ϫ1.30 (12 H, CH₂). Ϫ ¹³C NMR:

δ ϭ 125.7 (1), 123.2 (1), 74.5 (0), 60.6 (2), 38.2 (2), 35.7 (2), 29.9

(2), 21.8 (2).

(5 *,11 *)-8,8-Dimethyl-1,7,9-trioxabicyclo[5.4.0]undec-3-ene (3h):

Obtained from 2h (5.50 g, 26.0 mmol) as a colourless liquid. TLC:

cyclohexane/ether, 3:1. Purification by kugelrohr distillation, b.p.

160 °C (3 mbar). Yield: 4.40 g (92%). Ϫ C₁₀H₁₆O₃(184.2): calcd.

C 65.2, H 8.8; found C 65.5, H 8.7. Ϫ LRMS (EI); m/z: 183 (M^ϩ

1

Ϫ 1, 48%), 125 (58), 95 (60), 43 (100). Ϫ H NMR: δ ϭ 5.36 (dm,

1 H, J ϭ 10.3, H5), 5.31 (dm, 1 H, J ϭ 10.3, H4), 4.07 (dm, 1 H,

J ϭ 16.8, H6), 3.99 (dddd, 1 H, J ϭ 16.8, 4.5, 1.5, 1.5, H6), 3.86

(dd, 1 H, J ϭ 11.5, 4.5, C-2CHHO), 3.81 (dd, 1 H, J ϭ 11.5, 8.8,

C-2CHHO), 3.38 (dd, 1 H, J ϭ 12.1, 4.8, C-3CHHO), 3.33 (dd, 1

H, J ϭ 12.1, 10.0, C-3CHHO), 3.27 (ddd, 1 H, J ϭ 8.8, 8.8, 4.5,

H2), 2.47 (m, 1 H, H3), 1.28 (s, 3 H, CH₃), 1.27 (s, 3 H, CH₃). Ϫ

¹³C NMR: δ ϭ 127.7 (1), 125.4 (1), 101.3 (0), 78.6 (1), 67.0 (2),

64.8 (2), 62.3 (2), 43.2 (1), 25.1 (3), 25.0 (3). Ϫ IR (NaCl, neat):

ν˜ ϭ 3028 (m), 2940 (m), 1220 (s), 1094 (s), 1076 (s), 838 (m).

(5 *,10 *)-1-Oxabicyclo[4.4.0]dec-3-ene (3i): Obtained from 2i

(1.60 g, 10.0 mmol) as a colourless liquid. TLC: cyclohexane/ether,

40:1. Purification by kugelrohr distillation, b.p. 130 °C (7 mbar).

Yield: 1.30 g (95%). Ϫ LRMS (EI); m/z: 139 (M^ϩϩ 1, 100%), 121

1

(60). Ϫ H NMR: δ ϭ 5.60 (dm, 1 H, J ϭ 10.0, H3,4), 5.55 (dm,

1 H, J ϭ 10.0, H3,4), 4.21 (dm, 1 H, J ϭ 16.6, H6), 4.15 (dm, 1

2-Pentyl-2,5-dihydrofuran (9b):^[72]Obtained from 8b (2.00 g,

H, J ϭ 16.6, H6), 3.01 (ddd, 1 H, J ϭ 10.8, 9.0, 3.8, H2), 1.96Ϫ1.60 11.9 mmol) as a colourless liquid. TLC: cyclohexane/ether 50:1.

3154 Eur. J. Org. Chem. 2000, 3145Ϫ3163

Synthesis of Densely Functionalized 2,3-Dihydropyrans

FULL PAPER

Purification by kugelrohr distillation at 125 °C (7 mbar). Yield: stereomer

-4b: Colourless liquid. Yield: 0.31 g (33%). Ϫ [α]²_D⁰

ϭ

1

1.10 g (66%). Ϫ H NMR: δ ϭ 5.82 (dddd, 1 H, J ϭ 6.3, 2.0, 1.8, Ϫ41.7 (c ϭ 0.60, CHCl₃). Ϫ Diastereomer -4b: Colourless liquid.

1.8, H3,4), 5.74 (dm, 1 H, J ϭ 6.3, H3,4), 4.77 (m, 1 H, H2), 4.61

(dddd, 1 H, J ϭ 12.6, 5.8, 2.3, 1.5, H5), 4.55 (dddd, 1 H, J ϭ 12.6,

4.3, 2.3, 1.5, H5), 1.52Ϫ1.47 (2 H, CH₂) 1.40Ϫ1.20 (6 H, CH2),

0.88Ϫ0.80 (3 H, CH₃). Ϫ ¹³C NMR: δ ϭ 129.8 (1), 126.2 (1), 86.1

(1), 74.9 (2), 36.0 (2), 31.9 (2), 24.9 (2), 22.6 (2), 14.0 (3).

Yield: 0.30 g (32%). Ϫ [α]²_D⁰ϭ Ϫ47.0 (c ϭ 0.67, CHCl₃).

(1 *,4 *)-4-[( *)-1-Phenylethyl]-3,7-dioxabicyclo[4.1.0]heptane

(

-4d) and (1 *,4 *)-4-[( *)-1-Phenylethyl]-3,7-dioxabicy-

clo[4.1.0]heptane ( -4d): Obtained from 3d (1.00 g, 5.3 mmol).

Method A. TLC: cyclohexane/ether 20:1. Purification and separa-

tion of diastereomers by column chromatography on silica. Ϫ Dia-

2-(4-Methoxyphenyl)-2,5-dihydrofuran (9c): Obtained from 8c

(1.24 g, 6.1 mmol) as a colourless liquid. TLC: cyclohexane/ether

10:1. Purification by kugelrohr distillation at 125 °C (0.15 mbar).

Yield: 0.94 g (87%). Ϫ C₁₁H₁₂O₂(176.2): calcd. C 74.9, H 6.9;

found C 74.2, H, 7.1. Ϫ LRMS (EI); m/z: 176 (M^ϩ, 87%), 145 (49),

stereomer

-4d: Colourless crystals, m.p. 48 °C. Yield: 0.45 g

(42%). Ϫ C₁₃H₁₆O₂(204.3): calcd. C 76.4, H 7.9; found C 76.3, H

7.9. Ϫ LRMS (EI); m/z: 204 (M^ϩ, 35%), 99 (100), 71 (71), 45 (26).

Ϫ

¹H NMR: δ ϭ 7.32Ϫ7.13 (5 H, Ph), 4.27 (dd, 1 H, J ϭ 13.7,

1

4.0, H6_eq), 3.95 (d, 1 H, J ϭ 13.8, H6_ax), 3.40 (ddd, 1 H, J ϭ 11.0,

8.3, 2.5, H2), 3.28 (m, 1 H, H4), 3.24 (dd, 1 H, J ϭ 4.3, 4.0, H5),

2.61 (dq, 1 H, J ϭ 8.3, 6.8, CHCH₃), 1.74 (ddd, 1 H, J ϭ 14.6,

2.5, 2.0, H3_eq), 1.56 (ddd, 1 H, J ϭ 14.6, 11.0, 1.8, H3_ax), 1.30 (d,

3 H, J ϭ 6.8, CH₃). Ϫ ¹³C NMR: δ ϭ 143.4 (0), 128.4 (1), 127.9

(1), 126.5 (1), 74.5 (1), 66.1 (2), 51.2 (1), 51.1 (1), 45.3 (1), 29.7 (2),

18.5 (3). Ϫ IR (KBr, neat): ν˜ ϭ 2964 (s), 2854 (s), 1490 (m), 1454

(s), 1112 (s), 1011 (s), 814 (s), 758 (s). Ϫ Diastereomer -4d: Col-

ourless oil. Yield: 0.58 g (53%). Ϫ LRMS (EI); m/z: 204 (M^ϩ, 19%),

135 (100). Ϫ H NMR: δ ϭ 7.19 (d, 2 H, J ϭ 8.8, ortho-H, Ar),

6.85 (d, 2 H, J ϭ 8.8, meta-H, Ar), 6.00 (dddd, 1 H, J ϭ 6.3, 2.3,

1.8, 1.8, H3,4), 5.82 (dm, 1 H, J ϭ 6.3, H3,4), 5.71 (m, 1 H, H2),

4.81 (dddd, 1 H, J ϭ 12.8, 5.8, 2.0, 1.8, H5), 4.69 (dddd, 1 H, J ϭ

12.8, 4.3, 2.5, 1.8, H5), 3.76 (s, 3 H, OMe). Ϫ ¹³C NMR: δ ϭ 159.3

(0), 134.0 (0), 129.9 (1), 127.8 (1), 126.6 (1), 113.8 (1), 87.4 (1), 75.4

(2), 55.2 (3). Ϫ IR (NaCl, neat): ν˜ ϭ 2838 (m), 1611 (m), 1512 (s),

1245 (s), 1062 (s), 1035 (m), 829 (m).

General Procedure for the Preparation of Dihydropyran Oxides 4

and Dihydrofuran Oxides 10. ؊ Method A: MCPBA (70% w/w,

1.90 g, 7.5 mmol) was added in one portion to a solution of the

corresponding dihydropyran (6.0 mmol) in DCM (40 mL). The

mixture was stirred until the starting material had been completely

consumed (TLC). The reaction mixture was diluted with MTBE

(50 mL), and washed twice with saturated Na₂SO₃solution and

saturated Na₂CO₃solution. The organic layer was separated, dried

and evaporated. The residue was chromatographed on silica using

cyclohexane/MTBE mixtures.

1

99 (100), 71 (66), 45 (23). Ϫ H NMR: δ ϭ 7.33Ϫ7.14 (5 H, Ph),

4.27 (d, 1 H, J ϭ 13.3, H6), 3.84 (d, 1 H, J ϭ 13.3, H6), 3.23 (dd,

1 H, J ϭ 5.8, 4.3, H4), 3.20 (ddd, 1 H, J ϭ 11.3, 8.5, 4.0, H2), 3.04

(d, 1 H, J ϭ 4.3, H5), 2.63 (dq, 1 H, J ϭ 8.5, 6.8, CHCH₃), 1.70

(dd, 1 H, J ϭ 15.6, 11.3, H3_ax), 1.54 (ddd, 1 H, J ϭ 15.6, 5.8, 4.0,

H3_eq), 1.32 (d, 3 H, J ϭ 6.8, CH₃). Ϫ ¹³C NMR: δ ϭ 143.7 (0),

128.4 (1), 127.8 (1), 126.5 (1), 77.7 (1), 65.0 (2), 49.9 (1), 49.1 (1),

45.5 (1), 28.3 (2), 18.2 (3). Ϫ IR (NaCl, neat): ν˜ ϭ 2962 (s), 2843

(s), 1493 (m), 1453 (s), 1127 (s), 1007 (s), 807 (s), 703 (s).

(1 *,4 *)-4-[( *)-1-Phenylethyl]-3,7-dioxabicyclo[4.1.0]heptane

Method B: The corresponding dihydropyran (6.0 mmol) was dis-

solved in ethanol (30 mL) and water (19 mL). MMPP (7.0 g,

14.2 mmol) was added in three portions and the homogeneous so-

lution was stirred until the starting material had been completely

consumed (TLC). Most of the solvent was evaporated, and the res-

idue was dissolved in water (20 mL) and extracted with MTBE.

The organic layer was washed twice with saturated Na₂SO₃solu-

tion and saturated Na₂CO₃solution, dried and evaporated. The

residue was chromatographed on silica using cyclohexane/MTBE

mixtures.

(

-4e) and (1 *,4 *)-4-[( *)-1-Phenylethyl]-3,7-dioxabicy-

clo[4.1.0]heptane ( -4e): Obtained from 3e (0.75 g, 4.0 mmol).

Method A: TLC: cyclohexane/ether, 20:1. Purification and separa-

tion of diastereomers by column chromatography on silica. Ϫ Dia-

stereomer

-4e: Colourless oil. Yield: 0.40 g (49%). Ϫ ¹H NMR:

δ ϭ 7.32Ϫ7.25 (2 H, Ph), 7.23Ϫ7.14 (3 H, Ph), 4.16 (dd, 1 H, J ϭ

13.7, 4.3, H6_eq), 3.81 (d, 1 H, J ϭ 13.7, H6_ax), 3.51 (ddd, 1 H, J ϭ

11.2, 6.8, 2.3, H2), 3.36 (m, 1 H, H4), 3.21 (dd, 1 H, J ϭ 4.3, 4.3,

H5), 2.73 (dq, 1 H, J ϭ 7.3, 6.8, CHCH₃), 2.08 (ddd, 1 H, J ϭ

14.6, 2.3, 2.0, H3_eq), 1.68 (ddd, 1 H, J ϭ 14.6, 11.2, 1.8, H3_ax),

1.24 (d, 3 H, J ϭ 7.3, CH₃). Ϫ ¹³C NMR: δ ϭ 143.8 (0), 128.1 (1),

127.9 (1), 126.2 (1), 73.8 (1), 66.0 (2), 51.3 (1), 51.2 (1), 44.4 (1),

28.8 (2), 17.4 (3). Ϫ IR (KBr, neat): ν˜ ϭ 2966 (s), 2940 (s), 2906

(s), 1603 (m), 1494 (s), 1452 (s), 1380 (s), 1112 (s), 1094 (s), 815 (s),

767 (s). Ϫ Diastereomer -4e: Colourless oil. Yield: 0.25 g (31%).

Method C: A solution of dimethyldioxirane in acetone (0.1 ,

3.7 mmol, 37 mL) was added to a solution of the corresponding

dihydropyran (3.4 mmol) at 0 °C. The solution was warmed to

room temperature and stirred until the starting material had been

completely consumed. The reaction mixture was washed with

Na₂SO₃solution and the organic layer was separated, dried and

evaporated. The residue was purified by column chromatography

on silica using cyclohexane/MTBE mixtures.

1

Ϫ H NMR: δ ϭ 7.33Ϫ7.26 (2 H, Ph), 7.24Ϫ7.18 (3 H, Ph), 4.15

(d, 1 H, J ϭ 13.5, H6), 3.70 (dd, 1 H, J ϭ 13.5, 0.8, H6), 3.35 (dd,

1 H, J ϭ 5.5, 4.0, H4), 3.31 (ddd, 1 H, J ϭ 11.1, 7.3, 4.3, H2), 3.03

(d, 1 H, J ϭ 4.0, H5), 2.81 (qd, 1 H, J ϭ 7.3, 7.0, CHCH₃), 1.93

(ddd, 1 H, J ϭ 15.5, 5.5, 4.3, H3_eq), 1.85 (dd, 1 H, J ϭ 15.5, 11.1,

H3_ax), 1.23 (d, 3 H, J ϭ 7.0, CH₃). Ϫ ¹³C NMR: δ ϭ 143.8 (0),

128.2 (1), 127.7 (1), 126.2 (1), 77.1 (1), 65.0 (2), 49.8 (1), 49.0 (1),

44.5 (1), 26.8 (2), 16.6 (3). Ϫ IR (KBr, neat): ν˜ ϭ 2966 (s), 2940

(s), 1603 (m), 1494 (s), 1452 (s), 1112 (s), 1007 (s), 815 (s), 768 (s),

701 (s).

Method D: To a solution of the dihydropyran (12.0 mmol) in tolu-

ene (50 mL) was added VO(acac)₂(2 mol-%). After addition of

tert-butyl hydroperoxide (5.5

 solution in decane, 2.8 mL,

16 mmol) the solution was refluxed for 2 hours, washed with satur-

ated Na₂SO₃solution and water. The organic layer was dried with

MgSO₄, filtered and evaporated, and the residue was purified by

flash chromatography.

(1 *,4 *)-4-Methyl-4-phenyl-3,7-dioxabicyclo[4.1.0]heptane (

4f) and (1 *,4 *)-4-Methyl-4-phenyl-3,7-dioxabicyclo[4.1.0]heptane

-4f): Obtained from 3f (1.04 g, 6.0 mmol). Method B. TLC:

clo[4.1.0]heptane ( -4b): Obtained from (S)-3b (0.87 g, 4.6 mmol). cyclohexane/ether, 3:1. Purification and separation of diastereo-

-

(1 *,4 *,6 *)-4-(4-Methoxyphenyl)-3,7-dioxabicyclo[4.1.0]heptane

(

-4b) and (1 *, *,6 *)-4-(4-Methoxyphenyl)-3,7-dioxabicy-

(

Method A. TLC: cyclohexane/ether, 5:1. Purification and separa-

mers by column chromatography on silica. Ϫ Diastereomer

-

tion of diastereomers by column chromatography on silica. Ϫ Dia-

4f: Colourless solid, m.p. 54 °C. Yield: 0.63 g (52%). Ϫ C₁₂H₁₄O₂

Eur. J. Org. Chem. 2000, 3145Ϫ3163

3155

B. Schmidt, H. Wildemann

FULL PAPER

(190.2): calcd. C 75.8, H 7.4; found C 75.8, H 7.4. Ϫ LRMS (EI);

m/z: 190 (M^ϩ, 1%), 175 (86), 105 (100). Ϫ ¹H NMR: δ ϭ 7.45Ϫ7.25

ether 5:1. Purification and separation of diastereomers by column

chromatography on silica. Ϫ Diastereomer

-4i: Colourless oil.

(5 H, Ph), 3.98 (d, 1 H, J ϭ 13.8, H6), 3.56 (d, 1 H, J ϭ 13.8, H6), Yield: 0.48 g (33%). Ϫ C₉H₁₄O₂(154.2): calcd. C 70.1, H 9.2; found

3.45 (dd, 1 H, J ϭ 5.5, 4.4, H4), 2.86 (d, 1 H, J ϭ 4.0, H5), 2.74 C 70.0, H 9.5. Ϫ LRMS (EI ); m/z: 155 (M^ϩϩ 1, 50%), 137 (100).

(dd, 1 H, J ϭ 15.8, 5.5, H3), 2.13 (d, 1 H, J ϭ 15.8, H3), 1.24 (s, Ϫ ¹H NMR: δ ϭ 4.12 (dd, 1 H, J ϭ 13.6, 4.0, H6_eq), 3.94 (d, 1 H,

3 H, CH₃). Ϫ ¹³C NMR: δ ϭ 142.8 (0), 128.6 (1), 127.4 (1), 126.5 J ϭ 13.6, H6_ax), 3.22 (dd, 1 H, J ϭ 4.0, 4.0, H5), 3.12 (d, 1 H, J ϭ

(1), 73.0 (1), 59.8 (2), 49.3 (1), 48.6 (1), 32.5 (2), 31.8 (3). Ϫ IR

(KBr, disk): ν˜ ϭ 3058 (m), 3018 (m), 2986 (m), 2927 (s), 1444 (s),

4.0, H4), 3.07 (ddd, 1 H, J ϭ 10.8, 9.8, 4.3, H2), 1.85Ϫ1.57 (5 H,

CH₂ϩ H3), 1.36Ϫ1.13 (4 H, CH₂). Ϫ ¹³C NMR: δ ϭ 73.2 (1),

65.3 (2), 54.2 (1), 52.1 (1), 41.9 (1), 31.8 (2), 27.7 (2), 25.9 (2), 24.7

1280 (s), 1120 (s), 1051 (s), 808 (s)704 (s). Ϫ Diastereomer -4f:

1

Colourless oil. Yield: 0.18 g (15%). Ϫ H NMR: δ ϭ 7.41 (d, 2 H, (2). Ϫ IR (NaCl, neat): ν˜ ϭ 2931 (s), 2858 (s), 1446 (m), 1146 (m),

J ϭ 8.0, ortho-Ph), 7.33 (dd, 2 H, J ϭ 8.0, 7.3, meta-Ph), 7.24 (t,

1105 (s), 872 (m), 829 (m). Ϫ Diastereomer -4i: Colourless oil.

1 H, J ϭ 7.3, para-Ph), 4.19 (d, 1 H, J ϭ 13.8, H6), 4.14 (dd, 1 H, Yield: 0.43 g (30%). Ϫ LRMS (EI ); m/z: 155 (M^ϩϩ 1, 50%), 137

1

J ϭ 13.8, 1.8, H6), 3.44 (dd, 1 H, J ϭ 5.0, 4.5, H4), 3.20 (d, 1 H, (100), 119 (50), 95 (60). Ϫ H NMR: δ ϭ 4.17 (d, 1 H, J ϭ 13.3,

J ϭ 4.5, H2), 2.36 (d, 1 H, J ϭ 15.3, H3), 2.20 (dd, 1 H, J ϭ 15.3, H6), 3.81 (dd, 1 H, J ϭ 13.3, 1.0, H6), 3.03 (d, 1 H, J ϭ 4.0, H4,5),

5.0, H3), 1.50 (s, 3 H, CH₃). Ϫ ¹³C NMR: δ ϭ 146.6 (0), 128.1 (1), 2.95 (d, 1 H, J ϭ 4.0, H4,5), 2.66 (ddd, 1 H, J ϭ 10.3, 10.3, 3.8,

126.7 (1), 124.7 (1), 71.9 (0), 59.5 (2), 48.8 (1), 48.7 (1), 34.7 (2),

H2), 1.88Ϫ1.65 (4 H, CH₂, H3), 1.53 (ddd, 1 H, J ϭ 12.8, 10.0,

27.2 (3). Ϫ IR (NaCl, neat): ν˜ ϭ 2975 (m), 1494 (m), 1446 (s), 1114 3.5, CH₂, H3), 1.31Ϫ1.10 (4 H, CH₂, H3). Ϫ ¹³C NMR: δ ϭ 78.1

(s), 800 (m), 764 (s), 701 (s).

(1), 65.1 (2), 54.6 (1), 49.9 (1), 40.6 (1), 31.9 (2), 29.0 (2), 25.8 (2),

24.9 (2). Ϫ IR (NaCl, neat): ν˜ ϭ 2933 (s), 2857 (s), 1448 (m), 1122

(s), 1041 (m), 830 (m), 792 (m).

1-Oxaspiro[5,6]dodec-3-ene Oxide (4g): Obtained from 3g (0.70 g,

4.2 mmol). Method B. TLC: cyclohexane/ether 3:1. Purification by

column chromatography on silica. Colourless oil. Yield: 0.48 g

(63%). Ϫ C₁₁H₁₈O₂(182.3): calcd. C 72.5, H 10.0; found C 72.4,

H 10.3. Ϫ LRMS (EI ); m/z: 182 (M^ϩ, 10%), 125 (83), 112 (46), 55

(100). Ϫ ¹H NMR: δ ϭ 3.96 (d, 1 H, J ϭ 13.8, H6), 3.87 (dd, 1 H,

J ϭ 13.8, 1.6, H6), 3.23 (ddd, 1 H, J ϭ 4.3, 4.3, 1.6, H4), 3.05 (d,

1 H, J ϭ 4.3, H5), 1.75Ϫ1.18 (14 H, H3 ϩ CH₂). Ϫ ¹³C NMR:

δ ϭ 72.9 (0), 58.8 (2), 49.0 (1), 48.9 (1), 42.1 (2), 35.5 (2), 34.3 (2),

29.5 (2), 29.5 (2), 21.6 (2), 21.5 (2). Ϫ IR (NaCl, neat): ν˜ ϭ 2924

(s), 2856 (s), 1456 (m), 1112 (s).

(1 *,4 *,5 *,6 *)-4,5-Diphenyl-3,7-dioxabicyclo[4.1.0]heptane

(4j): Obtained from 3j (0.81 g, 3.4 mmol). Method C. TLC: cyclo-

hexane/ether, 20:1. Purification by column chromatography on sil-

ica. Colourless oil. Yield: 0.40 g (47%). Ϫ ¹H NMR: δ ϭ 7.21Ϫ6.85

(10 H, Ph), 4.92 (d, 1 H, J ϭ 2.8, H2), 4.56 (dd, 1 H, J ϭ 13.8,

3.8, H6_eq), 4.31 (d, 1 H, J ϭ 13.8, H6_ax), 3.50 (m, 1 H, H4), 3.45

(dd, 1 H, J ϭ 4.3, 3.8, H5), 3.33 (m, 1 H, H3). Ϫ ¹³C NMR: δ ϭ

139.7 (0), 136.4 (0), 129.9 (1), 127.7 (1), 127.6 (1), 127.0 (1), 126.8

(1), 125.6 (1), 74.2 (1), 65.7 (2), 54.9 (1), 51.1 (1), 46.8 (1).

(3 *,6 *,12 *)-9,9-Dimethyl-1,4,8,10-tetraoxatricyclo-

(1 ,4 ,5 ,6 )-4-Methyl-5-vinyl-3,7-dioxabicyclo[4.1.0]heptan-5-ol

(4k): Obtained from 3k (0.70 g, 5 mmol). Method D. Yield of crude

product: 0.75 g (96%). Purification by flash chromatography was

impossible because of rapid decomposition of the material on sil-

ica. Purification by kugelrohr distillation (0.2 mbar, 140 °C) leads

to significant decrease in the yield and did not give analytically

pure 3k. For preparative purposes crude 3k may be used. Ϫ

¹H NMR: δ ϭ 5.75 (dd, 1 H, J ϭ 17.6, 11.1, CHϭCH₂), 5.39 (dd,

1 H, J ϭ 17.6, 1.3, CH₂ϭCH), 5.22 (dd, 1 H, J ϭ 11.1, 1.3, CH₂ϭ

CH), 4.09 (d, 1 H, J ϭ 13.3, OϪCH₂), 3.73 (d, 1 H, J ϭ 13.6,

OϪCH₂), 3.23 (s, 2 H, CHϪOϪCH, isochron), 3.07 (q, 1 H, J ϭ

6.5, CHϪCH₃), 2.70 (br. s, 1 H, HO), 1.00 (d, 3 H, J ϭ 6.5,

CH₃ϪCH). Ϫ ¹³C NMR: δ ϭ 138.3 (1), 116.2 (2), 78.0 (1), 68.7

(0), 64.6 (2), 57.0 (1), 52.0 (1), 13.4 (3).

[5.4.0.0^3,6]dodecane (

-4h) and (3 *,6 *,12 *)-9,9-Dimethyl-

1,4,8,10-tetraoxatricyclo[5.4.0.0^3,6]dodecane ( -4h): Obtained from

3h (1.05 g, 5.7 mmol). Method A. TLC: cyclohexane/ether, 3:1.

Purification and separation of diastereomers by column chromato-

graphy on silica. Diastereomer trans-4h: Colourless crystals, m.p.

35 °C. Yield: 0.68 g (60%). C₁₀H₁₆O₄(200.2): calcd. C 60.0, H 8.0;

found C 59.9, H 7.8. Ϫ LRMS (EI ); m/z: 200 (M^ϩ, 1%), 185 (35),

1

142 (42), 112 (49), 82 (73), 43 (100). Ϫ H NMR: δ ϭ 4.12 (dd, 1

H, J ϭ 13.6, 3.3, H6_eq), 3.93 (d, 1 H, J ϭ 13.6, H6_ax), 3.67 (d, 1

H, J ϭ 7.0, OCHHCH3), 3.67 (d, 1 H, J ϭ 7.0, OCHHCH3), 3.56

(dd, 1 H, J ϭ 11.5, 4.6, OCHHCH2), 3.52 (dd, 1 H, J ϭ 11.5, 9.0,

OCHHCH2), 3.30 (ddd, 1 H, J ϭ 9.8, 9.0, 4.6, H2), 3.23Ϫ3.19 (2

H, H4,5), 2.05 (ddd, 1 H, J ϭ 9.8, 7.0, 7.0, H3), 1.30 (s, 3 H, CH₃),

1.26 (s, 3 H, CH₃). Ϫ ¹³C NMR: δ ϭ 101.1 (0, C(CH₃)₂), 73.2 (1,

C2), 65.4 (2, C6), 64.1 (2, OCH₂C2), 61.1 (2, OCH₂C3), 51.9, 50.5

(1, C4,5), 44.2 (1, C3), 24.9, 24.8 (3, CH₃). Ϫ IR (KBr, disk): ν˜ ϭ

2989 (s), 2976 (s), 1466 (m), 1381 (s), 1372 (s), 1208 (s), 1092 (s),

1072 (s), 1043 (s), 850 (s), 735 (s). Ϫ Diastereomer -4h: Colour-

(1 ,4 ,5 ,6 )-4-Phenyl-3,7-dioxabicyclo[4.1.0]heptan-5-ol (4l):

Obtained from 3l (2.12 g, 12 mmol). Method D. Yield of crude

product: 1.8 g (95%). Purification by flash chromatography was im-

possible because of rapid decomposition of the material on silica.

Purification by kugelrohr distillation (0.2 mbar, 160 °C) leads to

significant decrease of the yield and did not give analytically pure

4l. For preparative purposes crude 4l may be used. Ϫ ¹H NMR:

δ ϭ 7.31Ϫ7.16 (5 H, Ph), 4.29 (d, 1 H, J ϭ 13.6, OϪCH₂), 4.18

(d, 1 H, J ϭ 2.0, CHϪPh), 3.99 (ddd, 1 H, J ϭ 10.8, 5.5, 2.0,

CHϪOH), 3.86 (d, 1 H, J ϭ 13.6, OϪCH₂), 3.59 (dd, 1 H, J ϭ

5.5, 4.0, CHϪCHϪOϪCH), 3.26 (d, 1 H, J ϭ 4.0, CH₂ϪCHϪO),

2.33 (d, 1 H, J ϭ 10.8, CHϪOH). Ϫ ¹³C NMR: δ ϭ 137.2 (0),

128.1 (1), 127.5 (1), 126.0 (1), 79.7 (1), 65.2 (2), 64.1 (1), 52.4 (1),

51.5 (1).

1

less solid, m.p. 69 °C. Yield: 0.17 g (15%). Ϫ H NMR: δ ϭ 4.18

(d, 1 H, J ϭ 13.3, H6), 3.82 (d, 1 H, J ϭ 13.3, H6), 3.75 (dd, 1 H,

J ϭ 12.0, 4.6, OCHHCH3), 3.65 (dd, 1 H, J ϭ 11.8, 4.3,

OCHHCH2), 3.52 (dd, 1 H, J ϭ 12.0, 9.8, OCHHCH3), 3.49 (dd,

1 H, J ϭ 11.8, 7.0, OCHHCH2), 3.03 (d, 1 H, J ϭ 4.0, H4,5), 3.00

(m, 1 H, H2), 2.97 (d, 1 H, J ϭ 4.0, H4,5), 2.02 (ddd, 1 H, J ϭ

11.0, 9.8, 4.6, H3), 1.31 (s, 3 H, CH₃), 1.27 (s, 3 H, CH₃). Ϫ

¹³C NMR: δ ϭ 101.2 (0, C(CH₃)₂), 76.5 (1, C2), 65.4 (2, C6), 63.9

(2, OCH₂C2), 60.8 (2, OCH₂C3), 52.0, 49.1 (1, C4,5), 41.2 (1, C3),

24.6, 24.5 (3, CH₃). Ϫ IR (KBr, disk): ν˜ ϭ 2991 (m), 2947 (s), 1375

(s), 1260 (s), 1214 (s), 1109 (s), 1074 (s), 1031 (s), 819 (s).

1-Oxaspiro[4,5]dec-3-ene Oxide (10a): Obtained from 9a (0.46 g,

3.4 mmol) as a colourless liquid along with varying amounts of

ketone 10aЈ. Method A. TLC: cyclohexane/ether 5:1. Purification

by column chromatography on silica. Yield: 0.30 g (54%). Ϫ LRMS

(3 *,5 *,10 *)-Dioxatricyclo[4.4.0.0^3,5]undecane

(

-4i) and

-4i): Ob-

(

tained from 3i (1.30 g, 9.4 mmol). Method A. TLC: cyclohexane/

3156

Eur. J. Org. Chem. 2000, 3145Ϫ3163

Synthesis of Densely Functionalized 2,3-Dihydropyrans

FULL PAPER

1

(EI ); m/z: 155 (M^ϩϩ 1, 100%), 137 (60), 111 (40). Ϫ H NMR:

Ϫ H NMR (C₆D₆): δ ϭ 7.32 (d, 2 H, J ϭ 7.5, ortho-H, Ph), 7.16

δ ϭ 3.94 (d, 1 H, J ϭ 10.8, H5), 3.66 (d, 1 H, J ϭ 3.0, H3,4), 3.65 (dd, 2 H, J ϭ 7.5, 7.3, meta-H, Ph), 7.09 (d, 1 H, J ϭ 7.3, para-H,

(d, 1 H, J ϭ 10.8, H5), 3.49 (d, 1 H, J ϭ 3.0, H5), 1.67Ϫ1.35 (10, Ph), 6.48 (d, 1 H, J ϭ 6.0, H6), 4.97 (dd, 1 H, J ϭ 12.3, 1.8, H2),

CH₂). Ϫ ¹³C NMR: δ ϭ 79.5 (0), 65.3 (2), 59.9 (1), 55.3 (1), 31.3 4.83 (ddd, 1 H, J ϭ 6.0, 6.0, 1.5, H5), 3.90 (m, 1 H, H4), 1.94 (dd,

(2), 31.0 (2), 25.3 (2), 22.9 (2), 22.1 (2). Ϫ IR (KBr, neat): ν˜ ϭ 2934

(s), 2856 (s), 1448 (m), 1079 (s), 1059 (s), 1031 (s).

1 H, J ϭ 14.3, 1.8, H3_eq), 1.89 (s br., 1 H, OH), 1.71 (ddd, 1 H,

J ϭ 14.3, 12.3, 3.8, H3_ax). Ϫ ¹³C NMR (C₆D₆): δ ϭ 146.9 (1), 141.7

(0), 128.6 (1), 127.9 (1), 126.4 (1), 103.5 (1), 73.3 (1), 59.8 (1), 39.9

(2). Ϫ IR (NaCl, neat): ν˜ ϭ 3363 (vs, br.), 1642 (s), 1241 (s), 1056

(s).

1-Oxaspiro[4,5]dec-2-en-4-one (10aЈ): Obtained from 9a (0.46 g,

3.4 mmol) as a colourless liquid along with 10a. Yield 0.15 g (29%).

1

Ϫ LRMS (EI ); m/z: 153 (M^ϩϩ 1, 100%), 135 (10), 81 (20). Ϫ H

(2 *,4 *)-2-Phenyl-3,4-dihydro-2 -pyran-4-ol ( -11a): Obtained

from cis-4a (0.25 g, 1.6 mmol). TLC: cyclohexane/ether 3:1. Puri-

fication by flash chromatography on silica. Colourless oil. Yield:

0.19 g (76%). Ϫ LRMS (EI ); m/z: 177 (M^ϩϩ 1, 65%), 159 (100).

NMR: δ ϭ 7.41 (d, 1 H, J ϭ 5.6, H5), 5.94 (d, 1 H, J ϭ 5.6, H4),

1.80Ϫ1.22 (10 H, CH₂). Ϫ ¹³C NMR: δ ϭ 172.5 (0), 160.6 (1),

120.0 (1), 88.5 (0), 34.5 (2), 24.5 (2), 22.3 (2). Ϫ IR (KBr, neat):

ν˜ ϭ 2937 (s), 2862 (m), 1749 (s), 1449 (m), 1210 (m), 1138 (m), 971

(m), 818 (m).

1

Ϫ H NMR (C₆D₆): δ ϭ 7.23 (d, 2 H, J ϭ 8.5, ortho-H, Ph), 7.16

(dd, 2 H, J ϭ 8.5, 7.0, meta-H, Ph), 7.09 (tt, 1 H, J ϭ 7.0, 1.3,

para-H, Ph), 6.37 (dd, 1 H, J ϭ 6.3, 0.8, H6), 4.74 (ddd, 1 H, J ϭ

6.3, 2.0, 1.8, H5), 4.70 (dd, 1 H, J ϭ 12.0, 1.8, H2), 4.32 (dd, 1 H,

J ϭ 9.5, 6.5, H4), 2.05 (dddd, 1 H, J ϭ 13.1, 6.5, 1.8, 1.8, H3_eq),

1.84 (ddd, 1 H, J ϭ 13.1, 12.0, 9.5, H3_ax), 1.64 (s br., 1 H, OH).

2-Pentyl-3,6-dioxabicyclo[3.1.0]hexane (10b): Obtained from 9b

(1.80 g, 13.1 mmol) as an inseparable mixture of diastereomers.

Method A. Colourless liquid. TLC: cyclohexane/ether 10:1. Puri-

fication by flash chromatography. Yield: 1.60 g (76%). Ϫ C₉H₁₆O₂

(156.2): calcd. C 69.1, H 10.2; found C 68.4, H, 9.9. Ϫ LRMS (EI);

Ϫ

¹³C NMR (C₆D₆): δ ϭ 145.0 (1), 141.2 (0), 128.6 (1), 128.0 (1),

126.2 (1), 106.5 (1), 77.0 (1), 63.4 (1), 40.6 (2). Ϫ IR (NaCl, neat):

1

m/z: 157 (M^ϩϩ 1, 60%), 139 (100). Ϫ H NMR: δ ϭ 4.01Ϫ3.86

(2 H, CHHO, CHO), 3.72Ϫ3.49 (3 H, CHHO, CHO), 1.64Ϫ1.55

(1 H), 1.42Ϫ1.18 (7 H, CHH), 0.88Ϫ0.75 (3 H, CH₃). Ϫ ¹³C NMR:

δ ϭ 77.5 (1), 77.5 (1), 67.3 (2), 65.8 (2), 58.8 (1), 57.3 (1), 55.7 (1),

55.7 (1), 31.7 (2), 31.6 (2), 30.8 (2), 29.9 (2), 25.7 (2), 25.0 (2), 22.4

(2), 22.4 (2), 13.9 (3), 13.9 (3). Ϫ IR (NaCl, neat) 2956 (s), 2931

(s), 2858 (s), 1073 (s), 863 (s).

˜

ν ϭ 3363 (vs, br.), 1644 (s), 1234 (s), 1038 (s), 759 (s).

(2 *,4 *)-2-(4-Methoxyphenyl)-3,4-dihydro-2 -pyran-4-ol

(

-

11b): Obtained from trans-4b (0.57 g, 2.8 mmol). TLC: cyclohex-

ane/ether, 2:1. Purification by flash chromatography on silica. Col-

ourless oil. Yield: 0.43 g (75%). Ϫ C₁₂H₁₄O₃(206.2): calcd. C 69.9;

H 6.8; found C 69.5, H 6.8. Ϫ [α]²_D⁰ϭ ϩ86.0 (c ϭ 0.38, CHCl₃).

Ϫ LRMS (EI ); m/z: 206 (M^ϩ, 11%), 134 (100). Ϫ H NMR: δ ϭ

1

(2 *,5 *)-2-(4-Methoxyphenyl)-3,6-dioxabicyclo[3.1.0]hexane

(

-10c) and (2 *,5 *)-2-(4-Methoxyphenyl)-3,6-dioxabicy-

7.29 (d, 2 H, J ϭ 8.8, Ar), 6.89 (d, 2 H, J ϭ 8.8, Ar), 6.62 (d, 1 H,

J ϭ 6.3, H6), 5.04 (ddd, 1 H, J ϭ 6.3, 6.0, 1.8, H5), 4.86 (dd, 1 H,

J ϭ 12.3, 2.0, H2), 4.19 (m, 1 H, H4), 3.70 (s, 3 H, OMe), 2.04

(ddd, 1 H, J ϭ 14.3, 4.0, 2.0, H3_eq), 1.93 (ddd, 1 H, J ϭ 14.3, 12.3,

3.8, H3_ax), 1.92 (s br., 1 H, OH). Ϫ ¹³C NMR: δ ϭ 159.3 (0), 147.4

(1), 132.9 (0), 127.5 (1), 113.8 (1), 102.6 (1), 72.7 (1), 60.0 (1), 55.3

(3), 38.9 (2). Ϫ IR (NaCl, neat): ν˜ ϭ 3387 (vs, br.), 1641 (m), 1614

(m), 1518 (s), 1252 (s), 1239 (s), 1061 (s), 1040 (s), 826 (s).

clo[3.1.0]hexane ( -10c): Obtained from 9c (0.90 g, 5.1 mmol) as

a 4:1 mixture of diastereomers. Method A. TLC: cyclohexane/ether

5:1. Separation of diastereomers was achieved by column chroma-

tography. Diastereomer

-10c: Colourless solid, m.p. 58 °C.

Yield: 0.60 g (61%). Ϫ C₁₁H₁₂O₃(192.2): calcd. C 68.7, H 6.3;

found C 68.4, H, 6.3. Ϫ LRMS (EI ); m/z: 192 (M^ϩ, 100%), 175

(38), 135 (38), 121 (35). Ϫ ¹H NMR: δ ϭ 7.14 (d, 2 H, J ϭ 8.8,

Ar), 6.85 (d, 2 H, J ϭ 8.8, Ar), 5.02 (s, 1 H, H2), 4.08 (d, 1 H, J ϭ

10.5, H5), 3.91 (d, 1 H, J ϭ 10.5, Ar), 3.85, (d, 1 H, J ϭ 3.0, H3,4),

3.74 (s, 3 H, OMe), 3.73 (d, 1 H, J ϭ 3.0, H3,4). Ϫ ¹³C NMR: δ ϭ

159.3 (0), 130.3 (0), 127.1 (1), 114.0 (1), 78.7 (1), 67.0 (2), 59.7 (1),

56.6 (1), 55.1 (3). Ϫ IR (KBr, disk): ν˜ ϭ 2935 (w), 2870 (m), 1610

(m), 1513 (s), 1248 (s), 1064 (m), 1052 (m), 1028 (s), 856 (s), 830

(s), 820 (s). Ϫ Diastereomer -10c: Colourless liquid. Yield 0.20 g

(20%). Ϫ ¹H NMR: δ ϭ 7.37 (d, 2 H, J ϭ 8.8, Ar), 6.86 (d, 2 H, J ϭ

8.8, Ar), 4.71 (s, 1 H, H2), 4.22 (d, 1 H, J ϭ 10.8, H5), 3.81Ϫ3.76 (6

H, H3,4,5, OMe). Ϫ ¹³C NMR: δ ϭ 159.7 (0), 128.8 (0), 128.7 (1),

113.8 (1), 78.6 (1), 68.0 (2), 58.9 (1), 56.0 (1), 55.3 (3). Ϫ IR (KBr,

neat): ν˜ ϭ 2957 (m), 2857 (m), 1613 (s), 1514 (s), 1248 (s), 1230 (s),

1175 (s), 1069 (s), 1032 (s), 868 (s).

(2 *,4 *)-2-(4-Methoxyphenyl)-3,4-dihydro-2 -pyran-4-ol

(

-

11b): Obtained from cis-4b (0.22 g, 1.1 mmol). TLC: cyclohexane/

ether, 2:1. Purification by flash chromatography on silica. Colour-

less oil. Yield: 0.15 g (68%). [α]²_D⁰ϭ Ϫ11.0 (c ϭ 0.78, CHCl₃). Ϫ

LRMS (EI ); m/z: 206 (M^ϩ, 5%), 134 (100). Ϫ H NMR (C₆D₆):

1

δ ϭ 7.19 (d, 2 H, J ϭ 8.5, Ar), 6.79 (d, 2 H, J ϭ 8.5, Ar), 6.42 (d,

1 H, J ϭ 6.3, H6), 4.83 (d, 1 H, J ϭ 6.3, H5), 4.73 (d, 1 H, J ϭ

12.0, H2), 4.45 (ddm, 1 H, J ϭ 9.8, 6.6, H4), 3.33 (s, 3 H, OMe),

2.44 (s, br., 1 H, OH), 2.14 (dd, 1 H, J ϭ 12.8, 6.6, H3_eq), 1.97

(ddd, 1 H, J ϭ 12.8, 12.0, 9.8, H3_ax). Ϫ ¹³C NMR (C₆D₆): δ ϭ

160.3 (0), 145.7 (1), 133.8 (0), 128.2 (1), 114.6 (1), 107.0 (1), 77.4

(1), 64.2 (1), 55.3 (3), 40.9 (2). Ϫ IR (NaCl, neat): ν˜ ϭ 3302 (vs,

br.), 3232 (vs, br.), 1642 (m), 1613 (m), 1516 (s), 1461 (m), 1254 (s),

1234 (s), 1031 (s), 824 (s).

General Procedure for the Preparation of 2,3-Dihydropyrans 11: To

a solution of LDA or LiTMP (1.7 mmol) in THF (6 mL) was added

a solution of the epoxide (1.1 mmol) in THF (3 mL). The red solu-

tion was stirred at room temperature until conversion was com-

pleted (TLC). The mixture was diluted with MTBE (30 mL) and

washed with aqueous NH₄Cl solution. The organic layer was separ-

ated, dried, filtered and evaporated. The oily residue was purified

by flash chromatography on silica with hexane/MTBE mixtures

as eluents.

(2 *,4 *)-2-Cyclohexyl-3,4-dihydro-2 -pyran-4-ol (

-11c): Ob-

tained from trans-4c (0.80 g, 4.4 mmol). TLC: cyclohexane/ether

2:1. Purification by flash chromatography on silica. Colourless oil.

Yield: 0.64 g (80%). Ϫ C₁₁H₁₈O₂(182.3): calcd. C 72.4, H 10.0;

found C 71.9, H 10.0. Ϫ LRMS (EI ); m/z: 182 (M^ϩ, 40%), 110

1

(34), 81 (100). Ϫ H NMR: δ ϭ 6.62 (d, 1 H, J ϭ 6.0, H6), 4.90

(ddd, 1 H, J ϭ 6.0, 5.8, 1.8, H5), 4.09 (m, 1 H, H4), 3.62 (ddd, 1

H, J ϭ 12.3, 5.5, 1.8, H2), 1.87Ϫ1.40 (8 H, C₆H₁₁), 1.28Ϫ0.97 (5

H, C₆H₁₁). Ϫ ¹³C NMR: δ ϭ 147.5 (1), 102.3 (1), 75.1 (1), 69.9 (1),

41.7 (1), 33.7 (2), 28.6 (2), 28.2 (2), 26.4 (2), 26.2 (2), 26.1 (2). Ϫ

IR (NaCl, neat): ν˜ ϭ 3346 (vs, br.), 2925 (s), 2853 (s), 1641 (m),

(2 *,4 *)-2-Phenyl-3,4-dihydro-2 -pyran-4-ol

(

-11a): Ob-

tained from trans-4a (0.25 g, 1.6 mmol). TLC: cyclohexane/ether,

3:1. Purification by flash chromatography on silica. Colourless oil.

Yield: 0.18 g (72%). Ϫ LRMS (EI ); m/z: 159 (M^ϩϪ OH, 100%). 1450 (m), 1243 (s), 1048 (s).

Eur. J. Org. Chem. 2000, 3145Ϫ3163

3157

B. Schmidt, H. Wildemann

FULL PAPER

(2 *,4 *)-2-Cyclohexyl-3,4-dihydro-2 -pyran-4-ol

(

-11c): Ob-

44.2 (1), 34.8 (2), 17.5 (3). Ϫ IR (KBr, neat): ν˜ ϭ 3370 (s, br.), 2967

tained from cis-4c (0.27 g, 1.5 mmol) using LiTMP instead of LDA.

TLC: cyclohexane/ether 1:1. Purification by flash chromatography

on silica. Colourless oil. Yield: 0.17 g (63%). Ϫ LRMS (EI ); m/z:

(m), 1641 (s), 1241 (s), 1075 (m), 1049 (m), 701 (s).

(2 *,4 *)-2-(( *-1-Phenylethyl)-3,4-dihydro-2 -pyran-4-ol

(

-

11e): Obtained from cis-4e (0.27 g, 1.3 mmol). TLC: cyclohexane/

ether, 2:1. Purification by flash chromatography on silica. Colour-

less oil. Yield: 0.19 g (71%). Ϫ ¹H NMR: δ ϭ 7.34Ϫ7.18 (5 H, Ph),

6.33 (dd, 1 H, J ϭ 6.3, 1.0, H6), 4.67 (ddd, 1 H, J ϭ 6.3, 2.0, 1.8,

H5), 4.38 (dddd, 1 H, J ϭ 9.5, 6.5, 1.8, 1.5, H4), 4.05 (ddd, 1 H,

J ϭ 11.8, 6.0, 1.8, H2), 2.99 (qd, 1 H, J ϭ 7.3, 6.0, CHCH₃), 2.10

(dddd, 1 H, J ϭ 12.8, 6.5, 1.8, 1.5, H3_eq), 1.89 (s, br., 1 H, OH),

1.47 (dddd, 1 H, J ϭ 12.8, 11.8, 9.5, H3_ax), 1.34 (d, 3 H, J ϭ 7.3,

CH₃). Ϫ ¹³C NMR: δ ϭ 145.1 (1), 142.6 (0), 128.1 (1), 128.1 (1),

126.5 (1), 105.4 (1), 78.6 (1), 63.4 (1), 43.6 (1), 34.8 (1), 16.5 (3).

1

182 (M^ϩ, 2%), 151 (14), 99 (100), 71 (58). Ϫ H NMR: δ ϭ 6.31

(d, 1 H, J ϭ 6.0, H6), 4.67 (ddd, 1 H, J ϭ 6.0, 1.8, 1.8, H5), 4.28

(dd, 1 H, J ϭ 9.5, 6.5, H4), 3.50 (ddd, 1 H, J ϭ 11.8, 5.5, 1.0, H2),

1.85 (ddm, 1 H, J ϭ 12.8, 6.5, H3_eq), 1.80 (m, 1 H, C₆H₁₁),

1.73Ϫ1.62 (2 H, C₆H₁₁), 1.62Ϫ1.55 (3 H, C₆H₁₁), 1.53 (ddd, 1 H,

J ϭ 12.8, 11.8, 9.5, H3_ax), 1.35 (m, 1 H, C₆H₁₁), 1.21Ϫ0.95 (5 H,

C₆H₁₁). Ϫ ¹³C NMR: δ ϭ 145.1 (1), 106.2 (1), 79.2 (1), 63.8 (1),

42.1 (1), 35.5 (2), 28.8 (2), 28.3 (2), 26.8 (2), 26.5 (2), 26.4 (2). Ϫ

IR (NaCl, neat): ν˜ ϭ 3347 (vs, br.), 2926 (s), 2853 (s), 1642 (s),

1450 (m), 1233 (s), 1035 (s), 787 (s), 757 (m). If LDA was used as

a base, cis-11c and cis-12c were isolated as an inseparable 2.5:1

mixture of regioisomers. Ϫ Selected NMR spectroscopic data of

the by-product: (3 *,6 *)-6-cyclohexyl-3,6-dihydro-2 -pyran-3-ol

(2 *,4 *)-2-Methyl-2-phenyl-3,4-dihydro-2 -pyran-4-ol

(

-

11f): Obtained from trans-4f (0.20 g, 1.0 mmol) using LiTMP in-

stead of LDA. TLC: cyclohexane/ether, 3:1. Purification by flash

chromatography on silica. Colourless oil, contaminated with 5% of

the regioisomer trans-12f. Yield: 0.14 g (70%). Ϫ C₁₂H₁₄O₂(190.2):

calcd. C 75.8, H 7.4; found C 75.7, H 7.3. Ϫ LRMS (EI ); m/z: 190

(

-12c): ¹H NMR (C₆D₆): δ ϭ 5.86 (dm, 1 H, J ϭ 10.0, H3,4),

5.50 (dm, 1 H, J ϭ 10.0, H3,4), 3.89 (d, 1 H, J ϭ 11.8, H6),

3.72Ϫ3.56 (2 H, H2, 5), 3.34 (dd, 1 H, J ϭ 11.8, 2.0, H6). Ϫ

¹³C NMR (C₆D₆): δ ϭ 132.7 (1), 127.7 (1), 78.5 (1), 72.5 (2), 62.8

(1).

1

(M^ϩ, 3%), 172 (10), 118 (100). Ϫ H NMR (C₆D₆): δ ϭ 7.28 (dm,

2 H, J ϭ 8.0, ortho-H, Ph), 7.16 (dd, 2 H, J ϭ 8.0, 7.3, meta-H,

Ph), 7.07 (tt, 1 H, J ϭ 7.3, 1.3, para-H, Ph), 6.34 (dd, 1 H, J ϭ

6.3, 1.5, H6), 4.68 (ddd, 1 H, J ϭ 6.3, 2.0, 1.8, H5), 3.86 (ddm, 1

H, J ϭ 9.0, 6.0, H4), 2.44 (ddd, 1 H, J ϭ 13.3, 6.0, 1.3, H3_eq), 2.40

(s, br., 1 H, OH), 1.92 (dd, 1 H, J ϭ 13.3, 9.0, H3_ax), 1.47 (s, 3 H,

CH₃). Ϫ ¹³C NMR: δ ϭ 145.4 (0), 143.3 (1), 128.6 (1), 127.0 (1),

124.8 (1), 105.8 (1), 79.3 (0), 61.2 (1), 42.8 (2), 30.8 (3). Ϫ IR (KBr,

neat): ν˜ ϭ 3364 (s, br.), 2977 (m), 2929 (m), 1645 (s), 1446 (m),

1238 (s), 1078 (s), 1033 (s), 761 (m), 700 (s). If LDA was used as a

base, trans-11f and trans-12f were isolated as an inseparable 3:1

mixture of regioisomers. Ϫ Selected NMR spectroscopic data of

(2 *,4 *)-2-[( *-1-Phenylethyl]-3,4-dihydro-2 -pyran-4-ol

(

-

11d): Obtained from trans-4d (0.28 g, 1.4 mmol). TLC: cyclohex-

ane/ether, 2:1. Purification by flash chromatography on silica. Col-

ourless oil. Yield: 0.21 g (75%). Ϫ LRMS (EI ); m/z: 204 (M^ϩ,

20%), 99 (100), 91 (23), 71 (44). Ϫ ¹H NMR: δ ϭ 7.31Ϫ7.25 (2 H,

Ph), 7.22Ϫ7.16 (3 H, Ph), 6.49 (d, 1 H, J ϭ 6.3, H6), 4.87 (ddd, 1

H, J ϭ 6.3, 5.0, 1.8, H5), 3.98 (m, 1 H, H4), 3.93 (ddd, 1 H, J ϭ

12.1, 7.3, 2.0, H2), 2.88 (dq, 1 H, J ϭ 7.3, 7.0, CHCH₃), 2.19 (s

br., 1 H, OH), 1.61 (ddd, 1 H, J ϭ 14.3, 4.0, 2.0, H3_eq), 1.43 (ddd,

1 H, J ϭ 14.3, 12.1, 4.0, H2_ax), 1.38 (d, 3 H, J ϭ 7.0, CH₃). Ϫ

¹³C NMR: δ ϭ 147.0 (1), 143.3 (0), 128.3 (1), 127.8 (1), 126.4 (1),

102.5 (1), 75.0 (1), 59.5 (1), 44.2 (1), 34.7 (1), 17.3 (3). Ϫ IR (NaCl,

neat): ν˜ ϭ 3363 (vs, br.), 2926 (m), 1640 (s), 1452 (m), 1241 (s),

701 (s).

the by-product: (3 *,6 *)-6-methyl-6-phenyl-3,6-dihydro-2 -py-

1

ran-3-ol (

-12f): H NMR (C₆D₆): δ ϭ 5.94 (d, 1 H, J ϭ 10.2,

H3), 5.85 (dd, 1 H, J ϭ 10.2, 4.5, H4), 3.72 (d, 1 H, J ϭ 12.1, H6),

3.55 (m, 1 H, H5), 3.45 (dd, 1 H, J ϭ 12.1, 2.8, H6), 1.46 (s, 3 H,

CH₃). Ϫ ¹³C NMR (C₆D₆): δ ϭ 145.0 (0), 135.9 (1), 128.5 (1), 127.3

(1), 126.6 (1), 126.3 (1), 75.6 (0), 67.2 (1), 62.0 (2), 30.6 (3).

(2 *,4 *)-2-[( *-1-Phenylethyl]-3,4-dihydro-2 -pyran-4-ol

(

-

11d): Obtained from cis-4d (0.45 g, 2.2 mmol). TLC: cyclohexane/

ether, 2:1. Purification by flash chromatography on silica. Colour-

less oil. Yield: 0.40 g (89%). Ϫ LRMS (EI ); m/z: 204 (M^ϩ, 22%),

186 (22), 117 (55), 99 (100), 71 (60). Ϫ ¹H NMR (C₆D₆): δ ϭ

7.30Ϫ7.15 (5 H, Ph), 6.39 (dd, 1 H, J ϭ 6.3, 1.0, H6), 4.75 (ddd,

1 H, J ϭ 6.3, 1.8, 1.8, H5), 4.19 (dd, 1 H, J ϭ 9.5, 6.7, H4), 3.86

(ddd, 1 H, J ϭ 11.6, 8.0, 1.8, H2), 2.86 (dq, 1 H, J ϭ 8.0, 7.0,

CHCH₃), 1.85 (dddd, 1 H, J ϭ 12.8, 6.7, 1.8, 1.5, H3_eq), 1.75 (s,

br., 1 H, OH), 1.51 (ddd, 1 H, J ϭ 12.8, 11.6, 9.5, H3_ax), 1.41 (d,

3 H, J ϭ 7.0, CH₃). Ϫ ¹³C NMR (C₆D₆): δ ϭ 145.3 (1), 144.4 (0),

129.2 (1), 128.7 (1), 127.3 (1), 107.0 (1), 79.7 (1), 63.7 (1), 45.3 (1),

36.8 (2), 18.3 (3). Ϫ IR (NaCl, neat): ν˜ ϭ 3384 (vs, br.), 2965 (m),

1643 (s), 1452 (m), 1232 (s), 701 (s).

(2 *,4 *)-2-Methyl-2-phenyl-3,4-dihydro-2 -pyran-4-ol

(

-11f):

Obtained from -4f (0.18 g, 0.9 mmol). TLC: cyclohexane/ether,

3:1. Purification by flash chromatography on silica. Colourless oil.

Yield: 0.12 g (67%). Ϫ ¹H NMR (C₆D₆): δ ϭ 7.33 (dd, 2 H, J ϭ

8.3, 1.3, ortho-H, Ph), 7.14 (dd, 2 H, J ϭ 8.3, 7.0, meta-H, Ph),

7.03 (tt, 1 H, J ϭ 7.0, 1.3, para-H, Ph), 6.33 (dd, 1 H, J ϭ 6.3, 1.3,

H6), 4.78 (dd, 1 H, J ϭ 6.3, 3.3, H5), 4.08 (m, 1 H, H4), 2.08 (dd,

1 H, J ϭ 14.1, 6.0, H3), 1.96 (ddd, 1 H, J ϭ 14.1, 5.8, 0.8, H3),

1.34 (s, 3 H, CH₃). Ϫ ¹³C NMR: δ ϭ 145.4 (0), 143.6 (1), 128.5

(1), 127.1 (1), 125.2 (1), 105.0 (1), 78.1 (0), 61.1 (1), 43.3 (2), 27.8

(3). Ϫ IR (KBr, neat): ν˜ ϭ 3374 (s, br.), 2978 (m), 2928 (m), 1643

(s), 1446 (m), 1243 (s), 1080 (s), 1028 (s), 763 (s), 700 (s).

1-Oxaspiro[5,6]dodec-2-en-4-ol (11g): Obtained from 4g (0.48 g,

2.6 mmol). TLC: cyclohexane/ether 3:1. Purification by flash chro-

matography on silica. Colourless oil. Yield: 0.40 g (83%). Ϫ

C₁₁H₁₈O₂(182.3): calcd. C 72.4, H 10.0; found C 72.4, H 10.0. Ϫ

(2 *,4 *)-2-[( *-1-Phenylethyl]-3,4-dihydro-2 -pyran-4-ol

11e): Obtained from trans-4e (0.15 g, 0.7 mmol). TLC: cyclohex-

ane/ether, 2:1. Purification by flash chromatography on silica. Col-

(

-

ourless oil. Yield: 0.13 g (86%). Ϫ LRMS (EI ); m/z: 204 (M^ϩ, LRMS (EI ); m/z: 182 (M^ϩ, 39), 110, (85), 95 (73), 82 (100), 73

14%), 117 (31), 105 (63), 99 (100), 91 (32), 71 (62). Ϫ ¹H NMR (84). Ϫ ¹H NMR (C₆D₆): δ ϭ 6.24 (dd, 1 H, J ϭ 6.3, 1.5, H6),

(C₆D₆): δ ϭ 7.20Ϫ7.05 (5 H, Ph), 6.32 (dd, 1 H, J ϭ 6.0, H6), 4.70 4.75 (ddd, 1 H, J ϭ 6.3, 2.5, 1.3, H5), 4.15 (m, 1 H, H4), 2.02Ϫ1.84

(ddd, 1 H, J ϭ 6.0, 6.0, 1.8, H5), 4.07 (ddd, 1 H, J ϭ 12.6, 5.5,

(3 H, H3 ϩ OH), 1.75 (s br., 1 H, OH), 1.71Ϫ1.50 (6, CH₂),

1.8, H2), 3.84 (m, 1 H, H4), 2.76 (qd, 1 H, J ϭ 7.0, 5.5, CHCH₃), 1.46Ϫ1.39 (2 H, CH₂), 1.35Ϫ1.16 (3 H, CH₂). Ϫ ¹³C NMR: δ ϭ

2.15 (s, br., 1 H, OH), 1.65 (dm, 1 H, J ϭ 14.1, H3_eq), 1.27 (m, 1 143.3 (1), 105.3 (1), 80.4 (0), 61.1 (1), 43.3 (2), 40.1 (2), 37.0 (2),

H, H_3ax), 1.26 (d, 3 H, J ϭ 7.0, CH₃). Ϫ ¹³C NMR: δ ϭ 147.0 (1),

30.1 (2), 30.0 (2), 22.5 (2), 22.2 (2). Ϫ IR (KBr, film): ν˜ ϭ 3346 (s),

143.4 (0), 128.7 (1), 128.4 (1), 126.6 (1), 103.1 (1), 75.0 (1), 59.7 (1), 2925 (s), 1640 (s), 1241 (s), 1028 (s), 788 (m), 762 (m), 739 (m).

3158

Eur. J. Org. Chem. 2000, 3145Ϫ3163

Synthesis of Densely Functionalized 2,3-Dihydropyrans

FULL PAPER

(4 *,5 *,11 *)-8,8-Dimethyl-1,7,9-trioxabicyclo[5.4.0]dodec-2-en-

127.9 (1), 127.8 (1), 126.3 (1), 110.2 (0), 69.9 (2), 63.9 (1), 36.8 (2).

4-ol (

-11h): Obtained from trans-4h (0.20 g, 1.0 mmol). TLC:

Ϫ IR (KBr, neat): ν

˜ ϭ 3403 (s, br.), 3057 (m), 2925 (m), 1639 (m),

cyclohexane/ether, 1:1. Purification by flash chromatography on sil-

ica. Colourless solid, m.p. 98 °C. Yield: 0.17 g (85%). Ϫ C₁₃H₁₆O₄

(236.3): calcd. C 60.0, H 8.1; found C 60.0, H 8.1. Ϫ LRMS (EI );

1446 (m), 1237 (m), 1140 (m), 788 (s), 762 (s), 698 (s).

(2 ,3 ,4 )-2-Methyl-3-vinyl-3,4-dihydro-2 -pyran-3,4-diol (11k):

Obtained from 4k (1.60 g, 10.0 mmol). TLC: hexanes/MTBE 1:2.

Purification by kugelrohr distillation (0.2 mbar, 200 °C). Yield:

0.60 g (38%). Analytically pure samples can be obtained with signi-

ficant loss of material by subsequent column chromatography on

silica. Ϫ C₈H₁₂O₃(156.2): calcd. C 61.5, H 7.7; found C 61.2, H

7.9. Ϫ [α]²_D⁰ϭ ϩ32.9 (c ϭ 2.55, DCM). Ϫ LRMS (EI ); m/z: 157

(M^ϩϩ 1, Ͻ5), 139 (40), 121 (10), 111 (30), 93 (15), 83 (70), 73

(15), 55 (100). Ϫ ¹H NMR (C₆D₆): δ ϭ 6.35 (dd, 1 H, J ϭ 6.3, 1.5,

OϪCHϭCH), 5.59 (dd, 1 H, J ϭ 17.3, 10.8, CHϭCH₂), 5.45 (dd,

1 H, J ϭ 17.3, 1.5, CH₂ϭCH), 5.30 (dd, 1 H, J ϭ 10.8, 1.5, CH₂ϭ

CH), 4.71 (dd, 1 H, J ϭ 6.3, 2.0, CHϭCHϪO), 4.17 (br. s, 1 H,

HOϪCH), 3.85 (q, 1 H, J ϭ 6.5, CHϪCH₃), 2.24 (br. s, 1 H, HO),

2.12 (br. s, 1 H, HO), 1.17 (d, 3 H, J ϭ 6.5, CH₃ϪCH). Ϫ

¹³C NMR (C₆D₆): δ ϭ 144.5 (1), 137.6 (1), 116.8 (2), 103.3 (1),

1

m/z: 200 (M^ϩ, 42%), 112 (54), 83 (100), 43 (82). Ϫ H NMR: δ ϭ

6.46 (d, 1 H, J ϭ 6.0, H6), 5.01 (dd, 1 H, J ϭ 6.0, 5.6, H5), 4.06

(dd, 1 H, J ϭ 5.6, 3.5, H4), 3.90Ϫ3.65 (5 H, CH₂O ϩ H2), 1.69

(dddd, 1 H, J ϭ 10.8, 10.8, 3.5, 3.5, H3), 1.32 (s, 3 H, CH₃), 1.32

(s, 3 H, CH₃). Ϫ ¹³C NMR: δ ϭ 146.9 (1), 103.6 (1), 101.2 (0), 72.1

(1), 62.7 (2), 61.7 (1), 60.1 (2), 45.7 (1), 24.7 (3), 24.6 (3). Ϫ IR

(KBr, disk): ν˜ ϭ 3364 (vs, br.), 2950 (m), 1633 (s), 1384 (m), 1370

(m), 1261 (s), 816 (m).

(4 *,5 *,11 *)-8,8-Dimethyl-1,7,9-trioxabicyclo[5.4.0]dodec-2-en-

4-ol( -11h): Obtained from cis-4h (0.14 g, 0.7 mmol). TLC: cyclo-

hexane/ether, 1:1. Purification by flash chromatography on silica.

Colourless oil. Yield: 0.10 g (71%). Ϫ LRMS (EI ); m/z: 200 (M^ϩ,

1

5%), 83 (29), 55 (35), 43 (100). Ϫ H NMR (C₆D₆): δ ϭ 6.22 (dd,

1 H, J ϭ 6.0, 1.3, H6), 4.65 (dd, 1 H, J ϭ 6.0, 1.9, H5), 4.00 (dd, 75.6 (1), 71.6 (1), 67.6 (1), 14.2 (3). Ϫ IR (NaCl, neat): ν˜ ϭ 3455

1 H, J ϭ 12.3, 3.5, CHHO), 3.83 (dd, 1 H, J ϭ 11.6, 10.0, CHHO), (s), 2988 (m), 1652 (s), 1237 (s), 1095 (s), 1023 (s), 980 (s).

3.79Ϫ3.74 (2 H, CHHO ϩ H4), 3.50 (ddd, 1 H, J ϭ 10.6, 10.0,

(2 ,3 ,4 )-2-Phenyl-3,4-dihydro-2 -pyran-3,4-diol (11l): Ob-

4.3, H2), 3.35 (dd, 1 H, J ϭ 12.3, 10.8, CHHO), 2.50 (s, br., 1 H,

tained from 4l (1.90 g, 10.0 mmol). TLC: hexanes/MTBE, 1:2. Puri-

OH), 1.78 (dddd, 1 H, J ϭ 10.8, 10.8, 10.6, 3.5, H3), 1.26 (s, 3 H,

fication by kugelrohr distillation (0.2 mbar, 160 °C). Yield: 0.85 g

(45%). Analytically pure samples can be obtained with significant

loss of material by subsequent kugelrohr distillation and column

chromatography. Ϫ C₁₁H₁₂O₃(192.2): calcd. C 68.7, H 6.3; found

C 68.1, H 6.3. Ϫ LRMS (EI ); m/z: 175 (M^ϩϪ OH, 10), 159 (100),

131 (22), 105 (43), 91 (30), 79 (20), 70 (61), 55 (13). Ϫ ¹H NMR

(C₆D₆): δ ϭ 7.26Ϫ6.98 (5 H, Ph), 6.20 (dm, 1 H, J ϭ 6.0, OϪCHϭ

CH₃), 1.24 (s, 3 H, CH₃). Ϫ ¹³C NMR: δ ϭ 144.9 (1), 106.8 (1),

101.4 (0), 77.0 (1), 64.6 (2), 63.2 (1), 60.0 (2), 48.5 (1), 24.8 (3), 24.8

(3). Ϫ IR (KBr, neat): ν˜ ϭ 3429 (s, br.), 2989 (m), 2944 (m), 1643

(s), 1375 (s), 1220 (s), 1098 (s), 1078 (s), 1041 (s), 836 (m).

(4 *,5 *,10 *)-1-Oxabicyclo[4.4.0]dec-2-en-4-ol

(

-11i): Ob-

tained from trans-4i (0.48 g, 3.1 mmol). TLC: cyclohexane/ether,

5:1. Purification by flash chromatography on silica. Colourless CH), 4.54 (ddd, 1 H, J ϭ 6.3, 1.8, 1.5, HCϪCHϭCH), 4.47 (s, 1

solid, m.p. 38 °C. Yield: 0.42 g (87%). Ϫ LRMS (EI ); m/z: 154 H, CHϪPh), 4.18 (m, 1 H, HOϪCHϪCHϭCH), 3.62 (d, 1 H,

(M^ϩ, 55), 110 (67), 73 (98), 67 (100). Ϫ ¹H NMR (C₆D₆): δ ϭ 6.38 J ϭ 4.0, OHϪCHϪCHϪPh), 3.30 (br. s, 2 H, ϪOH). Ϫ ¹³C NMR

(d, 1 H, J ϭ 6.0, H6), 4.85 (dd, 1 H, J ϭ 6.0, 5.8, 2.2, H5), (C₆D₆): δ ϭ 144.8 (1), 138.6 (0), 128.4 (1), 127.9 (1), 127.0 (1),

3.70Ϫ3.60 (2 H, H2 ϩ H4), 2.09 (m, 1 H, H3), 1.75Ϫ0.80 (8 H, 103.4 (1), 78.7 (1), 68.6 (1), 65.3 (1). Ϫ IR (NaCl, neat): ν˜ ϭ 3396

CH₂). Ϫ ¹³C NMR (C₆D₆): δ ϭ 146.8 (1), 104.2 (1), 73.5 (1), 62.5 (s), 1647 (s), 1233 (s), 1142 (s), 1065 (s), 709 s.

(2), 44.4 (1), 32.9 (2), 26.6 (2), 26.4 (2), 25.1 (2). Ϫ IR (NaCl, neat):

1-Oxaspiro[4,5]dec-2-en-4-ol (14a): Obtained from 10a (0.21 g,

ν˜ ϭ 3406 (vs, br.), 2934 (s), 2862 (s), 1642 (s), 1237 (s), 1108 (s),

1.4 mmol). TLC: cyclohexane/ether 3:1. Colourless oil. Yield:

1064 (s).

0.20 g (95%). Ϫ LRMS (EI ); m/z: 153 (M^ϩϪ 1, 10), 137 (100). Ϫ

(4 *,5 *,10 *)-1-Oxabicyclo[4.4.0]dec-2-en-4-ol

tained from cis-4i (0.43 g, 2.8 mmol). TLC: cyclohexane/ether, 5:1.

(

-11i): Ob-

¹H NMR (C₆D₆): δ ϭ 6.27 (d, 1 H, J ϭ 2.5, H5), 4.88 (dd, 1 H,

J ϭ 2.5, 2.5, H4), 4.27 (d, 1 H, J ϭ 2.5, H3), 1.85Ϫ1.10 (11 H,

CH₂ϩ OH). Ϫ ¹³C NMR (C₆D₆): δ ϭ 149.0 (1), 103.0 (1), 88.4

Purification by flash chromatography on silica. Colourless solid,

m.p. 115 °C. Yield: 0.35 g (81%). Ϫ LRMS (EI ); m/z: 154 (M^ϩ, (0), 78.7 (1), 34.9 (2), 30.0 (2), 25.7 (2), 23.5 (2), 23.1 (2). Ϫ IR

53), 110 (46), 73 (100), 67 (71). Ϫ ¹H NMR: δ ϭ 6.29 (dd, 1 H,

J ϭ 6.3, 1.5, H6), 4.65 (dd, 1 H, J ϭ 6.3, 2.0, H5), 3.85 (d, 1 H, Selected NMR spectroscopic data for the rearrangement product

(KBr, film): ν˜ ϭ 3376 (s), 2934 (s), 2860 (m), 1613 (m), 1068 (s). Ϫ

1

J ϭ 8.8, H4), 3.53 (ddd, 1 H, J ϭ 10.8, 10.5, 4.5, H2), 2.16 (dm, 1

H, J ϭ 13.1, CHH), 1.96 (dm, 1 H, J ϭ 12.3, CHH), 1.75 (dm, 1

1-Oxaspiro[4,5]dec-3-en-2-ol (15): H NMR (C₆D₆): δ ϭ 6.03 (d, 1

H, J ϭ 6.1), 5.74 (d, 1 H, J ϭ 6.0), 5.57 (d, 1 H, J ϭ 6.1), 3.48 (d,

H, J ϭ 12.0, CHH), 1.67 (dm, 1 H, J ϭ 12.0, CHH), 1.47 (s br., 1 1 H, J ϭ 6.0, OH). Ϫ ¹³C NMR (C₆D₆): δ ϭ 139.0 (1), 127.1 (1),

H, OH), 1.41Ϫ1.12 (4 H, CHH), 0.90 (dddd, 1 H, J ϭ 13.0, 13.0,

13.0, 3.8, CHH). Ϫ ¹³C NMR: δ ϭ 144.7 (1), 105.4 (1), 77.2 (1),

68.2 (1), 46.1 (1), 31.7 (2), 28.8 (2), 25.0 (2), 24.4 (2). Ϫ IR (KBr,

disk): ν˜ ϭ 3406 (vs, br.), 2933 (s), 1645 (s), 1231 (s), 1043 (s),

1036 (s).

102.2 (1), 89.1 (0), 39.0 (2), 27.5 (2), 25.6 (2), 23.4 (2), 23.1 (2).

4-Benzyloxy-1-oxaspiro[4,5]dec-3-ene (16): Dihydrofuran 14a

(0.17 g, 1.1 mmol) was dissolved in THF (10 mL) and NaH (80 mg,

60% dispersion in mineral oil, 2.0 mmol) was added. The mixture

was heated to reflux for 30 min., and benzyl bromide (0.24 mL,

5,6-Diphenyl-3,4-dihydro-2 -pyran-3-ol (13): Obtained from 4j 2.0 mmol) was added. The mixture was again heated to reflux for

(0.40 g, 1.6 mmol). TLC: cyclohexane/ether, 5:1. Purification by

flash chromatography on silica. Colourless oil. Yield: 0.27 g (68%).

Ϫ LRMS (EI ); m/z: 252 (M^ϩ, 100%), 209 (57), 117 (64), 105 (99).

30 min, cooled to room temperature, diluted with MTBE and hy-

drolysed. The organic layer is separated, dried, and evaporated. The

residue is purified by flash chromatography on silica to give 16

1

Ϫ H NMR: δ ϭ 7.23Ϫ6.68 (10 H, Ph), 3.85 (dddd, 1 H, J ϭ 6.3,

(0.21 g, 78%). Ϫ LRMS (EI ); m/z: 243 (M^ϩϪ 1, 2%), 137 (100),

1

5.5, 5.3, 2.5, H5), 3.77 (dm, 1 H, J ϭ 10.3, H6), 3.72 (ddd, 1 H, 91 (20). Ϫ H NMR (C₆D₆): δ ϭ 7.32 (d, 2 H, J ϭ 7.3, Ph), 7.21

J ϭ 10.3, 6.3, 1.2, H6), 2.90 (s br., 1 H, OH), 2.47 (ddd, 1 H, J ϭ (dd, 2 H, J ϭ 7.3, Ph), 7.12 (t, 1 H, J ϭ 7.3, Ph), 6.36 (d, 1 H, J ϭ

17.3, 5.5, 1.2, H4), 2.33 (dd, 1 H, J ϭ 17.3, 5.3, H4). Ϫ ¹³C NMR:

2.8, H5), 4.99 (dd, 1 H, J ϭ 2.8, 2.3, H4), 4.42 (d, 1 H, J ϭ 12.0,

δ ϭ 149.5 (0), 141.8 (0), 136.6 (0), 130.0 (1), 129.8 (1), 128.4 (1), OCHHPh), 4.25 (d, 1 H, J ϭ 12.0, OCHHPh), 4.08 (d, 1 H, J ϭ

Eur. J. Org. Chem. 2000, 3145Ϫ3163

3159

B. Schmidt, H. Wildemann

FULL PAPER

2.3, H3), 2.15Ϫ1.18 (10 H, CH₂). Ϫ ¹³C NMR (C₆D₆): δ ϭ 149.5 (t, 2 H, J ϭ 7.5, FuϪCH₂-), 1.60 (m, 2 H, CH₂), 1.35Ϫ1.25 (4 H,

(1), 139.6 (0), 128.5 (1), 127.5 (1), 127.5 (1), 99.9 (1), 88.2 (2), 85.7

(1), 70.2 (2), 35.6 (2), 30.4 (2), 25.8 (2), 23.4 (2), 23.2 (2). Ϫ IR

(NaCl, neat): ν˜ ϭ 2934 (s), 2860 (m), 1612 (m), 1453 (m), 1088 (s),

1075 (s), 733 (m), 696 (m).

ϪCH₂CH₂-), 0.88 (t, 3 H, J ϭ 7.0, ϪCH₃). Ϫ ¹³C NMR: δ ϭ 156.6

(0), 140.6 (1), 110.0 (1), 104.5 (1), 31.4 (2), 27.9 (2), 27.7 (2), 22.4

(2), 14.0 (3).

2-(4-Methoxyphenyl)furan (17c):^[74]Obtained from dihydrofuran

oxide 10c (0.32 g, 1.7 mmol). Purification by column chromato-

graphy on silica, hexanes/MTBE, 10:1. Yield: 0.25 g (76%). Ϫ

¹H NMR: δ ϭ 7.60 (d, 1 H, J ϭ 9.0, Ar), 7.42 (dd, 1 H, J ϭ 1.8,

0.8, H5), 6.92 (d, 1 H, J ϭ 9.0, Ar), 6.51 (dd, 1 H, J ϭ 3.3, 0.8,

H3), 6.44 (dd, 1 H, J ϭ 3.3, 1.8, H4), 3.83 (s, 3 H, OMe). Ϫ

¹³C NMR: δ ϭ 159.0 (0), 154.0 (0), 141.3 (1), 125.2 (1), 124.0 (0),

114.1 (1), 111.5 (1), 103.3 (1), 55.2 (3).

Base-Induced Rearrangement of Dihydrofuran Oxide 10b: Following

the general procedure for base-induced rearrangements, 10b (1:1

mixture of diastereomers, 0.56 g, 3.6 mmol) was treated with LDA.

An inseparable 4:3:1 mixture of three compounds was obtained

(NMR spectroscopic data obtained from the mixture; only charac-

teristic data are listed). Ϫ (2 *,3 *)-2-Pentyl-2,3-dihydrofuran-3-ol

(

-14b): ¹H NMR (C₆D₆): δ ϭ 6.32 (d, 1 H, J ϭ 2.5, H5), 4.97

(dd, 1 H, J ϭ 2.5, 2.5, H4), 4.50 (m, 1 H, H3), 4.31 (m, 1 H, H2).

¹³C NMR (C₆D₆): δ ϭ 149.5 (1), 103.2 (1), 89.8 (1), 78.6 (1). Ϫ

(2 *,3 *)-2-Pentyl-2,3-dihydrofuran-3-ol

-14b): ¹H NMR

General Procedure for the Preparation of 6-Allylated 3,4-Dihydropy-

Ϫ

rans 18: To

a solution of the corresponding dihydropyran

(

(2.2 mmol) in DCM (10 mL) was added NEt₃(0.7 mL, 5.0 mmol)

and acetyl chloride (0.28 mL, 4.0 mmol) at 0 °C. The mixture was

stirred at 0 °C until conversion was complete and then the reaction

was quenched by addition of saturated aqueous NH₄Cl solution.

The organic layer was separated, dried and evaporated. The residue

was redissolved in dry DCM under an atmosphere of dry argon,

cooled to Ϫ78 °C, and allyltrimethylsilane (0.5 mL, 3.0 mmol) was

added, followed by BF₃OEt₂. The mixture was stirred at this tem-

perature until conversion was complete (TLC), warmed to room

temperature, diluted with MTBE (20 mL) and washed with satur-

ated aqueous Na₂CO₃solution. The organic layer is dried with

MgSO₄, evaporated and the residue was purified by flash chroma-

tography on silica with hexane/MTBE mixtures.

(C₆D₆): δ ϭ 6.39 (d, 1 H, J ϭ 2.5, H5), 5.07 (dd, 1 H, J ϭ 2.5, 2.5,

H4), 4.49 (m, 1 H, H3), 3.93 (ddd, 1 H, J ϭ 7.0, 7.0, 7.0, H2). Ϫ

¹³C NMR (C₆D₆): δ ϭ 150.3 (1), 104.6 (1), 86.1 (1), 73.1 (1). Ϫ 5-

Pentyl-2,3-dihydrofuran-3-ol (14bЈ): ¹H NMR (C₆D₆): δ ϭ 4.82 (br.

s, 1 H, H3), 4.74 (d (br.), 1 H, J ϭ 7.0, H4), 4.18 (dd, 1 H, J ϭ

10.5, 2.0, H5), 4.05 (dd, 1 H, J ϭ 10.5, 7.0, H5Ј). Ϫ ¹³C NMR

(C₆D₆): δ ϭ 164.2 (0), 98.7 (1), 78.3 (1), 74.3 (2).

Base-Induced Rearrangement of Dihydrofuran Oxides

- and

-

10c: Following the general procedure for base-induced rearrange-

ments, 10c (1:1 mixture of diastereomers, 0.56 g, 3.6 mmol) was

treated with LiTMP. In the case of trans-10c an inseparable 9:3:1

mixture of dihydrofurans 14cЈ, trans-14c and the elimination prod-

uct 17c was obtained. Ϫ 5-(4-Methoxyphenyl)-2,3-dihydrofuran-3-

ol (14cЈ): ¹H NMR (C₆D₆): δ ϭ 7.50 (d, 2 H, J ϭ 8.5, Ar), 6.70 (d,

2 H, J ϭ 8.5, Ar), 5.28 (d, 1 H, J ϭ 2.6, H3), 4.76 (ddd, 1 H, J ϭ

7.0, 2.6, 2.2, H4), 4.20 (dd, 1 H, J ϭ 10.6, 2.2, H5), 4.11 (dd, 1 H,

J ϭ 10.6, 7.0, H5Ј), 3.38 (s, 3 H, OMe). Ϫ ¹³C NMR (C₆D₆): δ ϭ

160.8 (0), 160.0 (0), 127.6 (1), 123.4 (0), 114.0 (1), 96.6 (1), 78.4 (2),

(2 *,6 *)-6-Allyl-2-phenyl-3,6-dihydro-2 -pyran (18a): Obtained

from 11a (0.25 g, 1.4 mmol). TLC: cyclohexane/ether 25:1. Puri-

fication by flash chromatography on silica. Colourless oil. Yield:

0.20 g (71%). Ϫ C₁₄H₁₆O (200.3): calcd. C 83.9, H 8.1; found C

83.9, H 8.1. Ϫ LRMS (EI ); m/z: 200 (M^ϩ, 1%), 159 (M^ϩϪ C₃H₅,

1

100), 91 (C₇H₇^ϩ, 75). Ϫ H NMR: δ ϭ 7.41Ϫ7.32 (4 H, Ph), 7.27

(tt, 1 H, J ϭ 7.3, 1.5, para-H, Ph), 5.96 (dm, 1 H, J ϭ 10.3, H4,5),

5.89 (dddd, 1 H, J ϭ 17.1, 10.3, 7.3, 6.8, CHHCHϭCH₂), 5.81

(dm, 1 H, J ϭ 10.3, H4,5), 5.12 (dddd, 1 H, J ϭ 17.1, 2.0, 1.5,

1.5, ϭCH₂), 5.07 (dm, 1 H, J ϭ 10.3, ϭCH₂), 4.75 (dd, 1 H, J ϭ

8.4, 4.6, H2), 4.32 (m, 1 H, H6), 2.52 (ddddd, 1 H, J ϭ 14.1, 7.8,

74.5 (1), 55.0 (3). Ϫ (2 *,3 *)-2-(4-Methoxyphenyl)-2,3-dihydrofu-

1

ran-3-ol (

-14c): H NMR (C₆D₆): δ ϭ 7.11 (d, 2 H, J ϭ 8.8,

Ar), 6.70 (d, 2 H, J ϭ 8.8, Ar), 6.45 (d, 1 H, J ϭ 2.5, H5), 5.16 (d,

1 H, J ϭ 2.5, H2), 4.92 (dd, 1 H, J ϭ 2.5, 2.5, H4), 4.64 (dd, 1 H,

J ϭ 2.5, 2.5, H3), 3.38 (s, 3 H, OMe). Ϫ ¹³C NMR (C₆D₆): δ ϭ

159.7 (0), 150.3 (1), 126.7 (1), 114.2 (1), 103.0 (1), 90.6 (1), 81.6 (1),

55.0 (3), signal for ipso-C overlapped by solvent signal. In the case

of cis-10c an inseparable mixture of unchanged starting material

and dihydrofuran cis-14c was obtained: (2 *,3 *)-2-(4-Methoxy-

6.8, 1.5, 1.5, CHHCHϭCH₂), 2.41Ϫ2.29 (3 H, H3

ϩ

CHHCHCH₂). Ϫ ¹³C NMR: δ ϭ 142.2 (0), 134.9 (1), 129.3 (1),

128.3 (1), 127.4 (1), 126.3 (1), 124.4 (1), 117.0 (2), 72.9 (1), 69.8 (1),

39.0 (2), 31.4 (2). Ϫ IR (NaCl, neat): ν˜ ϭ 3032 (m), 2922 (m), 2897

(m), 1641 (m), 1390 (m), 1080 (s), 1055 (s), 913 (m).

1

phenyl)-2,3-dihydrofuran-3-ol ( -14c): H NMR (C₆D₆): δ ϭ 7.45

(d, 2 H, J ϭ 8.5, Ar), 6.83 (d, 2 H, J ϭ 8.8, Ar), 6.48 (d, 1 H, J ϭ

2.5, H5), 5.12 (dd, 1 H, J ϭ 2.5, 2.5, H4), 5.01 (d, 1 H, J ϭ 6.8,

H2), 4.53 (dd, 1 H, J ϭ 6.8, 2.5, H3), 3.32 (s, 3 H, OMe). Ϫ

¹³C NMR (C₆D₆): δ ϭ 160.2 (0), 150.3 (1), 129.2 (1), 127.3 (0),

114.0 (1), 104.7 (1), 87.2 (1), 74.0 (1), 54.7 (3),

(2 ,6 )-6-Allyl-2-(4-methoxyphenyl)-3,6-dihydro-2 -pyran

(

-

18b): Obtained from 11b (0.17 g, 0.8 mmol). It is essential in this

case to quench the reaction at Ϫ80 °C by addition of Na₂CO₃

solution. TLC: cyclohexane/ether 20:1. Purification by flash chro-

matography on silica. Colourless oil. Yield: 0.16 g (87%). Ϫ [α]²_D⁰

ϭ

Ϫ60.3 (c ϭ 1.16, CHCl₃). Ϫ LRMS (EI ); m/z: 230 (M^ϩ, 10%), 189

Procedure for the Preparation of Furans from Dihydrofuran Oxides:

To a solution of LDA (12.0 mmol) in THF (10 mL) was added a

1

(44), 121 (100). Ϫ H NMR: δ ϭ 7.32 (d, 2 H, J ϭ 8.4, Ar), 6.88

(d, 2 H, J ϭ 8.4, Ar), 5.95 (dm, 1 H, J ϭ 10.3, H4,5), 5.89 (dddd,

1 H, J ϭ 17.2, 10.3, 7.3, 7.0, CHHCHϭCH₂), 5.80 (dm, 1 H, J ϭ

10.3, H4,5), 5.12 (dddd, 1 H, J ϭ 17.2, 1.8, 1.5, 1.5, ϭCH₂), 5.07

(dm, 1 H, J ϭ 10.3, ϭCH₂), 4.72 (dd, 1 H, J ϭ 8.5, 4.0, H2), 4.28

(m, 1 H, H6), 3.79 (s, 3 H, OMe), 2.51 (ddd, 1 H, J ϭ 14.0, 7.3,

6.5, CHHCHϭCH₂), 2.41Ϫ2.27 (3 H, H3 ϩ CHHCHCH₂). Ϫ

¹³C NMR: δ ϭ 158.9 (0), 134.9 (1), 134.3 (0), 129.3 (1), 127.6 (1),

124.4 (1), 116.9 (2), 113.6 (1), 72.7 (1), 69.4 (1), 55.2 (3), 39.0 (2),

31.2 (2). Ϫ IR (KBr, neat): ν˜ ϭ 3033 (w), 2930 (m), 2902 (m), 1613

(m), 1515 (s), 1248 (s), 1175 (s), 1037 (s), 827 (s).

solution of the corresponding dihydrofuran oxide 10b or

c

(6.0 mmol) in THF (10 mL). The mixture was stirred until the ep-

oxide was completely consumed, and then TosCl was added. The

mixture was stirred for 30 min., poured into water (20 mL) and

extracted with MTBE. The organic layer was dried and evaporated;

the residue was purified by kugelrohr distillation or by column

chromatography.

2-Pentylfuran (17b):^[73]Obtained from dihydrofuran oxide 10b

(0.90 g, 5.8 mmol). Purification by kugelrohr distillation at

1

15 mbar, 100 °C. Yield: 0.60 g (75%). Ϫ H NMR: δ ϭ 7.27 (m, 1

(2 ,6 )-6-Allyl-2-(4-methoxyphenyl)-3,6-dihydro-2 -pyran

(

-

H, H5), 6.52 (dd, 1 H, J ϭ 3.0, 1.8, H4), 5.95 (m, 1 H, H3), 2.58 18b): Obtained from 11b (0.14 g, 0.7 mmol). After addition of

3160 Eur. J. Org. Chem. 2000, 3145Ϫ3163

Synthesis of Densely Functionalized 2,3-Dihydropyrans

FULL PAPER

BF₃OEt₂the reaction mixture was allowed to warm to Ϫ10 °C and

stirring was continued at this temperature for 3 hours. Progress of

the reaction was monitored by TLC: cyclohexane/ether 20:1. Ratio

of diastereomers: cis/trans ϭ 7:1. Purification by chromatography

on silica. Colourless oil. Yield: 0.11 g (70%) of cis-18b and 0.01 g

(5%) of trans-18b. Ϫ [α]²_D⁰ϭ ϩ22.0 (c ϭ 0.80, CHCl₃). Ϫ LRMS

J ϭ 17.1, ϭCH₂), 5.10 (dm, 1 H, J ϭ 10.0, ϭCH₂), 4.23 (m, 1 H,

H6), 2.44 (ddd, 1 H, J ϭ 14.1, 7.0, 6.8, CHHCHϭCH₂), 2.35 (ddd,

1 H, J ϭ 14.1, 7.3, 6.8, CHHCHϭCH₂), 2.31 (dm, 1 H, J ϭ 17.1,

H3), 1.99 (ddd, 1 H, J ϭ 17.1, 5.5, 2.8, H3), 1.42 (s, 3 H, CH₃). Ϫ

¹³C NMR (C₆D₆): δ ϭ 149.7 (0), 135.3 (1, ϪCHϭ), 128.8 (1, C4),

128.3 (1, meta-C, Ph), 126.7 (1, para-C, Ph), 124.5 (1, ortho-C, Ph),

(EI ); m/z: 230 (M^ϩ, 9%), 189 (M^ϩϪ C₃H₅, 45%), 121 (100). Ϫ 123.8 (1, C4), 116.9 (2, ϭCH₂), 73.6 (0, C2), 69.4 (1, C6), 40.3

¹H NMR (500 MHz): δ ϭ 7.30 (d, 2 H, J ϭ 8.8, Ar), 6.87 (d, 2 H,

J ϭ 8.8, Ar), 5.91 (dddd, 1 H, J ϭ 17.0, 10.2, 7.0, 7.0, ϪCHϭ),

(2, ϪCHHCHϭ), 36.8 (2, C3), 24.5 (3, CH₃). Ϫ IR (NaCl, neat):

nu(tuilde) ϭ 3074 (m), 3031 (s), 2976 (s), 2930 (s), 1641 (m), 1494

5.90 (m, 1 H, H5), 5.73 (dm, 1 H, J ϭ 10.2, H4), 5.12 (dm, 1 H, (s), 1446 (s), 1087 (s), 1073 (s), 913 (s), 762 (s), 699 (s).

J ϭ 17.0, ϭCH₂), 5.08 (dm, 1 H, J ϭ 10.2, ϭCH₂), 4.55 (dd, 1 H,

2-Allyl-1-oxaspiro[5,6]dodec-3-ene (18g): Obtained from 11g

J ϭ 10.3, 3.5, H2), 4.36 (m, 1 H, H6), 3.79 (s, 3 H, OMe), 2.42

(0.45 g, 1.6 mmol). TLC: cyclohexane/ether 25:1. Purification by

flash chromatography on silica. Colourless oil. Yield: 0.38 g (74%).

(ddd, 1 H, J ϭ 14.0, 7.0, 6.5, ϪCHHCHϭ), 2.35 (ddd, 1 H, J ϭ

14.0, 7.5, 7.0, ϪCHHCHϭ), 2.27 (ddm, 1 H, J ϭ 17.0, 10.5, H3_ax),

Ϫ C₁₄H₂₂O (206.3): calcd. C 81.5, H 10.7; found C 81.4, H 10.7.

Ϫ LRMS (EI ); m/z: 206 (M^ϩ, 1%), 165 (M^ϩϪ C₃H₅, 100%). Ϫ

¹H NMR: δ ϭ 5.86 (dddd, 1 H, J ϭ 17.1, 10.3, 7.3, 6.3, ϪCHϭ),

5.69 (dddd, 1 H, J ϭ 10.3, 5.3, 2.0, 2.0, H4,5), 5.63 (dddd, 1 H,

J ϭ 10.3, 2.5, 1.3, 1.3, H4,5), 5.08 (dddd, 1 H, J ϭ 17.1, 2.0, 1.5,

1.5, ϭCH₂), 5.03 (dddd, 1 H, J ϭ 10.3, 2.0, 1.3, 1.3, ϭCH₂), 4.04

(m, 1 H, H6), 2.30 (ddddd, 1 H, J ϭ 14.1, 6.5, 6.5, 1.5, 1.5, CHH),

2.19 (ddddd, 1 H, J ϭ 14.1, 7.5, 6.8, 1.3, 1.3, CHH), 2.00Ϫ1.21 (14

H, CHH ϩ H3). Ϫ ¹³C NMR: δ ϭ 135.1 (1), 128.9 (1), 123.7 (1),

116.5 (2), 75.1 (0), 68.2 (1), 43.3 (2), 40.0 (2), 36.0 (2), 33.9 (2), 29.8

(2), 29.6 (2), 21.9 (2), 21.7 (2). Ϫ IR (NaCl, neat): ν˜ ϭ 2926 (s),

2857 (m), 1641 (w)m 1460 (w), 1038 (m).

2.18 (dm, 1 H, J ϭ 17.0, H3_eq). Ϫ ¹³C NMR: δ ϭ 158.9 (0), 135.1

(0), 134.5 (1), 129.6 (1), 127.0 (1), 125.0 (1), 117.0 (2), 113.7 (1),

75.3 (1), 74.9 (1), 55.2 (3), 39.9 (2), 33.1 (2). Ϫ IR (NaCl, neat):

ν˜ ϭ 2954 (m), 2836 (m), 1613 (s), 1514 (s), 1248 (s), 1175 (m), 1034

(s), 829 (m).

(2 *,6 *)-6-Allyl-2-cyclohexyl-3,6-dihydro-2 -pyran (18c): Ob-

tained from 11c (0.16 g, 0.9 mmol). TLC: cyclohexane/ether, 40:1.

Purification by flash chromatography on silica. Colourless oil.

Yield: 0.12 g (67%). Ϫ C₁₄H₂₂O (206.3): calcd. C 81.5, H 10.7;

found C 81.5, H 10.8. Ϫ LRMS (EI ); m/z: M^ϩnot observed, 165

1

(M^ϩϪ C₃H₅, 100%), 147 (34). Ϫ H NMR: δ ϭ 5.85 (dddd, 1 H,

J ϭ 17.1, 10.3, 7.3, 6.8, ϪCHϭ), 5.81 (dm, 1 H, J ϭ 10.3, H4,5),

5.68 (dm, 1 H, J ϭ 10.3, H4,5), 5.06 (dddd, 1 H, J ϭ 17.1, ϭCH₂),

5.03 (dm, 1 H, J ϭ 10.3, ϭCH₂), 4.18 (m, 1 H, H6), 3.33 (ddd, 1

H, J ϭ 7.3, 7.3, 5.3, H2), 2.39 (ddddd, 1 H, J ϭ 14.1, 8.3, 6.8, 1.5,

1.3, CHHCHϭCH₂), 2.20 (ddddd, 1 H, J ϭ 14.1, 7.3, 5.5, 1.3, 1.0,

CHHCHϭCH₂), 2.03Ϫ1.90 (3 H, C₆H₁₁ϩ H3), 1.75Ϫ1.58 (4 H,

C₆H₁₁ϩ H3), 1.35 (m, 1 H, C₆H₁₁ϩ H3), 1.28Ϫ1.10 (2 H, C₆H₁₁

ϩ H3), 1.03Ϫ0.80 (3 H, C₆H₁₁ϩ H3). Ϫ ¹³C NMR: δ ϭ 135.3 (1),

129.2 (1), 124.6 (1), 116.6 (2), 72.9 (1), 71.6 (1), 42.3 (1), 38.6 (2),

29.4 (2), 28.7 (2), 28.1 (2), 26.6 (2), 26.2 (2), 26.0 (2). Ϫ IR (NaCl,

neat): ν˜ ϭ 3078 (w), 2923 (s), 2852 (s), 1641 (w), 1450 (w), 1081

(s), 707 (m).

[(2 *,3 *,6 *)-6-Allyl-3-hydroxymethyl-3,6-dihydro-2 -pyran-2-

yl]methanol (18h): Obtained from 11h (0.20 g, 1.0 mmol). TLC:

cyclohexane/ethyl acetate 1:1. Purification by flash chromatography

on silica. Colourless oil. Yield: 0.09 g (49%). Attempts to obtain

analytically pure samples were not successful. A significant loss of

1

material occurred during workup. Ϫ H NMR: δ ϭ 5.80 (dddd, 1

H, J ϭ 17.1, 10.3, 7.0, 7.0, ϪCHϭ), 5.79 (d, 1 H, J ϭ 10.3, H4,5),

5.66 (ddd, 1 H, J ϭ 10.3, 2.5, 2.5, H4,5), 5.07 (d, 1 H, J ϭ 17.1, ϭ

CH₂), 5.04 (d, 1 H, J ϭ 10.3, ϭCH₂), 4.18 (m, 1 H, H6), 3.80Ϫ3.50

(5 H, CHHO, H2), 2.90 (s br., 2 H, OH), 2.40Ϫ2.15 (3 H, CHH,

H3). Ϫ ¹³C NMR: δ ϭ 134.4 (1), 130.6 (1), 125.1 (1), 117.3 (2),

72.0 (1), 70.7 (1), 64.0 (2), 63.6 (2), 38.7 (2), 38.7 (1).

(2 *,6 *)-6-Allyl-2-[( *-1-phenylethyl]-3,6-dihydro-2 -pyran

(18d): Obtained from 11d (0.45 g, 2.2 mmol). TLC: cyclohexane/

ether, 20:1. Purification by flash chromatography on silica. Colour-

less oil. Yield: 0.40 g (80%). Ϫ LRMS (EI ); m/z: M^ϩnot observed,

187 (M^ϩϪ C₃H₅, 47%), 105 (100, C₇H₇^ϩ). Ϫ ¹H NMR: δ ϭ

7.32Ϫ7.17 (5 H, Ph), 5.91 (dddd, 1 H, J ϭ 17.1, 10.3, 7.0, 7.0,

ϪCHϭ), 5.76Ϫ5.66 (2 H, H4,5), 5.13 (dddd, 1 H, J ϭ 17.1, 2.0,

1.5, 1.5, ϭCH₂), 5.09 (dm, 1 H, J ϭ 10.3, ϭCH₂), 4.30 (m, 1 H,

H6), 3.71 (ddd, 1 H, J ϭ 9.0, 8.8, 3.5, H2), 2.75 (dq, 1 H, J ϭ 8.8,

6.8, CHCH₃), 2.47 (ddd, 1 H, J ϭ 14.5, 7.0, 6.8, CHHCHϭCH₂),

2.28 (ddd, 1 H, J ϭ 14.5, 7.0, 5.3, CHHCHϭCH₂), 1.83 (ddm, 1

H, J ϭ 17.2, 9.0, H3_ax), 1.64 (ddd, 1 H, J ϭ 17.2, H3_eq), 1.38 (ddd,

1 H, J ϭ 6.8, CH₃). Ϫ ¹³C NMR: δ ϭ 144.4 (0), 135.2 (1), 128.9

(1), 128.3 (1), 127.8 (1), 126.3 (1), 124.5 (1), 116.7 (2), 72.7 (1), 72.6

(1), 45.0 (1), 38.7 (2), 29.0 (2), 18.6 (3). Ϫ IR (NaCl, neat) 3029

(w), 2963 (m), 1493 (m), 1452 (m), 1083 (m), 1019 (m), 701 (s).

(2 *,5 *,10 *)-2-Allyl-1-oxabicyclo[4.4.0]dec-3-ene (18i): Ob-

tained from 11i (0.25 g, 1.6 mmol). TLC: cyclohexane/ether, 20:1.

Purification by flash chromatography on silica. Colourless oil.

Yield: 0.23 g (80%). Ϫ LRMS (EI ); m/z: M^ϩnot observed, 137

(M^ϩϪ C₃H₅, 100%), 119 (19), 69 (40). Ϫ ¹H NMR: δ ϭ 5.85

(dddd, 1 H, J ϭ 17.1, 10.2, 7.3, 6.8, ϪCHϭ), 5.63 (dd, 1 H, J ϭ

10.0, 2.3, H4,5), 5.59 (d, 1 H, J ϭ 10.0, H4,5), 5.07 (dm, 1 H, J ϭ

17.1, ϭCH₂), 5.03 (dm, 1 H, J ϭ 10.2, ϭCH₂), 4.20 (m, 1 H, H6),

3.10 (ddd, 1 H, J ϭ 10.5, 9.3, 4.0, H2), 2.40 (ddd, 1 H, J ϭ 13.8,

8.3, 6.8, CHHCHϭCH₂), 2.24 (ddd, 1 H, J ϭ 13.8, 7.3, 6.3,

CHHCHϭCH₂), 1.88Ϫ1.61 (5 H, CHH), 1.35Ϫ1.17 (3 H, CHH),

1.00 (m, 1 H, CHH). Ϫ ¹³C NMR: δ ϭ 135.1 (1, ϪCHϭ), 130.2

(1, C4,5), 128.5 (1, C4,5), 116.8 (2, ϭCH₂), 73.4 (0, C6), 72.9 (1,

C2), 40.6 (1, C3), 39.2 (2, ϪCHHCHϭ), 32.0, 30.4, 25.8, 25.2 (2,

CHH). Ϫ IR (NaCl, neat): ν˜ ϭ 2930 (s), 2856 (m), 1640 (m), 1449

(m), 1102 (s), 712 (m).

(2 *,6 *)-6-Allyl-2-methyl-2-phenyl-3,6-dihydro-2 -pyran

(18f):

Obtained from 11f (0.13 g, 0.7 mmol). TLC: cyclohexane/ether Procedure for the Preparation of Benzyl Ethers

- and

-19i:

20:1. Purification by flash chromatography on silica. Colourless oil.

To a solution of the alcohols trans- or cis-11i (0.23 g, 1.5 mmol)

Yield: 0.11 g (78%). Ϫ LRMS (EI ); m/z: 214 (M^ϩ, 1%), 173 (M^ϩwas added NaH (60% dispersion in mineral oil, 120 mg, 3.0 mmol).

Ϫ C₃H₅, 100%), 121 (47), 105 (90), 79 (74). Ϫ ¹H NMR (C₆D₆): The mixture was heated to reflux for 30 min., and then benzyl

δ ϭ 7.55 (dd, 2 H, J ϭ 8.0, 1.3, ortho-H, Ph), 7.26 (dd, 2 H, J ϭ

8.0, 7.3, meta-H, Ph), 7.13 (t, 1 H, J ϭ 7.3, para-H, Ph), 6.01 (dddd, refluxed until the reaction was complete as indicated by TLC (hex-

1 H, J ϭ 17.1, 10.0, 7.0, 6.8, ϪCHϭ), 5.64 (dddd, 1 H, J ϭ 10.3, anes/MTBE, 10:1). After aqueous workup the residue was purified

bromide (0.23 mL, 2.0 mmol) was added. The mixture was again

5.5, 2.0, 1.8, H4), 5.57 (dm, 1 H, J ϭ 10.3, H5), 5.13 (dm, 1 H, by flash chromatography on silica.

Eur. J. Org. Chem. 2000, 3145Ϫ3163

3161

B. Schmidt, H. Wildemann

FULL PAPER

(4 *,4a *,8a *)-4-Benzyloxy-4a,5,6,7,8,8a-hexahydro-4

-

7.13 (t, 1 H, J ϭ 7.5, p-H, Ph), 5.88 (d, 1 H, J ϭ 7.5, OCHO), 5.03

(d, 1 H, J ϭ 11.0, OCHHPh), 4.65 (d, 1 H, J ϭ 11.0, OCHHPh),

3.55 (dd, 1 H, J ϭ 8.5, 5.0, CHOBn), 3.41 (ddd, 1 H, J ϭ 10.8,

10.8, 4.5, CH₂CHO), 3.14 (dd, 1 H, J ϭ 7.5, 5.0, CHCϭC), 2.11

chromene (

-19i): Obtained from trans-11i (0.23 g, 1.5 mmol).

Yield: 0.31 g (85%). Ϫ LRMS (EI ); m/z: 243 (M^ϩϪ 1, 5%), 137

1

(M^ϩϪ OBn, 100%), 91 (C₇H₇^ϩ, 30%). Ϫ H NMR: δ ϭ 7.34 (d,

2 H, J ϭ 7.5, o-H, Ph), 7.22 (dd, 2 H, J ϭ 7.5, 7.5, m-H, Ph), 7.13 (d, 1 H, J ϭ 15.8, CHHCMe₂), 2.05 (d, 1 H, J ϭ 15.8, CHHCMe₂),

(t, 1 H, J ϭ 7.5, p-H, Ph), 6.50 (d, 1 H, J ϭ 6.3, H6), 4.92 (dd, 1 2.05Ϫ1.95 (2 H, CHH), 1.96 (d, 1 H, J ϭ 17.6, CHHCMe₂), 1.87

H, J ϭ 6.3, 5.3, H5), 4.61 (d, 1 H, J ϭ 12.0, OCHHPh), 4.27 (d, (dd, 1 H, J ϭ 17.6, 2.0, CHHCMe₂), 1.60Ϫ1.25 (4 H, CHH),

1 H, J ϭ 12.0, OCHHPh), 4.00 (ddd, 1 H, J ϭ 11.1, 11.1, 4.8, H2), 1.07Ϫ0.60 (3 H, CHH), 0.82 (s, 3 H, Me), 0.75 (s, 3 H, Me). Ϫ

3.43 (dd, 1 H, J ϭ 5.3, 3.8, H4), 2.11 (dm, 1 H, J ϭ 12.5, CHH), ¹³C NMR: δ ϭ 102.1 (0), 174.8 (0), 139.7 (0), 128.7 (1), 128.4 (1),

1.70 (ddd, 1 H, J ϭ 13.0, 13.0, 3.3, CHH), 1.56Ϫ1.30 (5 H, CHH

ϩ H3), 1.14Ϫ0.95 (2 H, CHH). Ϫ ¹³C NMR: δ ϭ 146.7 (1), 139.9 45.2 (1), 41.8 (1), 37.7 (2), 33.0 (2), 32.5 (0), 29.7 (2), 29.0 (3), 27.6

(0), 128.5 (1), 127.7 (1), 127.5 (1), 100.3 (1), 73.7 (1), 69.7 (2), 68.5 (3), 25.6 (2), 24.7 (2). Ϫ IR (NaCl, neat): ν˜ ϭ 2934 (s), 2865 (s),

127.6 (1), 116.0 (0), 108.5 (1), 81.7 (1), 72.8 (1), 72.7 (2), 51.3 (2),

(1), 43.3 (1), 32.7 (2), 26.4 (2), 26.0 (2), 24.5 (2). Ϫ IR (NaCl, neat): 1654 (s), 1631 (s), 1401 (m), 1388 (s), 1189 (s), 1161 (s), 1113 (m).

ν˜ ϭ 3060 (m), 2936 (s), 2862 (s), 1640 (s), 1453 (s), 1254 (s), 1109

(s), 1058 (s), 735 (s), 697 (s).

Acknowledgments

(4 *,4a *,8a *)-4-Benzyloxy-4a,5,6,7,8,8a-hexahydro-4

-

This work was generously supported by the Fonds der Chemischen

Industrie (Liebig-Fellowship and financial support) and the

Deutsche Forschungsgemeinschaft (Fellowship support for B. S.

and financial support). We thank Ms. A. Danzmann and Dr. B.

Costisella for NMR spectroscopic investigations. Technical assist-

ance by Ms. M. Melzer and Ms. S. Vogt is gratefully acknowledged.

B. S. thanks Prof. Dr. P. Eilbracht for his continuous support and

interest in this study.

chromene ( -19i): Obtained from cis-11i (0.11 g, 0.7 mmol). Yield:

0.15 g (90%). Ϫ LRMS (EI ); m/z: 243 (M^ϩϪ 1, 5%), 137 (M^ϩ

Ϫ

1

OBn, 100%), 91 (C₇H₇^ϩ, 30%). Ϫ H NMR: δ ϭ 7.35 (d, 2 H, J ϭ

7.5, o-H, Ph), 7.23 (dd, 2 H, J ϭ 7.5, 7.5, m-H, Ph), 7.13 (t, 1 H,

J ϭ 7.5, p-H, Ph), 6.42 (dd, 1 H, J ϭ 6.3, 1.5, H6), 4.86 (dd, 1 H,

J ϭ 6.3, 1.5, H5), 4.53 (d, 1 H, J ϭ 12.0, OCHHPh), 4.29 (d, 1 H,

J ϭ 12.0, OCHHPh), 3.69 (ddd, 1 H, J ϭ 9.0, 1.5, 1.5, H4), 3.41

(ddd, 1 H, J ϭ 11.1, 11.1, 4.5, H2), 2.24 (dm, 1 H, J ϭ 13.8, CHH),

1.98 (dm, 1 H, J ϭ 12.3, CHH), 1.79 (dddd, 1 H, J ϭ 12.0, 11.1,

9.0, 3.7, H3), 1.55Ϫ1.30 (3 H, CHH), 1.05Ϫ0.93 (2 H, CHH), 0.65

(dddd, 1 H, J ϭ 13.0, 13.0, 13.0, 3.8, CHH). Ϫ ¹³C NMR: δ ϭ

145.3 (1), 139.6 (0), 128.5 (1), 127.8 (1), 127.5 (1), 102.1 (1), 77.5

(1), 75.2 (1), 69.7 (2), 43.4 (1), 32.2 82), 29.1 (2), 25.3 (2), 24.5 (2).

Ϫ IR (NaCl, neat): ν˜ ϭ 3062 (m), 2935 (s), 2858 (s), 1642 (s), 1452

(m), 1233 (m), 1113 (s), 1060 (s), 735 (s), 697 (s).

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3163

Article Doi

A synthesis of densely functionalized 2,3-dihydropyrans using ring-closing metathesis and base-induced rearrangements of dihydropyran oxides

DOI: 10.1002/1099-0690(200009)2000:18<3145::AID-EJOC3145>3.0.CO;2-B

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