The epoxy-Ramberg-Baecklund reaction (ERBR): A sulfone-based method for the synthesis of allylic alcohols

FULL PAPER

DOI: 10.1002/ejoc.200500956

The Epoxy-Ramberg–Bäcklund Reaction (ERBR): A Sulfone-Based Method

for the Synthesis of Allylic Alcohols

Paul Evans,^[a]Paul Johnson,^[a]and Richard J. K. Taylor*^[a]

Keywords: Epoxy-Ramberg–Bäcklund reaction / Allylic alcohols / Vinyl sulfones / Nucleophilic epoxidation

The epoxy-Ramberg–Bäcklund reaction (ERBR) is outlined,

in which α,β-epoxy sulfones are converted into a range of

mono-, di- and tri-substituted allylic alcohols, on treatment

with base. Modification of this method enabled the prepara-

tion of enantio-enriched allylic alcohols following the dia-

stereoselective epoxidation of enantio-enriched vinyl sul-

fones that were accessed efficiently from the chiral pool. The

scope, optimisation and limitations of the ERBR as a method

for the preparation of allylic alcohols are discussed.

Germany, 2006)

three-membered heterocyclic ring (Figure 2) and have de-

scribed preliminary studies in this area.^[18]This process rep-

resents a novel variant of the classic Ramberg–Bäcklund

reaction enabling the synthesis of allylic alcohols. Alkenes

possessing allylic substituents are valuable chemical build-

ing blocks and are substrates for important chemical meth-

odologies. Additionally, as a structural motif they are pres-

ent in a variety of diverse natural products and compounds

of biological importance. The key stage in this reaction

would involve a favoured 3-exo-tet ring opening but pro-

ceeds via a strained 1-hetero-4-thiaspiro[2.2]pentane transi-

tion state. The major advantage of this variant compared

to the traditional Ramberg–Bäcklund rearrangement is that

the alkene formation is accompanied by the introduction of

valuable allylic functionality.

Introduction

The base-mediated transformation of sulfones, substi-

tuted with a leaving group in the α-position, into regiodef-

ined alkenes – the Ramberg–Bäcklund reaction (Figure 1),

is a valuable method for carbon–carbon bond forma-

tion.^[1–6]Although some control in the geometry of the

double bond formed can be achieved, in acyclic examples

mixtures of cis- and trans-alkenes are often formed.^[1–6]

Typically α-chloro and bromo sulfones, preformed^[1–6]or

generated in situ,^[1–9]are employed and mechanistically this

halide leaving group is essential, enabling the rate-determin-

ing episulfone ring-closure process to occur.

Although other common leaving groups, e.g. io-

dide,^{[1–6,10,11]}sulfonate^[1–6,12]and sulfinate^{[1–6,13–17]}esters

have all been used successfully in Ramberg–Bäcklund-type

reactions, not a great deal of research into the use of dif-

ferent leaving groups in this process has been reported.

The successful implementation of this process is de-

scribed herein for the transformation of α,β-epoxy sulfones

We envisaged a new variant of the Ramberg–Bäcklund into a range of allylic alcohols possessing different alkenyl

reaction in which the leaving group is incorporated into a substitution patterns.

Figure 1. The Ramberg–Bäcklund Reaction [X = Cl, Br etc.; B = Base].

Figure 2. The epoxide (X = O), aziridine (X = NR⁵) and episulfide (X = S) variants of the Ramberg–Bäcklund reaction.

[a] Department of Chemistry, University of York,

Heslington, York YO10 5DD, UK

E-mail: rjkt1@york.ac.uk

1740

Eur. J. Org. Chem. 2006, 1740–1754

ERBR: A Sulfone-Based Method for the Synthesis of Allylic Alcohols

FULL PAPER

hoped-for allylic alcohol 5a was formed. Thus, the treat-

ment of 4a with 2 equiv. of LiOtBu in DMSO (Entry 1)

initiated a relatively rapid reaction after which 5a was iso-

lated in 82% yield. However, no double-bond discrimi-

nation was observed and a 50:50 mixture of isomers was

Results and Discussion

The epoxides required for this study were prepared using

the nucleophilic epoxidation of the corresponding vinyl sul-

fones (α,β-unsaturated sulfones) via the reliable tert-butyl

hydroperoxide (TBHP)/nBuLi procedure reported by Meth-

Cohn et al.^[19,20]In turn, the vinyl sulfones were prepared

following several established protocols.^[21,22]Generally,

these routes may be broadly grouped into 2 sets; either (a)

elimination of β-hydroxy/halo sulfones; or (b) via a

Horner–Wadsworth–Emmons reaction between a sulfonyl

phosphonate and various aldehydes; this latter method has

the advantage of being more convergent (see below).

Initial investigations of the feasibility of the proposed

ERBR process involved a study of the behaviour of the ep-

oxide 4a under basic conditions. This compound was se-

lected because of a combination of its relatively acidic α-

benzylic protons and because it was readily prepared by

nucleophilic epoxidation of the vinyl sulfone 2a, which was

prepared in turn either (a) by a three-step route from benzyl

mercaptan and styrene oxide (1) in 44% overall yield; or (b)

from benzaldehyde and (benzylsulfonylmethyl)phosphonate

3 in 70% yield. During these optimization studies it became

clear that under a variety of basic conditions (Figure 3, En-

tries 1–5) the desired process was indeed realised, and the

1

evident on inspection of the H NMR spectrum of the un-

purified product. Amide bases in THF were also investi-

gated; LHMDS (Entry 2) in particular was found to effec-

tively generate 5a in yields up to 63% with a selectivity for

the trans-alkene (E:Z, 82:18). However, the yields obtained

with this base were found to fluctuate. This was in part due

to loss of some material from accompanying O-silylation of

the allylic alcohol 5a by the base. Other amide bases includ-

ing LDA (Entry 3), LTMP (Entry 4) and Schlosser’s base^[23]

(Entry 5) all gave the desired product albeit in lower yield

than LHMDS, or LiOtBu in DMSO. It became apparent

that the use of 2 equiv. of base was optimal, possibly be-

cause of the formation of the anion, necessary to form the

episulfone, in equilibrium amounts.

Interesting results were obtained when the more standard

Ramberg–Bäcklund conditions were employed.^[1–6]For ex-

ample, KOtBu (2 equiv.) in THF (Entry 6) gave the ketone

6a in good yield. This product apparently arises from an

initially successful ERBR affording 5a, and then this species

participates in a precedented allylic anion/enolate isomeris-

Figure 3. Optimisation studies in the ERBR of benzylic α,β-epoxy sulfone 4a.

Eur. J. Org. Chem. 2006, 1740–1754

www.eurjoc.org

1741

P. Evans, P. Johnson, R. J. K. Taylor

FULL PAPER

ation process.^[24]Support for this hypothesis was obtained tivity. Epoxidation (LiO₂tBu) then gave the corresponding

when the ERBR product 5a was treated with 1 equiv. of epoxides 4b–g. Interestingly, when the epoxidation reaction

KOtBu in THF, which gave the ketone 6a in 97% yield after was attempted with vinyl sulfones prepared from electron-

2 hours. Surprisingly, the identical experiment using Li- rich aromatic aldehydes (for example: 2-methoxybenzalde-

OtBu did not give this rearrangement – nor did the formally hyde 2h and furfuraldehyde 2i) none of the desired epoxide

more basic amides. Use of LiOtBu (2 equiv.) in THF (Entry was obtained. In the case of 2h the vinyl sulfone was reco-

7) gave the dimer 7 as the sole isolable product in high and vered, whereas attempted epoxidation of 2i only resulted

reproducible yield as a 1:1 mixture of diastereomers. Fol- in unidentified decomposition products. These observations

lowing this reaction only the E,E-allylic ethers were de- apparently reflect the diminished electrophilicity of the β-

tected, which is perhaps indicative of a delocalised π-allylic carbon, and/or that the so-formed epoxides are intrinsically

intermediate species. The likelihood is that 7 was formed unstable.

during the work-up procedure as it was found that after

partitioning 7 between 1  HCl and dichloromethane for LiOtBu, THF, 25 °C) to the epoxides 4b–g gave the allylic

1 hour a 1:1 mixture of 7 and 5a was observed. alcohols 5b–g in moderate to good yield. In these instances,

Application of the optimised ERBR conditions (2 equiv.

In summary, these initial studies indicated that the pro- the ERBR processes were found to be generally highly se-

posed reaction was indeed viable, but that the presence of lective for the E-isomer (E:Z, Ͼ95:5) and none of the allylic

the β-phenyl substituent appears to complicate the forma- ether dimer 7 (see Figure 3) was encountered. It seems likely

tion of the desired allylic alcohol.

that the electron-withdrawing properties of the β-aryl sub-

In order to probe these effects further, we used the stituents shown in Figure 5 serve to disfavour the allylic

Horner–Wadsworth–Emmons reaction^[25–27]to obtain vari- carbocation implicated in the formation of 7.

ation of the β-substituent whilst maintaining the benzylic

sulfonyl moiety. Two alternative methods for the synthesis with LiOtBu this gave a mixture of 5e (26%, E:Z, 55:45)

of the phosphonate 3 are shown in Figure 4.^[28,29]

and the ketone 6e (28%), which were separated by flash

One anomaly is the 2-pyridyl epoxide 4e: when treated

Treatment of 3 with sodium hydride, followed by ad- column chromatography. Based on the previous observation

dition of a variety of aromatic aldehydes gave the requisite (Figure 3) it seems reasonable to assume that 6e arises

vinyl sulfones 2b–i in both high yield and trans-stereoselec- through the allylic anion/enolate isomerisation, facilitated

Figure 5. ERBR of benzylic α,β-epoxy aryl sulfones 4b–g.

Figure 4. Synthesis of sulfonyl phosphonate 3 and its use in the preparation of aryl α,β-epoxy sulfones 4b–g.

1742

www.eurjoc.org

Eur. J. Org. Chem. 2006, 1740–1754

ERBR: A Sulfone-Based Method for the Synthesis of Allylic Alcohols

FULL PAPER

in this instance by the 2-pyridyl heterocycle. Furthermore, tuted allylic alcohol 5k in 92% yield as one detectable

the mixture of double-bond isomers encountered, in con- double-bond isomer. The trans-alkene geometry was as-

trast to the other cases in this series, implies that this tauto- signed on the basis of chemical shift values reported in the

merisation may occur more readily on the trans-isomer of literature^[30]and nOe studies. Similarly, the phenyl deriva-

5e.

tive 4l gave the trisubstituted alkene trans-5l selectively.

In order to further demonstrate the scope and limitations These examples clearly demonstrate that the particular

of the ERBR as a means of preparing allylic alcohols with mechanistic features of the Ramberg–Bäcklund reaction fa-

different alkenyl substitution patterns, the α,β-epoxy sul- cilitate what is formally an S_N2-type process at a tertiary

fones 4j–m were prepared by a four-step sequence beginning carbon atom to occur during the episulfone formation (see

from the ring opening of an epoxide using benzyl mercap- Figure 2).

tan (8) (Figure 6). It was found that during the preparation

However, in the case of the epoxide 4m, which does not

of the cis-epoxide 4k the one-pot mesylation–elimination possess an activated α-sulfonyl proton, none of the desired

procedure gave a mixture of cis- and trans-vinyl sulfones alcohol 5m was detected under the standard LiOtBu ERBR

(Z:E, 66:33). However, the modification of this process fol- conditions. Use of the stronger base LHMDS did generate

lowing the preparation and isolation of the mesylate and the hoped-for product, albeit in low yield.

subsequent treatment with KOtBu gave the trans-vinyl sul-

If the ERBR was to constitute a synthetically useful

fone selectively (see preparation of 4m). This stereoselective method for the preparation of allylic alcohols, it was felt

elimination was also observed for the benzylic analogue, en- that additional structural functionality would need to be

abling the preparation of the trans-epoxide 4k (not shown). compatible with the basic reaction conditions. To this end,

When the α-protons to the sulfonyl group were benzylic, the silyl-protected epoxide 4o and its alcohol precursor 4n

such as in 4j–l, the ERBR proceeded smoothly and none of were prepared and their behaviour in the ERBR evaluated.

the by-products previously ascribed to the β-phenyl group The epoxy sulfones 4n and 4o were prepared from 2n as

were detected. For example, treatment of cis-4k with Li- shown in Figure 7 following the modification of a literature

OtBu (2 equiv. in THF) gave the corresponding trisubsti- report.^[31]On treatment with LiOtBu, compound 4n gave

Figure 6. Preparation and ERBR of α,β-epoxy sulfones 4j–m (^[a]: overall yields for four steps).

Figure 7. Alcohols and silyl ethers in the ERBR.

Eur. J. Org. Chem. 2006, 1740–1754

www.eurjoc.org

1743

P. Evans, P. Johnson, R. J. K. Taylor

FULL PAPER

the diol 5n in 50% yield (E:Z, 75:25), whereas, under iden- alcohol 5r and only the decomposition of the starting mate-

tical conditions, 4o gave 5o in 79% yield (E:Z, 93:7). The rial was detected.

stereochemical outcome of these processes are noteworthy;

In order to further investigate how structural changes to

presumably the increased steric bulk of the silyl protecting the benzylic position effect the ERBR the vinyl sulfone 2a

group explains the increased stereoselectivity observed. was converted into the α-methyl vinyl sulfone 2s. Treatment

TBAF removal of the TBS group in 5o proceeds in high of 2s with LiO₂tBu gave the epoxide 4s as an undetermined

yield with no alteration of double-bond stereochemistry. mixture of diastereomers (de 33%), which in turn gave the

One plausible explanation for the lower yield observed for allylic alcohol on treatment with LiOtBu (see Figure 9). It

the unprotected primary alcohol could be that the base de- proved necessary to convert this allylic alcohol into the ace-

protonates the primary alcohol leading to competing tate 15 in order to facilitate the purification of the product

Payne-type rearrangement–sulfinate elimination.^[20,32]

from remaining starting material. The overall yield of the

Moving from the synthesis of secondary allylic alcohols; trisubstituted allylic acetate was 48%, and in this instance

the synthesis of primary alcohols from terminal epoxides equal amounts of cis- and trans-alkenes were evident by

was investigated. Under identical conditions to those de- proton NMR spectroscopy. None of the dimeric allylic

scribed above, 4p (prepared in four steps from benzyl bro- ether species (see Figure 3) was encountered in this exam-

mide 12) gave cinnamyl alcohol (5p) as a mixture of isomers ple. Following a slightly different approach, the α-methyl

(E:Z, 65:35) in 35% yield. The related epoxide 4q was pre- epoxide 4t was prepared as a 1:1 mixture of diastereomers

pared from cinnamyl chloride (13). In this case, the epoxid- from trans-4k following lithiation and quenching of the re-

ation of the intermediate vinyl sulfone which results from 13 sultant anion with MeI.^[33]Treatment of this mixture with

was problematic, and only a 19% yield of 4q was observed. LiOtBu (2 equiv.) gave the tetrasubstituted allylic alcohol,

However, 4q participated in the ERBR and gave the corre- which was converted into the acetate 16 to facilitate the

sponding conjugated alcohol 5q in 79% yield. Presumably chromatographic separation from the remaining starting

this improvement compared to 4p, stems from an increased material 4t. The isolated yield was 19% as an undetermined

acidity of the α-sulfonyl protons which is, paradoxically the 90:10 mixture of stereoisomers. The lower yields encoun-

likely explanation for the difficulties associated with the tered in these examples indicate that the ERBR process is

epoxidation. Proton NMR spectroscopy indicated that the sensitive to substitution at the carbon atom, which is con-

E-styryl double bond was retained, and that the double verted into a carbanion during the reaction. Presumably

bond formed during the Ramberg–Bäcklund process was this observation is explained by increased steric hindrance

a mixture of isomers (E,E:E,Z; 60:40). The presence of a in both these cases.

substituent which increases the sulfonyl acidity is evidently

Currently there is not a generally applicable method

important to the ERBR process: this point is clearly dem- available for the enantioselective epoxidation of prochiral

onstrated by the last example given in Figure 8. In this in- vinyl sulfones.^[34]Therefore, a route was designed enabling

stance, treatment of 4r, prepared from the iodide 14, with the synthesis of homochiral allylic alcohols using a sub-

LiOtBu, or the more basic LHMDS fails to generate the strate-controlled diastereoselective epoxidation. The vinyl

Figure 8. ERBR of terminal α,β-epoxy sulfones 4p and 4q (^[a]: overall yields for four steps).

Figure 9. αЈ-Methylbenzylic α,β-epoxy sulfones 4s and 4t in the ERBR.

1744

www.eurjoc.org

Eur. J. Org. Chem. 2006, 1740–1754

ERBR: A Sulfone-Based Method for the Synthesis of Allylic Alcohols

FULL PAPER

sulfone 2u, possessing a γ-oxygen atom was prepared fol- 4u in both good yield and diastereoselectivity (80% de),

lowing the Horner–Wadsworth–Emmons reaction of (R)- from which the anti-diastereomer was readily obtained fol-

isopropylideneglyceraldehyde, obtained by a Swern oxi- lowing a single recrystallisation. The ERBR of dia-

dation and the phosphonate anion from 3. This reaction stereomerically pure 4u (LiOtBu, 2 equiv.) gave the allylic

furnished a mixture of geometric isomers (E:Z, 85:15) in alcohol 5u in 69% yield with no attendant loss in dia-

good yield, which were separable by careful flash column stereomeric purity. The geometric isomers (E:Z, 92:8) were

chromatography. There is some literature precedent for the separated by recrystallisation and X-ray crystal structural

diastereoselective epoxidation of similar vinyl sul- data (see Figure 11)^[39]demonstrated the anti-relationship

fones;^[35–38]depending on the desired isomer, these reports between the 2- and 3-oxygenated asymmetric centres, thus

suggest the use of bulky oxidants with non-oxophilic coun- confirming the anti-selective, sterically controlled epoxid-

terions (i.e. Na⁺or K⁺),^[35,36]or manipulation of the γ-oxy- ation of 2u. Removal of the isopropylidene protecting group

gen substituent group.^[37,38]Thus, the epoxidation of 2u gave the triol, anti-5v, whose data corresponded to those

with Meth-Cohn conditions (LiO₂tBu) gave the epoxide 4u reported.^[40]By exploiting the balance between steric en-

in good yield but poor diastereoselectivity (anti:syn, 45:55) cumbrance and counterion coordination, the complemen-

(see Figure 10). It is believed that in this case the chelation tary diastereomeric triol, syn-5v was synthesised. Thus, ini-

of the Li⁺counterion to the γ-oxygen atom serves to com- tial removal of the isopropylidene protecting group and

bat the steric repulsion of the approaching oxidant. How- epoxidation (LiO₂tBu) of the diol 2v, now under coordina-

ever, treatment of 2u with the sodium salt of Ph₃CO₂H gave tion control, gave predominantly the syn-epoxide 4v (84%

Figure 10. Application of ERBR for the preparation of optically active allylic alcohols.

Figure 11. ORTEP representation of anti-5u.

Eur. J. Org. Chem. 2006, 1740–1754

www.eurjoc.org

1745

P. Evans, P. Johnson, R. J. K. Taylor

FULL PAPER

ual protonated solvent or TMS; all J values are in Hz. Melting

points were recorded with a Electrothermal IA9000 Digital Melting

Point Apparatus and were uncorrected. Optical rotation values

were recorded with a JASCO model DIP-370 digital polarimeter at

20 °C using sodium D line; 589 nm radiation and with units of

10^–1degcm²g^–1.

de). Following purification by recrystallisation the Ram-

berg–Bäcklund reaction under standard conditions gave

syn-5v in low yield. The mixture of geometric isomers

proved separable by preparative TLC and comparison of

spectral and physical data of the major diastereomeric

products, syn-5v and anti-5v, demonstrated their non-equiv-

alence.

Representative Procedures for the Synthesis of Vinyl Sulfones

In summary, the examples discussed demonstrate, that

the ERBR is indeed a synthetically viable process, albeit

with some limitations. At this stage of optimisation, in or-

der to achieve an efficient conversion, an acidified α-sulfo-

nyl proton is important (represented by the benzylic sul-

fones used in this study). The compounds studied also indi-

cate that the ERBR is sensitive to substitution patterns

around the central α,β-epoxy sulfonyl moiety. For example,

it is evident that 1,2-di- and 1,1,2-trisubstituted α,β-epoxy

sulfones generate their corresponding alcohols in higher

yield than their 1-monosubstituted counterparts; addition-

ally substitution of the αЈ-position diminishes the yields of

ERBR products. Exploration of future applications of this

novel technology, particularly in the stereocontrolled syn-

thesis of natural products, is underway in our laboratories.

(a) trans-1-Benzylsulfonyl-2-phenylethene (2a): A dispersion of so-

dium hydride (60% w/w) in mineral oil (0.40 g, 10.0 mmol, 1 equiv.)

was added to a solution of diethyl benzylsulfonylmethylphos-

phonate (3) – prepared as described^[43–45](3.06 g, 10.0 mmol,

1 equiv.) in dry THF (100 mL) under nitrogen at 0 °C. After stir-

ring this mixture for 15 min, benzaldehyde (1.06 g, 1.0 mL,

10.0 mmol, 1 equiv.) was added, and the mixture warmed to room

temperature and stirred for a further 1.5 h. Upon disappearance

of the starting materials as detected by TLC , saturated aqueous

ammonium chloride solution (100 mL) was added to the mixture,

which was then extracted into EtOAc (100 mL), washed (H₂O,

50 mL) and dried with sodium sulfate, followed by filtration and

solvent removal in vacuo yielded the crude product, which was fur-

ther purified by column chromatography (silica gel, eluted with PE/

EtOAc, 4:1) to give 2a (1.81 g, 70%) as a colourless, crystalline

solid, m.p. 142–143 °C [ref.^[46]m.p. 145–146 °C] with consistent

spectroscopic data.

(b) trans-1-Benzylsulfonyl-2-(3-nitrophenyl)ethene (2b): Colourless

solid; m.p. 186–187 °C [ref.^[47]m.p. 184–186 °C] with consistent

spectroscopic data.

Experimental Section

General Remarks: The reagents described in the following section

were purchased from commercial sources and were used directly.

THF was dried with sodium and benzophenone and was distilled

prior to use. Similarly, dichloromethane was distilled from over cal-

cium hydride. PE refers to petroleum ether 40–60 °C. Potassium

tert-butoxide and lithium tert-butoxide were used both as solid and

as solutions in THF as purchased. LDA and LTMP were generated

from dry diisopropylamine and tetramethylpiperidine respectively,

via treatment of a THF solution with one equivalent of nBuLi at

0 °C. All procedures requiring inert atmospheres were performed

in dry glassware under an atmosphere of nitrogen. A dry tert-butyl

hydroperoxide (TBHP) solution in toluene was prepared from 80%

aqueous TBHP by extraction with toluene followed by heating the

resultant organic layer at reflux in a Dean–Stark apparatus. The

resultant dry TBHP solution was stored under nitrogen at 0 °C

(c) trans-1-Benzylsulfonyl-2-(4-fluorophenyl)ethene (2c): Colourless

solid; m.p. 170.5–171.5 °C (EtOAc/PE) [ref.^[47]m.p. 172–173 °C]

with consistent spectroscopic data.

(d) trans-1-Benzylsulfonyl-2-(3-pyridyl)ethene (2d): Colourless solid;

m.p. 145–147 °C (EtOAc). R_f= 0.10 (PE/EtOAc, 4:1). IR (nujol):

ν = 1614, 1568, 1313, 1290, 1124 cm^–1. ¹H NMR (270.1 MHz,

˜

CDCl₃): δ = 4.34 (s, 2 H), 6.80 (d, J = 15.5 Hz, 1 H), 7.31–7.43 (m,

7 H), 7.71 (dt, J = 2.0, 8.0 Hz, 1 H), 8.63–8.65 (m, 2 H) ppm. ¹³C

NMR (67.9 MHz, CDCl₃): δ = 61.7, 123.8, 126.1, 127.7, 128.1,

128.9, 129.0, 130.8, 134.7, 141.9, 149.8, 151.9 ppm. MS (EI): m/z

(%) = 259 (1) [M⁺], 91 (100) [C₇H₇⁺]. HRMS: C₁₄H₁₃NO₂S calcd.

259.066701; found 259.066575.

(e) trans-1-Benzylsulfonyl-2-(2-pyridyl)ethene (2e): Colourless solid;

1

and its concentration was calculated from H NMR spectroscopic

m.p. 119–119.5 °C (EtOAc). R_f= 0.10 (PE/EtOAc, 4:1). IR (nujol):

analysis.^[41,42]TLC analysis was performed using Merck 5554 alu-

minium backed plates. Compounds were visualised using UV

(254 nm) light, iodine, vanillin or a basic aqueous solution of po-

tassium permanganate, where appropriate. Flash column

chromatography was performed using ICN 33–64 silica under bel-

lows pressure. Low and high field resolution electron-ionisation

(EI) and chemical-ionisation (CI) mass spectrometry were per-

formed with a Fisons Analytical (VG) autospec machine. High res-

1

ν = 1626, 1579, 1304, 1146, 1113. H NMR (270.1 MHz, CDCl ):

˜

3

δ = 4.16 (s, 2 H), 7.10–7.21 (m, 9 H), 7.53 (dt, J = 2.0, 7.5 Hz, 1

H), 8.44–8.46 (m, 1 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ =

61.4, 125.1, 125.4, 127.6, 128.3, 128.7, 128.8, 130.9, 137.0, 143.6,

150.2, 150.5 ppm. MS (CI): m/z (%) = 260 (6) [MH⁺], 91 (100)

[C₇H₇⁺]. HRMS: C₁₄H₁₄NO₂S calcd. 260.074526; found

260.074524.

(f) trans-1-Benzylsulfonyl-2-(2-naphthyl)ethene (2f): Colourless so-

lid; m.p. 161–162 °C (EtOAc). R_f= 0.35 (PE/EtOAc, 4:1). IR (nu-

olution molecular ions described are within

5 ppm of the re-

quired molecular mass. The micro-analytical data quoted are

within the margin of error, 0.50%, and all data is reported to

two decimal places. Infra-red spectroscopy was carried out using a

ATI Mattson Genesis FT-IR spectrometer. The samples were either

recorded between NaCl plates as neat films, nujol mulls or in solu-

tion (CDCl₃, or CHCl₃). The ¹H and ¹³C NMR spectra were re-

corded with a Jeol EX270 spectrometer at 270.1 and 67.9 MHz,

respectively, at 300.1 MHz and 75.5 MHz with a Bruker AC300

jol): ν = 1606, 1311, 1292, 1115cm^–1. ¹H NMR (270.1 MHz,

˜

CDCl₃): δ = 4.36 (s, 2 H), 6.80 (d, J = 15.5 Hz, 1 H), 7.39–7.41

(m, 5 H), 7.49–7.61 (m, 4 H), 7.84–7.88 (m, 4 H) ppm. ¹³C NMR

(67.9 MHz, CDCl₃): δ = 62.4, 123.7, 124.3, 127.5, 128.3, 128.4,

128.6, 129.2, 129.3, 129.4, 129.5, 130.1, 131.4, 131.5, 133.55, 135.0,

146.1 ppm. MS (EI): m/z (%) = 308 (15) [M⁺], 91 (100) [C₇H₇⁺].

HRMS: C₁₉H₁₆O₂S calcd. 308.087102; found 308.087682.

spectrometer and at 500.1 MHz and 125.8 MHz with a Bruker (g) trans-1-Benzylsulfonyl-2-(4-phenyl)phenylethene (2g): Colourless

AMX500 spectrometer. The solutions were prepared in suitable

deuterated solvents and referencing was accomplished using resid-

solid; m.p. 194–195.5 °C. R = 0.30 (PE/EtOAc, 2:1). IR (nujol): ν

= 1622, 1294, 1157, 1119. H NMR (270.1 MHz, CDCl₃): δ = 4.35

˜

f

1

1746

www.eurjoc.org

Eur. J. Org. Chem. 2006, 1740–1754

ERBR: A Sulfone-Based Method for the Synthesis of Allylic Alcohols

FULL PAPER

(s, 2 H), 6.74 (d, J = 15.5 Hz, 1 H), 7.40–7.51 (m, 11 H), 7.60–7.66 Representative Procedure for the Synthesis of α,β-Epoxy Sulfones.

(m, 4 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 61.9, 123.5, Meth-Cohn Epoxidation

127.1, 127.7, 128.05, 128.1, 128.9, 129.0, 129.05, 131.0, 131.05,

(a) trans-1-Benzylsulfonyl-2-phenyloxirane (4a): n-Butyllithium

139.7, 144.1, 145.1. MS (EI): m/z (%) = 334 (9) [M⁺], 91 (100)

(1.10 mmol, 0.7 mL of a 1.6  solution in hexanes, 1.1 equiv.) was

[C₇H₇⁺]. HRMS: C₂₁H₁₈O₂S calcd. 334.102752; found 334.102573.

added to a solution of dry TBHP (1.50 mmol, 0.6 mL of a 2.63 

solution in toluene, 1.5 equiv.) in THF (20 mL) at –78 °C under

nitrogen. This solution was stirred for 15 min, before warming to –

15 °C. A solution of the vinyl sulfone 2a (258 mg, 1.00 mmol,

1 equiv.) in dry THF (5 mL) was then added. Stirring was contin-

ued for 2 h at –10 to –20 °C, after which time the starting sulfone

was judged, by TLC analysis, to be no longer present. Saturated

aqueous sodium sulfite (50 mL) was added, and the resultant mix-

ture extracted into ethyl acetate (2×100 mL). The combined or-

ganic extracts were dried with sodium sulfate. Filtration, concentra-

tion in vacuo and column chromatography (eluting with PE/

EtOAc, 3:1) gave 4a (192 mg, 70%) as a colourless crystalline solid.

(h) trans-1-Benzylsulfonyl-2-(2-methoxy)phenylethene (2h): Colour-

less solid; m.p. 94–95 °C. R = 0.15 (PE/EtOAc, 4:1). IR (nujol): ν

˜

f

1

= 1597, 1296, 1250, 1111. H NMR (270.1 MHz, CDCl₃): δ = 3.84

(s, 3 H), 4.31 (s, 2 H), 6.91–6.99 (m, 3 H), 7.30–7.43 (m, 7 H), 7.61

(d, J = 15.5 Hz, 1 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ =

55.3, 61.8, 111.2, 120.7, 120.9, 124.7, 128.2, 128.6, 130.8, 130.9,

132.5, 141.2, 158.7 ppm. MS (EI): m/z (%) = 288 (6) [M⁺], 91 (100)

[C₇H₇⁺]. HRMS: C₁₆H₁₆O₃S calcd. 288.082016; found 288.081964.

C₁₆H₁₆O₃S (288.36): calcd. C 66.64, H 5.59; found C 66.66, H 5.40.

(i) trans-1-Benzylsulfonyl-2-(2-furyl)ethene (2i): Colourless solid;

m.p. 130–132 °C. R = 0.15 (PE/EtOAc, 4:1). IR (nujol): ν = 1628,

˜

f

M.p. 145–146 °C. R = 0.30 (PE/EtOAc, 3:1). IR (nujol): ν = 1315,

˜

f

1308, 1257, 1115. ¹H NMR (270.1 MHz, CDCl₃): δ = 4.30 (s, 2 H),

6.48 (dd, J = 2.0, 3.5 Hz, 1 H), 6.60 (d, J = 15.0 Hz, 1 H), 6.64 (d,

J = 3.5 Hz, 1 H), 7.17 (d, J = 15.0 Hz, 1 H), 7.35–7.39 (m, 5 H),

7.50–7.51 (m, 1 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 61.8,

112.5, 117.2, 121.0, 128.0, 128.7, 130.9, 131.5, 145.8, 148.4 ppm.

MS (CI): m/z (%) = 266 (100) [MNH₄⁺]. HRMS: C₁₃H₁₆NO₃S

calcd. 266.085090; found 266.085237.

1140, 901, 741, 692cm^–1. H NMR (270.1 MHz, CDCl₃): δ = 3.93

1

(d, J = 1.5 Hz, 1 H), 4.23 (d, J = 14.0 Hz, 1 H), 4.39 (d, J =

14.0 Hz, 1 H), 4.43 (d, J = 1.5 Hz, 1 H), 7.12–7.43 (m, 10 H) ppm.

¹³C NMR (67.9 MHz, CDCl₃): δ = 56.8, 58.1, 67.6, 126.1, 126.5,

128.8, 129.2, 129.3, 129.6, 130.9, 132.4 ppm. MS (CI): m/z (%) =

292 (100) [MNH₄⁺], 276 (7) [MH⁺], 228 (10), 138 (31), 120 (10), 108

(31), 91 (16). HRMS: C₁₅H₁₄O₃S calcd. 292.1007; found 292.1012.

C₁₅H₁₄O₃S (274.33): calcd. C 65.67, H 5.11, S 11.68; found C 65.50,

H 5.13, S 11.68.

(j) 2-Benzylsulfanyl-1-phenylethan-1-ol^[48,49]and Its Regioisomer 2-

Benzylsulfanyl-2-phenylethan-1-ol:^[50]These compounds were pre-

pared from styrene oxide (1) and benzyl mercaptan (8) according

to the procedure described.

(b) trans-1-Benzylsulfonyl-2-(3-nitrophenyl)oxirane (4b): Colourless

solid; m.p. 125–126 °C. R = 0.45 (PE/EtOAc, 1:1). IR (nujol): ν =

˜

f

1535, 1352, 1315, 1140, 933, 899cm^–1. ¹H NMR (270.1 MHz,

CDCl₃): δ = 4.05 (d, J = 1.5 Hz, 1 H), 4.37 (d, J = 14.0 Hz, 1 H),

4.50 (d, J = 14.0 Hz, 1 H), 4.60 (d, J = 1.5 Hz, 1 H), 7.44–7.64 (m,

7 H), 8.06–8.08 (m, 1 H), 8.23 (dt, J = 2.0, 7.5 Hz, 1 H) ppm. ¹³C

NMR (67.9 MHz, CDCl₃): δ = 55.5, 58.3, 67.6, 126.2, 129.3, 129.5,

130.0, 130.9, 132.3, 134.9, 148.5 ppm. MS (CI): m/z (%) = 337

(100) [MNH₄⁺]. HRMS: C₁₅H₁₇N₂O₅S calcd. 337.085819; found

337.085168.

(k) 2-Benzylsulfonyl-1-phenylethan-1-ol: 2-Benzylsulfanyl-1-pheny-

lethan-1-ol (10.05 g, 41.13 mmol, 1 equiv.) in glacial acetic acid

(250 mL) was treated portionwise at room temperature with

NaBO₃·4H₂O (20.12 g, 130.77 mmol, 3.2 equiv.) and stirred for

12 h. The solvent was removed under reduced pressure and the resi-

due was taken up in H₂O (100 mL) and partitioned into EtOAc

(100 mL). The resultant aqueous layer was then extracted with

EtOAc (3×100 mL); the combined organic extracts were washed

with NaHCO₃(100 mL), then H₂O (100 mL) and finally brine

(100 mL) followed by solvent removal in vacuo to afford the crude

sulfone. Recrystallisation from boiling ethanol afforded the title

compound (10.89 g, 96%) as a colourless crystalline solid; m.p.

(c) trans-1-Benzylsulfonyl-2-(4-fluorophenyl)oxirane (4c): Colourless

viscous oil. R = 0.30 (PE/EtOAc, 4:1). IR (nujol): ν = 1317, 1238,

˜

f

1142, 906 cm^–1. ¹H NMR (270.1 MHz, CDCl₃): δ = 3.89 (d, J =

1.5 Hz, 1 H), 4.24 (d, J = 14.0 Hz, 1 H), 4.40 (d, J = 14.0 Hz, 1

H), 4.42 (d, J = 1.5 Hz, 1 H), 6.94–7.01 (m, 2 H), 7.11–7.19 (m, 2

H), 7.35–7.44 (m, 5 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ =

56.3, 58.1, 67.5, 116.0 (d, J = 20.0 Hz), 126.5, 128.0, 128.1 (d, J =

12.0 Hz), 129.2, 129.3, 131.0, 159.9 (d, J = 250.0 Hz) ppm. MS

(CI): m/z (%) = 310 (100) [MNH₄⁺]. HRMS: C₁₅H₁₇FNO₃S calcd.

310.091319; found 310.091713.

181–182 °C (EtOH). R = 0.05 (PE/EtOAc, 1:1). IR (nujol): ν =

˜

f

3483, 1377, 1175cm^–1. ¹H NMR (270.1 MHz, [D₆]DMSO): δ = 3.19

(dd, J = 2.5, 14.5 Hz, 1 H), 3.48 (dd, J = 10.0, 14.5 Hz, 1 H), 4.33

(d, J = 13.5 Hz, 1 H), 4.52 (d, J = 13.5 Hz, 1 H), 5.12–5.17 (m, 1

H), 7.28–7.44 (m, 10 H) ppm. ¹³C NMR (67.9 MHz, [D₆]DMSO):

δ = 59.0, 59.9, 67.8, 126.0, 127.6, 128.5, 128.7, 131.3, 143.3 ppm.

MS (EI): m/z (%) = 276 (1) [M⁺], 91 (100) [Bn⁺]. HRMS:

C₁₅H₁₆O₃S calcd. 276.0820; found 276.0822. C₁₅H₁₆O₃S (276.35):

calcd. C 65.19, H 5.84, S 11.60; found C 65.13, H 5.80, S 11.70.

(d) trans-1-Benzylsulfonyl-2-(3-pyridyl)oxirane (4d): Colourless vis-

cous oil. R = 0.30 (PE/EtOAc, 1:1). IR (nujol): ν = 1319, 1144,

˜

f

906, 829 cm^–1. ¹H NMR (270.1 MHz, CDCl₃): δ = 4.04 (d, J =

1.5 Hz, 1 H), 4.34 (d, J = 14.0 Hz, 1 H), 4.49 (d, J = 14.0 Hz, 1

H), 4.53 (d, J = 1.5 Hz, 1 H), 7.30 (dd, J = 5.0, 8.0 Hz, 1 H), 7.43–

7.54 (m, 6 H), 8.51 (d, J = 1.5 Hz, 1 H), 8.61 (dd, J = 1.5, 5.0 Hz,

1 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 54.9, 58.3, 67.3,

123.5, 126.3, 128.5, 129.3, 129.4, 130.9, 133.7, 147.9, 150.8 ppm.

MS (CI): m/z (%) = 276 (6) [MH⁺]. HRMS: C₁₄H₁₄NO₃S calcd.

276.069440; found 276.069416.

(l) trans-1-Benzylsulfonyl-2-phenylethene (2a): 2-Benzylsulfonyl-1-

phenylethan-1-ol (1.01 g, 3.65 mmol, 1 equiv.) in dry pyridine

(50 mL) was treated with MsCl (0.45 mL, 5.70 mmol, 1.6 equiv.) at

0 °C. The solution was warmed to room temperature and stirring

was continued for 12 h. The bulk of the pyridine was removed un-

der reduced pressure and the residue was taken up in EtOAc

(50 mL). Partitioning for 0.25 h with CuSO₄(5%, 100 mL) fol-

lowed by extraction with EtOAc (3×50 mL) and washing of the

combined organic layers successively with CuSO₄(5%, 25 mL),

H₂O (50 mL), brine (50 mL) and drying with MgSO₄gave, on fil-

tration followed by solvent removal in vacuo, the crude vinyl sul-

fone. Recrystallisation from EtOAc afforded 2a (0.71 g, 74%) as a

colourless crystalline solid with consistent spectroscopic data.^[46]

(e) trans-1-Benzylsulfonyl-2-(2-pyridyl)oxirane (4e): Colourless vis-

cous oil. R = 0.30 (PE/EtOAc, 1:1). IR (nujol): ν = 1325, 1146,

˜

f

1124, 916, 773 cm^–1. H NMR (270.1 MHz, CDCl₃): δ = 4.28 (d,

1

J = 14.0 Hz, 1 H), 4.41 (d, J = 14.0 Hz, 1 H), 4.45 (d, J = 1.5 Hz,

1 H), 4.50 (d, J = 1.5 Hz, 1 H), 7.20–7.45 (m, 7 H), 7.65 (dt, J =

2.0, 8.0 Hz, 1 H), 8.50 (ddd, J = 1.0, 2.0, 4.5 Hz, 1 H) ppm. ¹³C

Eur. J. Org. Chem. 2006, 1740–1754

www.eurjoc.org

1747

P. Evans, P. Johnson, R. J. K. Taylor

FULL PAPER

NMR (67.9 MHz, CDCl₃): δ = 56.3, 58.2, 66.5, 123.2, 124.4, 126.3,

and the mixture was extracted with EtOAc (3×50 mL). The com-

129.2, 129.25, 131.0, 136.9, 151.3 ppm. MS (CI): m/z (%) = 276 bined organic layers were washed with brine (20 mL) and dried

(100) [MH⁺]. HRMS: C₁₄H₁₄NO₃S calcd. 276.069440; found

276.069647.

with Na₂SO₄. Purification of the crude residue obtained after fil-

tration and solvent removal in vacuo by column chromatography

(PE/EtOAc, 19:1) furnished the allylic ether 7 (148 mg, 81%) as an

inseparable mixture (1:1) of diastereomers. R_f= 0.20 (PE/EtOAc,

(f) trans-1-Benzylsulfonyl-2-(2-naphthyl)oxirane (4f): Colourless vis-

cous oil. R = 0.35 (PE/EtOAc, 4:1). IR (nujol): ν = 1315, 1138,

˜

f

19:1). IR (CDCl ): ν = 3084, 3061, 3028, 2956, 2908, 2856, 1599,

˜

896 cm^–1. H NMR (270.1 MHz, CDCl₃): δ = 4.12 (d, J = 1.5 Hz,

1

3

1

1495, 1450 cm^–1. H NMR (500.1 MHz CDCl₃): δ = 5.11 (d, J =

1 H), 4.35 (d, J = 14.0 Hz, 1 H), 4.52 (d, J = 14.0 Hz, 1 H), 4.68

(d, J = 1.5 Hz, 1 H), 7.22 (dd, J = 1.5, 8.0 Hz, 1 H), 7.45–7.56 (m,

7 H), 7.79–7.85 (m, 4 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ =

57.1, 58.2, 67.7, 122.3, 126.5, 126.7, 126.8, 127.0, 127.8, 127.9,

128.8, 129.2, 129.3, 129.7, 131.0, 132.8, 133.8 ppm. MS (CI): m/z

(%) = 342 (100) [MNH₄⁺]. C₁₉H₂₀NO₃S calcd. 342.116391; found

342.117169.

7.0 Hz, 1 H), 5.13 (d, J = 7.0 Hz, 1 H), 6.36 (dd, J = 7.0, 16.0 Hz,

1 H), 6.38 (dd, J = 7.0, 16.0 Hz, 1 H), 6.61 (d, J = 16.0 Hz, 1 H),

6.63 (d, J = 16.0 Hz, 1 H), 7.23–7.47 (m, 20 H) ppm. ¹³C NMR

(67.9 MHz CDCl₃): δ = 79.1, 79.2, 126.6, 127.1, 127.6, 127.7, 127.9,

128.3, 128.5, 130.3, 130.4, 131.4, 131.5, 136.6, 141.1, 141.2 ppm.

MS (CI): m/z (%) = 420 (5) [MNH₄⁺], 404 (6) [MH⁺], 193 (100)

[C₁₅H₁₃⁺]. HRMS: C₃₀H₃₀NO calcd. 420.2327; found, 420.2326.

(g) trans-1-Benzylsulfonyl-2-(4-biphenylyl)oxirane (4g): Colourless

(e) trans-1-(3-Nitrophenyl)-3-phenylprop-2-en-1-ol (5b): Pale yellow

solid; m.p. 45–47 °C [ref.^[53]m.p. 46–47 °C] whose data was consis-

tent with literature.

solid; m.p. 155–160 °C. R = 0.40 (PE/EtOAc, 2:1). IR (nujol): ν =

˜

f

1315, 1140, 908 cm^–1. ¹H NMR (270.1 MHz, CD₃COCD₃): δ =

4.26 (d, J = 1.5 Hz, 1 H), 4.44 (d, J = 14.0 Hz, 1 H), 4.54 (d, J =

14.0 Hz, 1 H), 4.55 (d, J = 1.5 Hz, 1 H), 7.28–7.41 (m, 10 H), 7.53–

7.60 (m, 4 H) ppm. MS (EI): m/z (%) = 350 (10) [M⁺], 91 (100)

[C₇H₇⁺]. HRMS: C₂₁H₁₈O₃S requires 350.097666; found

350.098381.

(f) trans-1-(4-Fluorophenyl)-3-phenylprop-2-en-1-ol (5c): Colourless

clear oil.^[54]R = 0.20 (DCM). IR (film): ν = 3361, 1603, 1508,

˜

f

1223, 1157, 966, 744, 692 cm^–1. H NMR (270.1 MHz, CDCl₃): δ

1

= 2.41 (br. s, 1 H), 5.29 (d, J = 6.5 Hz, 1 H), 6.28 (dd, J = 6.5,

16.0 Hz, 1 H), 6.60 (d, J = 16.0 Hz, 1 H), 7.00 (t, J = 8.5 Hz, 2 H),

7.17–7.36 (m, 7 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 74.4,

115.4 (d, J = 20.5 Hz), 126.6, 127.9, 128.0 (d, J = 8.0 Hz), 128.6,

130.7, 131.3, 136.3, 138.4 (d, J = 3.0 Hz), 162.2 (d, J = 245.0 Hz)

ppm. MS (EI): m/z (%) = 228 (39) [M⁺], 209 (6), 133 (7), 123 (100),

115 (7), 105 (22), 95 (15), 77 (17), 51 (9). HRMS: C₁₅H₁₃FO calcd.

228.0950; found 228.0951.

General ERBR Procedures

(a) 1,3-Diphenyl-2-propen-1-ol (5a): A solution of LHMDS in THF

(0.88 mL, 1.0 , 0.88 mmol, 1.9 equiv.) was added dropwise to a

solution of 4a (128 mg, 0.467 mmol, 1 equiv.) in THF (15 mL), at

25 °C under nitrogen. Stirring was continued for 12 h before satu-

rated NH₄Cl (15 mL) was added, followed by extraction into

EtOAc (3×50 mL). The combined organic layers were washed with

brine (20 mL) and dried with MgSO₄. Filtration and solvent re-

moval in vacuo gave the crude product, which was purified by col-

umn chromatography (PE/EtOAc, 4:1) to yield the allylic alcohol

5a (62 mg, 63%) as a viscous yellow oil (E:Z, 65:35) whose data

was consistent to that reported.^[51]

(g) trans-3-Phenyl-1-(3-pyridyl)prop-2-en-1-ol (5d): Yellow oil whose

data was consistent with literature.^[55]

(h) cis/trans-3-Phenyl-1-(2-pyridyl)prop-2-en-1-ol (5e): Isolated as

colourless oils whose data was consistent with their assigned struc-

tures.^[56]3-Phenyl-1-(2-pyridyl)propan-1-one (6e): Isolated as

a

colourless oil whose data was consistent with the assigned struc-

(b) A solution of 4a (52 mg, 0.189 mmol, 1 equiv.) in dry DMSO

(5 mL) was treated at 25 °C with LiOtBu in THF (0.38 mL, 1.0 ,

0.38 mmol, 2 equiv.). Stirring was continued for 2 h. Water (10 mL)

was added and extraction was carried out with EtOAc (3×20 mL).

The combined organic extracts were washed with water (20 mL),

brine (20 mL) and dried with MgSO₄. Filtration and solvent re-

moval under reduced pressure afforded the crude material which

was purified by column chromatography (PE/EtOAc, 4:1). The al-

lylic alcohol 5a (32 mg, 82%) was obtained as a yellow oil (E:Z,

50:50).

ture.^[57]

(i) trans-1-(2-Naphthyl)-3-phenylprop-2-en-1-ol (5f): Colourless oil.

R = 0.35 (PE/EtOAc, 4:1). IR (film): ν = 3419, 3057, 2856, 1599,

˜

f

1495, 1448 cm^–1. ¹H NMR (270 MHz, CDCl₃): δ = 5.49 (d, J =

6.5 Hz, 1 H), 6.39 (dd, J = 6.5, 16.0 Hz, 1 H), 6.67 (d, J = 16.0 Hz,

1 H), 7.17–7.49 (m, 8 H), 7.59–7.82 (m, 4 H) ppm. ¹³C NMR

(67.9 MHz, CDCl₃): δ = 75.2, 124.5, 124.9, 126.0, 126.2, 126.6,

127.7, 127.8, 128.0, 128.4, 128.6, 130.8, 131.3, 133.3, 133.6, 136.5,

140.1 ppm. MS (EI): m/z (%) = 260 (25) [M⁺], 155 (100) [C₁₁H₇O⁺].

HRMS: C₁₉H₁₆O calcd. 260.120115; found 260.120375.

(c) 1,3-Diphenyl-1-propanone (6a): Under nitrogen, 4a (161 mg,

0.587 mmol, 1 equiv.) in THF (12 mL) was treated dropwise with

KOtBu in THF (1.2 mL, 1.0 , 1.2 mmol, 2 equiv.) at –78 °C. Stir-

ring was continued for 2 h before the reaction mixture was warmed

to room temperature and stirring was continued for 12 h before

saturated NH₄Cl (10 mL) was added. The resultant mixture was

extracted with EtOAc (3×25 mL), and the combined organic ex-

tracts were washed with brine (50 mL) and dried with MgSO₄. The

resultant yellow oil obtained after filtration and solvent removal

under reduced pressure was purified by flash column chromatog-

raphy (PE/EtOAc, 3:1) to yield the ketone 6a (87 mg, 71%) as a

colourless solid; m.p 66.5–67.5 °C [ref.^[52]m.p. 68–70 °C] whose

data was consistent.

(j) trans-3-Phenyl-1-[(4-phenyl)phenyl]prop-2-en-1-ol (5g): Colour-

less solid. m.p. 107–108 °C. R_f= 0.40 (PE/EtOAc, 2:1). IR (CHCl₃):

˜

CDCl₃): δ = 5.46 (d, J = 6.5 Hz, 1 H), 6.44 (dd, J = 6.5, 16.0 Hz,

1 H), 6.75 (d, J = 16.0 Hz, 1 H), 7.24–7.64 (m, 14 H) ppm. ¹³C

NMR (67.9 MHz, CDCl₃): δ = 74.9, 126.6, 126.8, 127.1, 127.4,

127.5, 127.8, 128.6, 128.8, 130.7, 131.4, 136.6, 140.7, 140.9, 141.8

ppm. MS (EI): m/z (%) = 286 (50) [M⁺], 181 (100) [C₁₃H₉O⁺].

HRMS: C₂₁H₁₈O calcd. 286.135765; found 286.134779.

ν = 3413, 3028, 1599, 1487, 1448 cm^–1. ¹H NMR (270 MHz,

Preparation of Allylic Alcohols 5j–m

(a) 3-Benzylsulfanylbutan-2-ol: Prepared from cis-2,3-epoxybutane

following a literature procedure.^[58]

(d) Bis(1,3-diphenyl-3-propenyl) Ether (7): A solution of 4a (250 mg,

0.91 mmol, 1 equiv.) in THF (20 mL) was treated with LiOtBu in

THF (1.82 mL, 1.0 , 1.82 mmol, 2 equiv.) dropwise at 25 °C. Stir-

ring was continued for 12 h. Saturated NH₄Cl (15 mL) was added

(b) 3-Benzylsulfonylbutan-2-ol: Colourless solid; m.p. 68.5–69 °C

(Et₂O) [ref.^[59]m.p. 60 °C] data consistent with the assigned struc-

ture.

1748

www.eurjoc.org

Eur. J. Org. Chem. 2006, 1740–1754

ERBR: A Sulfone-Based Method for the Synthesis of Allylic Alcohols

FULL PAPER

(c) cis/trans-2-Benzylsulfonyl-2-butene: A solution of 3-benzylsulfo-

nylbutan-2-ol (1.66 g, 7.26 mmol, 1 equiv.) in DCM (30 mL) and

methanesulfonyl chloride (0.69 mL, 8.71 mmol, 1.2 equiv.) were

treated at 0 °C dropwise with triethylamine (1.52 mL, 10.91 mmol,

1.5 equiv.). The reaction mixture was warmed to room temperature

and after 3 h the second portion of triethylamine (4.56 mL,

32.67 mmol, 4.5 equiv.) was added. After a further 1 h distilled

water (50 mL) was added, and the resultant aqueous layer was ex-

tracted with DCM (3×50 mL). Washing of the combined organic

layers with brine (100 mL) and drying with MgSO₄afforded crude

material which was purified by flash column chromatography (PE/

EtOAc, 1:1) affording the title compound (1.23 g, 81%) as a clear

oil containing a mixture of stereoisomers (Z*:E^#, 3:1). R_f= 0.50

5.7 mL, 9.15 mmol, 0.5 equiv.) at –78 °C to room temperature. Stir-

ring was continued for 24 h before work-up and flash column

chromatography (PE/EtOAc, 3:1) afforded the trans-epoxide 4k

(1.21 g, 29%) as a colourless viscous oil. R_f= 0.30 (PE/EtOAc,

3:1). IR (CDCl ): ν = 3072, 2982, 2930, 1496, 1456, 1321, 1305,

˜

3

1

1155, 1104 cm^–1. H NMR (270.1 MHz, CDCl₃): δ = 1.41 (d, J =

5.5 Hz, 3 H), 1.61 (s, 3 H), 3.83 (q, J = 5.5 Hz, 1 H), 4.32 (d, J =

13.5 Hz, 1 H), 4.46 (d, J = 13.5 Hz, 1 H), 7.36–7.52 (m, 5 H) ppm.

¹³C NMR (67.9 MHz, CDCl₃): δ = 12.7, 13.0, 55.8, 56.7, 72.7,

126.5, 128.8, 129.0, 131.1 ppm. MS (CI): m/z (%) = 244 (100)

[MNH₄⁺]. HRMS: C₁₁H₁₈NO₃S calcd. 244.1007; found 244.1004.

(g) trans-3-Methyl-4-phenyl-3-buten-2-ol (5k): Clear oil with spec-

troscopic data consistent with literature.^[30]

(PE/EtOAc, 1:1). IR (film): ν = 3064, 3034, 2978, 2926, 1651, 1497,

˜

1

1456, 1304, 1113 cm^–1. H NMR (270.1 MHz, CDCl₃): δ = 1.72–

(h) 1-Benzylsulfanylbutan-2-ol: Clear oil with spectroscopic data

consistent with literature.^[61]

1.77*^#(m, 3 H), 1.87–1.92*^#(m, 3 H), 4.17* (s, 2 H), 4.19^#(s, 2

H), 6.21^#(qq, J = 1.5, 7.5 Hz, 1 H), 6.52* (qq, J = 1.5, 7.0 Hz, 1

H), 7.28–7.38 (m, 5 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ =

12.0, 14.1, 14.6, 20.7, 59.1, 60.3, 128.1, 128.5, 128.6, 128.7, 128.75,

130.6, 130.8, 134.2, 135.1, 139.5, 140.2 ppm. MS (CI): m/z (%) =

228 (100) [MNH₄⁺]. HRMS: C₁₁H₁₈NO₂S calcd. 228.1058; found

(i) 1-Benzylsulfonylbutan-2-ol: Colourless solid; m.p. 93–94 °C

(EtOAc). R = 0.35 (PE/EtOAc, 1:1). 0.35. IR (nujol): ν = 3461,

˜

f

1377, 1117 cm^–1. H NMR (270.1 MHz, CDCl₃): δ = 0.95 (t, J =

1

7.5 Hz, 3 H), 1.46–1.64 (m, 2 H), 2.88 (dd, J = 1.5, 14.5 Hz, 1 H),

3.04 (dd, J = 10.0, 14.5 Hz, 1 H), 4.13–4.25 (m, 1 H), 4.30 (d, J =

14.0 Hz, 1 H), 4.41 (d, J = 14.0 Hz, 1 H), 7.39–7.46 (m, 5 H) ppm.

¹³C NMR (67.9 MHz, CDCl₃): δ = 9.4, 29.7, 56.4, 60.9, 67.6, 127.8,

129.1, 129.1, 130.9 ppm. MS (EI): m/z (%) = 228 (1) [M⁺], 91 (100)

[Bn⁺]. HRMS: C₁₁H₂₀NO₃S calcd. 246.1164; found 246.1167.

#

228.1064. * Corresponds to the cis-stereoisomer; corresponds to

the trans-stereoisomer whose data has been reported.^[60]

(d) trans-2-Benzylsulfonyl-2-butene: Prepared as a single stereoiso-

mer following isolation of the intermediate mesylate and subse-

quent treatment with KOtBu. The data for the resultant clear oil

was consistent with that described;^[60]b.p. 200 °C/1 Torr. R_f= 0.55

(PE/EtOAc, 1:1).

(j) trans-1-Benzylsulfonyl-1-butene: Colourless oil; b.p. 200 °C/

0.1 Torr. R = 0.20 (PE/EtOAc, 3:1). IR (film): ν = 3035, 2976,

˜

f

2937, 1633, 1315, 1117 cm^–1. H NMR (270.1 MHz, CDCl₃): δ =

1

1.02 (t, J = 7.5 Hz, 3 H), 2.17–2.28 (m, 2 H), 4.22 (s, 2 H), 6.13

(dt, J = 1.5, 15.0 Hz, 1 H), 6.77 (dt, J = 6.5, 15.0 Hz, 1 H), 7.35–

7.40 (m, 5 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 11.6, 24.8,

61.4, 126.1, 128.2, 128.7, 128.8, 130.8, 151.9 ppm. MS (CI): m/z

(%) = 228 (55) [MNH₄⁺], 91 (100) [Bn⁺]. HRMS: C₁₁H₁₈NO₂S

calcd. 228.1058; found 228.1066. C₁₁H₁₄O₂S (210.29): calcd. C

62.83, H 6.71, S 15.25; found C 62.85, H 6.67, S 15.22.

(e) cis-2-Benzylsulfonyl-2,3-dimethyloxirane (4k): Following the rep-

resentative Meth-Cohn epoxidation procedure described 4k was

prepared from the mixture of isomeric vinyl sulfones. A toluene

solution of TBHP (3.16 , 4.21 mL, 13.31 mmol, 2 equiv.) was dis-

solved in THF (40 mL) and treated with nBuLi (2.5 ) in hexanes

(2.93 mL, 7.32 mmol, 1.1 equiv.) at –78 °C. The mixture of sulfones

(1.40 g, 6.66 mmol, 1 equiv.) [Z:E, 66:33] in THF (30 mL) was then

added to the LiO₂tBu solution via cannula. The temperature was

raised to –10 °C and stirring was continued for 3 h. Solid Na₂SO₃

(ca. 1 g) was added, and the reaction mixture was stirred for a

further 0.25 h. Filtration through kieselgur, washing with diethyl

ether (2×100 mL), concentration in vacuo and purification by

flash column chromatography (PE/EtOAc, 1:1, R_f= 0.50) gave an

oil which solidified on cooling (1.00 g, 66%). Further purification

by recrystallisation afforded the cis-epoxide 4k (0.72 g, 48%) as a

colourless solid, m.p. 90 °C (EtOAc/PE). R_f= 0.30 (PE/EtOAc,

(k) trans-2-Benzylsulfonyl-3-ethyloxirane (4j): Colourless solid; m.p.

59–61 °C (PE/EtOAc). R = 0.30 (PE/EtOAc, 3:1). IR (CDCl ): ν

˜

f

3

= 3091, 3035, 2976, 1331, 1120 cm^–1. ¹H NMR (270.1 MHz,

CDCl₃): δ = 1.09 (t, J = 7.5 Hz, 3 H), 1.67–1.83 (m, 2 H), 3.68–

3.73 (m, 1 H), 3.82 (d, J = 1.5 Hz, 1 H), 4.33 (d, J = 14.0 Hz, 1

H), 4.49 (d, J = 14.0 Hz, 1 H), 7.36–7.58 (m, 5 H) ppm. ¹³C NMR

(67.9 MHz, CDCl₃): δ = 9.3, 23.4, 58.0, 58.2, 64.5, 126.7, 129.1,

129.15, 130.9 ppm. MS (CI): m/z (%) = 244 (100) [MNH₄⁺].

HRMS: C₁₁H₁₈NO₃S calcd. 244.1007; found 244.1005.

3:1). IR (KBr): ν = 3080, 3040, 2990, 2920, 1305, 1110 cm^–1. ¹H

˜

(l) 1-Phenyl-1-penten-3-ol (5j): Clear oil (E:Z, 90:10) with spectro-

NMR (300.1 MHz, CDCl₃): δ = 2.28 (d, J = 5.0 Hz, 3 H), 2.63 (d,

J = 6.0 Hz, 3 H), 3.15 (m, 1 H), 4.22 (d, J = 13.0 Hz, 1 H), 4.38

(d, J = 13.0 Hz, 1 H), 7.30–7.49 (m, 5 H) ppm. ¹³C NMR

(75.5 MHz, CDCl₃): δ = 13.3, 19.4, 58.0, 62.9, 73.4, 126.4, 129.0,

129.1, 131.2 ppm. MS (CI): m/z (%) = 244 (100) [MNH₄⁺]. HRMS:

C₁₁H₁₈NO₃S requires 244.1007; found 244.1004. C₁₁H₁₄O₃S

(226.29): calcd. C 58.38, H 6.23; found C 58.58, H 6.47.

scopic data consistent with literature.^[62]

(m) 2-Benzylsulfonyl-2-phenylethan-1-ol: Colourless solid; m.p. 138–

138.5 °C (EtOAc). R = 0.25 (PE/EtOAc, 1:1). IR (KBr): ν = 3500,

˜

f

3080, 3020, 2995, 2950, 2925, 2885, 1280, 1150 cm^–1. ¹H NMR

(270.1 MHz, CDCl₃): δ = 4.03 (dd, J = 4.5, 12.5 Hz, 1 H), 4.12 (d,

J = 14.0 Hz, 1 H), 4.17 (d, J = 14.0 Hz, 1 H), 4.27 (dd, J = 4.5,

8.0 Hz, 1 H), 4.51–4.61 (m, 1 H), 7.19–7.44 (m, 10 H) ppm. ¹³C

NMR (67.9 MHz, CDCl₃): δ = 58.6, 61.7, 68.5, 127.0, 128.8, 129.0,

129.1, 129.4, 129.6, 130.7, 131.0 ppm. MS (CI): m/z (%) = 294 (100)

[MNH₄⁺]. HRMS: C₁₅H₂₀NO₃S calcd. 294.1164; found 294.1168.

C₁₅H₁₆O₃S (276.35): calcd. C 65.19, H 5.84; found C 65.35, H 5.96.

(f) trans-2-Benzylsulfonyl-2,3-dimethyloxirane (4k): The trans-vinyl

sulfone (3.85 g, 18.0 mmol, 1 equiv.) in THF (100 mL) was added

to a solution of LiO₂tBu generated from TBHP in toluene (3.16 M,

8.7 mL, 27.0 mmol, 1.5 equiv.) and nBuLi in hexanes (1.6 ,

12.6 mL, 20.0 mmol, 1.1 equiv.) in THF (100 mL) at –78 °C. Stir-

ring was continued for 12 h at room temperature. ¹H NMR spectro-

scopic analysis of the crude material obtained after standard celite

work-up indicated incomplete conversion. Therefore, the mixture

was treated again with LiO₂tBu generated from TBHP in toluene

(2.55 , 4.3 mL, 11.0 mmol, 0.6 equiv.); nBuLi in hexanes (1.6 ,

(n) 1-Benzylsulfonyl-1-phenylethene: Colourless solid; m.p. 64–65 °C

(PE/EtOAc). R = 0.30 (PE/EtOAc, 4:1). IR (nujol): ν = 1302, 1132

˜

f

cm^–1. H NMR (270.1 MHz, CDCl₃): δ = 4.13 (s, 2 H), 5.98 (s, 1

1

H), 6.29 (s, 1 H), 7.16–7.66 (m, 10 H) ppm. ¹³C NMR (67.9 MHz,

CDCl₃): δ = 59.2, 128.0, 128.7, 129.1, 129.3, 130.3, 131.3, 133.0,

Eur. J. Org. Chem. 2006, 1740–1754

www.eurjoc.org

1749

P. Evans, P. Johnson, R. J. K. Taylor

FULL PAPER

140.2 ppm. MS (CI): m/z (%) = 276 (100) [MNH₄⁺]. HRMS: 123.5, 124.9, 125.2, 125.9, 128.2, 128.5, 128.4, 128.5, 138.8, 139.5,

C₁₅H₁₈NO₂S calcd. 276.1058; found 276.1059.

141.0 ppm. MS (EI): m/z (%) = 176 (20) [M⁺], 85 (100) [C₅H₉O⁺].

HRMS: C₁₂H₁₆O calcd. 176.1201; found 176.1199. * Denotes

trans-isomer; denotes cis-isomer.

(o) 2-Benzylsulfonyl-2-phenyloxirane (4l): Viscous colourless oil. R_f

#

= 0.20 (PE/EtOAc, 4:1). IR (CDCl ): ν = 3064, 3033, 2994, 2931,

˜

3

1320, 1124 cm^–1. H NMR (270.1 MHz, CDCl₃): δ = 3.00 (d, J =

1

Preparation of 4-Phenyl-3-buten-1,2-diol (5n) and 4-Phenyl-1-(tert-

butyldimethylsilyloxy)-3-buten-2-ol (5o)

6.0 Hz, 1 H), 3.88 (d, J = 6.0 Hz, 1 H), 4.09 (d, J = 14.5 Hz, 1 H),

4.25 (d, J = 14.5 Hz, 1 H), 7.26–7.47 (m, 6 H), 7.40–7.74 (m, 4 H)

ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 51.7, 55.6, 71.9, 125.5,

128.0, 128.7, 129.0, 130.0, 130.1, 131.2 ppm. MS (CI): m/z (%) =

292 (100) [MNH₄⁺]. HRMS: C₁₅H₁₈NO₃S calcd. 292.1007; found

292.1008.

(a) 1-Benzylsulfanyl-2-propene: Prepared according to literature

procedures.^[64]

(b) 1-Benzylsulfonyl-2-propene (11): Prepared according to litera-

ture procedures.^[64]

(c) trans-3-Bromo-1-benzylsulfonyl-1-propene: Prepared according

(q) trans-2,3-Diphenyl-2-propen-1-ol 5l: Clear oil with data consis-

to literature procedures.^[64]

tent to literature values.^[63]

(d) trans-3-Benzylsulfonyl-2-propene acetate: Prepared according to

(r) 3-(2-Phenylethylsulfanyl)butan-2-ol: Colourless oil; b.p. 170 °C/

literature procedures.^[64]

1 Torr. R = 0.30 (PE/EtOAc, 3:1). IR (film): ν = 3423, 3062, 3026,

˜

f

2972, 2925, 2871, 1496, 1452 cm^–1. ¹H NMR (270.1 MHz, CDCl₃):

δ = 1.25 (d, J = 6.5 Hz, 3 H), 1.33 (d, J = 6.5 Hz, 3 H), 2.65 (quin,

J = 6.5 Hz, 1 H), 2.80–2.95 (m, 4 H), 3.61 (quin, J = 6.5 Hz, 1 H),

7.20–7.36 (m, 5 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 18.02,

19.7, 31.7, 36.5, 49.5, 70.0, 126.4, 128.4, 128.45, 140.2 ppm. MS

(EI): m/z (%) = 210 (10) [M⁺], 105 (100) [Ph(CH₂)₂⁺]. HRMS:

C₁₂H₁₈OS calcd. 210.1078; found 210.1083.

(e) trans-3-Benzylsulfonyl-2-propen-1-ol (2n): Prepared according to

literature procedure.^[65]

(f) trans-2-Benzylsulfonyl-3-hydroxymethyloxirane (4n): Compound

2n (279 mg, 1.31 mmol, 1 equiv.) in THF (15 mL) was converted

into the corresponding epoxide 4n over 1.5 h at –5 °C upon treat-

ment with LiO₂tBu [generated at –78 °C from 2.55  TBHP in tolu-

ene (0.77 mL, 1.97 mmol, 1.5 equiv.) and 1.6  nBuLi in hexanes

(0.9 mL, 1.45 mmol, 1.1 equiv.) in THF (15 mL)]. Na₂SO₃(ca. 1 g)

was added and the reaction mixture was stirred for a further 0.25 h

at –5 °C. Filtration through celite, washing with diethyl ether

(2×50 mL), evaporation under reduced pressure followed by flash

column chromatography (PE/EtOAc, 1:1) gave the epoxide 4n

(203 mg, 68%) as a colourless solid; m.p. 93.5–95 °C. R_f= 0.20

(s) 3-(2-Phenylethylsulfonyl)butan-2-ol: Colourless solid; m.p. 80 °C

(EtOAc/PE). R = 0.25 (PE/EtOAc, 1:1). IR (nujol): ν = 3423, 1377,

˜

f

1105 cm^–1. ¹H NMR (270.1 MHz, CDCl₃): δ = 1.31 (d, J 6.5, 3 H),

1.34 (d, J = 7.5 Hz, 3 H), 2.96 (dq, J = 7.5, 8.5 Hz, 1 H), 3.17 (dd,

J = 2.0, 10.5 Hz, 1 H), 3.19 (d, J = 10.5 Hz, 1 H), 3.36 (d, J =

10.5 Hz, 1 H), 3.38 (dd, J = 2.0, 10.5 Hz, 1 H), 4.23 (dq, J = 6.5,

8.5 Hz, 1 H), 7.22–7.37 (m, 5 H) ppm. ¹³C NMR (67.9 MHz,

CDCl₃): δ = 10.9, 21.5, 27.9, 54.7, 64.4, 67.4, 127.4, 128.9, 129.3,

138.2 ppm. MS (CI): m/z (%) = 260 (90) [MNH₄⁺]. HRMS:

C₁₂H₂₂NO₃S calcd. 260.1320; found 260.1318. C₁₂H₁₈O₃S (242.33):

calcd. C 59.48, H 7.49, S 13.23; found C 59.19, H 7.52, S 13.36.

(PE/EtOAc, 1:1). IR (CDCl ): ν = 3309, 3055, 2983, 2935, 1497,

˜

3

1

1456, 1329, 1265. H NMR (270.1 MHz, CDCl₃): δ = 3.73 (dd, J

= 1.5, 2.5 Hz, 1 H), 3.74 (dd, J = 2.5, 14.0 Hz, 1 H), 3.96 (dd, J =

2.5, 14.0 Hz, 1 H), 4.10 (d, J = 1.5 Hz, 1 H), 4.28 (d, J = 14.0 Hz,

1 H), 4.41 (d, J = 14.0 Hz, 1 H), 7.40–7.43 (m, 5 H) ppm. ¹³C

NMR (67.9 MHz, CDCl₃): δ = 56.8, 58.2, 58.6, 62.2, 126.4, 129.2,

129.3, 130.9 ppm. MS (CI): m/z (%) = 246 (100) [MNH₄⁺]. HRMS:

C₁₀H₁₆NO₄S requires 246.0800; found 246.0801.

(t) trans-2-(2-Phenylethylsulfonyl)-2-butene: Colourless oil; b.p.

200 °C/1 Torr. R = 0.30 (PE/EtOAc, 3:1). IR (film): ν = 3085, 3062,

˜

f

3028, 2925, 1653, 1496, 1454, 1380, 1115 cm^–1. ¹H NMR

(270.1 MHz, CDCl₃): δ = 1.83 (dq, J = 1.5, 7.0 Hz, 3 H), 1.99

(quin, J = 1.5 Hz, 3 H), 3.00–3.10 (m, 2 H), 3.17–3.23 (m, 2 H),

6.81 (qq, J = 1.5, 7.0 Hz, 1 H), 7.16–7.34 (m, 5 H) ppm. ¹³C NMR

(67.9 MHz, CDCl₃): δ = 11.5, 14.1, 28.4, 52.9, 126.8, 128.3, 128.7,

135.6, 137.7, 138.4 ppm. MS (CI): m/z (%) = 242 (60) [MNH₄⁺],

104 (100) [Ph(CH₂)₂⁺]. HRMS: C₁₂H₂₀NO₂S calcd. 242.1215;

found 242.1214.

(g)

trans-2-Benzylsulfonyl-3-(tert-butyldimethylsilyloxymethyl)-

oxirane (4o): At room temperature a stirred solution of the epoxide

4n (42 mg, 0.184 mmol, 1 equiv.) in DCM (3 mL) and TBSCl

(36 mg, 0.239 mmol, 1.3 equiv.) were treated with imidazole (30 mg,

0.44 mmol, 2.4 equiv.). Stirring was continued for 2 h before the

reaction mixture was concentrated in vacuo and subjected directly

to flash column chromatography (PE/EtOAc, 1:1), which yielded

the silylated epoxide 4o as a clear oil (54 mg, 86%). R_f= 0.75 (PE/

(u)

trans-2,3-Dimethyl-2-(2-phenylethylsulfonyl)oxirane

(4m):

EtOAc, 1:1). IR (film): ν = 3035, 2954, 2931, 2858, 1327, 1142

˜

Colourless solid; m.p. 41–42 °C. R = 0.35 (DCM). IR (film): ν =

˜

f

1

cm^–1. H NMR (270.1 MHz, CDCl₃): δ = 0.02 (s, 6 H), 0.84 (s, 9

3085, 3028, 3003, 2935, 1497, 1454, 1317, 1105 cm^–1. ¹H NMR

(270.1 MHz, CDCl₃): δ = 1.50 (d, J = 5.5 Hz, 3 H), 1.82 (s, 3 H),

3.23–3.30 (m, 2 H), 3.32–3.43 (m, 2 H), 3.94 (q, J = 5.5 Hz, 1 H),

7.32–7.47 (m, 5 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 12.1,

13.1, 26.9, 50.2, 56.1, 72.6, 127.0, 128.4, 128.9, 137.7 ppm. MS

(CI): m/z (%) = 258 (100) [MNH₄⁺]. HRMS: C₁₂H₂₀NO₃S calcd.

258.1164; found 258.1162. C₁₂H₁₆O₃S (240.32): calcd. C 59.98, H

6.71, S 13.34; found C 60.20, H 6.50, S 13.28

H), 3.73 (m, 1 H), 3.81 (ddd, J = 2.5, 3.7 Hz5, 13.0, 1 H), 3.98–

4.02 (m, 2 H), 4.25 (d, J = 14.0 Hz, 1 H), 4.42 (d, J = 14.0 Hz, 1

H), 7.39–7.45 (m, 5 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = –

5.15, –5.1, 18.6, 26.1, 57.6, 58.6, 59.5, 62.0, 127.2, 129.5, 129.6,

131.3 ppm. MS (CI): m/z (%) = 360 (100) [MNH₄⁺]. HRMS:

C₁₆H₃₀NO₄SSi calcd. 360.1665; found 360.1649.

(h) 4-Phenyl-3-buten-1,2-diol (5n): Colourless solid [E:Z, 75:25]

with spectroscopic data consistent with literature.^[66]

(v) 3-Methyl-5-phenyl-3-penten-2-ol (5m): Yellow oil [E*:Z^#, 60:40].

R = 0.30 (PE/EtOAc, 3:1). IR (film): ν = 3357, 3062, 3026, 2974, (i) trans-4-Phenyl-1-(tert-butyldimethylsilyloxy)-3-buten-2-ol (5o):

˜

f

2922, 1603, 1493, 1452 cm^–1. H NMR (270.1 MHz, CDCl₃): δ = Clear oil [E:Z, 93:7]. R = 0.50 (PE/EtOAc, 3:1). IR (film): ν =

1

˜

f

1

1.30* (d, J = 6.5 Hz, 3 H), 1.31^#(d, J = 6.5 Hz, 3 H), 1.74–1.77*

3419, 2954, 2929, 2858 cm^–1. H NMR (270.1 MHz, CDCl₃): δ^‡=

(m, 3 H), 1.79^#(q, J = 1.5 Hz, 3 H), 3.39–3.45*^#(m, 2 H), 4.27* 0.11 (s, 6 H), 0.93 (s, 9 H), 1.27 (br. s, 1 H), 3.55 (dd, J = 7.7 Hz5,

(q, J = 6.5 Hz, 1 H), 4.93^#(q, J = 6.5 Hz, 1 H), 5.40–5.43^#(m, 1 10.0, 1 H), 3.75 (dd, J = 3.5, 10.0 Hz, 1 H), 4.32–4.41 (m, 1 H),

H), 5.62–5.64* (m, 1 H), 7.18–7.34 (m, 5 H) ppm. ¹³C NMR

(67.9 MHz, CDCl₃): δ = 11.6, 17.2, 21.3, 21.6, 33.3, 33.8, 65.6, 73.2,

6.18 (dd, J = 6.5, 16.0 Hz, 1 H), 6.70 (d, J = 16.0 Hz, 1 H), 7.25–

7.41 (m, 5 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = –5.3, 18.3,

1750

www.eurjoc.org

Eur. J. Org. Chem. 2006, 1740–1754

ERBR: A Sulfone-Based Method for the Synthesis of Allylic Alcohols

FULL PAPER

25.8, 67.2, 72.8, 126.4, 127.6, 127.8, 128.5, 131.7, 136.7 ppm. MS

(CI): m/z (%) = 296 (4) [MNH₄⁺], 278 (7) [M⁺], 261 (100) [M –

OH⁺]. HRMS: C₁₆H₃₀NO₂Si requires 296.2046; found 296.2042.

^‡Data given for the major trans-isomer only.

before MeI (0.15 mL, 2.41 mmol, 2 equiv.) was added to the red

solution. The colour rapidly disappeared and stirring was contin-

ued for a further 10 min at –78 °C. Saturated NH₄Cl (10 mL) was

added and the mixture was warmed to room temperature before

extraction was carried out with EtOAc (3×30 mL). The combined

extracts were washed with H₂O (20 mL) then brine (50 mL) before

drying with MgSO₄. Purification of the crude oil obtained after

filtration and solvent removal in vacuo, by flash column

chromatography (PE/EtOAc, 2:1) afforded the methylated com-

pound 2s (282 mg, 88%) as a colourless solid; m.p. 94–95 °C

Preparation of 3-Phenyl-2-propen-1-ol (5p) and 5-Phenyl-2,4-pen-

tadien-1-ol (5q):

(a) 2-Benzylsulfanylethan-1-ol: Preparation according to a literature

procedure.^[67]

(b) 2-Benzylsulfonylethan-1-ol: Preparation according to a literature

procedure.^[67]

(EtOAc/PE). R = 0.30 (PE/EtOAc, 3:1). IR (CHCl ): ν = 3086,

˜

f

3

3066, 3041, 3007, 2941, 1614, 1497, 1450, 1309, 1128 cm^–1. ¹H

NMR (270.1 MHz, CDCl₃): δ = 1.83 (d, J = 7.5 Hz, 3 H), 4.25 (q,

J = 7.5 Hz, 1 H), 6.56 (d, J = 16.0 Hz, 1 H), 7.35–7.45 (m, 11 H)

ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 14.0, 65.0, 122.8, 128.3,

128.6, 128.7, 128.8, 128.9, 129.3, 131.1, 132.2, 133.7, 145.6 ppm.

MS (CI): m/z (%) = 290 (100) [MNH₄⁺]. HRMS: C₁₆H₂₀NO₂S

(c) 2-Benzylsulfonylethene: Preparation according to a literature

procedure.^[67]

(d) 2-Benzylsulfonyloxirane (4p): Colourless solid; m.p. 68–69 °C

(EtOAc/PE). R = 0.45 (PE/EtOAc, 1:1). IR (CDCl ): ν = 3091,

˜

f

3

3035, 2955, 2930, 2925, 1336, 1153 cm^–1. ¹H NMR (270.1 MHz,

CDCl₃): δ = 3.09 (dd, J = 3.5, 5.5 Hz, 1 H), 3.42 (dd, J = 2.0, calcd. 290.1215; found 290.1212.

5.5 Hz, 1 H), 3.94 (dd, J = 2.0, 3.5 Hz, 1 H), 4.28 (d, J = 14.0 Hz,

(b) syn- and anti-trans-3-(1-Phenylethylsulfonyl)-2-phenyloxirane

1 H), 4.43 (d, J = 14.0 Hz, 1 H), 7.42–7.46 (m, 5 H) ppm. ¹³C

NMR (67.9 MHz, CDCl₃): δ = 44.6, 58.3, 59.7, 126.6, 129.2, 129.3,

130.9 ppm. MS (CI): m/z (%) = 216 (100) [MNH₄⁺]. HRMS:

C₉H₁₄NO₃S calcd. 216.0694; found 216.0695. C₉H₁₀O₃S (198.24):

calcd. C 54.53, H 5.08, S 16.18; found C 54.72, H 5.01, S 16.18.

(4s): Following the described epoxidation process, TBHP in toluene

(2.55 , 0.57 mL, 1.45 mmol, 1.5 equiv.) in THF (10 mL) and

nBuLi in hexanes (1.6 , 0.73 mL, 1.17 mmol, 1.2 equiv.) was used

to generate LiO₂tBu at –78 °C. The sulfone 2s (265 mg,

0.973 mmol, 1 equiv.) in THF (10 mL) was added and stirring was

continued over 4 h at –20 °C to room temperature. Na₂SO₃(ca.

1 g) was added and after 0.5 h the mixture was filtered through

celite and washed with diethyl ether (2×30 mL). Concentration of

the filtrate in vacuo followed by purification by flash column

chromatography (PE/EtOAc, 4:1) afforded 4s (206 mg, 73%) as a

separable mixture of the two diastereomers, 33% de. R_f= 0.30 and

(e) 3-Phenyl-2-propen-1-ol (5p): Clear oil [E:Z, 65:35] whose data

was consistent with that reported in the literature.^[68]

(f) 2-(3-Phenyl-2-propen-1-sulfanyl)ethan-1-ol: Prepared according

to a literature procedure.^[64]

(g) 2-(3-Phenyl-2-propen-1-sulfonyl)ethan-1-ol: Prepared according

to a literature procedure.^[64]

0.25 (PE/EtOAc, 4:1). IR (CHCl ): ν = 3065, 3034, 2987, 2939,

˜

3

2877, 1495, 1456, 1319, 1138 cm^–1. ¹H NMR (270.1 MHz, CDCl₃):

δ = 1.85* (d, J = 7.5 Hz, 3 H), 1.92^#(d, J = 7.5 Hz, 3 H), 3.73*

(d, J = 1.5 Hz, 1 H), 4.10^#(d, J = 1.5 Hz, 1 H), 4.42^#(q, J =

7.5 Hz, 1 H), 4.45^#(d, J = 1.5 Hz, 1 H), 4.46* (d, J = 1.5 Hz, 1

H), 4.47* (q, J = 7.5 Hz, 1 H), 7.14–7.57 (m, 10 H) ppm. ¹³C NMR

(67.9 MHz, CDCl₃): δ = 13.7, 15.9, 57.3, 58.0, 63.4, 64.7, 68.5, 68.9,

127.4, 127.5, 129.9, 130.0, 130.1, 130.3, 130.5, 130.8, 130.9, 133.2

133.9, 134.6 ppm. MS (CI): m/z (%) = 306 (100) [MNH₄⁺]. HRMS:

C₁₆H₂₀NO₃S calcd. 306.1164; found 306.1171. * Defines major dia-

(h) 3-Phenyl-2-propen-1-sulfonylethene: Prepared according to a lit-

erature procedure.^[64]

(i) 2-(3-Phenyl-2-propen-1-sulfonyl)oxirane (4q): Prepared according

to a literature procedure.^[64]

(j) 5-Phenyl-2,4-pentadien-1-ol (5q): Pale yellow solid [E:E:E:Z,

65:35] whose data was consistent with that reported in the litera-

ture.^[69]

(k) 2-(2-Phenylethylsulfanyl)ethan-1-ol: Prepared according to a lit-

#

stereomer; defines minor diastereomer.

erature procedure.^[70]

(c) 1,3-Diphenyl-2-butenyl Acetate (15): Under nitrogen, LiOtBu in

THF (1.28 mL, 1.0 , 1.28 mmol, 2 equiv.) was added to a solution

of the epoxide 4s (185 mg, 0.64 mmol, 1 equiv.) in THF (15 mL) at

25 °C. Stirring was continued for 24 h before saturated NH₄Cl

(5 mL) was added. The resultant mixture was extracted with EtOAc

(3×20 mL), and the combined extracts were washed with brine

(20 mL) and dried with MgSO₄. Filtration, evaporation in vacuo

and flash column chromatography (PE/EtOAc, 3:1) afforded a yel-

low oil (111 mg) containing the allylic alcohol and unreacted epox-

ide 4s. This residue was taken up in Ac₂O (3 mL) and pyridine

(0.1 mL, 1.2 mmol) was added. The reaction mixture was stirred

for 12 h before ether (10 mL) and water (10 mL) were added. After

partitioning for 10 min and separation the aqueous layer was ex-

tracted with diethyl ether (3×10 mL). The combined ethereal ex-

tracts were washed with NaHCO₃(20 mL), water (20 mL) and

brine (20 mL) before finally drying with MgSO₄. The material ob-

tained after filtration and solvent evaporation under reduced pres-

sure was purified by column chromatography (PE/EtOAc, 6:1) to

give the recovered epoxide 4s (29 mg, 16%) and the allylic acetate

15 (82 mg, 48%) as a clear oil [E:Z, 50:50]. R_f= 0.50 (PE/EtOAc,

(l) 2-(2-Phenylethylsulfonyl)ethan-1-ol: Prepared according to a lit-

erature procedure.^[70]

(m) 2-(2-Phenylethylsulfonyl)ethene: Prepared according to a litera-

ture procedure.^[70]

(n) 2-(2-Phenylethylsulfonyl)oxirane (4r): Colourless solid; m.p. 77–

79 °C. R = 0.35 (PE/EtOAc, 1:1). IR (CDCl ): ν = 3087, 3078,

˜

f

3

3030, 2982, 2931, 1496, 1456, 1317, 1151, 1126 cm^–1. ¹H NMR

(270.1 MHz, CDCl₃): δ = 3.05 (dd, J = 4.0, 5.5 Hz, 1 H), 3.14–3.28

(m, 2 H), 3.30–3.43 (m, 3 H), 3.95 (dd, J = 2.0, 4.0 Hz, 1 H), 7.21–

7.35 (m, 5 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 27.7, 44.2,

53.2, 61.0, 127.1, 128.4, 128.9, 137.2 ppm. MS (CI): m/z (%) =

230 (100) [MNH₄⁺]. HRMS: C₁₀H₁₆NO₃S calcd. 230.0851; found

230.0849. C₁₀H₁₂O₃S (212.26): calcd. C 56.59, H 5.70, S 15.11;

found C 56.72, H 5.65, S 14.99.

Preparation of 1,3-Diphenyl-2-butenyl Acetate (15) and 1,2-Di-

methyl-3-phenyl-2-butenyl Acetate (16)

(a) trans-1-(1-Phenylethylsulfonyl)-2-phenylethene (2s): Under N₂

at –78 °C the vinyl sulfone 2a (306 mg, 1.18 mmol, 1 equiv.) in dry

THF (10 mL) was treated with nBuLi in hexanes (2.5 , 0.52 mL, 6:1). IR (CDCl ): ν = 3082, 3061, 3032, 2972, 2916, 1736, 1601,

˜

3

1.3 mmol, 1.1 equiv.). Stirring at –78 °C was continued for 10 min

1495, 1444 cm^–1. ¹H NMR (270.1 MHz, CDCl₃): δ = 2.05 (s, 3 H),

Eur. J. Org. Chem. 2006, 1740–1754

www.eurjoc.org

1751

P. Evans, P. Johnson, R. J. K. Taylor

FULL PAPER

2.10 (d, J = 1.5 Hz, 3 H), 2.13 (s, 3 H), 2.24 (d, J = 1.5 Hz, 3 H),

5.75 (dq, J = 1.5, 9.5 Hz, 1 H), 5.99 (dq, J = 1.5, 9.0 Hz, 1 H),

6.18 (d, J = 9.5 Hz, 1 H), 6.70 (d, J = 9.0 Hz, 1 H), 7.18–7.56 (m,

10 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ = 16.6, 21.3, 25.9,

73.0, 73.9, 125.2, 125.9, 126.5, 126.6, 126.7, 127.4, 127.5, 127.6,

127.8, 127.9, 128.2, 128.3, 128.5, 128.6, 138.8, 140.1, 140.6, 140.7,

141.3, 142.1, 169.7, 170.2 ppm. MS (EI): m/z (%) = 266 (10) [M⁺].

HRMS: C₁₆H₁₆O₂calcd. 266.1307; found 266.1314.

Preparation of Enantio-enriched Allylic Alcohols via the ERBR

(a) trans-2-Benzylsulfonyl-1-(2,2-dimethyl-1,3-dioxolan-4-yl)ethene

(2u): Under nitrogen at –65 °C, DMSO (2 mL, 28.18 mmol,

3.5 equiv.) was added dropwise to a solution of oxalyl chloride

(1.2 mL, 13.76 mmol, 1.7 equiv.) in DCM (20 mL). Stirring was

continued for 10 min before (S)-isopropylideneglycerol (17, 1.0 mL,

8.17 mmol, 1 equiv.) was added over 4.5 min. After a further

10 min stirring at –65 °C triethylamine (3.4 mL, 24.39 mmol,

3 equiv.) was added dropwise to the cloudy solution. After 5 min

the reaction was warmed to –10 °C for 0.5 h before filtration

through celite. The residue was washed with cold DCM (15 mL)

and cold ether (2×15 mL). The bulk of the solvent was removed

under reduced pressure at 25 °C. The resultant crude glyceralde-

hyde was then added to a pre-prepared solution of the anion, gener-

ated from the phosphonate 3 (3.72 g, 12.14 mmol, 1.5 equiv.) and

NaH dispersion in oil (60%, 389 mg, 9.72 mmol, 1.2 equiv.) in

THF (160 mL). Stirring was continued for 40 min before the ad-

dition of water (50 mL) followed by EtOAc (50 mL). The resultant

aqueous layer was further extracted with EtOAc (2 × 50 mL). The

combined organic layers were washed with water (100 mL) and

brine (100 mL) and dried with Na₂SO₄. The crude oil obtained

after filtration and solvent removal was purified by flash column

chromatography (PE/EtOAc, 2:1) affording 2u as a clear oil (1.72 g,

75%), which proved to be a separable mixture of stereoisomers;

E:Z, 85:15 (PE/EtOAc, 3:1). R_f= 0.17 (Z) and 0.15 (E) (PE/EtOAc,

(d) syn- and anti-trans-2,3-Dimethyl-2-(1-phenylethylsulfonyl)oxir-

ane (4t): At –78 °C under nitrogen the trans-epoxide 4k (57.5 mg,

0.254 mmol, 1 equiv.) in THF (5 mL) was treated with nBuLi in

hexanes (1.6 , 0.14 mL, 0.224 mmol, 0.9 equiv.) over 5 min. After

10 min methyl iodide (1.6 µL, 0.257 mmol, 1 equiv.) was added.

Stirring was continued for a further 10 min at –78 °C, then for 1 h

at room temperature. Saturated NH₄Cl (5 mL) was added and the

mixture was extracted with EtOAc (3×15 mL). The combined or-

ganic layers were washed with brine (30 mL) and dried with

MgSO₄. Filtration followed by solvent removal under reduced pres-

sure afforded the crude product as a mixture of diastereomers

which was purified by flash column chromatography (PE/EtOAc,

3:1) yielding 4t as a separable mixture of clear oils (26 mg, 47%;

24 mg, 44%). R = 0.35 and 0.30 (PE/EtOAc, 3:1). IR (CDCl ): ν

˜

f

3

= 3064, 2991, 2934, 1496, 1456, 1317, 1300, 1151, 1103 cm^–1. ¹H

NMR (270.1 MHz, CDCl₃) upper spot: δ = 1.19 (d, J = 5.5 Hz, 3

H), 1.20 (s, 3 H), 3.58 (q, J = 5.5 Hz, 1 H), 4.44 (q, J = 7.5 Hz, 1

H), 7.38–7.52 (m, 5 H) ppm; lower spot: δ = 1.29 (d, J = 5.5 Hz, 3

H), 1.56 (s, 3 H), 1.81 (d, J = 7.5 Hz, 3 H), 3.63 (q, J = 5.5 Hz, 1

H), 4.42 (q, J = 7.5 Hz, 1 H), 7.33–7.50 (m, 5 H) ppm. ¹³C NMR

(67.9 MHz, CDCl₃) upper spot: δ = 13.0, 13.1, 13.5, 56.9, 60.7,

72.6, 128.9, 129.2, 129.6, 133.6 ppm; lower spot: δ = 14.2, 14.4,

15.9, 56.5, 63.1, 74.1, 130.1, 130.4, 130.6, 134.3 ppm. MS (CI):

m/z (%) = 258 (100) [MNH₄⁺]. HRMS: C₁₂H₂₀NO₃S calcd.

258.1164; found 258.1161.

3:1). Data for (E)-vinyl sulfone. IR (film): ν = 3064, 3015, 2986,

˜

2937, 2889, 1638, 1496, 1456, 1315, 1117 cm^–1. ¹H NMR

(270.1 MHz, CDCl₃): δ = 1.39 (s, 3 H), 1.40 (s, 3 H), 3.52 (dd, J =

7.0, 8.5 Hz, 1 H), 4.13 (dd, J = 7.0, 8.5 Hz, 1 H), 4.24 (s, 2 H), 4.63

(dddd, J = 1.5, 4.0, 7.0 Hz, 8.0, 1 H), 6.50 (dd, J = 1.5, 15.0 Hz, 1

H), 6.65 (dd, J = 4.0, 15.0 Hz, 1 H), 7.32–7.46 (m, 5 H) ppm. ¹³C

NMR (67.9 MHz, CDCl₃): δ = 25.4, 26.2, 61.2, 68.0, 73.7, 110.5,

127.5, 127.9, 128.7, 130.8, 146.6 ppm. MS (CI): m/z (%) = 300 (100)

[MNH₄⁺]. HRMS: C₁₄H₂₂NO₄S calcd. 300.1270; found 300.1268.

[α]_D= +7.4 (c = 1.0, CHCl₃).

(e) 1,2-Dimethyl-3-phenyl-2-butenyl Acetate (16): Following the

ERBR protocol described, the epoxide 4t (226 mg, 0.94 mmol,

1 equiv.) in THF (18 mL) was treated with LiOtBu in THF

(1.03 mL, 1.0 , 1.03 mmol, 1.1 equiv.) at 25 °C. Stirring was main-

(b) trans-(2R,3R)-2-Benzylsulfonyl-3-(2,2-dimethyl-1,3-dioxolan-4-

yl)oxirane (anti-4u): A solution of Ph₃CO₂H (498 mg, 1.8 mmol,

3 equiv.) in THF (6 mL) at –78 °C was treated with NaH dispersion

in oil (60%, 36 mg, 0.9 mmol, 1.5 equiv.). The mixture was warmed

to 25 °C and stirred for 0.5 h before cooling to –78 °C and addition

of the vinyl sulfone 2u (169 mg, 0.597 mmol, 1 equiv.) in THF

(6 mL) [washed further, THF (2 mL)] was added. Stirring was con-

tinued at –78 °C for 0.25 h and then at –20 °C to –10 °C for 1 h.

The reaction mixture was cooled again to –78 °C and NH₄Cl

(10 mL) was added. Warming to 25 °C followed by extraction with

EtOAc (3×20 mL), washing of the combined organic layers with

brine (30 mL) and drying with Na₂SO₄afforded the crude epoxide

upon filtration and solvent removal. Purification by flash column

chromatography (PE/EtOAc, 3:1) gave an inseparable mixture of

the diastereomeric epoxides (148 mg, 83%), 80% de. The major

anti-epoxide 4u was obtained as a colourless solid by recrystalli-

sation; m.p. 102–103 °C (EtOAc/PE). R_f= 0.30 (PE/EtOAc, 3:1).

1

tained for 15 h before the standard work-up was implemented. H

NMR spectroscopic analysis revealed a significant amount of start-

ing material. Hence, the residue was taken up in THF (18 mL) and

treated again with LiOtBu solution (1.4 mL, 1.4 mmol, 1.5 equiv.).

After stirring for a further 48 h satd. NH₄Cl (10 mL) was added,

and the standard work-up was carried out. Purification by flash

column chromatography (PE/EtOAc, 3:1) afforded an inseparable

mixture of 4t and the tetrasubstituted allylic alcohol. The residue

(138 mg) was taken up in Ac₂O (3 mL), and pyridine (0.16 mL,

2 mmol) was added at 25 °C. After 15 h an identical work-up to

that described above was implemented. Purification by flash col-

umn chromatography (PE/EtOAc, 3:1) afforded the epoxide 4t

(10 mg, 4%) and the title compound 16 (39 mg, 19%) as a yellow

oil. The allylic acetate was formed as an undetermined 90*:10^#

mixture of stereoisomers. R_f= 0.55 (PE/EtOAc, 3:1). IR (CDCl₃):

ν = 3078, 2983, 2933, 2862, 1724, 1601, 1493, 1443. ¹H NMR

IR (CDCl ): ν = 3064, 3033, 2987, 2935, 2891, 1496, 1456, 1373,

˜

3

˜

1325, 1151, 1117 cm^–1. ¹H NMR (270.1 MHz, CDCl₃): δ = 1.34 (s,

3 H), 1.40 (s, 3 H), 3.70–3.73 (m, 1 H), 3.83–3.90 (m, 1 H), 3.94

(d, J = 1.5 Hz, 1 H), 4.08–4.16 (m, 2 H), 4.28 (d, J = 14.0 Hz, 1

H), 4.40 (d, J = 14.0 Hz, 1 H), 7.41–7.45 (m, 5 H) ppm. ¹³C NMR

(67.9 MHz, CDCl₃): δ = 25.0, 26.2, 56.7, 58.3, 63.0, 66.3, 72.7,

110.6, 126.4, 129.1, 129.3, 130.9 ppm. MS (CI): m/z (%) = 316 (100)

[MNH₄⁺]. HRMS: C₁₄H₂₂NO₅S calcd. 316.1219; found 316.1216.

[α]_D= +85.2 (c = 0.5, CHCl₃).

(270.1 MHz, CDCl₃): δ = 1.22^#(d, J = 6.5 Hz, 3 H), 1.38* (d, J =

6.5 Hz, 3 H), 1.54* (q, J = 1.5 Hz, 3 H), 1.79^#(q, J = 1.0 Hz, 3

H), 1.96^#(q, J = 1.0 Hz, 3 H), 1.99^#(s, 3 H), 2.05* (q, J = 1.5 Hz,

3 H), 2.08* (s, 3 H), 5.34^#(q, J = 6.5 Hz, 1 H), 5.95* (q, J = 6.5 Hz,

1 H), 7.09–7.36 (m, 5 H) ppm. ¹³C NMR (67.9 MHz, CDCl₃): δ

= 12.0, 13.8, 18.6, 19.0, 20.3, 21.2, 21.3, 21.5, 70.4, 71.9, 126.2,

126.4, 127.8, 128.0, 128.1, 128.2, 129.7, 130.2, 133.3, 134.2, 143.3,

144.5, 170.0, 170.4 ppm. MS (EI): m/z (%) = 218 (5) [M⁺]. HRMS:

C₁₄H₁₈O₂calcd. 218.1307; found 218.1303. * Denotes major ste-

(c) (1S)-1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-3-phenyl-2-propen-

1-ol (anti-5u): The anti-epoxide 4u (45 mg, 0.15 mmol, 1 equiv.) in

#

reoisomer; denotes minor stereoisomer.

1752

www.eurjoc.org

Eur. J. Org. Chem. 2006, 1740–1754

ERBR: A Sulfone-Based Method for the Synthesis of Allylic Alcohols

FULL PAPER

THF (3 mL) was treated with LiOtBu in THF (0.3 mL, 1.0 ,

0.3 mmol, 2 equiv.). Stirring was continued for 36 h before NH₄Cl

(5 mL) was added. The resultant mixture was extracted with EtOAc

(3×10 mL). The combined organic extracts were washed with brine

(2 mL) was treated with a solution of LiO₂tBu in THF (3 mL),

generated from TBHP in toluene (2.63 , 0.14 mL, 0.368 mmol,

1.5 equiv.) and nBuLi in hexanes (1.6 , 0.17 mL, 0.272 mmol,

1.1 equiv.) over 3 h at –15 °C to –5 °C. Following the work-up pro-

(15 mL) and dried with Na₂SO₄. Filtration and solvent removal cedure described above the crude product was purified by flash

under reduced pressure furnished the crude product which was

purified by flash column chromatography (PE/EtOAc, 2:1). The

title compound 5u (24 mg, 69%) was obtained as a colourless solid

[E:Z, 92:8], recrystallisation gave the trans-stereoisomer, m.p. 59 °C

column chromatography (PE/EtOAc, 1:1 to EtOAc) to yield the

epoxide 4v (20 mg, 32%) as a colourless solid, syn-4v/anti-4v, 92:8

(84% de). Recrystallisation gave the major syn-diastereomer as a

fine colourless crystalline solid; m.p. 140 °C (EtOAc). R_f= 0.40

(Et O/PE). R = 0.30 (PE/EtOAc, 3:1). IR (CHCl ): ν = 3467, 3055,

(EtOAc). IR (CHCl ): ν = 3464, 3050, 2958, 2923, 2861, 1458,

˜

2

f

3

3010, 2988, 2890, 1653, 1496, 1457 cm^–1. ¹H NMR (500.1 MHz,

1398, 1319, 1109 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 3.74

‡

CDCl₃): δ = 1.39 (s, 3 H), 1.49 (s, 3 H), 2.25 (br. s, 1 H), 3.98 (dd, J = 2.0, 3.0 Hz, 1 H), 3.75 (dd, J = 6.0, 11.0 Hz, 1 H), 3.80

(dd, J = 7.0, 8.0 Hz, 1 H), 4.01 (dd, J = 7.0, 8.0 Hz, 1 H), 4.23

(ddd, J = 5.0, 7.0, 7.0 Hz, 1 H), 4.49–4.50 (m(br), 1 H), 6.18 (dd,

J = 6.0, 16.0 Hz, 1 H), 6.73 (d, J = 16.0 Hz, 1 H), 7.25–7.41 (m, 5

(dd, J = 4.0, 11.0 Hz, 1 H), 3.88 (ddd, J = 3.0, 4.0, 6.0 Hz, 1 H),

4.09 (d, J = 2.0 Hz, 1 H), 4.29 (d, J = 14.0 Hz, 1 H), 4.40 (d, J =

14.0 Hz, 1 H), 7.40–7.65 (m, 5 H) ppm. ¹³C NMR (67.9 MHz,

CDCl₃): δ = 57.2, 58.5, 62.0, 64.5, 68.0, 126.5, 129.2, 129.4, 131.0

ppm. MS (CI): m/z (%) = 212 (50) [MNH₄⁺]. HRMS: C₁₁H₁₈NO₅S

‡

H) ppm. ¹³C NMR (125.8 MHz, CDCl₃): δ = 25.1, 26.4, 64.7,

71.7, 78.3, 109.5, 126.5, 126.7, 127.8, 128.5, 132.0, 136.2 ppm. MS

(EI): m/z (%) = 234 (5) [M⁺], 101 (100) [C₅H₉O₂⁺]. HRMS: calcd. 276.0906; found 276.0909. [α]_D= –134.0 (c = 0.25, EtOH).

C₁₄H₁₈O₃calcd. 234.1256; found 234.1268. [α]_D= +22.1 (c = 0.5,

(g) (2R,3R)-trans-5-Phenyl-4-penten-1,2,3-triol (syn-5v): The syn-

epoxide 4v (12 mg, 0.0465 mmol, 1 equiv.) in THF (1 mL) was

‡

CHCl₃). Data given for the major trans-isomer only.

treated with LiOtBu in THF (0.14 mL, 1.0 , 0.14 mmol, 3 equiv.)

for 12 h at room temp. Saturated NH₄Cl (2 mL) was added and

the mixture was extracted with EtOAc (3×10 mL). The combined

organic extracts were washed with brine (15 mL) and dried with

MgSO₄. Filtration followed by solvent removal in vacuo gave the

crude triol (3 mg, 33%) [E:Z, 76:24] as a clear oil. The cis and

(d)

(2R,3S)-trans-5-Phenyl-4-penten-1,2,3-triol

(anti-5v):

TsOH·H₂O (3 mg, 0.016 mmol, 0.23 equiv.) was added to a solu-

tion of the alcohol anti-5u (16.5 mg, 0.071 mmol, 1 equiv.) in

MeOH (2 mL). Stirring was continued for 12 h. Water (10 mL) and

EtOAc (10 mL) were added. The resultant aqueous layer was ex-

tracted with EtOAc (3×15 mL) and the combined organic extracts

were washed with NaHCO₃(15 mL), brine (15 mL) and dried with

Na₂SO₄. The crude colourless solid obtained after filtration and

solvent removal in vacuo was recrystallised to afford anti-5v

(9.5 mg, 70%); m.p. 121–122 °C (acetone) [ref.^[20]m.p. 123 °C (ace-

trans-stereoisomers were separated by preparative TLC. R_f= 0.15

1

(E) and 0.20 (Z) (EtOAc). H NMR (270.1 MHz, CD₃OD): δ^‡

=

3.59 (dd, J = 6.0, 10.0 Hz, 1 H), 3.63–3.68 (m, 1 H), 3.74 (dd, J =

3.5, 10.0 Hz, 1 H), 4.30 (ddd, J = 1.0, 5.0, 6.5 Hz, 1 H), 6.37 (dd,

J = 6.5, 16.5 Hz, 1 H), 6.70 (d, J = 16.5 Hz, 1 H), 7.22–7.48 (m, 5

H) ppm. ¹³C NMR (67.9 MHz, CD₃OD): δ^‡= 64.3, 74.21, 76.4,

127.5, 128.6, 129.6, 130.4, 132.6, 138.4 ppm. [α]_D= +10 (c = 0.05,

tone)]. R = 0.20 (EtOAc). IR (CHCl ): ν = 3619, 3294, 3209, 3018,

˜

f

3

2958, 2927, 2856, 1601, 1464 cm^–1. ¹H NMR (270.1 MHz, [D₆]

acetone): δ = 3.52 (d, J = 5.0 Hz, 1 H), 3.47–3.58 (m, 3 H), 3.72

(d, J = 4.5 Hz, 1 H), 4.01 (d, J = 5.0 Hz, 1 H), 4.14 (q, J = 5.0 Hz,

1 H), 6.43 (dd, J = 6.0, 16.0 Hz, 1 H), 6.65 (d, J = 16.0 Hz, 1 H),

7.18–7.45 (m, 5 H) ppm. ¹³C NMR (67.9 MHz, [D₆]acetone): δ =

64.5, 74.5, 75.7, 127.1, 128.0, 129.3, 130.9, 131.4, 138.2 ppm. MS

(CI): m/z (%) = 212 (30) [MNH₄⁺], 177 (100) [M – OH⁺]. HRMS:

C₁₁H₁₈NO₃calcd. 212.1287; found 212.1282. [α]_D= –18.7 (c =

0.125, THF).

‡

EtOH). Data given for the major trans-isomer only.

Acknowledgments

We wish to thank Dr. T. A. Dransfield and Mr. B. R. Glennie at

the University of York for mass spectroscopic data. Mr. A. W.

Saunders of the University of East Anglia is thanked for elemental

analyses, and S. Foxon and C. Boxwell for X-ray crystallographic

structural determination. We would also like to thank Prof.

R. F. W. Jackson for helpful advice and the kind donation of a

sample of trityl hydroperoxide.

(e) (2S)-trans-4-Benzylsulfonyl-3-buten-1,2-diol (2v): Following the

procedure described above the vinyl sulfone 2u (144 mg, 0.51 mmol,

1 equiv.) in MeOH (10 mL) was treated with TsOH·H₂O (19 mg,

0.10 mmol, 0.2 equiv.) at room temp. for 12 h. Water (10 mL) and

EtOAc (10 mL) were added and the subsequent aqueous layer was

further extracted with EtOAc (3×20 mL). The combined extracts

were washed with NaHCO₃(20 mL) and brine (25 mL) and dried

with MgSO₄. The crude product obtained after filtration followed

by solvent removal under reduced pressure was purified by flash

column chromatography (PE/EtOAc, 1:1 to EtOAc) to give the diol

2v (85 mg, 70%) as a colourless crystalline solid; m.p. 110–111 °C

[1] L. Ramberg, B. Bäcklund, Ark. Chim. Mineral. Geol. 1940, 27,

vol. 13A, 1–50.

[2] L. A. Paquette, Org. React. 1977, 25, 1–71.

[3] S. Oae, Y. Uchida, The Chemistry of Sulphones and Sulphoxides

(Eds.: S. Patai, Z. Rappoport, C. J. M. Stirling), Wiley, Chich-

ester, 1988, chapter 12, pp. 649–664 and S. Braverman, chapter

13, pp. 691–698.

[4] J. M. Clough, Comp. Org. Synth. (Eds.: B. M. Trost, I. Flem-

ing), Permagon Press, Oxford, 1991, chapter 3.8, pp. 861–886.

[5] N. S. Simpkins, Sulphones in Organic Chemistry, Permagon

Press, Oxford, 1993.

[6] R. J. K. Taylor, G. Casy, Org. React. 2003, 62, 357–475.

[7] C. Y. Meyers, A. M. Malte, W. S. Matthews, J. Am. Chem. Soc.

1969, 91, 7510–7512.

(CHCl /PE). R = 0.45 (EtOAc). IR (CHCl ): ν = 3477, 3057, 2985,

˜

3

f

3

2925, 2875, 1635, 1309, 1117 cm^–1. ¹H NMR (270.1 MHz, CDCl₃):

δ = 3.44 (dd, J = 6.0, 11.0 Hz, 1 H), 3.68 (dd, J = 4.0, 11.0 Hz, 1

H), 4.26 (s, 2 H), 4.39–4.44 (m, 1 H), 6.57 (dd, J = 2.0, 15.0 Hz, 1

H), 6.67 (dd, J = 3.0, 15.0 Hz, 1 H), 7.33–7.41 (m, 5 H) ppm. ¹³C

NMR (67.9 MHz, CDCl₃): δ = 61.2, 64.9, 70.9, 127.9, 128.1, 128.9,

129.0, 130.9, 147.9 ppm. MS (CI): m/z (%) = 260 (100) [MNH₄⁺].

HRMS: C₁₁H₁₈NO₄S calcd. 260.0957; found 260.0954. [α]_D= –

22.1 (c = 0.25, CHCl₃).

[8] E. Vedejs, S. P. Singer, J. Org. Chem. 1978, 43, 4884–4885.

[9] X.-P. Cao, T.-L. Chan, H.-F. Chow, Tetrahedron Lett. 1996, 37,

1049–1052.

(f) (3S)-trans-2-Benzylsulfonyl-3-[(2R)-1,2-dihydroxyethyl]oxirane

(syn-4v): The vinyl sulfone 2v (59 mg, 0.24 mmol, 1 equiv.) in THF

[10] H.-R. Sliwka, H.-J. Hansen, Helv. Chim. Acta 1984, 67, 434–

440.

Eur. J. Org. Chem. 2006, 1740–1754

www.eurjoc.org

1753

P. Evans, P. Johnson, R. J. K. Taylor

FULL PAPER

[11]

[12]

[42] J. G. Hill, K. B. Sharpless, C. M. Exon, R. Regenye, Org. Synth.

1984, 63, 66–78.

[43] M. Mikolajczyk, S. Grzejszczak, A. Chefczynska, A. Zatorski,

J. Org. Chem. 1979, 44, 2967–2972.

[44] G. D. McAllister, D. E. Paterson, R. J. K. Taylor, Angew.

Chem. Int. Ed. 2003, 42, 1387–1391.

[45] M. Sindt, S. B. Schneider, J. L. Mieloszynski, Phosphorus Sul-

fur Silicon Relat. Elem. 2001, 174, 163–176.

[46] E. Larsson, Tetrahedron 1971, 27, 2553–2556.

[47] M. V. R. Reddy, S. Reddy, Acta Chim. Hung. 1984, 115, 269–

272.

G. Casy, R. J. K. Taylor, Tetrahedron 1989, 45, 455–466.

C. Y. Meyers, D. H. Hua, N. J. Peacock, J. Org. Chem. 1980,

45, 1719–1721.

D. H. Hua, N. J. Peacock, C. Y. Meyers, J. Org. Chem. 1980,

45, 1717–1719.

H. Matsuyama, Y. Miyazawa, Y. Takei, M. Kobayashi, J. Org.

Chem. 1987, 52, 1703–1710.

M. G. Ranasinghe, P. L. Fuchs, J. Am. Chem. Soc. 1989, 111,

779–782.

D. Scarpetti, P. L. Fuchs, J. Am. Chem. Soc. 1990, 112, 8084–

8090.

J. B. Hendrickson, P. S. Palumbo, J. Org. Chem. 1985, 50, 2110–

2112.

P. Evans, R. J. K. Taylor, Tetrahedron Lett. 1997, 38, 3055–

3058.

O. Meth-Cohn, C. Moore, H. C. Taljaard, J. Chem. Soc., Per-

kin Trans. 1 1988, 2663–2674.

M. Ashwell, W. Clegg, R. F. W. Jackson, J. Chem. Soc., Perkin

Trans. 1 1991, 897–908.

P. L. Fuchs, T. F. Braish, Chem. Rev. 1986, 86, 903–917.

N. S. Simpkins, Tetrahedron 1990, 46, 6951–6984.

M. Schlosser, Pure Appl. Chem. 1988, 60, 1627–1634.

M. H. Nomura, Bull. Chim. Soc., Fr. 1925, 1245–1247.

B. E. Maryanoff, A. B. Reitz, Chem. Rev. 1989, 89, 863–927.

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[48] D. J. Pasto, J. L. Miesel, J. Am. Chem. Soc. 1963, 85, 2118–

2124.

[49] M. Node, K. Nishide, Y. Shigeta, K. Obata, H. Shiraki, H.

Kunishiga, Tetrahedron 1997, 53, 12883–12894.

[50] N. Iranpoor, I. M. Baltork, F. S. Zardaloo, Tetrahedron 1991,

47, 9861–9866.

[51] J. M. Dickinson, J. A. Murphy, C. W. Patterson, N. F. Wooster,

J. Chem. Soc., Perkin Trans. 1 1990, 1179–1184.

[52] T. Kawakami, M. Miyatake, I. Shibata, A. Baba, J. Org. Chem.

1996, 61, 376–379.

[53] A. M. Easton, M. J. A. Habib, J. Park, W. E. Watts, J. Chem.

Soc., Perkin Trans. 2 1972, 2290–2297.

[54] E. Keinan, M. Peretz, J. Org. Chem. 1983, 48, 5302–5309.

[55] M. Cussac, A. Boucherle, Bull. Chim. Soc., Fr. 1974, 1437–

1441.

[21]

[22]

[23]

[24]

[25]

[26] K. C. Nicolaou, M. W. Härter, J. L. Gunzner, A. Nadin, Lie-

[56] R. A. Gase, V. K. Pandit, J. Am. Chem. Soc. 1979, 101, 7059–

bigs Ann./Recueil 1997, 1283–1301.

7064.

[27] W. S. Wadsworth Jr, Org. React. 1977, 25, 73–253.

[28] I. Shahak, J. Almog, Synthesis 1969, 170–172.

[29] I. Shahak, J. Almog, Synthesis 1970, 145–147.

[30] N. Tanno, S. Terashima, Chem. Pharm. Bull. 1983, 31, 837–

851.

[31] J. J. Eisch, J. E. Galle, J. Org. Chem. 1979, 44, 3277–3279.

[32] P. Evans, M. Leffray, Tetrahedron 2003, 59, 7973–7981.

[33] C. H. Heathcock, B. L. Finkelstein, E. T. Jarvi, P. A. Radel,

C. R. Haley, J. Org. Chem. 1988, 53, 1922–1942.

[34] J.-M. Lopez-Pedrosa, M. R. Pitts, S. M. Roberts, S. Samina-

than, J. Whittall, Tetrahedron Lett. 2004, 45, 5073–5075.

[35] A. D. Briggs, R. F. W. Jackson, W. Clegg, M. R. J. Elsegood, J.

Kelly, P. A. Brown, Tetrahedron Lett. 1994, 35, 6945–6948.

[36] Y. Mori, K. Yaegashi, H. Furukawa, J. Am. Chem. Soc. 1996,

118, 8158–8159.

[57] H. Chikishita, M. Miyazaki, K. Itoh, J. Chem. Soc., Perkin

Trans. 1 1987, 699–706.

[58] H. Yamashita, Bull. Chem. Soc. Jpn. 1988, 61, 1213–1220.

[59] R. L. Crumbie, B. S. Deol, J. E. Nemorin, D. D. Ridley, Austr.

J. Chem. 1978, 31, 1965–1980.

[60] A. P. Dishington, R. E. Douthwaite, A. Mortlock, A. B. Muc-

cioli, N. S. Simpkins, J. Chem. Soc., Perkin Trans. 1 1997, 323–

338.

[61] Y. Takeuchi, K. Sakagawa, M. Kubo, M. Yamato, Chem.

Pharm. Bull. 1986, 34, 1323–1327.

[62] M. Ishizaki, K. Fujita, M. Shimamoto, O. Hoshino, Tetrahe-

dron: Asymmetry 1994, 5, 411–424.

[63] T. E. Nalesnik, J. G. Fish, S. W. Horgan, M. Orchin, J. Org.

Chem. 1981, 46, 1987–1990.

[64] P. Evans, R. J. K. Taylor, J. Sulf. Chem. 2005, 26, 481–497.

[65] C. C. J. Culvenor, W. Davies, W. E. Savige, J. Chem. Soc. 1949,

2198–2206.

[37] R. F. W. Jackson, S. P. Standen, W. Clegg, J. Chem. Soc., Perkin

Trans. 1 1995, 149–156.

[38] R. F. W. Jackson, S. P. Standen, W. Clegg, A. McCamley, J.

Chem. Soc., Perkin Trans. 1 1995, 141–148.

[66] L. H. P. Meijer, V. K. Pandit, Tetrahedron 1985, 41, 467–472.

[67] K. E. Bashford, A. L. Cooper, P. D. Kane, C. J. Moody, S. Mu-

thusamy, E. Swann, J. Chem. Soc., Perkin Trans. 1 2002, 1672–

1687.

[68] T. Hudlicky, H. F. Olivo, M. G. Natchus, E. F. Umpierrez, E.

Pandolfi, C. Volonterio, J. Org. Chem. 1990, 55, 4767–4770.

[69] X.-P. Cao, Tetrahedron 2002, 58, 1301–1308.

[70] A. Leblanc, L. Fosset, G. Magnaud, G. Delmas, M. Des-

granges, H. Sentenac-Roumanou, C. Lion, C. Charvy, A.

Mohri, Phosphorus Sulfur Silicon 1993, 79, 141–146.

Received: December 7, 2005

[39] Crystal structure for compound anti-5u: C₁₄H₁₈O₃M = 234.28,

monoclinic space group P2₁, a = 6.404(9) Å, b = 8.368(7) Å, c

= 12.496(7) Å, β = 97.95(7)°, U = 663.2(12) Å³, T = 293(2) K,

Z = 2, λ (Mo-K_α) = 0.7107 Å, 1258 reflections collected, R_int

= 3.2%. CCDC-290132 contains the supplementary crystallo-

graphic data for this paper. These data can be obtained free of

charge from The Cambridge Crystallographic Data Centre via

www.ccdc.cam.ac.uk/data_request/cif.

[40] R. Polt, T. Wijayaratne, Tetrahedron Lett. 1991, 32, 4831–4834.

[41] T. Katsuki, V. S. Martin, Org. React. 1996, 48, 1–301.

Published Online: January 30, 2006

1754

www.eurjoc.org

Eur. J. Org. Chem. 2006, 1740–1754

Article Doi

The epoxy-Ramberg-Baecklund reaction (ERBR): A sulfone-based method for the synthesis of allylic alcohols

DOI: 10.1002/ejoc.200500956

Source and publish data:

Authors:

Article abstract of DOI:10.1002/ejoc.200500956

Full text of DOI:10.1002/ejoc.200500956

Products guided by the article

R&D Labs maybe for 889862-11-7

Relevant to this article

Hot Product