Enantiomerically Pure Vinylcyclopropylboronic Esters

FULL PAPER

DOI: 10.1002/ejoc.200900414

[a]

[b]

ˇ

Erwin Hohn, Jirí Palecek, Jörg Pietruszka,* and Wolfgang Frey

Dedicated to Professor Dr. Armin de Meijere on the occasion of his 70th birthday

Keywords: Boron / Cyclopropane / Asymmetric synthesis / Palladium / Natural products

Vinylcyclopropanes are versatile intermediates and products

in organic synthesis. The corresponding enantiomerically

pure boronic esters should lead to highly flexible building

blocks with a variety of applications. A detailed study

towards the selective synthesis of (E)- and (Z)-vinyl deriva-

tives starting from the known diastereo- and enantiopure cy-

clopropylmethanols 3 and 4 is presented. The boronic esters

were activated via their trifluoroboronates; the optimization

of the reaction is discussed. The endeavour culminated in the

synthesis of (–)-(1S,2S)-dictyopterene A (38).

Germany, 2009)

A highly flexible approach was reported by Markó and

coworkers.^[7]The group synthesized vinylcyclopropyl-

boronic esters by direct cyclopropanation of the corre-

sponding diene with diazomethane, hence allowing further

transformations of the boron moiety. The concept matched

our own approach towards the corresponding enantiomer-

ically pure intermediates. The key building blocks that

stemmed from our search for highly stable boron intermedi-

ates^[8]were the cyclopropylmethanols 3 and 4 (Figure 2).^[9]

We have previously demonstrated their use in a variety of

transformations of both the side-chain,^[10]for example, fur-

nishing vinylcyclopropylboronates 5 and 6 by an oxidation/

Horner–Wadsworth–Emmons chain elongation,^[11]and the

boron group.^[9–12]Herein we describe the full details of our

findings, focussing on the selective synthesis of substituted

vinylcyclopropane derivatives and the activation of the ro-

bust boronic esters.

Introduction

Vinylcyclopropanes are attractive synthetic intermediates

for the synthesis of physiologically active components as

well as natural products.^[1]Especially noteworthy in this re-

spect are oligocyclopropane-containing natural products

such as the FR-900848 (1)^[2]or ambruticin (2; Figure 1).^[3]

Vinylcyclopropanes are also important intermediates, for

example, they have been used as intermediates in the syn-

thesis of cyclopentanoid terpenes^[4]using a [4+1] annulation

strategy.^[5]Consequently, a number of strategies have been

devised for the enantioselective synthesis of the motif.^[6]

Figure 1. Naturally occurring vinylcyclopropanes.

[a] Institut für Bioorganische Chemie der Heinrich-Heine-

Universität Düsseldorf im Forschungszentrum Jülich,

Stetternicher Forst, Geb. 15.8, 52426 Jülich, Germany

Fax: +49-2461-616196

E-mail: j.pietruszka@fz-juelich.de

[b] Institut für Organische Chemie, Universität Stuttgart,

Pfaffenwaldring 55, 70569 Stuttgart, Germany

Figure 2. Key intermediates in the synthesis of vinylcyclopropyl-

boronic esters.

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Results and Discussion

Synthesis by Cross-Metathesis

The starting point of our endeavour was the readily avail-

able alcohol 3, which we used in a selective oxidation step,

either performing the reaction under the conditions estab-

lished by Ley et al. (92%; NMO: N-methylmorpholine N-

oxide; TPAP: tetra-n-propylammonium perruthenate)^[13]or

by using the Dess–Martin periodinane 7 (95%).^[14]The ole-

fination of aldehyde 8 was achieved by a conventional Wit-

tig reaction (90%) or a Peterson reaction (85%).^[15]Both

sequences were performed numerous times and proved to

be equally reliable for providing vinylcyclopropane 9 in high

yield (Scheme 1).

Scheme 2. Cross-metathesis of ester 9 with various terminal olefins

RCH=CH₂. [a] +14% 13. Abbreviations: Cy = cyclohexyl, TES =

Et₃Si.

Scheme 1. Synthesis of vinylcyclopropane 9.

Next we investigated the ability of vinylcyclopropane 9

to act as a coupling partner in a cross-metathesis to give

vinylcyclopropanes 10 (and 5) using the commercially avail-

able Grubbs catalysts 11 and 12 (Scheme 2).^[16]The first

results indicated that catalyst 11 would be of limited use:^[10a]

although styrene worked perfectly well to give compound

10a in high yield and selectivity (95%, E/Z Ͼ 98:2), even

methyl acrylate caused problems. The reaction was sluggish

and gave the desired E product 5 in moderate yield (52%)

only. “Dimer” 13 was obtained as a side-product in 14%

yield; this derivative could actually be obtained in high yield

(81–95%) when no other olefin was added to the reaction

mixture. Catalyst 12 proved to be superior in all respects.

The yield of product 10 or 5 was generally higher (70–96%)

and there were hardly any limitations in the substrates that

could be used: simple alkyl groups (10b,c) as well as silyl

protecting groups (10d,e) were tolerated. Only allyl acetate

Figure 3. X-ray crystallographic structures of esters 10a and 10b.^[17]

Synthesis by Wittig-Type Olefination

It has already been established that standard transforma-

(10f) or unprotected allyl alcohol (10g) did not form the tions, the oxidation of alcohol 4 to aldehyde 14 (95% yield)

desired vinylcyclopropanes. Although the E/Z selectivity with the Dess–Martin reagent 7 followed by reaction with

was fair in most cases, a major drawback of the procedure a stabilized ylide, led to the E product 6 exclusively (90%;

was the difficulty of separating the diastereoisomers. Scheme 3).^[11]We assumed that after a conventional re-

Attempts to obtain pure isomers by chromatographic meth- duction (to alcohol 15; 89% yield)Ϫoxidation sequence, the

ods failed and in only two cases (products 10a,b) did selec- aldehyde 16 (95% yield) would be an ideal starting material

tive crystallization enable their purification, also providing for a selective synthesis of diene 17, as required, for exam-

proof of their configurations by X-ray structural analysis ple, for the synthesis of dictyopterene B (see below).^[18,19]

(Figure 3).^[17]Therefore, we were looking for alternative As expected,^[20]the consecutive Wittig reaction was highly

methods to synthesize one isomer selectively.

Z-selective and could be influenced by the choice of solvent

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Enantiomerically Pure Vinylcyclopropylboronic Esters

(THF, DME and dichloromethane were used) and counter-

ion (lithium vs. sodium and potassium; entries 1–5, ratio

determined from the crude product by a 600-MHz ¹H-

NMR study). It proved to be most convenient to use THF

as the solvent and potassium hexamethyldisilazide

(KHMDS) as the base, which provided the highest yield of

the desired diene 17 (entry 4: 96%, E/Z = 3:97). With the

high selectivity observed, purification by selective crystalli-

zation of the Z isomer was readily achieved.

Scheme 4. Schlosser procedure. The reaction conditions were same

for all experiments, only the bases were modified.

70% yield and in an 80:20 ratio (entry 4). Nevertheless, the

approach was still not satisfactory for preparative purposes.

The Julia–Kocienski reaction proved to be the method of

choice.^[22]The required reagent was readily synthesized

from thiol 18 and n-pentanol in two steps: Mitsunobu reac-

tion (92%) followed by oxidation (88%) furnished the sul-

fone 19. The observed E selectivity was high (Ͼ99:1) right

from the start (Scheme 5, entry 1), but the yield needed to

be increased (20%). Although increasing the amount of

KHMDS did slightly improve the yield (36%, entry 2),

changing the counter-ion to sodium (NaHMDS) led to a

decrease in the selectivity (43% yield, dr 97:3; entry 3). In-

stead of using commercially available solutions of base in

toluene, we next used neat KHMDS as the base, hence per-

forming the transformation in DME as the only solvent

(entries 4–8), thus further increasing the rate of the reac-

tion. By optimizing the conditions (–60 °C, 10 min,

1.8 equiv. KHMDS and 1.5 equiv. 19, entry 8) up to 93%

yield of olefin 10b was obtained; although the minor dia-

Scheme 3. Wittig procedure: a) for all experiments only bases or

solvents were modified; b) the minor diastereoisomer was removed

by crystallization.

To gain access to the E isomers and, in view of our en- stereoisomer was detectable in the crude product by NMR

deavour towards the synthesis of dictyopterene A (see be- spectroscopy (not with a 300 MHz spectrometer), a single

low), in particular to the n-butyl derivative 10b, we were crystallization allowed the isolation of the E isomer.

looking for alternatives that were also compatible with the

Summing up, the Wittig-type olefinations investigated

boronic ester moiety. First, we tested the Schlosser reac- were compatible with the boronic ester moiety. Separation

tion^[21]starting from aldehyde 8; this procedure led to the of the E/Z isomers was difficult if possible at all, hence an

olefin 10b, albeit in poor yield and selectivity (Scheme 4). almost perfect selectivity was required. Despite the fact that

However, by altering the bases used for the two consecutive the Julia–Kocienski reaction gave superb isomeric ratios,

steps (from phenyllithium to n-butyllithium) as well as the circumventing the optimization step for each substrate

equivalents used (from 2 to 1 equiv.), the efficiency could would be highly desirable. Cross-coupling reactions of sub-

be increased and the desired E isomer 10b was obtained in strates with a given configuration might be an alternative.

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investigation, we were pleased to find that the starting mate-

rials were obtained in high purity and in the case of the

trans isomer 22a even as a crystalline solid.

Scheme 5. Julia–Kocienski procedure. a) Base was added over

5 min to sulfone 19. The resulting solution was stirred for 1 h (en-

try 8: 5 min) and the aldehyde 8 was added over 5 min. b) Base was

added over 20 min to sulfone 19 and aldehyde 8. c) The reactions

were in progress for the times shown, that is, after addition of all

components to the reaction mixture, and then quenched with H₂O.

d) The minor (Z)-olefin corresponding to 10b was only detected by

¹H NMR (600 MHz); it was removed by recrystallization. e) The

yield was slightly lower (91%) when performing the transformation

on a larger scale (6.95 mmol).

Scheme 6. Synthesis of the required iodide 22a.

Prior to our investigation,^[10b]only a few cross-coupling

reactions^[8c,24]of cyclopropyl iodides had been reported, de-

spite the fact that the starting cyclopropanes are readily

Synthesis by Cross-Coupling

We have previously reported the two-step sequence from available.^[25]To optimize the reaction we used different con-

alcohol 3 via the acid 20, its “Barton ester” (preferentially ditions, those reported in the literature essentially for cyclo-

generated with “HOTT reagent” 21),^[23]to the iodides 22a propanes (conditions A–G, Scheme 7).^[24b,26,9]

and 22b (Scheme 6).^[10b]The ruthenium-catalysed oxidation

Although the product was detectable in some cases, in

of cyclopropylmethanol proceeded smoothly to furnish the our hands the most reliable procedure was reported by Hil-

corresponding crystalline acid 20 in high yield (90%), again debrand and Marsden {conditions D: [Pd(PPh₃)₄], KOtBu,

not affecting the boron moiety. The following radical decar- DME, 80 °C}.^[26a]With phenylboronic acid (23h), the first

boxylation proved to be sensitive; it was essential that the model substrate, product 10h was obtained in high yield

required “Barton thiohydroxamic ester” was obtained in (87%).^[27]Obvious limitations for the process are halides in

high purity. Although the approach via the acid chloride the aromatic ring as the cyclopropyl iodide reacts relatively

was feasible, the yield was poor (33%). The standard pro- sluggishly; hence no product was obtained with boronic

cedure using dicyclohexylcarbodiimide (DCC) for the direct acid 10i. On the other hand, a heterocyclic substituent, as

esterification also furnished an inseparable side-product in the thiophene derivative 23j, represents no problem (yield

that interfered with the following radical step. As men- of cyclopropane 10j: 79%). Even cyclopropane/cyclopro-

tioned before, use of the “HOTT reagent” 21^[23]was the pane coupling was achieved in good yield (67% of dicyclo-

method of choice. The separable iodides 22a,b were synthe- propane 10k); instead of using the boronic acid, the corre-

sized in 70% yield as a 6:1 mixture after the radical trans- sponding dioxaborinane 23k^[28]was used. In all cases the

formation in the presence of iodoform. Because the follow- boron derivative 23 was added in access (1.5 equiv.) as a

ing Pd-catalysed coupling was a critical reaction for our dramatic decrease in yield was observed when only

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Enantiomerically Pure Vinylcyclopropylboronic Esters

Scheme 8. Heck reaction of vinylcyclopropylboronic ester

([BMIM]Br: 1-butyl-3-methylimidazolium bromide).

9

Activation of Boronic Esters

Before applying the synthesized vinylboronates, a conve-

nient protocol to deprotect the boronic esters was required

as the previously established procedure (activation with

LiAlH₄or MeLi)^[8–11]is not compatible with many func-

tional groups and especially not with the vinylcyclopro-

panes (e.g., starting from substrate 9 would yield the corre-

sponding 1,3,2-dioxaborinane in 41% yield only^[30,32]). A

different approach was based on an alternative mode of ac-

tivation, as shown by Genêt and Deng and their coworkers

who used and modified the procedures of Vedejs et al. as

well as Thierig and Umland for converting boronic acids

and esters into the corresponding trifluoroborates with

KHF₂.^[33]As model substrates we chose the benzyl-pro-

tected cyclopropylmethanols 24a,b, which are readily avail-

able in our group (Scheme 9).^[12a,12b]When treating these

substrates in methanol/water with 7 equiv. of KHF₂at

room temperature, no conversion was detected by TLC af-

ter 15 h. Increasing the reaction temperature and the equiv-

alents of the reagents did initiate a slow conversion (25 h,

40 °C, 14 equiv. KHF₂). The optimum temperature was

reached at 80 °C (ca. 90% conversion, ca. 70% yield of

slightly impure 25); complete conversion was not observed.

However, increasing the amount of fluoride reagent to

50 equiv. did shift the equilibrium to furnish the product 25

after 2 d in 91% yield; no starting material was recovered.

The work-up procedure towards pure product 25 needed

some optimization. We found that the best results were ob-

tained when the solvents were first evaporated under re-

Scheme 7. Suzuki coupling of iodide 22a.

1.0 equiv. was used. In view of the present vinylcyclopro- duced pressure: the residue, the solids, were fractionally

pane study we were especially pleased to find that substrates washed easily first with diethyl ether (extracting the diol)

23l,b^[28,29]do not represent any problem: the products 10l,b followed by acetonitrile (extracting the product 25) leaving

were obtained in 65 and 62% yields, respectively. The pro- the inorganic salts on the filter. The work-up procedure was

tected boron moiety of the products remained intact and further simplified by omitting water as the solvent from the

could be further elaborated in consecutive steps (see below). transformation; the products 25 and ent-25 were obtained

Although the formation of dicyclopropane 10k was pos- in 93% yield as pure crystalline solids, as determined by ¹⁹

sible, simple alkylboronic acids (e.g., 23m) could not, as ex- NMR spectroscopy, the structures of which could be solved

F

pected, be successfully coupled.

by X-ray crystallography.

We had previously shown that cyclopropyl iodides were

We were pleased to find that the isolated borates could

not ideal reaction partners for the Stille or Heck reac- be readily exposed to the coupling conditions, as reported

tion,^[30]for example, iodide 22a did not react under the re- by Deng and coworkers^[33e], to furnish the desired enantio-

cently reported^[31]conditions with styrene, methyl acrylate merically pure cyclopropanes 27 and 28 in 66 and 85%

or 1-heptene using ionic liquids. However, when reversing yields, respectively (Scheme 10). However, for the envisaged

the reaction partners and exposing vinylcyclopropane 9 and use of the boron compounds in a Matteson homologa-

iodobenzene to the reaction conditions (Scheme 8), the tion,^[34]the reactivity of the intermediates 25 and ent-25

known product 10a was selectively formed as a single iso- would be too low. A number of protocols have been devised

mer (91%). Thus, a new alternative protocol to the cross- for the activation and hence the liberation of the corre-

metathesis reaction was established.

sponding acids. Kim and Matteson reported that SiCl₄can

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yield (conditions V: 92%). With these findings, transforma-

tion of the sensitive vinylcyclopropanes also seemed feas-

ible.

Scheme 10. Suzuki coupling of borates 25 and ent-25.

Scheme 9. Generation of borates 25 and ent-25.

activate trifluoroborates to form dichloroborane intermedi-

ates; these were directly converted into simple boronic es-

ters.^[35]The procedure was successfully applied to cyclopro-

pane 25: depending on the diol used either 1,3,2-dioxabori-

nane (29, 91%; Scheme 11) or 1,3,2-dioxaborolane 30

(quant.) was obtained, intermediates that were previously

Scheme 11. Activation of borate 25.

Synthetic Approach Towards the Dictyopterenes

Finally, we tried to apply the synthesized building blocks

shown to be ideal reaction partners for the Suzuki–Miyaura to a small natural product synthesis: dictyopterenes are un-

coupling and the Matteson homologation. However, be- saturated C₁₁-hydrocarbons bearing vinylcyclopropane sub-

cause the formation of HCl during the transformation can- units.^[18,19]The natural compounds were first isolated by

not be prevented, sensitive substrates (including vinylcyclo- Moore et al. as major components from the odoriferous oil

propane 9) are not compatible with these conditions. An of the Hawaiian seaweeds, genus Dictyopteris;^[19a]the 1R,2R

alternative to the one-pot sequence was reported by Yuen configuration was established, although later (1S,2S)-

and Hutton:^[36]under basic conditions the boronic acid was dictyopterene B was discovered to be a minor component in

first formed, which was subjected to esterification (condi- female gametes and essential oils of the Scytosiphonaceae,

tions II: 29 was prepared in 75% yield over two steps), and Chordariaceae and Dictyotacea families.^[19m]All com-

under acidic conditions, using trimethylsilyl chloride in an pounds exhibit remarkable activity, including their sperm-

aqueous environment, the acid was also formed and ulti- attracting physiological ability. They are also responsible for

mately the ester 29 (conditions III: 94% over two steps). the intense ocean smell. Although most synthetic ap-

Slightly modifying the original protocol led in one-pot to proaches lead to mixtures of undesired isomers, few of the

the target compound: when forming the dichloroborane in reported procedures afforded the optically pure dictyopter-

the absence of water and adding 1,3-propanediol after enes.^[37]

5 min, the desired product 29 was furnished in 95% yield

Starting from the enantio- and diastereomerically pure

(conditions IV). However, acidic conditions were not omit- boronic esters 10b and 17, we first needed to deprotect and

ted. We solved the problem by adding triethylamine to activate the boron moiety. We applied the optimized condi-

quench the HCl formed without negatively influencing the tions to form the borates 31 and 32 (Scheme 12; MeOH,

transformation. Again, product 29 was isolated in good KHF₂, 80 °C) in 89 and 87% yields, respectively, followed

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Enantiomerically Pure Vinylcyclopropylboronic Esters

by the transformation to the reactive boronic esters 33 and

34 (90% yields). The pure compounds were obtained after

distillation of the crude products. The Matteson procedure,

treatment with chloromethyllithium and subsequent oxi-

dation with basic hydrogen peroxide, proved to be the bot-

tle-neck in the sequence: Only with pure starting material

could the transformation to alcohol 35 be successfully per-

formed, albeit in moderate yield (48%); several attempts to

convert the 1,3,2-dioxaborinane 34 into the desired product

36 failed. However, oxidation of the primary alcohol 35

with Dess–Martin periodinane 7^[14]proceeded smoothly to

furnish aldehyde 37. As expected, Wittig reaction^[20]af-

forded in the last step (1S,2S)-dictyopterene A (38). The

spectroscopic data were in full agreement with those pre-

viously reported.^[19d]

Conclusions

We have developed, optimized and evaluated a) various

new approaches to enantio- and diastereomerically pure vi-

nylcyclopropylboronic acids, including (for the first time) a

Heck reaction in an ionic liquid, b) the deprotection of

highly stable boronic esters to furnish borates and c) the

activation of the borates forming 1,3,2-dioxaborinanes. The

sequence was applied to the synthesis of dictyopterenes: al-

though the Matteson homologation approach failed to

yield (1R,2R)-dictyopterene B (39), it allowed the synthesis

of (1S,2S)-dictyopterene A (38).

Experimental Section

General: Unless specified the reactions were carried out by using

standard Schlenk techniques under dry N₂with magnetic stirring.

Glassware was oven-dried at 120 °C overnight. Solvents were dried

and purified by conventional methods prior to use; tetrahydrofuran

(THF) was freshly distilled from sodium/benzophenone. Common

solvents for chromatography (petroleum ether, EtOAc) were dis-

tilled prior to use; petroleum ether refers to the fraction with a

boiling point in the range 40–60 °C. Column chromatography and

flash column chromatography were performed on silica gel 60

(0.040–0.063 mm, 230–400 mesh). TLC (monitoring the course of

the reactions) was performed on precoated plastic sheets (Poly-

gram® SIL G/UV254, Macherey–Nagel) with detection by UV

(254 nm) or by colouration with cerium molybdenum solution

[phosphomolybdic acid (25 g), Ce(SO₄)₂·H₂O (10 g), concd. H₂SO₄

(60 mL), H₂O (940 mL)]. Preparative medium-pressure liquid

chromatography (MPLC) was performed with a Labomatic pump

(MD-50/80/100), a packed column (25ϫ300 mm or 40ϫ475 mm),

1

LiChroprep, Si 60 (15–25 µm) and UV detector (254 nm). H and

¹³C NMR spectra were recorded at room temp. in CDCl₃(unless

stated otherwise) with a Bruker ARX 300, ARX 500, DRX 600 or

a Varian Inova 400 spectrometer. Chemical shifts are given in ppm

relative to TMS as the internal standard [¹H, Si(CH₃)₄δ =

0.00 ppm] or to the resonance of the solvent (¹³C, CDCl₃δ =

77.0 ppm); coupling constants J are given in Hz. Higher-order δ

and J values are uncorrected. ¹³C NMR signals were assigned on

the basis of H–H COSY and HSQC or HMBC spectroscopy.

Microanalyses were performed at the Institut für Organische

Chemie, Stuttgart. Melting points or softening ranges (Büchi 510

and B-540, respectively) are uncorrected. Specific rotations were

measured at 20 °C (Perkin–Elmer 241 MC or precisely 341). IR

spectra were obtained with a Perkin–Elmer 283, Bruker IFS 28 or

a Perkin–Elmer Spectrum One spectrometer. MS were recorded

with a Finnigan MAT 95 [FAB (NBA: 3-nitrobenzyl alcohol), EI],

a Varian MAT 711 (EI) or an Applied Biosystems/MDS SCIEX

4000 Q TRAP (ESI, LC–MS/MS) spectrometer.

Nomenclature: For convenience and easy data comparison the bo-

ron moieties were set to lowest substituent priority in contradiction

to the IUPAC nomenclature guidelines.

Synthesis of Vinylcyclopropane 9

(4R,5R,1ЈR,2ЈR)-Aldehyde 8. Method A:^[11]Cyclopropylmethanol 3

(1.10 g, 2.06 mmol, 1.00 equiv.), N-methylmorpholine N-oxide

(390 mg, 2.88 mmol, 1.40 equiv.), 4 Å molecular sieves (1.5 g) and

dry dichloromethane (10 mL) were placed in a Schlenk flask under

dry nitrogen. The mixture was cooled to 0 °C, TPAP (40 mg,

0.10 mmol, 0.05 equiv.) was added and stirring was continued for

15 h at room temp. After filtration through a pad of Celite, the

Scheme 12. Synthetic route towards the dictyopterenes.

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residue was washed with dichloromethane and the organic solvent

was removed under reduced pressure. Chromatography (silica gel,

petroleum ether/ethyl acetate, 9:1) yielded the aldehyde 8 (1.01 g,

1.89 mmol, 92%).

623, 613 cm^–1. H NMR (CDCl₃, 500 MHz): δ = –0.44 (ddd, J =

9.9, J = 6.6, J = 5.2 Hz, 1 H, 1Ј-H), 0.29 (ddd, J = 10.2, J = 6.6,

J = 3.5 Hz, 1 H, 3Ј-H_a), 0.41 (ddd, J = 9.9, J = 8.6, J = 3.5 Hz, 1

H, 3Ј-H_b), 1.35 (dddd, J = 10.2, J = 8.6, J = 8.6, J = 5.2 Hz, 1 H,

2Ј-H), 3.00 (s, 6 H, OCH₃), 4.75 (dd, J = 10.1, J = 1.8 Hz, 1 H, 5Ј-

H_a), 4.97 (dd, J = 17.0, J = 1.8 Hz, 1 H, 5Ј-H_b), 5.11 (ddd, J =

17.0, J = 10.1, J = 8.6 Hz, 1 H, 4Ј-H), 5.26 (s, 2 H, 4-H, 5-H),

7.24–7.35 (m, 20 H, arom. H) ppm. ¹³C NMR (CDCl₃, 125 MHz):

δ = 5.0 (C-1Ј), 12.7 (C-3Ј), 22.0 (C-2Ј), 51.7 (CPh₂OCH₃), 77.6 (C-

4 and C-5), 83.2 (CPh₂OCH₃), 111.9 (C-5Ј), 127.1, 127.3, 127.5,

127.8, 128.4, 129.7 (arom. CH), 141.1, 141.3 (arom. C_ipso), 142.2

(C-4Ј) ppm. MS (EI, 70 eV): m/z (%) = 530 (Ͻ5) [M]⁺, 197 (100)

[Ph₂COCH₃]⁺. C₃₅H₃₅BO₄(530.46): calcd. C 79.25, H 6.65; found

C 79.13, H 6.67.

1

Method B: Cyclopropylmethanol 3 (1.00 g, 1.87 mmol, 1.00 equiv.)

was dissolved in dichloromethane (60 mL) and Dess–Martin

periodinane (7; 0.83 g, 1.96 mmol, 1.05 equiv.) was added. The re-

action mixture was stirred for 15 h at room temp., quenched with

a 1  aqueous solution of Na₂S₂O₃(50 mL) and washed with aque-

ous saturated NaHCO₃(50 mL); the aqueous layer was finally ex-

tracted with dichloromethane (3ϫ50 mL). The combined organic

layers were dried (MgSO₄), filtered and concentrated under re-

duced pressure. The crude product 8 was purified by flash column

chromatography (silica gel, petroleum ether/ethyl acetate, 9:1) to

afford aldehyde 8 (954 mg, 1.79 mmol, 95%) as colourless crystals;

softening range 89–95 °C. [α]²_D⁰= –96.7 (c = 1.00, CHCl₃). IR

Synthesis by Cross-Metathesis

General Procedure for Cross-Metathesis (CM): Vinylcyclopropane

9 (1.0 equiv.), the terminal olefin RCH=CH₂(5.0–15.0 equiv.) and

the Grubbs catalyst 11 (A) or 12 (B; 0.01–0.05 equiv.) were dis-

solved in abs. dichloromethane (15 mL/mmol). The mixture was

heated at reflux at 40 °C up to full conversion of the vinylcyclopro-

pane 9 (check by TLC) and then filtered through Celite, rinsed with

diethyl ether and the solvents were removed under reduced pres-

sure. The crude product 5 or 10 were purified by column

chromatography (silica gel, petroleum ether to petroleum ether/

ethyl acetate, 98:2).

(film): ν = 3056, 3025, 2938, 2831, 2723, 1710, 1445, 1425, 1395,

˜

1308, 1192, 1074, 1032, 1015, 966, 924, 896, 796, 698 cm^–1. ¹H

NMR (CDCl₃, 500 MHz): δ = 0.27 (ddd, J = 10.2, J = 7.5, J =

4.8 Hz, 1 H, 1Ј-H), 0.94 (ddd, J = 7.6, J = 7.5, J = 3.9 Hz, 1 H,

3Ј-H_a), 1.06 (ddd, J = 10.2, J = 4.3, J = 3.9 Hz, 1 H, 3Ј-H_b), 1.28

(dddd, J = 7.6, J = 6.3, J = 4.8, J = 4.3 Hz, 1 H, 2Ј-H), 2.80 (s, 6

H, OCH₃), 5.12 (s, 2 H, 4-H, 5-H), 7.05–7.11 (m, 20 H, arom. H),

8.30 (d, J = 6.3 Hz, 1 H, CHO) ppm. ¹³C NMR (CDCl₃,

125 MHz):

δ = 3.0 (C-1Ј), 11.8 (C-2Ј), 28.6 (C-3Ј), 52.1

(CPh₂OCH₃), 78.2 (C-4, C-5), 83.6 (CPh₂OCH₃), 127.8, 127.9,

128.1, 128.3, 128.7, 130.1 (arom. CH), 141.3 (arom. C_ipso), 200.4

(C-4Ј) ppm. MS (EI, 70 eV): m/z (%) = 532 (Ͻ5) [M]⁺, 197 (100)

[Ph₂COCH₃]⁺. C₃₄H₃₃BO₅(532.43): calcd. C 76.70, H 6.25; found

C 75.72, H 6.26.

(1ЈR,2ЈR,4R,5R)-2-{2Ј-[(E)-2-Methoxycarbonylethenyl]cyclo-

propyl}-4,5-bis(methoxydiphenylmethyl)-1,3,2-dioxaborolane (5):^[11]

A) Vinylcyclopropane 9 (75 mg, 0.14 mmol, 1.0 equiv.), methyl ac-

rylate (20 mg, 0.28 mmol, 2.0 equiv.) and Grubbs catalyst 11

(10 mg, 10 µmol, 0.07 equiv.) in dichloromethane (4 mL) were al-

lowed to react according to the general procedure for 5 d. The bo-

ronic ester 5 was isolated as colourless crystals (44 mg, 74 µmol,

52 %); E/Z Ͼ 95:5. B) Vinylcyclopropane 9 (0.10 g, 0.19 mmol,

1.0 equiv.), methyl acrylate (0.16 g, 1.9 mmol, 10 equiv.) and the

Grubbs catalyst 12 (10 g, 10 µmol, 0.05 equiv.) in dichloromethane

(4 mL) were allowed to react according to the general procedure for

2 d. The boronic ester 5 was isolated as colourless crystals (0.10 g,

0.17 mmol, 91%); E/Z Ͼ 95:5; m.p. 157 °C. [α]²_D⁰= –85.0 (c = 0.96,

(4R,5R,1ЈR,2ЈR)-Vinylcyclopropane 9. Method A: Ph₃PMeBr

(0.17 g, 0.48 mmol, 1.05 equiv.) was dissolved in dry THF (8 mL)

and the mixture was cooled to 0 °C in a Schlenk flask. nBuLi

(0.30 mL of a 1.6  solution in hexane; 0.48 mmol, 1.05 equiv.) was

added and stirring was continued for 1 h at 0 °C. The solution

turned bright orange and aldehyde 8 (0.24 g, 0.46 mmol, 1 equiv.)

in THF (1 mL) was added dropwise; the reaction mixture turned

yellow. The cooling bath was removed and the mixture was stirred

for 15 h at room temp. After the addition of saturated aqueous

NH₄Cl solution (10 mL) the phases were separated and the aque-

ous phase extracted with diethyl ether (3ϫ10 mL). The combined

organic phases were dried with MgSO₄and the solvent was re-

moved under reduced pressure. The crude product 9 was purified

by column chromatography (petroleum ether/ethyl acetate, 95:5) to

CHCl ). IR (film): ν = 3058, 3026, 2934, 1720, 1652, 1493, 1421,

˜

3

1371, 1262, 1193, 1067, 1033, 1018, 969, 938, 856, 757, 738,

1

702 cm^–1. H NMR (CDCl₃, 500 MHz): δ = –0.19 (ddd, J = 10.2,

J = 7.1, J = 5.1 Hz, 1 H, 1Ј-H), 0.39 (ddd, J = 7.5, J = 7.1, J =

3.7 Hz, 1 H, 3Ј-H_a), 0.52 (ddd, J = 10.2, J = 4.9, J = 3.7 Hz, 1 H,

3Ј-H_b), 1.46 (dddd, J = 10.1, J = 7.5, J = 5.1, J = 4.9 Hz, 1 H, 2Ј-

H), 3.00 (s, 6 H, CPh₂OCH₃), 3.67 (s, 3 H, CO₂CH₃), 5.29 (s, 2 H,

4-H, 5-H), 5.78 (d, J = 15.4 Hz, 1 H, 5Ј-H), 6.19 (dd, J = 15.4, J

= 10.1 Hz, 1 H, 4Ј-H), 7.25–7.33 (m, 20 H, arom. H) ppm. ¹³C

NMR (CDCl₃, 125 MHz): δ = –4.2 (C-1Ј), 14.1 (C-3Ј), 21.1 (C-

2Ј), 51.3 (CPh₂OCH₃), 51.8 (CO₂CH₃), 77.4 (C-4 and C-5), 83.3

(CPh₂OCH₃), 117.7 (C-5Ј), 127.4, 127.5, 127.6, 127.8, 128.4, 129.7

(arom. CH), 141.0, 141.1 (arom. C_ipso), 153.9 (C-4Ј), 167.0

(CO₂CH₃) ppm. The spectroscopic data for boronic ester 5 were in

full agreement with the previously reported data.^[11].

yield the vinylcyclopropane

0.42 mmol, 90%).

9 as colourless crystals (0.22 g,

Method B: Aldehyde 8 (700 mg, 1.31 mmol, 1.00 equiv.) was dis-

solved in dry Et₂O (2 mL) and cooled to 0 °C in a Schlenk flask.

Me₃SiCH₂MgCl (1.71 mL of a 1  solution in Et₂O; 1.71 mmol,

1.30 equiv.) was added and stirring was continued at 0 °C for 1 h.

The reaction was quenched with sulfuric acid (1.3 mL of a 30%

aqueous solution). After stirring at room temp. for 1 h, a 1  aque-

ous NaOH solution was added to neutralize the reaction mixture.

Separation of the phases was followed by the extraction of the

aqueous layer with Et₂O (3ϫ50 mL). The combined organic layers

were dried with MgSO₄, filtered and the solvent was removed under

reduced pressure. The residue was purified by column chromatog-

raphy (silica gel, petroleum ether/ethyl acetate, 97:3) to yield olefin

9 (592 mg, 1.12 mmol, 85%) as a colourless solid; softening range

(1ЈR,2ЈR,4R,5R)-4,5-Bis(methoxydiphenylmethyl)-2-[(E)-2Ј-styryl-

cyclopropyl]-1,3,2-dioxaborolane (10a). Method A: Vinylcyclopro-

pane 9 (75 mg, 0.14 mmol, 1.0 equiv.), styrene (30 mg, 0.28 mmol,

2 equiv.) and Grubbs catalyst 11 (10 mg, 10 µmol, 0.07 equiv.) in

dichloromethane (8 mL) were allowed to react according to the ge-

neral procedure for 5 d. The boronic ester 10a was isolated as

colourless crystals (82 mg, 0.13 mmol, 95%); E/Z Ͼ 98:2.

76–83 °C. [α]²_D⁰= –92.2 (c = 0.45, CHCl ). IR (film): ν = 3040,

˜

3

3010, 2980, 2940, 2919, 2815, 1481, 1450, 1435, 1423, 1399, 1355,

1305, 1230, 1199, 1061, 1017, 1003, 951, 920, 880, 819, 735, 678,

Method B: Vinylcyclopropane 9 (0.20 g, 0.38 mmol, 1.0 equiv.),

styrene (0.39 g, 3.8 mmol, 10 equiv.) and Grubbs catalyst 12

3772

www.eurjoc.org

Eur. J. Org. Chem. 2009, 3765–3782

Enantiomerically Pure Vinylcyclopropylboronic Esters

(10 mg, 10 µmol, 0.03 equiv.) in dichloromethane (8 mL) were al-

lowed to react according to the general procedure for 1 d. The bo-

ronic ester 10a was isolated as colourless crystals (0.22 g,

0.36 mmol, 96%); E/Z Ͼ 98:2; m.p. 115 °C. [α]²_D¹= –77.0 (c = 0.40,

0.05 equiv.) in dichloromethane (4 mL) were allowed to react ac-

cording to the general procedure for 1 d. The boronic ester 10c was

isolated as colourless crystals (55 mg, 90 µmol, 81%), E/Z = 85:15.

The analytical data were determined from the mixture of diastereo-

CHCl ). IR (film): ν = 3058, 3024, 2934, 2850, 2833, 1493, 1446,

isomers; softening range 98–107 °C. IR (film): ν = 3088, 3058,

3024, 2955, 2927, 2854, 2833, 1493, 1445, 1420, 1400, 1364, 1238,

˜

3

1421, 1365, 1240, 1215, 1193, 1067, 1033, 1019, 757, 701 cm^–1. H

1

NMR (CDCl₃, 500 MHz): δ = –0.32 (ddd, J = 9.9, J = 6.6, J = 1183, 1074, 1032, 1018, 1002, 963, 941, 920 cm^–1. (E)-Olefin 10c:

5.2 Hz, 1 H, 1Ј-H), 0.39 (ddd, J = 7.7, J = 6.7, J = 3.5 Hz, 1 H, ¹H NMR (CDCl₃, 500 MHz): δ = –0.47 (ddd, J = 9.8, J = 6.5, J

3Ј-H_a), 0.52 (ddd, J = 9.9, J = 5.1, J = 3.5 Hz, 1 H, 3Ј-H_b), 1.47–

1.52 (m, 1 H, 3Ј-H), 3.01 (s, 6 H, OCH₃), 5.29 (s, 2 H, 4-H, 5-H),

= 5.3 Hz, 1 H, 1Ј-H), 0.29 (ddd, J = 7.8, J = 6.3, J = 3.4 Hz, 1 H,

3Ј-Ha), 0.39 (ddd, J = 9.8, J = 6.5, J = 3.4 Hz, 1 H, 3Ј-H_b), 0.91

5.51 (dd, J = 15.7, J = 8.9 Hz, 1 H, 4Ј-H), 6.36 (d, J = 15.7 Hz, 1 (t, J = 7.2 Hz, 3 H, 7ЈЈ-H), 1.17–1.27 (m, 1 H, 2Ј-H), 1.28–1.36 (m,

H, 5Ј-H), 7.14–7.37 (m, 25 H, arom. H) ppm. ¹³C NMR (CDCl₃, 6 H, 4ЈЈ-H, 5ЈЈ-H, 6ЈЈ-H), 1.95 (m, 2 H, 3ЈЈ-H), 2.99 (s, 6 H, OCH₃),

125 MHz): δ = 2.8 (C-1Ј), 13.2 (C-3Ј), 21.8 (C-2Ј), 51.7

(CPh₂OCH₃), 77.5 (C-4, C-5), 83.2 (CPh₂OCH₃), 125.5, 126.5,

127.2, 127.3, 127.5, 127.8, 128.3, 128.4 (arom. CH), 129.7 (C-4Ј),

134.6 (C-5Ј), 137.7, 141.1, 141.2 (arom. C_ipso) ppm. MS (FAB, NBA

+ NaI): m/z (%) = 629 (8) [M + Na]⁺, 575 (Ͻ5) [M – OCH₃]⁺, 197

(100) [Ph₂COCH₃]⁺. C₄₁H₃₉BO₄(606.55): calcd. C 81.19, H 6.48;

found C 81.17, H 6.73. The spectroscopic data for boronic ester

10a were in full agreement with the literature.^[10a].

4.79 (dt, J = 15.1, J = 8.5 Hz, 1 H, 2ЈЈ-H), 5.25 (s, 2 H, 4-H, 5-H),

5.51 (dd, J = 15.1, J = 6.9 Hz, 1 H, 1ЈЈ-H), 7.27–7.34 (m, 20 H,

arom. H) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ = 1.8 (C-1Ј), 12.4

(C-7ЈЈ), 12.9 (C-3Ј), 16.7 (C-6ЈЈ), 21.0 (C-5ЈЈ), 22.1 (C-4ЈЈ), 27.2 (C-

2Ј), 31.8 (C-3ЈЈ), 51.7 (CPh₂OCH₃), 77.4 (C-4, C-5), 83.2

(CPh₂OCH₃), 127.1, 127.2, 127.4, 127.7, 128.1, 128.3, (arom. CH),

129.6 (C-1ЈЈ), 133.4 (C-2ЈЈ), 141.1, 141.3 (arom. C_ipso) ppm. (Z)-

Olefin 10c: ¹H NMR (CDCl₃, 500 MHz): δ = –0.50 (ddd, J = 10.8,

J = 6.5, J = 5.2 Hz, 1 H, 1Ј-H), 0.29 (overlaid with the E dia-

stereoisomer, 1 H, 3Ј-H_a), 0.39 (overlaid with the E diastereoisomer,

1 H, 3Ј-H_b), 0.80 (t, J = 7.1 Hz, 3 H, 7ЈЈ-H), 1.11–1.22 (m, 7 H,

2Ј-H, 4ЈЈ-H, 5ЈЈ-H, 6ЈЈ-H), 1.97 (ddt, J = 7.4, J = 2.7, J = 1.5 Hz,

2 H, 3ЈЈ-H), 2.99 (s, 6 H, OCH₃), 4.53 (ddt, J = 12.5, J = 11.7, J

= 1.6 Hz, 1 H, 1ЈЈ-H), 5.19 (ddt, J = 10.8, J = 7.4, J = 0.8 Hz, 1

H, 2ЈЈ-H), 5.25 (s, 2 H, 4-H, 5-H), 7.25–7.35 (m, 20 H, arom.

H) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ = 2.2 (C-1Ј), 12.4 (C-3Ј),

16.7 (C-7ЈЈ), 21.0 (C-4ЈЈ, C-5ЈЈ, C-6ЈЈ), 22.4 (C-4ЈЈ, C-5ЈЈ, C-6ЈЈ),

29.5 (C-3ЈЈ), 31.5 (C-2Ј), 32.3 (C-4ЈЈ, C-5ЈЈ, C-6ЈЈ), 51.7

(CPh₂OCH₃), 77.7 (C-4, C-5), 83.4 (CPh₂OCH₃), 127.1, 127.2,

127.4, 127.7, 128.2, 128.4, 128.5, (arom. CH), 129.7 (C-2ЈЈ), 133.4

(C-2ЈЈ), 141.3, 141.4 (arom. C_ipso) ppm. MS (EI, 70 eV): m/z (%) =

600 (Ͻ1) [M]⁺, 568 (1) [M – CH₃OH]⁺, 197 (100) [Ph₂COCH₃]⁺.

C₄₀H₄₁BO₄(600.59): calcd. C 79.99, H 7.55; found C 79.63, H 7.33.

(1ЈR,2ЈR,4R,5R)-2-{2Ј-[(E/Z)-Hex-1ЈЈ-enyl]cyclopropyl}-4,5-bis-

(methoxydiphenylmethyl)-1,3,2-dioxaborolane (10b): Vinylcyclopro-

pane 9 (0.10 g, 0.19 mmol, 1.0 equiv.), 1-hexene (0.32 g, 3.77 mmol,

20 equiv.) and Grubbs catalyst 12 (10 mg, 10 µmol, 0.05 equiv.) in

dichloromethane (4 mL) were allowed to react according to the ge-

neral procedure for 2 d. The boronic ester 10b was isolated as

colourless crystals (92 mg, 0.16 mmol, 83%), E/Z = 85:15. The pure

E isomer was obtained by crystallization from n-pentane. (E)-Ole-

fin 10b: M.p. 113 °C. [α]²_D⁰= –79.7 (c = 1.0, CHCl ). IR (film): ν =

˜

3

3060, 3024, 2956, 2932, 2833, 1493, 1446, 1421, 1366, 1239, 1184,

1075, 1032, 1019, 965, 921, 857 cm^–1. ¹H NMR (600 MHz, CDCl₃):

δ = –0.53 (ddd, J = 9.8, J = 6.5, J = 5.3 Hz, 1 H, 1Ј-H), 0.24 (ddd,

J = 7.8, J = 6.4, J = 3.4 Hz, 1 H, 3Ј-H_a), 0.34 (ddd, J = 9.8, J =

6.5, J = 3.4 Hz, 1 H, 3Ј-H_b), 0.91 (t, J = 7.2 Hz, 3 H, 6ЈЈ-H), 1.17–

1.27 (m, 1 H, 2Ј-H), 1.28–1.36 (m, 4 H, 4ЈЈ-H, 5ЈЈ-H), 1.95 (m, 2

H, 3ЈЈ-H), 2.99 (s, 6 H, OCH₃), 4.79 (dd, J = 15.1, J = 8.5 Hz, 1

H, 1ЈЈ-H), 5.25 (s, 2 H, 4-H, 5-H), 5.51 (dt, J = 15.1, J = 6.9 Hz,

1 H, 2ЈЈ-H), 7.27–7.34 (m, 20 H, arom. H) ppm. ¹³C NMR

(125 MHz, CDCl₃): δ = 1.8 (C-1Ј), 12.4 (C-6ЈЈ), 13.8 (C-3Ј), 21.0

(C-5ЈЈ), 22.1 (C-4ЈЈ), 27.2 (C-2Ј), 31.8 (C-3ЈЈ), 51.7 (CPh₂OCH₃),

77.7 (C-4, C-5), 83.3 (CPh₂OCH₃), 127.1, 127.2, 127.4, 127.7,

128.1, 128.3 (arom. CH), 129.6 (C-1ЈЈ), 133.5 (C-2ЈЈ), 141.1, 141.3

(arom. C_ipso) ppm. MS (FAB, NBA + NaI): m/z (%) = 609 (Ͻ5)

[M + Na]⁺, 197 (100) [Ph₂COCH₃]⁺. C₃₉H₄₃BO₄(586.57): calcd. C

79.86, H 7.39; found C 79.91, H 7.31. (Z)-Olefin 10b (determined

from the mixture of diastereoisomers): ¹H NMR (CDCl₃,

500 MHz): δ = –0.50 (ddd, J = 10.8, J = 6.5, J = 5.2 Hz, 1 H, 1Ј-

H), 0.3 (overlaid with the E diastereoisomer, 1 H, 3Ј-H_a), 0.4 (over-

laid with the E diastereoisomer, 1 H, 3Ј-H_b), 0.80 (t, J = 7.1 Hz, 3

H, 6ЈЈ-H), 1.11–1.22 (m, 7 H, 2Ј-H, 4ЈЈ-H, 5ЈЈ-H), 1.97 (ddt, J =

7.4, J = 2.7, J = 1.5 Hz, 2 H, 3ЈЈ-H), 2.99 (s, 6 H, OCH₃), 4.53

(ddt, J = 12.5, J = 11.7, J = 1.6 Hz,1 H, 1ЈЈ-H), 5.19 (ddt, J = 10.8,

J = 7.4, J = 0.8 Hz,1 H, 2ЈЈ-H), 5.25 (s, 2 H, 4-H, 5-H), 7.25–7.35

(m, 20 H, arom. H) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ = 2.2

(C-1Ј), 12.4 (C-3Ј), 16.7 (C-6ЈЈ), 21.0 (C-4ЈЈ/C-5ЈЈ), 22.4 (C-4ЈЈ/C-

5ЈЈ), 29.5 (C-3ЈЈ), 31.5 (C-2Ј), 51.7 (CPh₂OCH₃), 77.7 (C-4, C-5),

83.4 (CPh₂OCH₃), 127.1, 127.2, 127.4, 127.7, 128.2, 128.4, 128.5,

(arom. CH), 129.7 (C-1ЈЈ), 133.4 (C-2ЈЈ), 141.3, 141.4 (arom.

C_ipso) ppm.

(1ЈR,2ЈR,4R,5R)-4,5-Bis(methoxydiphenylmethyl)-2-{2Ј-[(E/Z)-3ЈЈ-

(trimethylsilyl)prop-1ЈЈ-enyl]cyclopropyl}-1,3,2-dioxaborolane (10d):

Vinylcyclopropane 9 (0.15 g, 0.28 mmol, 1.0 equiv.), allyltrimethyl-

silane (0.32 g, 2.8 mmol, 10 equiv.) and Grubbs catalyst 12 (10 g,

10 mmol, 0.04 equiv.) in dichloromethane (6 mL) were allowed to

react according to the general procedure for 1 d. The boronic ester

10d was isolated as colourless crystals (123 mg, 0.20 mmol, 70%);

E/Z = 50:50. The analytical data were determined from the mixture

of diastereoisomers; softening range 66–73 °C. IR (film): ν = 3058,

˜

3025, 2999, 2853, 2904, 2898, 2832, 1493, 1446, 142, 1393, 1363,

1245, 1184, 1156, 1075, 1032, 1016, 964, 839, 774, 756, 698 cm^–1.

(E)-Olefin 10d: ¹H NMR (CDCl₃, 500 MHz): δ = –0.43 (ddd,

³J_1Ј,3Јb= 9.8, J = 6.5, J = 5.1 Hz, 1 H, 1Ј-H), 0.05 [s, 9 H, Si(CH₃)

₃], 0.31 (ddd, J = 9.7, J = 6.5, J = 3.4 Hz, 1 H, 3Ј-H_a), 0.42 (ddd,

J = 9.8, J = 8.6, J = 3.4 Hz, 1 H, 3Ј-H_b), 1.39 (dddd, J = 9.7, J =

9.5, J = 8.6, J = 5.1 Hz, 1 H, 2Ј-H), 1.42 (dd, J = 7.9, J = 1.4 Hz,

1 H, 3ЈЈ-H), 3.10 (s, 6 H, OCH₃), 4.75 (ddt, J = 15.1, J = 9.5, J =

1.4 Hz, 1 H, 1ЈЈ-H), 5.36 (s, 2 H, 4-H, 5-H), 5.46 (ddt, J = 15.1, J

= 7.9, J = 0.6 Hz, 1 H, 2ЈЈ-H), 7.35–7.46 (m, 20 H, arom. H) ppm.

¹³C NMR (CDCl₃, 125 MHz): δ = –2.01 [Si(CH₃)₃], 11.4 (C-3Ј),

22.5 (C-2Ј), 51.7 (CPh₂OCH₃), 77.5 (C-4, C-5), 83.3 (CPh₂OCH₃),

123.9 (C-2ЈЈ), 127.1, 127.2, 127.4, 127.7, 128.4, (arom. CH), 132.1

(C-1ЈЈ), 141.1, 141.3 (arom. C_ipso) ppm. (Z)-Olefin 10d: ¹H NMR

(CDCl₃, 500 MHz): δ = –0.39 (ddd, J = 9.9, J = 6.6, J = 5.3 Hz, 1

(1ЈR,2ЈR,4R,5R)-2-{2Ј-[(E/Z)-Hept-1ЈЈ-enyl]cyclopropyl}-4,5-bis- H, 1Ј-H), 0.05 [s, 9 H, Si(CH₃)₃], 0.38 (ddd, J = 9.8, J = 6.5, J =

(methoxydiphenylmethyl)-1,3,2-dioxaborolane (10c): Vinylcyclopro-

pane 9 (60 mg, 0.11 mmol, 1 equiv.), 1-heptene (110 mg,

3.5 Hz, 1 H, 3Ј-H_a), 0.52 (ddd, J = 9.9, J = 8.6, J = 3.5 Hz, 1 H,

3Ј-H_b), 1.49 (dddd, J = 10.8, J = 9.8, J = 8.6, J = 5.3 Hz, 1 H, 2Ј-

1.10 mmol, 10 equiv.) and Grubbs catalyst 12 (6 mg, 0.05 mmol, H), 1.58 (dd, J = 9.6, J = 1.4 Hz, 1 H, 3ЈЈ-H), 3.11 (s, 6 H, OCH₃),

Eur. J. Org. Chem. 2009, 3765–3782

www.eurjoc.org

3773

E. Hohn, J. Palecˇek, J. Pietruszka, W. Frey

FULL PAPER

4.63 (ddt, J = 12.2, J = 10.8, J = 1.4 Hz, 1 H, 1ЈЈ-H), 5.33–5.40

(m, overlaid with the E diastereoisomer, 1 H, 2ЈЈ-H), 5.36 (s, 2 H,

[M + Na]⁺, 1024 (Ͻ5) [M + Na – OCH₃]⁺, 197 (100) [Ph₂CO-

CH₃]⁺. C₆₈H₆₆B₂O₈(1032.87): calcd. C 79.07, H 6.45; found C

4-H, 5-H), 7.35–7.46 (m, 20 H, arom. H) ppm. ¹³C NMR (CDCl₃, 78.81, H 6.44.

125 MHz): δ = –1.91 [Si(CH₃)₃], 12.4 (C-3Ј), 21.1 (C-2Ј), 53.3

(CPh₂OCH₃), 77.7 (C-4, C-5), 83.4 (CPh₂OCH₃), 124.0 (C-2ЈЈ),

127.1, 127.2, 127.4, 127.7, 128.4, (arom. CH), 132.1 (C-1ЈЈ), 141.2,

141.3 (arom. C_ipso) ppm; (C-1Ј) was not detectable in the spectrum.

C₃₉H₄₅BO₄Si (616.66): calcd. C 75.96, H 7.36; found C 75.83, H

7.31. MS (FAB, NBA + NaI): m/z (%) = 639 (10) [M + Na]⁺, 197

(100) [Ph₂COCH₃]⁺. C₃₉H₅₄BO₄Si (616.66): calcd. C 75.96, H 7.36;

found C 75.83, H 7.31.

Synthesis by Wittig-Type Olefination

(1ЈS,2ЈS,4R,5R)-2-(2Ј-Formylcyclopropyl)-4,5-bis(methoxydiphenyl-

methyl)-1,3,2-dioxaborolane (14): Cyclopropylmethanol 4 (8.80 g,

16.5 mmol, 1 equiv.) was dissolved in dichloromethane (500 mL)

and Dess–Martin periodinane 7 (7.7 g, 18.2 mmol, 1.1 equiv.) was

added. The reaction mixture was stirred for 24 h at room temp.,

quenched with a 1  aq. solution of Na₂S₂O₃(250 mL) and aq.

saturated NaHCO₃(250 mL) and finally extracted with dichloro-

(1ЈR,2ЈR,4R,5R)-4,5-Bis(methoxydiphenylmethyl)-2-{2Ј-[(E/Z)-(2ЈЈ- methane (3ϫ300 mL). The combined organic layers were dried

triethylsilyloxymethyl)ethenyl]cyclopropyl}-1,3,2-dioxaborolane (MgSO₄), filtered and concentrated under reduced pressure. The

(10e): Vinylcyclopropane 9 (0.15 g, 0.28 mmol, 1.0 equiv.), tri-

ethylsilyl-protected allyl alcohol (0.73 g, 4.24 mmol, 15 equiv.) and

Grubbs catalyst 12 (10 g, 10 µmol, 0.04 equiv.) in dichloromethane

(6 mL) were allowed to react according to the general procedure

for 1 d. The boronic ester 10e was isolated as colourless crystals

(173 mg, 0.26 mmol, 90%); E/Z = 85:15. The analytical data were

determined from the mixture of diastereoisomers; softening range

crude product 14 was purified by flash column chromatography

(silica gel, petroleum ether/ethyl acetate, 9:1) to afford the aldehyde

14 (8.33 g, 15.6 mmol, 95%) as colourless crystals; m.p. 79–85 °C.

[α]²_D⁰= –60.5 (c = 1.00, CHCl ). IR (film): ν = 3060, 3025, 2940,

˜

3

2833, 2729, 1709, 1446, 1426, 1396, 1309, 1190, 1074, 1033, 1015,

967, 924, 897, 758, 698 cm^–1. ¹H NMR (CDCl₃, 500 MHz): δ =

0.23 (ddd, J = 10.1, J = 7.1, J = 4.9 Hz, 1 H, 1Ј-H), 0.91 (ddd, J

56–61 °C. IR (film): ν = 3088, 3059, 3022, 2954, 2936, 2881, 2834, = 10.1, J = 5.6, J = 4.0 Hz, 1 H, 3Ј-H_a), 1.05 (ddd, J = 8.1, J =

˜

1507, 1493, 1447, 1366, 1321, 1239, 1197, 1155, 1074, 1032, 967,

947, 924, 891, 844, 791, 757, 745, 732, 697, 667 cm^–1. (E)-Olefin

10e: ¹H NMR (CDCl₃, 500 MHz): δ = –0.47 (ddd, J = 9.9, J = 6.6,

J = 5.2 Hz, 1 H, 1Ј-H), 0.27 (ddd, J = 10.2, J = 6.6, J = 3.5 Hz, 1

7.1, J = 4.0 Hz, 1 H, 3Ј-H_b), 1.23 (m, 1 H, 2Ј-H), 3.08 (s, 6 H,

OCH₃), 5.32 (s, 2 H, 4-H, 5-H), 7.04–7.12 (m, 20 H, arom. H), 8.52

(d, J = 6.4 Hz, 1 H, 4Ј-H) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ

= 2.0 (C-1Ј), 11.4 (C-2Ј), 28.3 (C-3Ј), 51.8 (CPh₂OCH₃), 77.8 (C-4,

H, 3Ј-H_a), 0.39 (ddd, J = 9.9, J = 8.6, J = 3.5 Hz, 1 H, 3Ј-H_b), 0.57 C-5), 83.2 (CPh₂OCH₃), 127.4, 127.6, 127.7, 127.9, 128.3, 129.7

(q, J = 7.9 Hz, 6 H, 4ЈЈ-H), 0.93 (t, J = 7.9 Hz, 9 H, 5ЈЈ-H), 1.32 (arom. CH), 140.9 (arom. C_ipso), 200.2 (CH=O) ppm. MS (EI,

(dddd, J = 10.2, J = 8.7, J = 8.6, J = 5.2 Hz, 1 H, 2Ј-H), 2.99 (s,

6 H, OCH₃), 4.02 (dd, J = 5.5, J = 1.5 Hz, 2 H, 3ЈЈ-H), 4.97 (ddt,

J = 15.2, J = 8.7, J = 1.5 Hz, 1 H, 1ЈЈ-H), 5.26 (s, 2 H, 4-H, 5-H),

5.51 (dt, J = 15.2, J = 5.7 Hz, 1 H, 2ЈЈ-H), 7.25–7.35 (m, 20 H,

arom. H) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ = 4.5 (C-4ЈЈ), 6.7

(C-5ЈЈ), 12.6 (C-3Ј), 20.5 (C-2Ј), 51.7 (CPh₂OCH₃), 63.4 (C-3ЈЈ),

77.6 (C-4, C-5), 83.3 (CPh₂OCH₃), 126.9 (C-2ЈЈ), 127.2, 127.3,

127.5, 127.8, 128.4, 129.7 (arom. CH), 135.0 (C-1ЈЈ), 141.1, 141.3

(arom. C_ipso) ppm; (C-1Ј) was not detectable in the spectrum. MS

(EI, 70 eV): m/z (%) = 674 (Ͻ5) [M]⁺, 643 (6) [M – CH₃OH]⁺,

543 (8) [M – (C₂H₅)₃SiO]⁺, 197 (100) [Ph₂COCH₃]⁺. C₄₂H₅₁BO₅Si

(674.74): calcd. C 74.76, H 7.62; found C 74.63, H 7.65.

70 eV): m/z (%) = 532 (Ͻ5) [M]⁺, 501 (Ͻ5) [M – OCH₃]⁺, 197 (100)

[Ph₂COCH₃]⁺. MS (+EMS): m/z (%) = 555 (24) [M + Na]⁺, 197

(29) [Ph₂COCH₃]⁺. C₃₄H₃₃BO₅(532.43): calcd. C 76.70, H 6.25;

found C 76.43, H 6.25.

(1ЈS,2ЈS,4R,5R)-2-{2-[(E)-2-Methoxycarbonylethenyl]cyclopropyl}-

4,5-bis(methoxydiphenylmethyl)-1,3,2-dioxaborolane (6): Trimethyl

phosphonoacetate (2.58 g, 14.2 mmol, 2 equiv.) was added drop-

wise through a cannula to a stirred suspension of NaH (95 %,

0.34 g, 14.2 mmol, 2 equiv.) in anhydrous THF (30 mL) at 0 °C un-

der dry N₂. After 1 h aldehyde 14 (3.78 g, 7.10 mmol, 1 equiv.) in

anhydrous THF (30 mL) was added dropwise. The resulting reac-

tion mixture was stirred for 2 d at room temp., then quenched with

aq. saturated NH₄Cl (40 mL) and extracted with Et₂O (3ϫ40 mL).

The combined organic layers were dried (MgSO₄), filtered and con-

centrated under reduced pressure. The crude product 6 was purified

by flash column chromatography (silica gel, petroleum ether/ethyl

acetate, 9:1) to furnish the ester 6 (6.81 g, 11.6 mmol, 90 %) as

colourless crystals; m.p. 90–95 °C. [α]²_D⁰= +21.0 (c = 0.3, CHCl₃).

(E)-1,2-Bis{(1R,2R)-2-[(4R,5R)-4,5-bis(methoxydiphenylmethyl)-

1,3,2-dioxaborolan-2-yl]cyclopropyl}ethene (13). Method A: Vinylcy-

clopropane 9 (0.10 g, 0.18 mmol, 1.0 equiv.) and Grubbs catalyst

11 (10 mg, 10 µmol, 0.015 equiv.) in dichloromethane (2 mL) were

allowed to react according to the general procedure for 6 d. The

boronic ester 13 was isolated as colourless crystals (79 mg, 76 µmol,

81%). B) Vinylcyclopropane 9 (280 mg, 0.57 mmol, 1 equiv.) and

Grubbs catalyst 12 (10 mg, 10 µmol, 0.02 equiv.) in dichlorometh-

ane (8 mL) were allowed to react according to the general pro-

cedure for 1 d. The boronic ester 13 was isolated as colourless crys-

tals (287 mg, 0.27 mmol, 95%); softening range 143–151 °C. [α]²_D¹

IR (Film): ν = 3058, 3025, 2950, 2834, 1720, 1651, 1494, 1422,

˜

1370, 1263, 1193, 1147, 1076, 1033, 1016, 969, 939, 856, 759, 738,

1

703 cm^–1. H NMR (CDCl₃, 500 MHz): δ = –0.22 (ddd, J = 9.8, J

= 7.1, J = 5.1 Hz, 1 H, 1Ј-H), 0.61 (ddd, J = 9.8, J = 4.8, J =

3.7 Hz, 1 H, 3Ј-H_a), 0.78 (ddd, J = 7.6, J = 7.1, J = 3.7 Hz, 1 H,

3Ј-H_b), 1.01 (dddd, J = 10.1, J = 7.6, J = 5.1, J = 4.8 Hz, 1 H, 2Ј-

H), 2.95 (s, 6 H, CPh₂OCH₃), 3.64 (s, 3 H, CO₂CH₃), 5.26 (s, 2 H,

4-H, 5-H), 5.78 (d, J = 15.4 Hz, 1 H, 2ЈЈ-H), 6.19 (dd, J = 15.4, J

= 10.1 Hz, 1 H, 1ЈЈ-H), 7.25–7.32 (m, 20 H, arom. H) ppm. ¹³C

NMR (CDCl₃, 125 MHz): δ = 2.0 (C-1Ј), 14.1 (C-3Ј), 21.0 (C-2Ј),

51.3 (CPh₂OCH₃), 51.7 (CO₂CH₃), 77.5 (C-4, C-5), 83.3

(CPh₂OCH₃), 117.9 (C-2ЈЈ), 127.2, 127.3, 127.6, 127.8, 128.4, 129.7

(arom. CH), 141.0, 141.1 (arom. C_ipso), 154.1 (C-1ЈЈ), 167.0

(CO₂CH₃) ppm. MS (FAB, NBA + NaI): m/z (%) = 611 (32) [M +

Na]⁺, 197 (100) [Ph₂COCH₃]⁺. C₃₇H₃₇BO₆(588.50): calcd. C 75.51,

H 6.34; found C 75.50, H 6.52.

= –119.5 (c = 0.63, CHCl ). IR (film): ν = 3023, 2993, 2904, 2897,

˜

3

1445, 1421, 1361, 1319, 1248, 1236, 1183, 1157, 1032, 1018, 1001,

966, 950, 915, 870, 850, 795, 769 cm^{–1 1}H NMR (CDCl₃,

.

500 MHz): δ = –0.56 (ddd, J = 9.8, J = 6.4, J = 5.3 Hz, 2 H, 2Ј-

H), 0.17 (ddd, J = 7.8, J = 6.4, J = 3.4 Hz, 2 H, 3Ј-H_a), 0.26 (ddd,

J = 9.8, J = 9.9, J = 5.3, J = 3.4 Hz, 2 H, 3Ј-H_b), 1.18 (dddd, J =

9.9, J = 9.8, J = 7.8, J = 5.2, J = 2.6 Hz, 2 H, 1Ј-H), 2.97 (s, 12

H, OCH₃), 4.74 (dd, J = 5.2, J = 2.6 Hz, 2 H, 1-H), 5.23 (s, 4 H, 4ЈЈ-

H, 5ЈЈ-H), 7.23–7.31 (m, 40 H, arom. H) ppm. ¹³C NMR (CDCl₃,

125 MHz): δ = 1.8 (C-2Ј), 12.5 (C-1Ј), 20.8 (C-3Ј), 51.7

(CPh₂OCH₃), 77.5 (C-4ЈЈ, C-5ЈЈ), 83.2 (CPh₂OCH₃), 127.1, 127.2,

127.4, 127.7, 128.4, 129.6 (arom. CH), 131.4 (C-1), 141.1, 141.3 (1ЈS,2ЈS,4R,5R)-2-{2-[(E)-2-Hydroxymethylethenyl]cyclopropyl}-

(arom. C_ipso) ppm. MS (FAB, NBA + NaI): m/z (%) = 1055 (10) 4,5-bis(methoxydiphenylmethyl)-1,3,2-dioxaborolane (15): DIBAL-

3774

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Eur. J. Org. Chem. 2009, 3765–3782

Enantiomerically Pure Vinylcyclopropylboronic Esters

H (1  in THF, 29.4 mL, 29.4 mmol, 3.0 equiv.) was added drop- temp. The orange solution of the formed ylide was stirred for

wise through a cannula to a stirred solution of ester 6 (5.76 g,

9.79 mmol, 1.0 equiv.) in anhydrous THF (150 mL) at –78 °C under

N₂. After stirring for 3 h at –78 °C the reaction mixture was slowly

warmed to room temp. and stirred overnight. It was then quenched

30 min and cooled to –78 °C. Then the aldehyde 16 (3.70 g,

6.63 mmol, 1.0 equiv.) in anhydrous THF (50 mL) was added drop-

wise through a cannula over 5 min. The reaction mixture was

stirred for 1 h at –78 °C and then slowly warmed to room temp.

with distilled H₂O (5 mL) and NaOH (8 mL of a 2  aq. solution). and stirred overnight. The reaction mixture was quenched with aq.

After additional stirring for 30 min at room temp., a white precipi-

tate was filtered off and washed thoroughly with Et₂O. The organic

layer was dried (MgSO₄), filtered and concentrated under reduced

pressure. The crude product 15 was purified by flash column

chromatography (silica gel, petroleum ether/ethyl acetate, 8:2) to

furnish alcohol 15 (4.89 g, 89%) as colourless crystals; m.p. 153–

saturated NaHCO₃(150 mL) and extracted with Et₂O

(3ϫ150 mL). The combined organic layers were dried (MgSO₄),

filtered and concentrated under reduced pressure. The crude prod-

uct 17 was purified by flash column chromatography (silica gel,

petroleum ether/ethyl acetate, 95:5) to furnish the (Z)-olefin 17

(3.72 g, 6.36 mmol, 96 %) as colourless crystals; Z/E = 97:3 (as

1

154 °C. [α]²_D⁰= –23.0 (c = 1.3, CHCl ). IR (Film): ν = 3130, 3080,

judged by 600 MHz H NMR spectroscopy). The minor E isomer

˜

3

3012, 2949, 2870, 1720, 1650, 1494, 1446, 1422, 1369, 1304, 1263,

17 was removed by a single recrystallization from n-pentane. (Z)-

1193, 1147, 1076, 1033, 1016, 969, 759, 736, 702, 650, 636 cm^–1. ¹H

Olefin 17; m.p. 88–89 °C. [α]²_D⁰= +13.1 (c = 1.25, CHCl₃). IR

NMR (CDCl₃, 500 MHz): δ = –0.47 (ddd, J = 9.6, J = 6.8, J = (Film): ν = 3063, 3024, 2960, 2933, 2870, 2836, 1494, 1447, 1420,

˜

5.1 Hz, 1 H, 1Ј-H), 0.42 (ddd, J = 9.6, J = 5.1, J = 3.5 Hz, 1 H, 1407, 1390, 1368, 1338, 1235, 1195, 1183, 1076, 1062, 1033, 1017,

3Ј-H_a), 0.62 (ddd, J = 7.6, J = 6.8, J = 3.5 Hz, 1 H, 3Ј-H_b), 0.92

(dddd, J = 9.0, J = 7.6, J = 5.1, J = 5.1 Hz, 1 H, 2Ј-H), 1.13 (t, J 732, 672, 663, 655 cm^–1. ¹H NMR (CDCl₃, 600 MHz): δ = –0.39

= 5.9 Hz, 1 H, OH), 3.01 (s, 6 H, CPh₂OCH₃), 3.98–4.03 (m, 2 H, (ddd, J = 9.0, J = 7.2, J = 5.1 Hz, 1 H, 1Ј-H), 0.49 (ddd, J = 9.0,

1ЈЈЈ-H), 4.96 (dd, J = 15.2, J = 9.0 Hz, 1 H, 1ЈЈ-H), 5.24 (s, 2 H, J = 4.9, J = 3.6 Hz, 1 H, 3Ј-H_a), 0.69 (ddd, J = 10.9, J = 7.2, J =

1002, 985, 964, 949, 941, 920, 899, 870, 853, 794, 775, 759, 747,

4-H, 5-H), 5.61 (dt, J = 15.2, J = 5.9 Hz, 1 H, 2ЈЈ-H), 7.25–7.32

3.6 Hz, 1 H, 3Ј-H_b), 0.95 (m, 1 H, 2Ј-H), 1.02 (t, J = 7.6 Hz, 3 H,

(m, 20 H, arom. H) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ = 2.0 6ЈЈ-H), 2.21 (m_c, 2 H, 5ЈЈ-H), 3.01 (s, 6 H, OCH₃), 5.15 (dd, J =

(C-1Ј), 12.4 (C-3Ј), 20.4 (C-2Ј), 51.5 (CPh₂OCH₃), 63.4 (CH₂OH), 9.2, J = 15.1 Hz, 1 H, 1ЈЈ-H), 5.27 (dd, J = 10.9, J = 7.7 Hz, 1 H,

77.3 (C-4, C-5), 83.9 (CPh₂OCH₃), 126.5 (C-1ЈЈ), 126.9, 127.3,

127.5, 127.6, 128.3, 129.5 (arom. CH), 137.2 (C-2ЈЈ), 140.9, 141.0

4ЈЈ-H), 5.28 (s, 2 H, 4-H, 5-H), 5.82 (t, J = 10.9 Hz, 1 H, 3ЈЈ-H),

6.31 (dd, J = 15.1, J = 10.9 Hz, 1 H, 2ЈЈ-H), 7.21–7.56 (m, 20 H,

(arom. C_ipso) ppm. MS (EI, 70 eV): m/z (%) = 560 (Ͻ0.1) [M]⁺, 528 arom. H) ppm. ¹³C NMR (CDCl₃, 151 MHz): δ = 3.0 (C-1Ј), 13.3

(1.5) [M – CH₂OH]⁺, 197 (100) [Ph₂COCH₃]⁺. C₃₆H₃₇BO₅(C-3Ј), 14.4 (C-6ЈЈ), 21.0 (C-5ЈЈ), 21.6 (C-2Ј), 51.7 (CPh₂OCH₃),

(560.49): calcd. C 77.14, H 6.65; found C 76.80, H 6.73.

77.5 (C-4, C-5), 83.3 (CPh₂OCH₃), 123.9 (C-2ЈЈ), 127.1, 127.3,

127.5, 127.7, 129.1, 129.7 (arom. CH), 128.4 (C-3ЈЈ), 130.9 (C-4ЈЈ),

137.9 (C-1ЈЈ), 141.2, 141.3 (arom. C_ipso) ppm. MS (+EPI): m/z (%)

= 607 (33) [M + Na]⁺, 413 (20), 381 (100), 249 (30), 218 (12), 197

(90) [Ph₂COCH₃]⁺. C₃₉H₄₁BO₄(584.55): calcd. C 80.13, H 7.07;

found C 80.57, H 7.33.

(E)-3-{(1S,2S)-2-[(4R,5R)-4,5-Bis(methoxydiphenylmethyl)-1,3,2-di-

oxaborolan-2-yl]cyclopropyl}acrylaldehyde (16): Alcohol 15 (4.50 g,

8.03 mmol, 1.0 equiv.) was dissolved in dichloromethane (270 mL)

and Dess–Martin periodinane 7 (3.75 g, 8.83 mmol, 1.1 equiv.) was

added. The reaction mixture was stirred for 1 h at room temp.,

quenched with aq. Na₂S₂O₃(150 mL of a 1  solution) and aq.

saturated NaHCO₃(150 mL) and finally extracted with dichloro-

methane (3 ϫ200 mL). The combined organic layers were dried

(MgSO₄), filtered and concentrated under reduced pressure. The

crude product 16 was purified by flash column chromatography

(silica gel, petroleum ether/ethyl acetate, 9:1) to furnish aldehyde

16 (4.26 g, 7.63 mmol, 95%) as colourless crystals; m.p. 72–75 °C.

5-(n-Pentylsulfonyl)-1-phenyl-1H-tetrazole (19): DEAD (40% solu-

tion in THF, 38 g, 87.4 mmol, 1.1 equiv.) was added dropwise to a

stirred solution of n-pentanol (7.00 g, 79.4 mmol, 1.0 equiv.), tri-

phenylphosphane (22.9 g, 87.4 mmol, 1.1 equiv.) and 1-phenyl-1H-

tetrazole-5-thiol (18; 15.6 g, 87.4 mmol, 1.1 equiv.) in THF

(250 mL) at room temp. The solution was stirred at room temp.

overnight. After concentration under reduced pressure, the residue

was treated with a mixture of petroleum ether/ethyl acetate (5:1).

The precipitate was removed by filtration and the solid washed

three times with the same mixture of solvents. The filtrate was con-

[α]²_D⁰= +51.3 (c = 1.00, CHCl ). IR (Film): ν = 3063, 3023, 2940,

˜

3

2830, 1735, 1683, 1634, 1495, 1447, 1422, 1394, 1370, 1340, 1241,

1185, 1110, 1075, 1033, 1014, 968, 940, 926, 865, 758, 734 cm^–1. ¹H

NMR (CDCl₃, 600 MHz): δ = –0.07 (ddd, J = 9.4, J = 7.1, J = centrated and the residue purified by flash column chromatography

5.3 Hz, 1 H, 1Ј-H), 0.76 (ddd, J = 9.4, J = 5.1, J = 4.3 Hz, 1 H, (silica gel, dichloromethane) to furnish the thioether 18a (19.9 g,

3Ј-H_a), 0.96 (ddd, J = 7.6, J = 7.1, J = 4.3 Hz, 1 H, 3Ј-H_b), 1.18

(m, 1 H, 2Ј-H), 3.06 (s, 6 H, OCH₃), 5.32 (s, 2 H, 4-H, 5-H), 5.98

(dd, J = 9.8, J = 15.3 Hz, 1 H, 1ЈЈ-H), 6.15 (dd, J = 7.7, J =

15.3 Hz, 1 H, 2ЈЈ-H), 7.18–7.51 (m, 20 H, arom. H), 9.35 (d, J =

7.9 Hz, 1 H, 3ЈЈ-H) ppm. ¹³C NMR (CDCl₃, 151 MHz): δ = 2.0

(C-1Ј), 15.1 (C-3Ј), 21.7 (C-2Ј), 51.7 (CPh₂OCH₃), 77.7 (C-4, C-5),

80.1 mmol, 92%) as an oil. IR (Film): ν = 2957, 2929, 2859, 1597,

˜

1499, 1463, 1438, 1410, 1385, 1277, 1241, 1176, 1119, 1087, 1074,

1054, 1015, 978, 914, 759, 721, 693 cm^–^{1 1}H NMR (CDCl₃,

.

600 MHz): δ = 0.89 (t, J = 7.1 Hz, 3 H, CH₃), 1.42 (m, 4 H, 3Ј-H,

4Ј-H), 1.83 (tt, J = 7.3, J = 7.3 Hz, 2 H, 2Ј-H), 3.39 (t, J = 7.3 Hz,

2 H, 1Ј-H), 7.44–7.69 (m, 5 H, arom. H) ppm. ¹³C NMR (CDCl₃,

83.2 (CPh₂OCH₃), 127.3, 127.4, 127.7, 127.9, 128.4, 129.7 (arom. 125 MHz): δ = 13.9 (CH₃), 22.1 (CH₂), 28.8 (CH₂), 30.7 (CH₂),

CH), 130.5 (C-2ЈЈ), 140.9, 141.0 (arom. C_ipso), 163.6 (C-1ЈЈ), 193.1 33.3 (CH₂), 123.8, 129.8, 130.1 (arom. CH), 133.7 (arom. C_ipso),

(CH=O) ppm. MS (+EMS): m/z (%) = 581 (100) [M + Na]⁺.

C₃₆H₃₅BO₅·½H₂O (567.26): calcd. C 76.21, H 6.39; found C 76.06,

H 6.39.

154.5 (CS) ppm. MS (+EPI): m/z (%) = 249 (100) [M + 1]⁺.

NaHCO₃(32.1 g, 382.5 mmol, 5 equiv.) followed by a solution of

MCPBA (33.0 g, 191 mmol, 2.5 equiv.) in dichloromethane

(300 mL) were added to a stirred solution of thioether 18a (19.0 g,

76.5 mmol, 1.0 equiv.) in dichloromethane (300 mL). Stirring was

continued at room temp. overnight. The mixture was poured into

a solution of aq. saturated NaHCO₃(200 mL) and Na₂S₂O₃

(200 mL), the organic layer was separated and the aqueous layer

extracted with dichloromethane (3ϫ300 mL). The combined or-

(1ЈS,2ЈS,4R,5R)-{2Ј-[(1ЈЈE,3ЈЈZ)-Hexa-1ЈЈ,3ЈЈ-dienyl]cyclopropyl}-

4,5-bis(methoxydiphenylmethyl)-1,3,2-dioxaborolane (17): Represen-

tative procedure for Wittig olefination – Scheme 3, entry 4. A solu-

tion of n-propyltriphenylphosphonium bromide (10.2 g,

26.5 mmol, 4.0 equiv.) and KHMDS (5.29 g, 26.5 mmol, 4.0 equiv.)

in anhydrous THF (300 mL) was stirred under dry N₂at room

Eur. J. Org. Chem. 2009, 3765–3782

www.eurjoc.org

3775

E. Hohn, J. Palecˇek, J. Pietruszka, W. Frey

FULL PAPER

ganic layers were dried (MgSO₄), filtered and concentrated under

reduced pressure. The crude product 19 was purified by flash col-

umn chromatography (silica gel, dichloromethane) to furnish sul-

fone 19 (18.9 g, 67.4 mmol, 88%) as orange crystals; m.p. 37–39 °C.

anhydrous DME (60 mL), a solution of KHMDS (2.5 g,

12.5 mmol, 1.8 equiv.) in anhydrous DME (45 mL) and aldehyde 8

(3.7 g, 6.95 mmol, 1 equiv.) in anhydrous DME (45 mL) were used.

Yield of ester 10b: 3.98 g (6.77 mmol, 91%).

IR (film): ν = 2954, 2932, 2871, 1728, 1594, 1497, 1459, 1426, 1399,

˜

Representative Procedure for the Julia–Kocienski Olefination

(Scheme 5, Entry 6). Method B: A solution of KHMDS (0.07 g,

0.34 mmol, 1.8 equiv.) in anhydrous DME (4 mL) was added drop-

wise through a cannula to a stirred solution of the aldehyde 8

(0.10 g, 0.19 mmol, 1.0 equiv.) and sulfone 19 (0.07 g, 0.24 mmol,

1.3 equiv.) in anhydrous DME (4 mL) over 20 min at –60 °C under

dry N₂. Stirring was continued for 15 min at –60 °C and then

quenched with H₂O (0.3 mL). The mixture was stirred vigorously

whilst warming to room temp. and then diluted with Et₂O (4 mL)

and H₂O (4 mL) and extracted with Et₂O (3ϫ4 mL). The com-

bined organic layers were dried (MgSO₄) and concentrated under

reduced pressure. The crude product 10b was purified by flash col-

umn chromatography (silica gel, petroleum ether/ethyl acetate,

95:5) to furnish olefin 10b (E/Z Ͼ 99:1 as judged by 300 MHz

NMR spectroscopy; 0.08 g, 0.14 mmol, 73%) as colourless crystals.

1348, 1301, 1255, 1229, 1153, 1107, 1077, 1058, 1015, 998, 926,

1

768, 729, 690 cm^–1. H NMR (CDCl₃, 600 MHz): δ = 0.92 (t, J =

7.2 Hz, 3 H, CH₃), 1.42 (m_c, 4 H, 2 CH₂), 1.95 (m_c, 2 H, CH₂),

3.73 (m_c, 2 H, 1Ј-H), 7.57–7.72 (m, 5 H, arom. H) ppm. ¹³C NMR

(CDCl₃, 125 MHz): δ = 14.1 (CH₃), 22.0 (CH₂), 22.4 (CH₂), 30.6

(CH₂), 56.4 (CH₂), 125.5, 130.1, 131.9 (arom. CH), 133.5 (arom.

C

_ipso), 153.9 (CS) ppm. MS (+EMS): m/z (%) = 303 (65) [M +

Na]⁺, 281 (100) [M + 1]⁺. The spectroscopic data for sulfone 19

were in full agreement with those reported in the literature.^[22a]

Synthesis of Boronic Ester 10b

Representative Procedure for the Wittig–Schlosser Olefination

(Scheme 4, Entry 4): nBuLi (1.6  in hexane, 0.12 mL, 0.19 mmol,

1 equiv.) was added dropwise through a cannula to a stirred solu-

tion of n-pentyltriphenylphosphonium bromide (0.08 g, 0.19 mmol,

1.0 equiv.) and LiBr (0.10 g, 1.13 mmol, 6.0 equiv.) in anhydrous

THF (2 mL) and diethyl ether (1.5 mL) at room temp. under dry

N₂. After 20 min of vigorous stirring at room temp., the red solu-

tion was cooled to –78 °C and aldehyde 8 (0.10 g, 0.19 mmol,

1.0 equiv.) in THF (1 mL) was added. Stirring was continued for

20 min at –30 °C before nBuLi (1.4  in hexane, 0.13 mL,

0.19 mmol, 1.0 equiv.) was added. The resulting dark-red betaine

ylide solution was kept for 30 min at room temp. and for 15 min

at –78 °C. Then a 2  solution of HCl in diethyl ether (0.09 mL,

0.19 mmol, 1.0 equiv.) was added causing immediate decolouriz-

ation. The cooling bath was removed and the reaction was stirred

for 10 min at room temp. KOtBu (0.02 g, 0.19 mmol, 1.0 equiv.)

was added and the reaction mixture was stirred for an additional

1 h and then quenched with H₂O (1 mL), diluted with Et₂O (4 mL)

and H₂O (4 mL) and extracted with Et₂O (3ϫ4 mL). The com-

bined organic layers were dried (MgSO₄), filtered and concentrated

under reduced pressure. The crude product 10b was purified by

flash column chromatography (silica gel, petroleum ether/ethyl ace-

tate, 95:5) to furnish olefin 10b (0.08 g, 0.14 mmol, 70%) as colour-

The analytical data for boronic ester 10b were presented in the

cross-metathesis section (see above).

Synthesis by Cross-Coupling

(1ЈR,2ЈR,4R,5R)- and (1ЈS,2ЈS,4R,5R)-2-(2Ј-Iodocyclopropyl)-4,5-

bis(methoxydiphenylmethyl)-1,3,2-dioxaborolane (22a and 22b):

[RuCl₃·3H₂O] (0.06 g, 0.24 mmol, 0.05 equiv.) was added to a vig-

orously stirred solution of cyclopropylmethanol 3 (2.61 g,

4.88 mmol, 1.0 equiv.) and NaIO₄(3.13 g, 14.65 mmol, 3.0 equiv.)

in a mixture of CCl₄/H₂O/CH₃CN (6 mL/8 mL/6 mL) at room

temp. The reaction was heated at reflux for 2–3 h at 40 °C and then

aq. saturated NH₄Cl (60 mL) was added. The reaction mixture was

filtered through a pad of Celite and washed with ethyl acetate. The

aqueous layer was extracted with ethyl acetate (3ϫ80 mL) and the

combined organic layers were dried (MgSO₄) and the solvent re-

moved under reduce pressure. The crude product 20 was purified

by column chromatography (petroleum ether/ethyl acetate, 8:2 +

1% AcOH) to furnish the carboxylic acid 20 as colourless crystals

(2.41 g, 4.40 mmol, 90%); m.p. 188–189 °C. [α]²_D¹= –111.9 (c =

1.00, CHCl ). IR (film): ν = 3027, 2950, 2902, 2834, 1690, 1487,

˜

3

1

less crystals; E/Z = 80:20 (as judged by 300 MHz H NMR spec-

1446, 1402, 1334, 1295, 1243, 1192, 1077, 1026, 959, 923, 699, 653,

troscopy).

1

601 cm^–1. H NMR (CDCl₃, 500 MHz): δ = 0.21 (ddd, J = 10.4, J

Representative Procedure for the Julia–Kocienski Olefination

(Scheme 5, Entry 8). Method A: A solution of KHMDS (0.07 g,

0.34 mmol, 1.8 equiv.) in anhydrous DME (2 mL) was added drop-

wise through a cannula to a stirred solution of the sulfone 19

(0.08 g, 0.28 mmol, 1.5 equiv.) in anhydrous DME (4 mL) over

5 min at –60 °C under dry N₂. The yellow-orange solution was

stirred for 5 min and the aldehyde 8 (0.10 g, 0.19 mmol, 1.0 equiv.)

in anhydrous DME (2 mL) was added dropwise through a cannula

over 5 min. Stirring was continued for 10 min at –60 °C. The reac-

tion was then quenched with H₂O (1 mL) and the mixture vigor-

ously stirred whilst warming to room temp. It was then diluted with

Et₂O (4 mL) and H₂O (4 mL) and extracted with Et₂O (3ϫ4 mL).

The combined organic layers were dried (MgSO₄), filtered and con-

centrated under reduced pressure. The crude product 10b was puri-

fied by flash column chromatography (silica gel, petroleum ether/

ethyl acetate, 95:5) to afford the (E)-olefin 10b (0.10 g, 0.17 mmol,

93%) as colourless crystals; E/Z Ͼ 99:1 (as judged by 300 MHz ¹H

NMR spectroscopy). The minor Z isomer 6 was only detected by

600 MHz ¹H NMR spectroscopy (E/Z = 98:2) and was removed

by a single recrystallization from n-pentane.

= 7.6, J = 5.0 Hz, 1 H, 1Ј-H), 0.39 (ddd, J = 10.5, J = 7.6, J =

3.1 Hz, 1 H, 3Ј-H_a), 0.98 (ddd, J = 10.4, J = 7.5, J = 3.1 Hz, 1 H,

3Ј-H_b), 1.45 (ddd, J = 10.5, J = 7.5, J = 5.0 Hz, 1 H, 2Ј-H), 3.01

(s, 6 H, OCH₃), 5.31 (s, 2 H, 4-H, 5-H), 7.24–7.35 (m, 20 H, arom.

H), 11.5 (br. s, COOH) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ =

–0.9 (C-1Ј), 13.6 (C-3Ј), 18.6 (C-2Ј), 51.7 (CPh₂OCH₃), 77.7 (C-4,

C-5), 83.3 (CPh₂OCH₃), 127.3, 127.4, 127.6, 127.8, 128.3, 129.6

(arom. CH), 140.8, 140.9 (arom. C_ipso), 180.2 (COOH) ppm. MS

(FAB, NBA + NaI): m/z (%) = 593 (65) [M + 2 Na]⁺, 571 (2) [M

+ Na]⁺, 197 (100) [Ph₂COCH₃]⁺.

In a Schlenk flask covered with aluminium foil, carboxylic acid 20

(0.29 g, 0.50 mmol, 1.0 equiv.), “HOTT” reagent 21 (0.24 g,

0.60 mmol, 1.2 equiv.) and DMAP (0.03 g, 0.30 mmol, 0.6 equiv.)

were dissolved in abs. CH₃CN (1 mL). THF (3 mL) and Et₃N

(0.22 mL, 1.6 mmol, 3.2 equiv.) were added and the mixture was

stirred for 1 h at room temp (TLC control: petroleum ether/ethyl

acetate, 7:3). Half of the solvent was removed under reduced pres-

sure and abs. cyclohexene (1 mL) and iodoform (0.63 g, 1.59 mmol,

3.2 equiv.) were added. The mixture was heated at 80 °C (reflux)

for 15 h. The solvents and volatile compound were then removed

under reduced pressure. The remaining dark oil was diluted with

diethyl ether (20 mL) and the insoluble precipitates were removed

Representative Procedure on a Larger Scale According to Scheme 5,

Entry 8. Method A: Sulfone 19 (2.92 g, 10.4 mmol, 1.5 equiv.) in

3776

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Eur. J. Org. Chem. 2009, 3765–3782

Enantiomerically Pure Vinylcyclopropylboronic Esters

by filtration through a pad of Celite and rinsed thoroughly with

diethyl ether. The organic layer was washed with a 1  solution of

Na₂S₂O₃(10 mL) and brine (10 mL) and the aqueous layer was

extracted with diethyl ether (2 ϫ20 mL). The combined organic

layers were dried (MgSO₄) and the solvent was removed under re-

duced pressure. The crude product 22 was purified by column

chromatography (petroleum ether to petroleum ether/ethyl acetate,

99:1) to furnish a mixture of the trans isomer 22a and the cis isomer

22b (6:1); yield 0.23 g (0.37 mmol, 70%). The diastereoisomers were

separated by MPLC (petroleum ether/ethyl acetate, 99.3:0.7). Both

iodocyclopropanes 22 were obtained as colourless crystals. Isomer

22a: Softening range 125–130 °C. [α]²_D¹= –105.2 (c = 0.48, CHCl₃).

0.14 mmol, 1.0 equiv.), phenylboronic acid (23h; 30 mg, 0.21 mmol,

1.5 equiv.), the catalyst [Pd(PPh₃)₄] (13 mg, 0.01 mmol, 0.07 equiv.)

and KOtBu (1  in n-butanol, 0.29 mL, 0.29 mmol, 2.0 equiv.) in

abs. DME (1.5 mL) were allowed to react according to the general

procedure for 20 h. The product 10h was isolated as colourless crys-

tals (72 mg, 0.12 mmol, 87%). All the spectroscopic data for bo-

ronic ester 10h were in full agreement with those reported previous-

ly.^[8a]

(1ЈR,2ЈR,4R,5R)-4,5-Bis(methoxydiphenylmethyl)-2-[2Ј-(thiophen-

3ЈЈ-yl)cyclopropyl]-1,3,2-dioxaborolane (10j): Iodocyclopropane 22a

(80 mg, 0.13 mmol, 1.0 equiv.), thiophene-3-boronic acid (23j;

20 mg, 0.19 mmol, 1.5 equiv.), the catalyst [Pd(PPh₃)₄] (12 mg,

0.01 mmol, 0.07 equiv.) and KOtBu (1  in n-butanol, 0.28 mL,

0.28 mmol, 2.0 equiv.) in abs. DME (1.5 mL) were allowed to react

according to the general procedure for 20 h. The product 10j was

isolated as colourless crystals (58 mg, 0.10 mmol, 79%). All the

spectroscopic data for boronic ester 10j were in full agreement with

those reported previously.^[10b]

IR (film): ν = 3057, 3025, 2925, 2848, 2832, 1493, 1445, 1404, 1369,

˜

1248, 1228, 1182, 1074, 1032, 1016, 967, 955, 916, 899, 879 cm^–1.

¹H NMR (CDCl₃, 500 MHz): δ = –0.08 (ddd, J = 10.6, J = 7.1, J

= 4.9 Hz, 1 H, 1Ј-H), 0.50 (ddd, J = 7.1, J = 7.1, J = 4.9 Hz, 1 H,

3Ј-H_a), 0.76 (ddd, J = 10.6, J = 4.7, J = 4.7 Hz, 1 H, 3Ј-H_b), 2.14

(ddd, J = 7.1, J = 4.8, J = 4.7 Hz, 1 H, 2Ј-H), 3.01 (s, 6 H, OCH₃),

5.30 (s, 2 H, 4-H, 5-H), 7.22–7.37 (m, 20 H, arom. H) ppm. ¹³C

NMR (CDCl₃, 125 MHz): δ = –15.9 (C-2Ј), 6.0 (C-1Ј), 15.6 (C-3Ј),

51.7 (CPh₂OCH₃), 77.6 (C-4, C-5), 83.2 (CPh₂OCH₃), 127.1, 127.2,

127.4, 127.6, 127.7, 127.8, 128.3, 128.4, 129.6 (arom. C), 140.9

(arom. C_ipso) ppm. MS (FAB, NBA + NaI): m/z (%) = 653 (20) [M

+ Na]⁺, 527 (2) [M + Na – I]⁺, 197 (100) [Ph₂COCH₃]⁺. HRMS

(FAB, NBA + NaI): calcd. for [M + Na]⁺653.1336; found

653.1331. C₃₃H₃₂BIO₄(630.32): C 62.88, H 5.12; found C 63.80, H

5.95. Isomer 22b: Softening range 85–92 °C. [α]²_D¹= –153.3 (c =

(1ЈR,2ЈR,4R,5R)-4,5-Bis(methoxydiphenylmethyl)-2-[2Ј-(2ЈЈ-phenyl-

cyclopropyl)cyclopropyl]-1,3,2-dioxaborolane (10k): Iodocyclopro-

pane 22a (80 mg, 0.13 mmol, 1 equiv.), the rac-phenylcyclopropyl-

boronic ester 23k^[28](0.04 g, 0.19 mmol, 1.5 equiv.), the catalyst

[Pd(PPh₃)₄] (12 g, 0.01 mmol, 0.07 equiv.) and KOtBu (1  in n-

butanol, 0.28 mL, 0.28 mmol, 2.0 equiv.) in abs. DME (1.5 mL)

were allowed to react according to the general procedure for 25 h.

The product 10k was isolated as colourless crystals (53 mg,

0.09 mmol, 67%). All the spectroscopic data for boronic ester 10k

were in full agreement with those reported previously.^[10b]

0.40, CHCl ). IR (film): ν = 3055, 3026, 2930, 2847, 2831, 1493,

˜

3

1445, 1411, 1375, 1320, 1252, 1193, 1074, 1032, 1016, 968, 923,

1

896, 858 cm^–1. H NMR (CDCl₃, 500 MHz): δ = –0.20 (ddd, J =

(1ЈR,2ЈR,4R,5R)-{2Ј-[(E)-Hept-1ЈЈ-enyl]cyclopropyl}-4,5-bis(meth-

oxydiphenylmethyl)-1,3,2-dioxaborolane (10l): Iodocyclopropane

22a (150 mg, 0.24 mmol, 1.0 equiv.), (E)-hept-1-enylboronic acid

(23b; 44 mg, 0.31 mmol, 1.3 equiv.), the catalyst [Pd(PPh₃)₄]

(25 mg, 0.02 mmol, 0.07 equiv.) and KOtBu (1  in n-butanol,

0.72 mL, 0.72 mmol, 3.0 equiv.) in abs. DME (3 mL) were allowed

to react according to the general procedure for 24 h. The product

10l was isolated as colourless crystals (94 mg, 0.16 mmol, 65%).

All the spectroscopic data for boronic ester 10l were in full agree-

ment with those reported previously.^[10b]

10.9, J = 8.0, J = 8.0 Hz, 1 H, 1Ј-H), 0.23 (ddd, J = 7.9, J = 5.1,

J = 5.0 Hz, 1 H, 3Ј-H_a), 1.09 (ddd, J = 10.9, J = 7.4, J = 5.0 Hz,

1 H, 3Ј-H_b), 2.50 (ddd, J = 7.6, J = 7.6, J = 5.3 Hz, 1 H, 2Ј-H),

3.02 (s, 6 H, OCH₃), 5.29 (s, 2 H, 4-H, 5-H), 7.21–7.48 (m, 20 H,

arom. H) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ = –13.9 (C-2Ј), 3.0

(C-1Ј), 15.5 (C-3Ј), 51.7 (CPh₂OCH₃), 77.6 (C-4, C-5), 83.3

(CPh₂OCH₃), 127.2, 127.3, 127.4, 127.7, 128.7, 129.8 (arom. CH),

141.3 (arom. C_ipso) ppm. MS (FAB, NBA + NaI): m/z (%) = 653

(15) [M + Na]⁺, 197 (100) [Ph₂COCH₃]⁺. C₃₃H₃₂BIO₄(630.32):

calcd. C 62.88, H 5.12; found C 62.86, H 5.19.

Procedure for the Heck Coupling Reaction

General Procedure for the Suzuki Coupling Reaction of Iodocyclo-

propane 22a (Scheme 7, Condition D): Iodocyclopropane 22a

(1.0 equiv.) was dissolved in 1,2-dimethoxyethane (10 mL/mmol).

After addition of the boron derivative 23 (1.5 equiv.), [Pd(PPh₃)₄]

(5 mol-%) and KOtBu (2 mL/mmol 22a of a 1  solution in

tBuOH) the mixture was carefully deoxygenated by the freeze tech-

nique. After 15–24 h at 80 °C the mixture was diluted with diethyl

ether, filtered through a pad of Celite, rinsed with diethyl ether

and the solvents were removed under reduced pressure. The crude

product 10 was purified by flash column chromatography (silica

gel, petroleum ether/diethyl ether, 99:1).

(1ЈR,2ЈR,4R,5R)-4,5-Bis(methoxydiphenylmethyl)-2-[(E)-2Ј-styryl-

cyclopropyl]-1,3,2-dioxaborolane (10a): Vinylcyclopropane 9

(40 mg, 0.08 mmol, 1 equiv.), Pd(OAc)₂(3.0 mg, 0.03 mmol,

0.1 equiv.) and NaOAc (10 mg, 0.08 mmol, 1.1 equiv.) were dis-

solved in the ionic liquid [BMIM]Br (20 mL) by vigorously stirring

at 75 °C. The solution was carefully deoxygenated by the freeze

technique. After the addition of PhI (30 mg, 0.15 mmol, 2.0 equiv.),

the mixture was heated for 1 d at 100 °C. After the addition of

water (80 mL), the mixture was transferred into a separation fun-

nel. The layer was extracted with diethyl ether (3ϫ40 mL) and the

combined organic layers were dried (MgSO₄), filtered and concen-

trated under reduced pressure. The crude product 10a was purified

by flash column chromatography (petroleum ether/diethyl ether,

99:1) to furnish boronic ester 10a (42 mg, 69 µmol, 91%) as colour-

less crystals. The analytical data for boronic ester 10a were pre-

sented in the cross-metathesis section (see above).

(1ЈR,2ЈR,4R,5R)-{2Ј-[(E)-Hex-1ЈЈ-enyl]cyclopropyl}-4,5-bis(meth-

oxydiphenylmethyl)-1,3,2-dioxaborolane (10b): Iodocyclopropane

22a (150 mg, 0.24 mmol, 1.0 equiv.), (E)-hex-1-enylboronic acid

(23b; 40 mg, 0.31 mmol, 1.3 equiv.), the catalyst [Pd(PPh₃)₄]

(25 mg, 0.02 mmol, 0.07 equiv.) and KOtBu (1  in n-butanol,

0.72 mL, 0.72 mmol, 3.0 equiv.) in abs. DME (3 mL) were allowed

to react according to the general procedure for 24 h. The product

10b was isolated as colourless crystals (87 mg, 0.15 mmol, 62%).

The analytical data for the boronic ester 10b were presented in the

cross-metathesis section (see above).

By extracting the remaining aqueous layer with dichloromethane,

drying the organic layer with MgSO₄and removing the dichloro-

methane, about 50% of the ionic liquid could be recovered.

Activation of the Boronic Esters

(1ЈR,2ЈR,4R,5R)-4,5-Bis(methoxydiphenylmethyl)-2-(2Ј-phenylcyclo- Synthesis of Cyclopropyltrifluoroborates 25 and ent-25: KHF₂

propyl)-1,3,2-dioxaborolane (10h): Iodocyclopropane 22a (90 mg,

(50 equiv.) was placed in a round-bottomed Teflon^®flask and dis-

Eur. J. Org. Chem. 2009, 3765–3782

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3777

E. Hohn, J. Palecˇek, J. Pietruszka, W. Frey

FULL PAPER

solved in MeOH (80–100 mL/mmol boronic ester). The boronic es-

ter (1 equiv.), dissolved in a minimum amount of dichloromethane,

was added and the mixture heated at 80 °C for 1–3 d. The solvents

were removed under reduced pressure and the remaining colourless

solids transferred to a Büchner funnel and washed with diethyl

ether (or n-pentane) to elute the diol 26. The product (alkyltrifluo-

roborate) was dissolved in acetonitrile, the solvent was removed

under reduced pressure and the remaining solid, if required, recrys-

tallized from acetonitrile.

CH₂Ph), 6.98 –7.43 (m, 10 H, arom. H) ppm. ¹³C NMR (CDCl₃,

125 MHz): δ = 14.2 (C-3Ј), 21.4 (C-2Ј), 22.6 (C-1Ј), 72.5 (CH₂Ph),

73.5 (C-1), 125.0, 125.8, 127.5, 127.6, 128.2, 128.4 (arom. CH),

138.4, 142.6 (arom. C_ipso) ppm. The spectroscopic data for cy-

clopropylbenzene 27 were in full agreement with those reported in

the literature.^[39]

(1R,2R)-[2-(Benzyloxymethyl)cyclopropyl]naphthalene (28): Borate

ent-25 (79 mg, 0.30 mmol, 1.0 equiv.), 1-bromonaphthalene (70 mg,

0.36 mmol, 1.2 equiv.), [Pd(PPh₃)₄] (6.0 mg, 5.0 µmol, 0.05 equiv.)

and K₃PO₄(0.21 g, 0.98 mmol, 3.0 equiv.) in toluene/H₂O

(3:1;0.6 mL) were allowed to react according to the general pro-

Potassium (1S,2S)-[2-(Benzyloxymethyl)cyclopropyl]trifluoroborate

(25): KHF₂(18.1 g, 232 mmol, 50 equiv.) and cyclopropylboronic

ester 24a^[12a,12b](2.90 g, 4.64 mmol, 1.0 equiv.) in MeOH (460 mL) cedure for 15 h at 100 °C. The crude product 28 was purified by

were heated at reflux at 80 °C for 2 d according to the representa-

tive procedure. The residue was washed in a Büchner funnel with

diethyl ether to elute the diol 26. The borate 25 was dissolved in

acetonitrile. The product 25 was isolated as colourless crystals

(0.97 g, 3.62 mmol, 78%^[38]); m.p. 198 °C. [α]²_D⁰= +16.4 (c = 0.50,

flash column chromatography (SiO₂, n-pentane, then petroleum

ether/ethyl acetate, 98:2) to furnish cyclopropylnaphthalene 28

(73 mg, 0.25 mmol, 85%) as a colourless oil. [α]²_D⁰= –13.1 (c = 0.65,

CHCl ). IR (film): ν = 3061, 3043, 3003, 2926, 2853, 1594, 1508,

˜

3

1495, 1453, 1392, 1357, 1260, 1203, 1166, 1091, 1072, 1027, 963,

797, 775, 732, 695 cm^–1. ¹H NMR (CDCl₃, 500 MHz): δ = 1.00

(ddd, J = 10.0, J = 5.1, J = 4.7 Hz, 1 H, 4-H_a), 1.13 (ddd, J = 8.4,

J = 5.4, J = 4.7 Hz, 1 H, 4-H_b), 1.48 (dddd, J = 10.0, J = 7.2, J =

6.2, J = 5.4, J = 5.2 Hz, 1 H, 2-H), 2.28 (ddd, J = 8.4, J = 5.1, J

= 5.2 Hz, 1 H, 3-H), 3.61 (dd, J = 10.2, J = 7.2 Hz, 1 H, 1-H_a),

DMSO). IR (film): ν = 3063, 3030, 3000, 2945, 2888, 2864, 1496,

˜

1470, 1454, 1417, 1374, 1358, 1305, 1246, 1205, 1169, 1130, 1101,

1090, 1076, 1065, 1038, 942, 888, 820, 805, 743, 698 cm^–1. ¹H NMR

([D₆]DMSO, 400 MHz): δ = –0.87 (ddd, J = 9.6, J = 6.5, J =

3.4 Hz, 1 H, 1-H), –0.17 (ddd, J = 9.6, J = 3.7, J = 2.9 Hz, 1 H,

3-H_a), 0.09 (ddd, J = 6.8, J = 6.5, J = 2.9 Hz, 1 H, 3-H_b), 0.58– 3.72 (dd, J = 10.2, J = 6.2 Hz, 1 H, 1-H_b), 4.61 (d, J = 12.0 Hz, 1

0.66 (m, 1 H, 2-H), 3.06 (dd, J = 10.2, J = 7.5 Hz, 1 H, 4-H_a), 3.31 H, 1Ј-H_a), 4.65 (d, J = 12.0 Hz, 1 H, 1Ј-H_b), 7.25–7.28 (m, 1 H,

(dd, J = 10.2, J = 6.1 Hz, 1 H, 4-H_b), 4.43 (d, J = 12.2 Hz, 1 H,

arom. 2ЈЈЈ-H), 7.28–7.32 (m, 1 H, arom. 3ЈЈЈ-H), 7.34–7.39 (m, 3

5-H_a), 4.49 (d, J = 12.2 Hz, 1 H, 5-H_b), 7.22–7.36 (m, 5 H, arom. H, arom. 2ЈЈ,4ЈЈ,6ЈЈ-H), 7.40–7.43 (m, 2 H, arom. 3ЈЈ,5ЈЈ-H), 7.45–

H) ppm. ¹³C NMR ([D₆]DMSO, 100 MHz): δ = 7.0 (C-3), 13.6 (C- 7.51 (m, 2 H, arom. 7ЈЈЈ, 8ЈЈЈ-H), 7.68–7.71 (m, 1 H, arom. 4ЈЈЈ-H),

2), 70.6 (C-5), 76.5 (C-4), 127.0, 127.3, 128.1 (arom. C), 139.2

7.81–7.85 (m, 1 H, arom. 6ЈЈЈ-H), 8.48–8.50 (m, 1 H, arom. 9ЈЈЈ-

(arom. C_ipso) ppm. ¹⁹F NMR ([D₆]DMSO, 400 MHz): δ = –140.07 H) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ = 11.1 (C-4), 19.6 (C-3),

(s, 3 F, BF₃K) ppm. MS (ES): m/z (%) = 285 (40) [M + NH₃]⁺, 307

20.3 (C-2), 72.6 (C-1Ј), 74.1 (C-1), 124.0 (C-2ЈЈЈ), 124.6 (C-9ЈЈЈ),

125.4, 125.6 (C-2ЈЈ or C-4ЈЈ or C-6ЈЈ), 125.8 (C-7ЈЈЈ, C-8ЈЈЈ), 126.8

(C-4ЈЈЈ), 127.5 (C-3ЈЈЈ), 127.6 (C-3ЈЈ, C-5ЈЈ), 128.3 (C-2ЈЈ or C-4ЈЈ

or C-6ЈЈ), 128.4 (C-6ЈЈЈ), 133.4 (C-10ЈЈЈ), 133.5 (C-5ЈЈЈ), 137.9 (C-

1ЈЈ), 138.6 (C-1ЈЈЈ) ppm. MS (EI, 70 eV): m/z (%) = 288 (100)

[M]⁺, 197 (30) [M – C₇H₇]⁺, 181 (50) [M – C₇H₇O]⁺, 167 (100)

[M – C₈H₉O]⁺. C₂₁H₂₀O (288.38): calcd. C 87.27, H 6.99; found C

86.81, H 6.99.

(100) [M + K]⁺.

Potassium (1R,2R)-[2-(Benzyloxymethyl)cyclopropyl]trifluoroborate

(ent-25): KHF₂(5.50 g, 70.5 mmol, 50 equiv.) and cyclopropylbo-

ronic ester 24b (0.88 g, 1.41 mmol, 1.0 equiv.) in MeOH (150 mL)

were heated at reflux at 80 °C for 2 d according to the representa-

tive procedure. The product ent-25 was isolated as colourless crys-

tals (0.345 g, 1.29 mmol, 93%); m.p. 197 °C. [α]²_D⁰= –16.4 (c = 0.50,

DMSO). All the spectroscopic data for borate ent-25 were in full

agreement with those reported previously.^[10b]

Synthesis of Boronic Esters from Borate 25

(1ЈS,2ЈS)-2-[2Ј-(Benzyloxymethyl)cyclopropyl]-1,3,2-dioxaborinane

(29). Method I: Borate 25 (0.20 g, 0.75 mmol, 1.0 equiv.) was sus-

pended in abs. THF (1.0 mL). SiCl₄(1.49 mL, 1.49 mmol, 1  solu-

tion in dichloromethane, 2.0 equiv.) was added dropwise at room

temp. A clear solution formed and stirring was continued for 1 h.

The mixture was cooled to 0 °C and methanol (0.30 mL,

7.45 mmol) was added followed after 10 min by 1,3-propanediol

(0.04 mL, 0.74 mmol, 1.0 equiv.). The volatiles were removed under

reduced pressure after 15 h at room temp. The residue was diluted

with n-pentane and neutralized by adding Et₃N dropwise. The pre-

cipitates were filtered off and washed with n-pentane. The mother

liquor was concentrated under reduced pressure and the remaining

oil containing the crude product 29 was purified by column

chromatography (SiO₂, petroleum ether/ethyl acetate, 98:2 to 92:8)

to furnish boronic ester 29 as a colourless oil (167 mg, 0.68 mmol,

91%).

Suzuki Coupling of the Borates: A suspension of the cyclopropyltri-

fluoroborate 25/ent-25 (1 equiv.), 5–10 mol-% [Pd(PPh₃)₄] and

K₃PO₄(3.0 equiv.) in toluene/H₂O (3:1; 8 mL/mmol borate) was

deoxygenated by the freeze technique. The aryl bromide (1.2 equiv.)

was added at room temp. The mixture was stirred at 100 °C until

complete conversion was detected (as judged by TLC). After fil-

tration through a pad of Celite and MgSO₄and extensive rinsing

with diethyl ether, the solvent was removed under reduce pressure.

The crude product 27/28 was purified by column chromatography.

(1S,2S)-[2-(Benzyloxymethyl)cyclopropyl]benzene (27): Borate 25

(79 mg, 0.30 mmol, 1.0 equiv.), phenyl bromide (40 µL, 0.36 mmol,

1.2 equiv.), [Pd(PPh₃)₄] (30 mg, 30 µmol, 0.05 equiv.) and K₃PO₄

(0.21 g, 0.99 mmol, 3.0 equiv.) in toluene/H₂O (3:1; 2.4 mL) were

allowed to react according to the general procedure for 2 d at

100 °C. The crude product 27 was purified by column chromatog-

raphy (SiO₂, petroleum ether/ethyl acetate, 98:2) to furnish cy-

clopropylbenzene 27 (48 g, 0.2 mmol, 66 %) as a colourless oil.

Method II: Borate 25 (0.13 g, 0.48 mmol, 1.0 equiv.) was suspended

in acetonitrile (5.0 mL) and water (24 µL) under argon. LiOH

(40 mg, 1.7 mmol, 3.5 equiv.) was added and a clear solution

formed. Stirring was continued for 20 h at room temp. The solution

was treated with an aqueous saturated NH₄Cl solution (4 mL) and

1  aqueous hydrochloric acid (1 mL). The aqueous layer was re-

peatedly extracted with ethyl acetate and the combined organic lay-

ers were dried with Na₂SO₄. The solvent was removed under re-

1

[α]²_D⁰= +101.2 (c = 0.41, CHCl₃). H NMR (CDCl₃, 500 MHz): δ

= 0.91 (ddd, J = 8.8, J = 5.3, J = 5.2 Hz, 1 H, 3Ј-H_a), 0.96 (ddd,

J = 8.4, J = 5.2, J = 5.1 Hz, 1 H, 3Ј-H_b), 1.43 (ddddd, J = 8.4, J

= 6.8, J = 6.4, J = 5.3, J = 5.3 Hz, 1 H, 1Ј-H), 1.78 (ddd, J = 8.8,

J = 5.1, J = 5.3 Hz, 1 H, 2Ј-H), 3.42 (dd, J = 10.3, J = 6.8 Hz, 1

H, 1-H_a), 3.51 (dd, J = 10.3, J = 6.4 Hz, 1 H, 1-H_b), 4.53 (s, 2 H,

3778

www.eurjoc.org

Eur. J. Org. Chem. 2009, 3765–3782

Enantiomerically Pure Vinylcyclopropylboronic Esters

duced pressure and the boronic acid obtained was dissolved in a

minimum amount of dichloromethane and treated with pentane

(2.5 mL). 1,3-Propanediol (30 µL, 0.41 mmol) was added and the

mixture was stirred for 10 h at room temp., dried with Na₂SO₄,

filtered and concentrated under reduced pressure to furnish the

product 29 as a colourless oil (76 mg, 0.30 mmol, 75%).

were filtered off and washed with n-pentane. The mother liquor

was concentrated under reduced pressure and the remaining oil

containing the crude product 30 was purified by column

chromatography (SiO₂, petroleum ether/ethyl acetate, 98:2 to 92:8)

to furnish boronic ester 30 as a colourless oil (0.21 g, 0.74 mmol,

99 %). The spectroscopically pure product was used for further

transformations as obtained. [α]²_D⁰= –7.4 (c = 0.73, CHCl₃). IR

Method III: Borate 25 (0.13 g, 0.48 mmol, 1.0 equiv.) was sus-

pended in acetonitrile (5.0 mL) and water (24 µL) under argon.

Chlorotrimethylsilane (0.18 mL, 1.45 mmol, 3.0 equiv.) was added

and stirring was continued for 24 h at room temp. The mixture was

treated with an aqueous saturated NaHCO₃solution (0.75 mL),

dried with Na₂SO₄, filtered and thoroughly washed with ethyl ace-

tate. The solvent was removed under reduced pressure and the bo-

ronic acid obtained was dissolved in a minimum amount dichloro-

methane and treated with pentane (2.5 mL). 1,3-Propanediol

(30 µL, 0.41 mmol) was added and the mixture was stirred for 10 h

at room temp., dried with Na₂SO₄, filtered and concentrated under

reduced pressure to furnish the product 29 as a colourless oil

(107 mg, 0.43 mmol, 94%).

(film): ν = 3066, 3027, 2977, 2931, 2856, 1496, 1469, 1454, 1425,

˜

1388, 1378, 1364, 1336, 1316, 1260, 1215, 1165, 1143, 1087, 1027,

1008, 967, 932, 903, 838, 800, 734, 696, 673 cm^–^{1 1}H NMR

.

(CDCl₃, 400 MHz): δ = –0.23 (ddd, J = 9.6, J = 6.2, J = 5.8 Hz, 1

H, 1Ј-H), 0.55 (ddd, J = 9.6, J = 5.1, J = 3.5 Hz, 1 H, 3Ј-H_a), 0.77

(ddd, J = 8.1, J = 6.5, J = 3.5 Hz, 1 H, 3Ј-H_b), 1.21 (s, 12 H, CH₃),

1.34–1.38 (m, 1 H, 2Ј-H), 3.25 (dd, J = 10.4, J = 7.1 Hz, 1 H, 4Ј-

H_a), 3.45 (dd, J = 10.4, J = 6.1 Hz, 1 H, 4Ј-H_b), 4.53 (s, 2 H,

5Ј-H), 7.23–7.35 (m, 5 H, arom. H) ppm. ¹³C NMR ([D₆]DMSO,

100 MHz): δ = –1.6 (C-1Ј), 9.6 (C-3Ј), 17.2 (C-2Ј), 24.6, 24.7 (CH₃),

72.3 (C-4Ј), 74.8 (C-5Ј), 82.9 (C-4, C-5), 127.4, 127.6, 128.3 (arom.

CH), 138.6 (arom. C_ipso) ppm.

Synthetic Approach Towards the Dictypterenes

Method IV: Borate 25 (0.10 g, 0.37 mmol, 1.0 equiv.) was sus-

pended in acetonitrile (4.0 mL) under argon. The mixture was

treated with chlorotrimethylsilane (0.14 mL, 1.12 mmol, 3.0 equiv.)

and stirring was continued for 5 min at room temp. before 1,3-

propanediol (25 µL, 0.35 mmol) was added. After 30 min at room

temp., the mixture was dried with Na₂SO₄, filtered and concen-

trated under reduced pressure to furnish the product 29 as a colour-

less oil (83 mg, 0.33 mmol, 95%).

Potassium (1R,2R)-2-[(E)-Hex-1Ј-enyl]cyclopropyltrifluoroborate

(31): KHF₂(13.3 g, 171 mmol, 100 equiv.) was suspended in meth-

anol (400 mL) and cyclopropylboronic ester 10b (1.00 g,

1.71 mmol, 1.00 equiv.) was added. The mixture was heated at

80 °C (reflux) for 5 d. The solvent was removed completely under

reduced pressure and the residue was washed in a Büchner funnel

first with n-pentane, eluting the diol 26, followed by acetonitrile,

eluting the product 31. The solvent was removed under reduced

pressure to furnish borate 31 as a colourless solid (0.35 g,

1.52 mmol, 89%). Decomp. at 210 °C. [α]²_D⁰= –8.5 (c = 0.40, ace-

Method V: Borate 25 (50 mg, 0.19 mmol, 1.0 equiv.) was suspended

in acetonitrile (2.0 mL) and Et₃N (78 µL, 0.56 mmol) under argon.

The mixture was treated with chlorotrimethylsilane (70 µL,

0.56 mmol, 3.0 equiv.) and stirring was continued for 5 min at room

temp. before 1,3-propanediol (10 µL, 0.18 mmol) was added. After

30 min at room temp., the mixture was directly concentrated under

reduced pressure to furnish the crude product 29. Filtration

through a pad of Celite (eluent: n-pentane/ethyl acetate, 9:1) yielded

the boronic ester 29 as a colourless oil (40 mg, 0.16 mmol, 92%).

The spectroscopically pure products were used for further transfor-

tone). IR (film): ν = 3060, 2999, 2958, 2926, 2873, 2859, 1610,

˜

1456, 1391, 1358, 1313, 1231, 1074, 1023, 930, 892, 852, 729,

1

695 cm^–1. H NMR ([D₆]acetone, 400 MHz): δ = –0.52 (ddd, J =

9.7, J = 7.2, J = 3.5 Hz, 1 H, 1-H), 0.05 (ddd, J = 9.7, J = 3.5, J

= 2.7 Hz, 1 H, 3-H_a), 0.41 (ddd, J = 7.2, J = 7.2, J = 2.7 Hz, 1 H,

3-H_b), 0.85 (m, 3 H, 6Ј-H), 1.10 (dddd, J = 9.0, J = 7.2, J = 3.5, J

= 3.5 Hz, 1 H, 2-H), 1.26 (m, 4 H, 4Ј-H, 5Ј-H), 1.91 (ddt, J = 7.3,

J = 6.7, J = 1.3 Hz, 2 H, 3Ј-H), 4.86 (ddt, J = 15.2, J = 9.0, J =

1.3 Hz, 1 H, 1Ј-H), 5.30 (dt, J = 15.2, J = 6.7 Hz, 1 H, 2Ј-H) ppm.

¹³C NMR ([D₆]acetone, 100 MHz): δ = 11.7 (C-3), 15.2 (C-6Ј), 18.9

(C-2), 23.8 (C-4, C-5Ј), 34.0 (C-3Ј), 125.8 (C-2Ј), 140.2 (C-1Ј) ppm;

no signal for C-1 observed. ¹⁹F NMR ([D₆]acetone, 400 MHz): δ

= –144.35 (s, 3 F, BF₃K) ppm. MS (ESI): m/z (%) = 253 (50) [M +

Na]⁺.

mations as obtained. [α]²_D⁰= –47.0 (c = 0.93, CHCl ). IR (film): ν

˜

3

= 3065, 3033, 2999, 2945, 2889, 2855, 1481, 1453, 1420, 1397, 1356,

1324, 1291, 1274, 1225, 1203, 1137, 1091, 1073, 1027, 990, 963,

1

935, 916, 847, 736, 697, 665 cm^–1. H NMR (CDCl₃, 500 MHz): δ

= –0.38 (ddd, J = 9.6, J = 6.3, J = 5.1 Hz, 1 H, 1Ј-H), 0.43 (ddd,

J = 8.4, J = 5.1, J = 3.4 Hz, 1 H, 3Ј-H_a), 0.67 (ddd, J = 7.7, J =

6.3, J = 3.4 Hz, 1 H, 3Ј-H_b), 1.24 (ddddd, J = 9.6, J = 8.4, J = 7.7,

J = 6.9, J = 6.6 Hz, 1 H, 2Ј-H), 1.88 (q, J = 5.5 Hz, 2 H, 5-H),

3.28 (dd, J = 10.2, J = 6.9 Hz, 1 H, 4Ј-H_a), 3.33 (dd, J = 10.2, J =

6.6 Hz, 1 H, 4Ј-H_b), 3.91 (t, J = 5.5 Hz, 4 H, 4/6-H), 4.51 (d, J =

12.1 Hz, 1 H, 5Ј-H_a), 4.68 (d, J = 12.1 Hz, 1 H, 5Ј-H_b), 7.23–7.34

(m, 5 H, arom. H) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ = ≈1.9

(C-1Ј), 9.1 (C-3Ј), 16.8 (C-2Ј), 27.3 (C-5), 61.5 (C-4/6), 72.3 (C-5Ј),

75.1 (C-4Ј), 127.2, 128.3, 129.6 (arom. CH), 138.7 (arom.

C_ipso) ppm.

Potassium {(1S,2S)-2-[(1ЈE,3ЈZ)-Hexa-1Ј,3Ј-dienyl]cyclopropyl}-

trifluoroborate (32): KHF₂(20.0 g, 256 mmol, 100 equiv.) was sus-

pended in methanol (500 mL) and cyclopropylboronic ester 17

(1.50 g, 2.56 mmol, 1 equiv.) was added. The mixture was heated at

80 °C (reflux) for 5 d. The solvent was removed completely under

reduced pressure and the residue was washed in a Büchner funnel

first with n-pentane, eluting the diol 26, followed by acetonitrile,

eluting the product 32. The solvent was removed under reduced

pressure to furnish the borate 32 as a colourless solid (0.51 g,

(1ЈS,2ЈS)-2-[2Ј-(Benzyloxymethyl)cyclopropyl]-4,4,5,5-tetramethyl-

1,3,2-dioxaborolane (30): Borate 25 (0.20 g, 0.75 mmol, 1.0 equiv.) 2.24 mmol, 87%). Decomp. at 208 °C. [α]²_D⁰= +4.05 (c = 0.37,

was suspended in abs. THF (1.0 mL). SiCl₄(1.49 mL, 1.49 mmol,

1  solution in dichloromethane, 2.0 equiv.) was added dropwise at

room temp. A clear solution formed and stirring was continued

for 1 h. The mixture was cooled to 0 °C and methanol (0.30 mL,

7.45 mmol) was added followed after 10 min by pinacol (0.18 g,

1.50 mmol, 2.0 equiv.). The volatiles were removed under reduced

pressure after 10 h at room temp. The residue was diluted with n-

pentane and neutralized by adding Et₃N dropwise. The precipitates

DMSO). IR (film): ν = 2965, 2927, 2876, 1666, 1645, 1618, 1459,

˜

1373, 1306, 1203, 1071, 1019, 897, 870, 742, 697 cm^–1. ¹H NMR

([D₆]acetone, 600 MHz): δ = –0.40 (m_c, 1 H, 1-H), 0.15 (m_c, 1 H,

3-H_a), 0.55 (ddd, J = 9.5, J = 7.1, J = 2.4 Hz, 1 H, 3-H_b), 0.95 (t,

J = 7.5 Hz, 3 H, 6Ј-H), 1.21 (m_c, 1 H, 2-H), 2.15 (m_c, 2 H, 5Ј-H),

5.08 (dd, J = 10.8, J = 7.5 Hz, 1 H, 4Ј-H), 5.13 (dd, J = 9.6, J =

14.9 Hz, 1 H, 1Ј-H), 5.83 (t, J = 11.1 Hz, 1 H, 3Ј-H), 6.27 (dd, J =

14.9, J = 11.1 Hz, 1 H, 2Ј-H) ppm. ¹³C NMR ([D₆]acetone,

Eur. J. Org. Chem. 2009, 3765–3782

www.eurjoc.org

3779

E. Hohn, J. Palecˇek, J. Pietruszka, W. Frey

FULL PAPER

151 MHz): δ = 12.1 (C-1, C-3), 14.8 (C-6Ј), 19.0 (C-2), 21.5 (C-5Ј),

(0.45 mL, 6.06 mmol, 1.8 equiv.) was added. The reaction mixture

121.2 (C-2Ј), 128.5 (C-4Ј), 129.9 (C-3Ј), 144.8 (C-1Ј) ppm. ¹⁹F was cooled to –78 °C before tBuLi (3.6 mL of a 1.7  solution in

NMR ([D₆]DMSO, 565 MHz): δ = –148.12 (s, 3 F, BF₃K) ppm.

MS (–EMS): m/z (%) = 251 (4) [M + Na]⁺, 223 (31) [M + Na –

C₂H₄]⁺, 189 (100) [C₉H₁₃BF₃]⁺.

n-pentane, 6.06 mmol, 1.8 equiv.) was slowly added. After 30 min

the cooling bath was removed and the mixture stirred for 4 d at

room temp. The mixture was carefully quenched with aqueous sat-

urated NaHCO₃(4.2 mL) and 30% H₂O₂(8.4 mL) at 0 °C. After

10 min the cooling bath was removed and the mixture was stirred

for 3 h at room temp. The layers were separated and the aqueous

layer extracted with Et₂O (3ϫ8 mL). The combined organic layers

were dried (MgSO₄), filtered and concentrated under reduced pres-

sure. The crude product 35 was purified by column chromatog-

raphy (silica gel, n-pentane/diethyl ether, 2:1) to furnish cyclopro-

pylmethanol 35 (0.25 g, 1.62 mmol, 48%) as a colourless liquid.

(1ЈR,2ЈR)-2-{2Ј-[(E)-Hex-1ЈЈ-enyl]cyclopropyl}-1,3,2-dioxaborinane

(33): Borate 31 (800 mg, 3.48 mmol, 1.0 equiv.) was suspended in

CH₃CN (32 mL) and Et₃N (1.5 mL, 10.4 mmol, 3.0 equiv.) and tri-

methylsilyl chloride (1.3 mL, 10.4 mmol, 3.0 equiv.) was added. The

suspension became coarse-grained/milky. The mixture was kept for

5 min at room temp. before 1,3-propanediol (0.25 mL, 3.30 mmol,

0.95 equiv.) was added. Stirring was continued for 30 min, followed

by removal of the volatiles under reduced pressure. The crude prod-

uct 33 was filtered through a pad of Celite (n-pentane/ethyl acetate,

9:1) to remove the precipitates and was further purified by distil-

lation (b.p. 120–125 °C/7 Torr) to furnish dioxaborinane 33 (0.65 g,

3.13 mmol, 90%) as a colourless oil. [α]²_D⁰= –94 (c = 0.60, CHCl₃).

[α]²_D⁰= –13.5 (c = 0.40, CHCl ). IR (film): ν = 3332, 3001, 2956,

˜

3

2925, 2872, 1456, 1408, 1378, 1318, 1266, 1238, 1149, 1039, 1017,

958, 868, 789, 727 cm^–1. ¹H NMR (CDCl₃, 600 MHz): δ = 0.48–

0.55 (m, 2 H, 3Ј-H), 0.81 (t, J = 7.2 Hz, 3 H, 6ЈЈ-H), 0.99–1.04 (m,

1 H, 1Ј-H), 1.18–1.26 (m, 4 H, 4ЈЈ-H, 5ЈЈ-H), 1.26–1.31 (m, 1 H,

2Ј-H), 1.89 (ddt, J = 7.2, J = 6.8, J = 1.4 Hz, 2 H, 3ЈЈ-H), 1.99 (s,

1 H, OH), 3.41 (dd, J = 11.2, J = 7.0 Hz, 1 H, 1-H_a), 3.44 (dd, J

= 11.2, J = 6.8 Hz, 1 H, 1-H_b), 4.95 (ddt, J = 15.2, J = 8.2, J =

1.4 Hz, 1 H, 1ЈЈ-H), 5.42 (ddt, J = 15.2, J = 6.8, J = 0.7 Hz, 1 H,

2ЈЈ-H) ppm. ¹³C NMR (CDCl₃, 151 MHz): δ = 11.3 (C-3Ј), 13.9

(C-6ЈЈ), 19.4 (C-1Ј), 22.2 (C-5ЈЈ), 22.6 (C-2Ј), 31.7 (C-4ЈЈ), 32.1 (C-

3ЈЈ), 66.4 (C-1), 129.1 (C-2ЈЈ), 131.8 (C-2Ј) ppm. The spectroscopic

data for alcohol 35 were in full agreement with those reported in

the literature.^[37f]

IR (film): ν = 2977, 2957, 2926, 2856, 1481, 1438, 1417, 1389, 1370,

˜

1318, 1276, 1215, 1165, 1142, 1112, 1087, 959, 912, 855, 697,

672 cm^–1. ¹H NMR (CDCl₃, 400 MHz): δ = –0.26 (m_c, 1 H, 1Ј-H),

0.53 (m_c, 1 H, 3Ј-H_a), 0.78 (m_c, 1 H, 3Ј-H_b), 0.88 (t, J = 6.8 Hz, 3

H, 6ЈЈ-H), 1.26–1.32 (m, 4 H, 4ЈЈ-H, 5ЈЈ-H), 1.44–1.51 (m, 1 H, 2Ј-

H), 1.91 (q, J = 5.5 Hz, 2 H, 5-H), 1.95 (dt, J = 7.0, J = 6.8 Hz, 1

H, 3ЈЈ-H), 3.94 (t, J = 5.5 Hz, 4 H, 4-H, 6-H), 4.91 (ddt, J = 15.2,

J = 8.7, J = 1.4 Hz, 1 H, 1ЈЈ-H), 5.52 (dt, J = 15.2, J = 6.8 Hz, 1

H, 2ЈЈ-H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 12.1 (C-3Ј), 13.9

(C-6ЈЈ), 20.1 (C-2Ј), 22.2 (C-5ЈЈ), 24.7 (C-5), 31.8 (C-4ЈЈ), 32.2 (C-

3ЈЈ), 61.7 (C-4, C-6), 128.3 (C-2ЈЈ), 133.9 (C-1ЈЈ) ppm; no signal for

C-1Ј observed. GC–MS (EI, 70 eV): m/z (%) = 208 (30) [M]⁺, 179

(30) [M – C₂H₅]⁺, 165 (100) [M – C₃H₇]⁺, 151 (25) [M – C₄H₉]⁺,

137 (18) [M – C₅H₁₁]⁺.

(1R,2R)-2Ј-[(E)-Hex-1ЈЈ-enyl]cyclopropane-1Ј-carbaldehyde

(37):

Cyclopropylmethanol 35 (198 mg, 1.28 mmol, 1.0 equiv.) was dis-

solved in dichloromethane (10 mL). Dess–Martin periodinane 7

(825 mg, 1.95 mmol, 1.5 equiv.) and pyridine (0.30 mL, 3.89 mmol,

3.0 equiv.) were added and the mixture stirred for 1 h at room temp.

The reaction mixture was diluted with n-pentane (5 mL), directly

filtered through a short pad of silica gel and concentrated under

reduced pressure. The crude product 37 was purified by flash col-

umn chromatography (silica gel, n-pentane/dichloromethane, 1:1)

to furnish aldehyde 37 (173 g, 1.14 mmol, 88%) as a colourless li-

(1ЈS,2ЈS)-2-{2Ј-[(1ЈЈE,3ЈЈZ)-Hexa-1ЈЈ,3ЈЈ-dienyl]cyclopropyl}-1,3,2-

dioxaborinane (34): Borate 32 (1.00 g, 4.38 mmol, 1.0 equiv.) was

suspended in CH₃CN (44 mL) and Et₃N (1.8 mL, 13.2 mmol,

3.0 equiv.) and trimethylsilyl chloride (1.7 mL, 13.2 mmol,

3.0 equiv.) was added. The suspension became coarse-grained/

milky. The mixture was kept for 5 min at room temp. before 1,3-

propanediol (0.30 mL, 4.38 mmol, 0.95 equiv.) was added. Stirring

was continued for 30 min, followed by removal of the volatiles un-

der reduced pressure. The crude product 34 was filtered through a

pad of Celite (n-pentane/ethyl acetate, 9:1) to remove the precipi-

tates and was further purified by distillation (b.p. 140–145 °C/

11 Torr) to furnish dioxaborinane 34 (0.81 g, 3.93 mmol, 90%) as

quid. [α]²_D⁰= –97.5 (c = 0.20, CHCl ). IR (film): ν = 2953, 2921,

˜

3

2853, 1737, 1711, 1457, 1377, 1314, 1260, 1145, 1088, 1019, 968,

1

859, 801, 721, 700 cm^–1. H NMR (CDCl₃, 300 MHz): δ = 0.88 (t,

J = 7.1 Hz, 3 H, 6ЈЈ-H), 1.14 (ddd, J = 8.6, J = 6.4, J = 5.0 Hz, 1

H, 3Ј-H_a), 1.22–1.36 (m, 4 H, 4ЈЈ-H, 5ЈЈ-H), 1.47 (ddd, J = 8.6, J

= 5.0, J = 5.0 Hz, 1 H, 3Ј-H_b), 1.85 (dddd, J = 8.6, J = 5.0, J =

5.0, J = 3.7 Hz, 1 H, 1Ј-H), 1.98 (ddt, J = 7.2, J = 6.8, J = 1.4 Hz,

2 H, 3ЈЈ-H), 2.07 (dddd, J = 8.6, J = 8.2, J = 6.4, J = 3.7 Hz, 1 H,

1Ј-H), 5.03 (ddt, J = 15.2, J = 8.2, J = 1.5 Hz, 1 H, 1ЈЈ-H), 5.63

(ddt, J = 15.2, J = 6.8, J = 0.6 Hz, 1 H, 2ЈЈ-H), 9.13 (d, J = 5.0 Hz,

1 H, 1-H) ppm. ¹³C NMR (CDCl₃, 76 MHz): δ = 13.9 (C-6ЈЈ), 15.1

(C-3Ј), 22.2 (C-5ЈЈ), 25.2 (C-2Ј), 31.4 (C-1Ј), 31.7 (C-4ЈЈ), 32.1 (C-

3ЈЈ), 128.4 (C-2ЈЈ), 132.4 (C-2Ј), 199.9 (C-1) ppm. GC–MS (EI,

70 eV): m/z (%) = 152 (15) [M]⁺, 134 (18) [M – H₂O]⁺, 123 (19)

[M – C₂H₅]⁺, 95 (52) [M – C₄H₉]⁺, 81 (100) [M – C₅H₁₁]⁺. The

spectroscopic data for aldehyde 37 were in full agreement with

those reported in the literature.^[37f]

a colourless oil. [α]²_D⁰= +37.2 (c = 0.60, CHCl ). IR (film): ν =

˜

3

2948, 2891, 1712, 1601, 1484, 1420, 1329, 1280, 1226, 1202, 1164,

1

1130, 1056, 983, 922, 866, 843, 789, 744, 691, 666 cm^–1. H NMR

(CDCl₃, 600 MHz): δ = –0.16 (ddd, J = 9.7, J = 6.7, J = 5.2 Hz, 1

H, 1Ј-H), 0.62 (ddd, J = 9.7, J = 4.8, J = 3.5 Hz, 1 H, 3Ј-H_a), 0.88

(ddd, J = 7.4, J = 6.7, J = 3.5 Hz, 1 H, 3Ј-H_b), 0.99 (t, J = 7.7 Hz,

3 H, 6ЈЈ-H), 1.59 (dddd, J = 9.3, J = 7.4, J = 5.2, J = 4.8 Hz, 1 H,

2Ј-H), 1.91 (q, J = 5.4 Hz, 2 H, 5-H), 2.17 (m_c, 2 H, 5ЈЈ-H), 3.94

(t, J = 5.4 Hz, 4 H, 4-H, 6-H), 5.01 (dd, J = 9.3, J = 15.0 Hz, 1 H,

1ЈЈ-H), 5.11 (dd, J = 10.8, J = 7.4 Hz, 1 H, 4ЈЈ-H), 5.74 (t, J =

11.1, J = 10.8 Hz, 1 H, 3ЈЈ-H), 6.28 (dd, J = 15.0, J = 11.1 Hz, 1

H, 2ЈЈ-H) ppm. ¹³C NMR (CDCl₃, 151 MHz): δ = 8.6 (C-1Ј), 12.9

(C-3Ј), 14.4 (C-6ЈЈ), 20.9 (C-2Ј), 21.0 (C-5ЈЈ), 27.4 (C-5), 61.7 (C-4,

C-6), 123.5 (C-1ЈЈ), 127.8 (C-4ЈЈ), 130.9 (C-3ЈЈ), 136.5 (C-2ЈЈ) ppm.

GC–MS (EI, 70 eV): m/z (%) = 206 (29) [M]⁺, 177 (32) [M –

C₂H₅]⁺, 163 (7) [M – C₃H₇]⁺.

(–)-(1S,2S)-Dictyopterene A (38): nBuLi (1.78 mL of 1.6  solution

in hexane, 2.86 mmol, 2.9 equiv.) was added dropwise through a

cannula to a stirred solution of methyltriphenylphosphonium bro-

mide (1.06 g, 2.96 mmol, 3.0 equiv.) in anhydrous diethyl ether

(10 mL) at 0 °C under N₂. The yellow-orange solution was stirred

for 30 min before aldehyde 37 (0.15 g, 0.99 mmol, 1.0 equiv.) in an-

hydrous diethyl ether (2 mL) was added dropwise through a can-

nula over a period of 5 min. The reaction mixture was stirred over-

night. The mixture was then diluted with n-pentane (5 mL), directly

(1ЈR,2ЈR)-{2Ј-[(E)-Hex-1ЈЈ-enyl]cyclopropyl}methanol (35): Di-

oxaborinane 33 (0.70 g, 3.36 mmol, 1.0 equiv.) was dissolved in an-

hydrous THF (5 mL) at room temp. and chloroiodomethane

3780

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Enantiomerically Pure Vinylcyclopropylboronic Esters

de Meijere, Chem. Rev. 2003, 103, 931–1647; for a review on

stereoselective cyclopropane synthesis, see: k) H. Lebel, J.-F.

Marcoux, C. Molinaro, A. B. Charette, Chem. Rev. 2003, 103,

977–1050.

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filtered through a short pad of silica gel and concentrated under

reduced pressure. The crude product 38 was purified by flash col-

umn chromatography (silica gel, n-pentane) to furnish dictyopter-

ene A (38; 0.12 g, 0.80 mmol, 81%) as a colourless liquid. [α]²_D⁰

=

[7]

[8]

–69.3 (c = 0.40, CHCl₃) [ref.^[19d][α]²_D²= +72.0 (c = 6.74, CHCl₃)

for the (1R,2R) enantiomer]. ¹H NMR (600 MHz, CDCl₃): δ =

0.75–0.84 (m, 2 H, 3Ј-H), 0.87 (t, J = 7.0 Hz, 3 H, 6ЈЈ-H), 1.25–

1.35 (m, 4 H, 4ЈЈ-H, 5ЈЈ-H), 1.36–1.41 (m, 2 H, 1Ј-H, 2Ј-H), 1.95–

2.05 (m, 2 H, 3ЈЈ-H), 4.84 (dd, J = 10.2, J = 2.3 Hz, 1 H, 2-H_a),

4.98 (dd, J = 17.2, J = 2.3 Hz, 1 H, 2-H_b), 5.03 (dd, J = 15.1, J =

6.1 Hz, 1 H, 1ЈЈ-H), 5.36 (ddd, J = 10.2, J = 17.2, J = 6.7 Hz, 1 H,

1-H), 5.46 (dt, J = 15.1, J = 6.9 Hz, 1 H, 2ЈЈ-H) ppm. ¹³C NMR

(151 MHz, CDCl₃): δ = 14.1 (C-6ЈЈ), 14.8 (C-3Ј), 22.3 (C-5ЈЈ), 23.6

(C-2Ј), 24.3 (C-1Ј), 31.8 (C-4ЈЈ), 32.2 (C-3ЈЈ), 111.8 (C-2), 129.2 (C-

2ЈЈ), 131.6 (C-1ЈЈ), 140.9 (C-1) ppm. GC–MS (EI, 70 eV): m/z (%)

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=

150 (100) [M]⁺, 135 (15) [M CH₃]⁺, 122 (24) [M

– –

CH₂=CH₂]⁺, 121 (60) [M – C₂H₅]⁺. The spectroscopic data for

dictyopterene 38 were in full agreement with those reported in the

literature.^[37]

Acknowledgments

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We gratefully acknowledge the Deutsche Forschungsgemeinschaft

(DFG), the Otto-Röhm-Gedächtnisstiftung, the Landesgraduiert-

enförderung Baden Württemberg (grant to E. H.) and Deutscher

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we thank Vera Ophoven and Truc Pham for their support.

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Received: April 15, 2009

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Published Online: June 17, 2009

3782

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Article Doi

Enantiomerically Pure Vinylcyclopropylboronic Esters

DOI: 10.1002/ejoc.200900414

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