A stereocontrolled approach to ethers with two α stereocentres

Article abstract of DOI:10.1002/ejoc.200800634

The stereocontrolled synthesis of enantiomeric pairs of four ethers, in which the oxygen atom is flanked by two α stereocentres, has been achieved using a chiral base/arene chromium tricarbonyl activation approach. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800634

FULL PAPER
DOI: 10.1002/ejoc.200800634
A Stereocontrolled Approach to Ethers with Two α Stereocentres
Robert Felstead,[a] Susan E. Gibson,*[a] Aaron Rooney,[a] and Eric S. Y. Tse[a]
Keywords: Alkylation / Asymmetric synthesis / Chiral base / Chromium / Ether compounds
The stereocontrolled synthesis of enantiomeric pairs of four
ethers, in which the oxygen atom is flanked by two α
stereocentres, has been achieved using a chiral base/arene
chromium tricarbonyl activation approach.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
ine) ligand 7,[2b] and dendrimers with either a homochiral
or a heterochiral relationship between their layers such as 8
(Figure 1).[4]
Introduction
Some time ago, we demonstrated that tricarbonylchro-
mium(0) complexes of alkyl benzyl ethers (1) react with the
chiral diamide derived from butyllithium/chiral diamine 2
and an electrophile to give the chiral ether complexes 3 in
high yield and enantiomeric excess (Scheme 1).[1]
Scheme 1. Asymmetric functionalisation of alkyl benzyl ethers.
More recently we extended this chemistry to the C3-sym-
metric tris-ether 4, and found that it was possible to install
three methyl groups in one pot in good yield and with good
stereoselectivity to produce 5 (Scheme 2).[2]
Figure 1. C3-Symmetric molecules made using chiral base chemis-
try.
Pursuing the idea of using the chemistry described above
to install more than one stereocentre in one pot, we elected
to study the reactivity of the chromium complex 9 (Fig-
ure 2). Successful introduction of two stereocentres into this
molecule would provide the foundation for a new route to
Scheme 2. Formation of three stereocentres in one pot.
We subsequently employed this chemistry to make a
range of enantiopure C3-symmetric compounds[3] including
the borane-protected tris(phosphane) 6,[2b] the tris(pyrid-
[a] Department of Chemistry, Imperial College London,
South Kensington Campus, London SW7 2AY, UK
Fax: +44-207-594-5804
E-mail: s.gibson@imperial.ac.uk
Figure 2. Hexacarbonyl(dibenzyl ether)dichromium(0).
Eur. J. Org. Chem. 2008, 4963–4971
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 4963

R. Felstead, S. E. Gibson, A. Rooney, E. S. Y. Tse
FULL PAPER
enantio-enriched ethers in which the oxygen atom is flanked
Attempts by others to synthesise the ether 11 have been
by two chiral centres. The results of our study are presented based on nucleophilic substitution reactions. The stability
here.
of benzylic cations, however, imparts a considerable degree
of SN1 character to such reactions and renders them diffi-
cult to control. In a typical example, treatment of racemic
α-methylbenzyl alcohol with a catalytic amount of lantha-
num triflate gave a 2:1 mixture of the  and meso isomers
of ether 11 (Scheme 4).[7]
Results and Discussion
Hexacarbonyl(dibenzyl ether)dichromium(0) (9) was pre-
pared according to a reported procedure.[5] Thermolysis of
dibenzyl ether and hexacarbonylchromium(0) in a 5:1 mix-
ture of di-n-butyl ether and THF, followed by work-up,
gave 9 as a stable yellow solid in 85% yield (Scheme 3). To
deprotonate the ether 9, the diamine (+)-2 (2 equiv.)[6] was
treated with butyllithium and lithium chloride, and complex
9 was added to the resulting deep red solution. After the
addition of iodomethane and work-up, a yellow solid was
obtained that was identified as the dimethylated complex
Scheme 4. A typical nucleophilic substitution approach to bis[1-(1-
phenylethyl)] ether.
In an isolated solution to the problem of stereoselectivity
in these reactions, a 1:2 inclusion crystal between (S)-(–)-1-
phenylethanol and (R,R)-(–)-trans-4,5-bis[hydroxy(diphen-
yl)methyl]-2,2-dimethyl-1,3-dioxacyclopentane (12) (Fig-
ure 3), was treated with TsOH in the solid state. This gave
enantiomerically and diastereoisomerically pure (S,S)-(–)-
11 in unreported yield.[8] It was proposed that the high de-
gree of stereocontrol in this reaction originated from a well-
defined and relatively rigid orientation of the two reaction
partners in the solid state. Attack of one alcohol of the pair
on the carbocation of the other alcohol was thus able to
take place with complete retention of configuration.
10 on the basis of its elemental analysis, IR, H NMR, 13C
1
NMR, and mass spectra. In order to establish the stereoiso-
meric composition of 10, the reaction was repeated using
diamine (–)-2. Analysis of both products by chiral HPLC
revealed that the C2-symmetric isomer had been formed in
each case in Ն 99% ee, but that the samples were contami-
nated with small amounts of the meso product (7%). The
syntheses of (–)- and (+)-10 were repeated but using the
base/electrophile/base/electrophile sequence depicted for
(–)-10 in Scheme 3, and, pleasingly, this generated samples
of (–)- and (+)-10 that were essentially enantiopure (99%
ee) and diastereomerically pure (99% de). The tricarbonyl-
chromium(0) units were subsequently removed from the
samples of (–)- and (+)-10 by air/light oxidation to give the
C2-symmetric ethers (+)- and (–)-11 respectively. These were
1
both uncontaminated by the meso isomer, according to H
NMR spectroscopy, revealing that epimerisation had not Figure 3. Inclusion compound used to generate stereochemically
pure bis[1-(1-phenylethyl)] ether.
occurred. It was therefore assumed that both samples were
enantiomerically pure.
Attempts to synthesise enantio-enriched C2-symmetric
acyclic ethers with chiral centres α to the ether oxygen that
lack an aromatic α-substituent have proven more amenable
to the development of synthetically useful nucleophilic sub-
stitutions. For example, very careful control of the reaction
conditions used for the synthesis of the bisester 13 from
lactic acid derivatives led to an 89% yield of enantiomer-
ically pure 13 accompanied by just a trace of the corre-
sponding meso isomer (Scheme 5).[9]
Scheme 5. Non-aromatic chiral ethers can be generated from lactic
acid derivatives.
Scheme 3. Synthesis of (+)-(1R,1ЈR)-bis[1-(1-phenylethyl)] ether.
4964
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4963–4971

A Stereocontrolled Approach to Ethers with Two α Stereocentres
In view of the excellent stereoselectivity achieved in our philes (MeOD, MeI, allyl bromide), however, consistently
deprotonation/alkylation approach to ether 11, compared led either to the recovery of 15 or to an intractable mixture
to that obtained through typical nucleophilic substitution of products. (In contrast, treatment with tBuOK led to the
routes to this compound, we decided to proceed to probe rapid production of a black solution, which after quenching
the scope and limitations of our synthesis.
and work-up gave a yellow solid that was identified as the
Deprotonation of complex 9 with the base derived from alkene complex 16.[10] The mechanism for the formation of
(+)-2 and quenching with allyl bromide was examined un- 16 is as yet undetermined, but its formation serves to under-
der a range of conditions. It was disappointing to discover, score the difficulty in introducing a second electrophile into
however, that all of these experiments led to a mixture of the monoallylated complex 15.)
the diallylated complex 14 and the monoallylated complex
Having discovered that the monoallylated complex 15
15 (Scheme 6). On one occasion, the mixture was separated could not be converted into disubstituted derivatives, our
by column chromatography to yield samples of (+)-14 and attention turned to the monomethylated complex 17 to see
(–)-15 in 19 and 35% isolated yield respectively. Repetition if this compound would afford ethers with two chiral
of this reaction using the amine (–)-2 provided samples of centres α to the ether oxygen. Deprotonation of the diben-
(–)-14 and (+)-15, and chiral HPLC analysis revealed that zyl ether complex 9 with 0.7 equiv. of the chiral amide fol-
both the diallyl and the monoallyl complexes had been gen- lowed by quenching with iodomethane led to (–)-17 in satis-
erated in Ն 97% ee in both reactions (the meso isomer of factory yield (59%) and excellent enantiopurity (98% ee)
14 was undetectable by NMR spectroscopy and HPLC (Scheme 7). Pleasingly, the deprotonation of (–)-17 followed
analysis).
by addition of benzyl bromide or allyl bromide led to the
It was clear from these experiments, and similar results generation of the disubstituted complexes (+)-18 and (+)-
obtained using benzyl bromide as the electrophile (not 19 in good yields and excellent enantiopurities (the meso
documented here), that the introduction of the second allyl isomers of 18 and 19 were undetectable by NMR spec-
(or benzyl) substituent was problematic. In order to probe troscopy and HPLC analysis). Oxidative removal of the
the second substitution further, a sample of (–)-15 was pre- chromium carbonyl groups proceeded efficiently to give the
pared using one equivalent of the chiral base. This reaction ethers (+)-20 and (+)-21.
proceeded smoothly to give an 89% yield of the monoallyl-
The ether 20 is a novel compound, whilst the ether 21
ated complex in Ն 99% ee. Treatment of (–)-15 with several has been synthesised by the reaction of benzaldehyde with
bases (tBuLi, NaH, LiNMe2, [(+)-2/nBuLi]) and electro- (S)-1-phenyl-1-(triethylsilyloxy)ethane followed by the ad-
Scheme 6. Synthesis of allylated derivatives of ether complex 9.
Eur. J. Org. Chem. 2008, 4963–4971
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4965

R. Felstead, S. E. Gibson, A. Rooney, E. S. Y. Tse
FULL PAPER
Scheme 7. Asymmetric synthesis of the ethers 20 and 21.
dition of allyl(trimethyl)silane (Scheme 8).[11] Ether (–)-21 butyl analogue 25 (Scheme 9). The achiral ether 22, re-
was formed in 77% yield by this route, but was heavily con- quired for asymmetric elaboration, has previously been syn-
taminated with the meso isomer (56% de), an observation thesised by the action of catalytic amounts of Nafion-H®
attributed to the ease of formation of a benzylic carbo- on the trimethylsilyl ether derivative of 4-tert-butylbenzyl
cation thus promoting an SN1 type transition state during alcohol,[12] but we chose to deprotonate the alcohol and
the allylation step.
Scheme 8. An alternative non-selective approach to ether 21.
In order to start to access analogues of the C2-symmetric
ether 11, in preparation for a study of applications of these
ethers, we have synthesised both enantiomers of the tert- Scheme 9. Asymmetric synthesis of C2-symmetric ether 25.
4966
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4963–4971

A Stereocontrolled Approach to Ethers with Two α Stereocentres
performed using BDH silica gel (particle size 33–70 µm). Melting
points were recorded with a Sanyo Gallenkamp melting point ap-
paratus in open capillaries and are uncorrected. Optical rotations
were recorded with an AA 10 polarimeter from Index Instruments
or with a Perkin–Elmer 241 polarimeter using a 1-dm path length;
concentrations are given as g/100 mL. IR spectra were recorded
with a Perkin–Elmer Spectrum RX FT-IR spectrometer. NMR
spectra were recorded at room temperature with Bruker AC 300F,
DRX 400, AV 400 or AV 500 instruments in CDCl3, unless other-
wise stated. J values are reported in Hertz and chemical shifts in
ppm. Mass spectra were recorded with Micromass Platform II and
Micromass AutoSpec-Q instruments by the mass spectrometry ser-
vice at Imperial College London. Elemental analyses were per-
formed by the London Metropolitan University microanalytical
service. The diamines (+)- and (–)-2 were prepared according to a
literature method.[6]
react it with the corresponding bromide. Complexation of
ether 22, dimethylation using the bases derived from both
(+)-2 and (–)-2, and decomplexation all proceeded
smoothly to generate samples of (+)- and (–)-25 that were
essentially enantiomerically and diastereoisomerically pure.
Racemic 25 has been observed previously as a byproduct
of the hydrolysis of the corresponding chloride
(Scheme 10).[13]
Hexacarbonyl(dibenzyl ether)dichromium(0) (9):[5] Dibenzyl ether
(2.25 mL, 11.8 mmol) and hexacarbonylchromium(0) (5.5 g,
24.9 mmol) were added to dry di-n-butyl ether (71 mL) and THF
(14 mL) and the mixture was degassed 10 times and shielded from
ambient light. The reaction mixture was heated under reflux for
72 h at 135 °C and then cooled to room temperature. The solvent
was removed under reduced pressure and the crude mixture was
pre-absorbed onto silica (30 g). Purification was carried out by
flash column chromatography (SiO2; hexane/ethyl acetate, 70:30)
to yield complex 9 (4.73 g, 85%) as a yellow solid; m.p. 126–128 °C
(ref.[5] 126–127 °C). Rf = 0.13 (SiO2; hexane/ethyl acetate, 80:20).
Scheme 10. An earlier approach to ether 25 is unselective.
Conclusions
IR (CHCl ): ν =1973 (s, υ
), 1899 (υCO, s) cm–1. 1H NMR
˜
3
CO
We have developed a new approach to ethers with two α
stereocentres. The method is limited by the constraint that
the first electrophile introduced cannot be larger than iodo-
methane. On the other hand, the enantio- and diastereocon-
trol achieved in the new method is significantly superior to
conventional approaches based on nucleophilic substitution
reactions, especially for α-aryl-substituted ethers. It has thus
proven possible to synthesise both enantiomers of the ethers
11, 20, 21, and 25 for the first time in a highly stereocon-
trolled manner. In light of i) the success of the amine ana-
logue of ether 11 in inducing stereoselectivity when used,
for example, in its own right as a chiral base,[14] or when
incorporated in a monodentate phosphoramidite ligand,[15]
and ii) evidence that the presence of an ether can affect the
outcome of a range of catalytic reactions,[16] it is anticipated
that these molecules will find applications as chiral addi-
tives.
(400 MHz): δ = 4.38 (s, 4 H, OCH2ϫ2), 5.28–5.32 (m, 2 H,
CrHparaϫ2), 5.38–5.43 (m, 8 H, CCrHorthoϫ4, CCrHmetaϫ4). 13C
NMR (100 MHz): δ = 71.2 (CCrCH2ϫ2), 91.7 (CCr paraϫ2), 91.8,
C
H
92.6 (CCrHorthoϫ4, CCrHmetaϫ4), 106.9 (CCrϫ2), 232.6 (CϵOϫ6)
ppm. MS (EI): m/z (%) = 470 (50) [M+], 386 (26) [M+ – 3CO], 302
(100) [M+ – 6CO].
(–)-(1R,1ЈR)-Hexacarbonyl{bis[1-(1-phenylethyl) ether]}dichromium(0)
[(–)-10]: n-Butyllithium (0.11 mL, 2.50  in hexane, 0.27 mmol) was
added dropwise to a stirred solution of the diamine (+)-2 (59 mg,
0.14 mmol) in THF (4 mL) at –78 °C. The solution was warmed to
room temperature over 30 min. The resulting deep red solution was
then recooled to –78 °C. A solution of heat gun-dried lithium chlo-
ride (6 mg, 0.14 mmol) in THF (3 mL) was added through a can-
nula and the reaction mixture was stirred for a further 5 min before
a precooled solution (–78 °C) of complex 9 (94 mg, 0.20 mmol) in
THF (3 mL) was added dropwise through a cannula. The reaction
was stirred at –78 °C for 40 min before iodomethane (12 µL,
0.20 mmol) was added through a micro-syringe into the reaction
mixture. Stirring was continued for a further 15 min at –78 °C.
Meanwhile, in another reaction flask, n-butyllithium (0.16 mL,
2.50  in hexane, 0.40 mmol) was added dropwise to a stirred solu-
tion of the diamine (+)-2 (84 mg, 0.20 mmol) in THF (4 mL) at
–78 °C. The solution was warmed to room temperature over 30 min
and the resulting deep red solution was then recooled to –78 °C. A
solution of heat gun-dried lithium chloride (9 mg, 0.20 mmol) in
THF (4 mL) was added through a cannula and the mixture was
stirred for an additional 5 min. The bisamide solution was transfer-
red through a cannula into the reaction mixture, which was stirred
for a further 30 min. Addition of iodomethane (37 µL, 0.60 mmol)
at –78 °C gave a yellow solution after stirring for 60 min. The reac-
tion mixture was quenched using MeOH (1 mL) and the solvent
was removed in vacuo to give a crude yellow solid. Purification by
flash column chromatography (SiO2; hexane/ethyl acetate, 100:0 Ǟ
80:20) yielded complex (–)-10 (86 mg, 86%) as a yellow solid; m.p.
137–140 °C. Rf = 0.15 (SiO2; hexane/ethyl acetate, 80:20). Enantio-
Experimental Section
General: All reactions and manipulations involving organometallic
compounds were performed under dry nitrogen, using standard
vacuum line and Schlenk techniques.[17] Reactions and operations
involving the use of (arene)tricarbonylchromium(0) complexes were
protected from light. Tetrahydrofuran was distilled from sodium
benzophenone ketyl and used immediately. Dichloromethane was
distilled from calcium hydride. The concentration of n-butyllithium
was determined by titration against diphenylacetic acid in tetra-
hydrofuran.[18] All other chemicals were used as purchased from
commercial sources. Thin-layer chromatography (TLC) was per-
formed on Merck silica gel glass plates 60 (F254), using UV light
(254 nm) as visualizing agent and/or vanillin or potassium perman-
ganate as developing agents. Flash column chromatography was
Eur. J. Org. Chem. 2008, 4963–4971
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4967

R. Felstead, S. E. Gibson, A. Rooney, E. S. Y. Tse
FULL PAPER
metric excess was determined by HPLC analysis (Chiralcel AD,
n-hexane/iPrOH, 90:10, 1.0 mL/min, 330 nm); (S)-enantiomer tr =
15.0 min (minor); (R)-enantiomer tr = 16.7 min (major): Ն 99% ee.
2 H, OCHCHЈHϫ2), 4.51 (t, J = 6.0 Hz, 2 H, OCHϫ2), 5.05 (dd,
J = 1.0, 17.0 Hz, 2 H, CH=CHЈH x 2), 5.12 (dd, J = 1.0, 10.0 Hz,
2 H, CH=CHЈHϫ2), 5.22–5.51 (m, 8 H, CArHϫ8), 5.72–5.84 (m,
4 H, CArHϫ2 and CH=CH2ϫ2) ppm. 13C NMR (100 MHz): δ
= 42.7 (CH2CH=CH2ϫ2), 76.7 (OCHϫ2), 90.1 (CCrHϫ2), 90.4
[α]2D0 = –13, (c = 1.00, CHCl ). IR (film): ν = 1953 (υCO, s), 1860
˜
3
1
(υCO, s) cm–1. H NMR (400 MHz): δ = 1.50 (d, J = 7.0 Hz, 6 H,
CHCH3ϫ2), 4.46 (q, J = 7.0 Hz, 2 H, CHCH3), 5.27–5.69 (m, 10 (CCrHϫ2), 92.3 (CCrHϫ2), 93.5 (CCrHϫ2), 94.4 (CCrHϫ2), 111.5
H, C6H5ϫ2). 13C NMR (100 MHz): δ = 23.6 (OCHCH3ϫ2), 72.9 (CCrϫ2), 119.2 (CH=CH2ϫ2), 132.6 (CH=CH2ϫ2), 232.9
(OCHϫ2), 91.1 (CCrHϫ2), 91.2 (CCrHϫ2), 91.6 (CCrHϫ2), 92.1 (CϵOϫ6) ppm. MS (EI): m/z (%) = 550 (71) [M+], 466 (44) [M+
–
(CCrHϫ2), 93.6 (CCrHϫ2), 113.8 (CCrϫ2), 232.9 (CϵOϫ6) ppm.
3CO], 382 (97) [M+ – 6CO], 312 (100) [M+ – Cr – 6CO], 278 (23)
MS (CI): m/z (%) = 516 (21) [MNH4+], 680 (12) [MNH4 – Cr – [M+ – 2Cr – 6CO]. C26H22Cr2O7 (550.44): calcd. C 56.73, H 4.03;
+
3CO], 241 (100) [MH+ – OCH2(CH3)Ph – Cr – 3CO]. C22H18Cr2O7 found C 56.78, H 4.04.
(498.37): calcd. C 53.01, H 3.61; found C 53.02, H 3.70.
(+)-(1R,1ЈR)-Hexacarbonyl{bis[1-(1-phenylbut-3-enyl)] ether}di-
(+)-(1S,1ЈS)-Hexacarbonyl{bis[1-(1-phenylethyl) ether]}dichromium(0)
[(+)-10]: Complex (+)-10 was prepared from 9 (94 mg, 0.20 mmol)
and diamine (–)-2 (143 mg, 1.06 mmol) following the procedure de-
scribed for (–)-10. 82% yield, yellow solid. [α]2D0 = +12 (c = 1.00,
CHCl3). ee Ն 99%. All other analytical data were identical to those
obtained for (–)-10.
chromium(0) [(+)-14]: Complex (+)-14 was prepared from 9
(188 mg, 0.4 mmol) and (+)-2 (336 mg, 0.80 mmol) following the
procedure described for (–)-14. 17% yield, orange solid. [α]2D0 = +18
(c = 0.82, CHCl3). ee Ն 99%. All other analytical data were iden-
tical to those obtained for (–)-14. Monoallylated complex (–)-15 as
a yellow oil (68 mg, 35%, Ն 99% ee).
(+)-(1R,1ЈR)-Bis[1-(1-phenylethyl)] Ether [(+)-11]: Complex (–)-10
(–)-(R)-Hexacarbonyl{benzyl [1-(1-phenylbut-3-enyl)] ether}di-
(48.7 mg, 0.098 mmol) was dissolved in a mixture of DCM (20 mL) chromium(0) [(–)-15]: n-Butyllithium (1.38 mL, 1.60  in hexane,
and Et2O (2 mL) and left for 24 h by the window. The solvent was
removed from the mixture under reduced pressure. Purification by
column chromatography (SiO2; hexane/diethyl ether, 98:2) gave a
colourless oil (21.5 mg, 97%). Rf = 0.28 (SiO2; hexane/diethyl ether,
2.20 mmol) was added to a solution of the diamine (+)-2 (463 mg,
1.10 mmol) in THF (12 mL) at –78 °C. The solution was warmed
to room temperature over 30 min. The deep red solution was reco-
oled to –78 °C. A solution of heat gun-dried lithium chloride
(47 mg, 1.10 mmol) in THF (6 mL) was added and the reaction
mixture was stirred for a further 5 min before a precooled solution
98:2). [α]2D0 = +224 (c = 1.00, CHCl ). IR (film): ν = 1091 (υ
,
˜
3
C–O–C
s) cm–1 1H NMR (400 MHz): δ = 1.41 (d, J = 6.5 Hz, 6 H,
.
CHCH3ϫ2), 4.28 (q, J = 6.5 Hz, 2 H, CHCH3ϫ2), 7.28–7.41 (m, (–78 °C) of complex 9 (470 mg, 1.00 mmol) in THF (6 mL) was
10 H, CArHϫ10) ppm. 13C NMR (100 MHz): δ = 24.7 (CH3ϫ2),
added. On addition of the complex, the reaction mixture slowly
74.6 (CHCH3ϫ2), 126.3 (CArHϫ4), 127.4 (CArHϫ2), 128.5 turned orange. After stirring for 40 min at –78 °C, allyl bromide
(CArHϫ4), 144.2 (CArϫ2) ppm. MS (CI): m/z (%) = 244 (100) [M
(0.26 mL, 3.00 mmol) was added. Stirring was continued for a fur-
+ NH4+], 122 (13) [M – C6H5CHCH3 + NH4+], 122 (75) [M – ther 20 min before quenching with methanol (2 mL). The solvent
C6H5CHCH3 + H+], 105 (12) [C6H5CHCH3+]. HRMS (CI): calcd. was removed in vacuo leaving a yellow residue. Purification by col-
for C16H22NO+ (244.1701); found 244.1711.
umn chromatography (SiO2; hexane/ethyl acetate, 95:5 Ǟ 85:15)
afforded complex (–)-15 (451 mg, 89%) as a yellow oil. Rf = 0.25
(SiO2; hexane/ethyl acetate, 80:20). Enantiometric excess was deter-
mined by HPLC analysis (Chiralcel AD, n-hexane/iPrOH, 90:10,
1.0 mL/min, 330 nm); (S)-enantiomer tr = 16.1 min (minor); (R)-
enantiomer tr = 19.7 min (major): Ն 99% ee. [α]2D0 = –10 (c = 0.70
(–)-(1S,1ЈS)-Bis[1-(1-phenylethyl)] Ether [(–)-11]: Ether (–)-11 was
prepared from (+)-10 (39.5 mg, 0.079 mmol) following the pro-
cedure described for (+)-11. 98% yield, colourless oil. [α]2D0 = –234
(c = 1.00, CHCl3). All other analytical data were identical to those
obtained for (+)-11.
in CHCl ). IR (CHCl ): ν= 1974 (υCO, s), 1897 (υCO, s), 1642 (υC=C
,
˜
3
3
w) cm– 1 1 H NMR (400 MHz): δ = 2.57–2.61 (m, 2 H,
.
(–)-(1S,1ЈS)-Hexacarbonyl{bis[1-(1-phenylbut-3-enyl)] ether}di-
chromium(0) [(–)-14]: n-Butyllithium (0.32 mL, 2.50  in hexane,
0.80 mmol) was added to a solution of the diamine (–)-2 (168 mg,
0.40 mmol) in THF (2 mL) at –78 °C. The solution was warmed to
room temperature over a period of 30 min. The deep red solution
was recooled to –78 °C. A solution of heat gun-dried lithium chlo-
ride (17 mg, 0.40 mmol), dissolved in THF (2 mL) was added and
the reaction mixture was stirred for a further 5 min before a pre-
cooled solution (–78 °C) of complex 9 (94 mg, 0.20 mmol) in THF
(2 mL) was added. After stirring for 60 min at –78 °C, allyl bromide
(0.10 mL, 1.20 mmol) was added. Stirring was continued for a fur-
ther 2 h after which the reaction was quenched with methanol
(1 mL). The solvent was removed in vacuo leaving a red residue.
Purification by column chromatography (SiO2; hexane/ethyl ace-
tate, 95:5 Ǟ 80:20) afforded complex (–)-14 as an orange solid
(21 mg, 19%) and the monoallylated bischromium complex (+)-15
(66 mg, 35%, 97% ee) as determined by HPLC analysis, 1H and
13C NMR spectroscopy; m.p. 105–107 °C. Rf = 0.27 (SiO2; hexane/
ethyl acetate, 80:20). Enantiometric excess was determined by
HPLC analysis (Chiralcel AD, n-hexane/iPrOH, 90:10, 0.25 mL/
min, 330 nm); (S)-enantiomer tr = 32.5 min (major); (R)-enantio-
mer tr = 35.1 min (minor): Ն 99% ee. [α]2D0 = –18 (c = 0.82, CHCl3).
CH2CH=CH2), 4.24 (t, J = 6.0 Hz, 1 H, OCHCH2), 4.38 (d, J =
11.5 Hz, 1 H, OCHЈH), 4.59 (d, J = 11.5 Hz, 1 H, OCHЈH), 5.10–
5.18 (m, 2 H, CH=CH2), 5.27–5.68 (m, 10 H, CCrHϫ10), 5.79–
5.90 (m, 1 H, CH=CH2) ppm. 13C NMR (100 MHz): δ = 42.3
(CH2CH=CH2), 70.2 (OCH2), 77.2 (OCHCH2), 91.1 (CCrH), 91.4
(CCrH), 91.56 (CCrH), 91.61 (CCrH), 92.0 (CCrH), 92.1 (CCrHϫ2),
92.3 (CCrHϫ2), 93.2 (CCrH), 107.3 (CCr), 111.2 (CCr), 119.1
(CH=CH2), 132.6 (CH=CH2), 232.7 (CϵOϫ3), 232.9 (CϵOϫ3)
ppm. MS (EI): m/z (%) = 510 (69) [M+], 426 (39) [M+ – 3CO], 398
(12) [M+ – 4CO], 370 (16) [M+ – 5CO], 342 (100) [M+ – 6CO], 290
(55) [M+ – Cr – 6CO], 238 (34) [M+ – 2Cr – 6CO]. C23H18Cr2O7
(510.38): calcd. C 54.13, H 3.55; found C 54.06, H 3.43.
(+)-(S)-Hexacarbonyl{benzyl [1-(1-phenylbut-3-enyl)] ether}di-
chromium(0) [(+)-15]: Complex (+)-15 was prepared from 9
(204 mg, 0.43 mmol) and (–)-2 (200 mg, 0.43 mmol) following the
procedure described for (–)-15. 86% yield, yellow oil. [α]2D0 = +6.4
(c = 1.85, CHCl3). ee Ն 99%. All other analytical data were iden-
tical to those obtained for (–)-15.
Tricarbonyl[1-phenylbut-3-ene]chromium(0) (16):[10] Potassium tert-
butoxide (27 mg, 0.24 mmol) and THF (1 mL) were placed in a
small Schlenk tube at room temperature. Complex (–)-15 (95 mg,
0.91 mmol), dissolved in THF (2 mL), was added using a syringe.
IR (CHCl ): ν= 1961 (υCO, s), 1868 (υCO, s) cm–1
.
1H NMR
˜
3
(400 MHz): δ = 2.51–2.59 (m, 2 H, OCHCHЈHϫ2), 2.63–2.70 (m,
4968
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4963–4971

A Stereocontrolled Approach to Ethers with Two α Stereocentres
The reaction mixture slowly darkened to red then black. After stir-
ring for 19.5 h, MeOD was added and the solvent was removed
under reduced pressure leaving a black residue. Purification by col-
umn chromatography (SiO2; ethyl acetate/hexane, 80:20) gave com-
plex 16 (32 mg, 62%) as a yellow oil. Rf = 0.50 (SiO2; ethyl acetate/
added. Stirring was continued for a further 60 min before quench-
ing with methanol (2 mL). The solvent was removed in vacuo leav-
ing a yellow residue. Purification by column chromatography (SiO2;
hexane/ethyl acetate, 95:5 Ǟ 85:15) afforded (+)-18 (95 mg, 63%)
as a yellow solid; m.p. 134–136 °C. Rf = 0.27 (SiO2; hexane/ethyl
hexane, 80:20). IR (CHCl ): ν= 1970 (υCO, s), 1896 (υCO, s) cm–1. acetate, 80:20). Enantiometric excess was determined by HPLC
˜
3
1H NMR (400 MHz): δ = 2.36 (m, 2 H, CH2CH=CH2), 2.50 (t, J analysis (Chiralcel AD, n-hexane/iPrOH, 90:10, 1.0 mL/min,
= 7.5 Hz, 2 H, CH2CH2CH=CH2), 5.03–5.10 (m, 2 H, CH=CH2), 330 nm); (R)-enantiomer tr = 10.7 min (major); (S)-enantiomer tr
5.19–5.24 (m, 3 H, CCrHortho,ϫ2, CCrHpara), 5.39–5.42 (m, 2 H, = 12.9 min (minor): 99% ee. [α]2D0 = +35 (c = 1.34 in CHCl3). IR
1
C
CrHmetaϫ2), 5.78–5.89 (m, 1 H, CH=CH2) ppm. 13C NMR (film): ν= 1964 (υCO, s), 1875 (υCO) cm–1. H NMR (400 MHz): δ
˜
(100 MHz): δ = 34.5 (CH2CH=CH2), 35.1 (CH2CH2CH=CH2), = 1.54 (d, J = 6.5 Hz, 3 H, OCHCH3), 2.90 (dd, J = 6.5, 13.5 Hz,
90.4 (CCr), 92.7 (CCr metaϫ2), 93.7 (CCr orthoϫ2), 112.9 1 H, CHHЈC6H5), 3.16 (dd, J = 7.0, 13.5 Hz, 1 H, CHHЈC6H5),
H
H
(CCrHpara), 116.3 (CH=CH2), 136.4 (CH=CH2), 232.1 (CϵOϫ3) 4.42 (dd, J = 6.5, 7.0 Hz, 1 H, CHCHЈHC6H5), 4.53 (q, J = 6.5 Hz,
ppm. MS (EI): m/z (%) = 268 (38) [M+], 184 (100) [M+ – 3CO].
1 H, CHCH3), 5.04–5.72 (m, 10 H, CCrHϫ10), 7.06–7.09 (m, 2 H,
C
A r Hϫ2), 7.23–7.31 (m, 3 H, CAr Hϫ3) ppm. 13 C NMR
(–)-(R)-Hexacarbonyl{benzyl [1-(1-phenylethyl)] ether}dichromium(0)
[(–)-17]: n-Butyllithium (0.56 mL, 2.50  in hexane, 1.40 mmol) was
added to a solution of the diamine (+)-2 (294 mg, 0.70 mmol) in
THF (12 mL) at –78 °C. The solution was warmed to room tem-
perature over 30 min and the resulting deep red solution was reco-
oled to –78 °C. A solution of heat gun-dried lithium chloride
(30 mg, 0.70 mmol) in THF (10 mL) was added and the reaction
mixture was stirred for a further 10 min. A precooled solution
(–78 °C) of complex 9 (470 mg, 1.0 mmol) in THF (10 mL) was
added, upon which the reaction mixture slowly turned orange. Af-
ter stirring the reaction mixture at –78 °C for 40 min, iodomethane
(0.06 mL, 1.0 mmol) was added. Stirring was continued for 30 min
and the reaction was quenched with methanol (2 mL). The solvent
was removed in vacuo leaving a yellow residue. Purification by col-
umn chromatography (SiO2; hexane/ethyl acetate, 95:5 Ǟ 80:20)
afforded complex (–)-17 (288 mg, 59%) as a yellow solid; m.p. 102–
103 °C. Rf = 0.19 (SiO2; hexane/ethyl acetate, 80:20). Enantiometric
excess was determined by HPLC analysis (Chiralcel OD-H, n-hex-
ane/iPrOH, 80:20, 1.0 mL/min, 330 nm); (S)-enantiomer tr =
31.6 min (minor); (R)-enantiomer tr = 36.8 min (major): Ն 99% ee.
(100 MHz): δ = 23.9 (OCHCH3 ), 45.2 (OCHCH2 ), 73.7
(OCHCH3), 78.1 (OCHCH2), 89.7 (CCrH), 90.2 (CCrH), 90.7
(CCrH), 90.9 (CCrH), 92.17 (CCrH), 92.23 (CCrH), 92.7 (CCrH), 93.5
(CCrH), 93.6 (CCrH), 94.7 (CCrH), 110.9 (CCr), 113.2 (CCr), 126.8
(CArHpara) 128.5 (CArHorthoϫ2, CArHmetaϫ2), 136.5 (CAr), 233.52
(CϵOϫ6) ppm. MS (EI): m/z (%) = 524 (19) [M+], 440 (9) [M+
–
3CO], 356 (35) [M+ – 6CO], 304 (88) [M+ – 6CO – Cr], 52 (100)
[Cr+]. C28H22Cr2O7 (574.46): calcd. C 58.54, H 3.86; found C 58.60,
H 3.82.
(–)-(1S,1ЈS)-Hexacarbonyl{[1-(1,2-diphenylethyl)] [1-(1-phenylethyl)]}
etherdichromium(0) [(–)-18]: Complex (–)-18 was prepared from
(+)-17 (93 mg, 0.22 mmol) and (–)-2 (78 mg, 0.22 mmol) following
the procedure described for (+)-18. 70% yield, yellow oil. [α]2D0
=
–35 (c = 1.48, CHCl3). ee Ն 99%. All other analytical data were
identical to those obtained for (+)-18.
(+)-(1R,1ЈR)-Hexacarbonyl{[1-(1-phenylbut-3-enyl)] [1-(1-phenylethyl)]
ether}dichromium(0) [(+)-19]: n-Butyllithium (0.32 mL, 2.50  in
hexane, 0.80 mmol) was added to a solution of the diamine (+)-2
(168 mg, 0.40 mmol) in THF (4 mL) at –78 °C. The solution was
warmed to room temperature over 30 min before recooling to
–78 °C. Heat gun-dried lithium chloride (17 mg, 0.40 mmol) in
THF (4 mL) was added and the reaction mixture was stirred for
10 min before a precooled solution (–78 °C) of complex (–)-17
(194 mg, 0.40 mmol) in THF (4 mL) was added. After stirring for
40 min at –78 °C, allyl bromide (0.10 mL, 1.20 mmol) was added.
Stirring was continued for a further 45 min before quenching with
methanol (2 mL). The solvent was removed in vacuo leaving a yel-
low residue. Purification by column chromatography (SiO2; hexane/
ethyl acetate, 95:5 Ǟ 85:15) afforded complex (+)-19 (152 mg, 72%)
as a yellow oil. Rf = 0.28 (SiO2; hexane/ethyl acetate, 80:20). En-
antiometric excess was determined by HPLC analysis (Chiralcel
OD-H, n-hexane/iPrOH, 90:10, 1.0 mL/min, 330 nm); (R)-enanti-
omer tr = 18.4 min (major); (S)-enantiomer tr = 20.9 min (minor):
[α]2D0 = –15 (c = 1.20 in CHCl ). IR (CHCl ): ν = 1973 (υCO, s),
˜
3
3
1
1898 (υCO, s) cm–1. H NMR (400 MHz): δ = 1.55 (d, J = 6.5 Hz,
3 H, CHCH3), 4.34 (q, J = 6.5 Hz, 1 H, CHCH3), 4.37 (d, J =
11.5 Hz, 1 H, OCHHЈ), 4.48 (d, J = 11.5 Hz, 1 H, OCHHЈ), 5.29–
5.63 (m, 10 H, CCrHϫ10) ppm. 13C NMR (100 MHz): δ = 22.9
(OCH2CH3), 69.3 (OCH2), 75.9 (OCHCH3), 91.1 (CCrH), 91.2
(CCrH), 91.7 (CCrH), 91.78, 91.83, 92.58 (CCrHϫ5), 92.60 (CCrH),
92.8 (CCrH), 107.7 (CCr), 113.1 (CCr), 232.7 (CϵOϫ3), 232.9
(CϵOϫ3) ppm. MS (EI): m/z (%) = 484 (35) [M+], 400 (19) [M+
–
2Cr – 3CO], 316 (100) [M+ – 6CO], 264 (47) [M+ – Cr – 6CO].
C21H16Cr2O7 (484.39): calcd. C 52.08, H 3.33; found C 52.15, H
3.36.
(+)-(S)-Hexacarbonyl{benzyl [1-(1-phenylethyl)] ether}dichromium(0)
[(+)-17]: Complex (+)-17 was prepared from 9 (470 mg, 1.00 mmol)
and (–)-2 (294 mg, 0.70 mmol) following the procedure described
for (–)-17. 66% yield, yellow solid. [α]2D0 = +15 (c = 1.57, CHCl3).
ee Ն 99%. All other analytical data were identical to those ob-
tained for (–)-17.
ee Ն 99%. [α]2D0 = +11 (c = 0.54 in CHCl ). IR (CHCl ): ν = 1961
˜
3
3
1
(υCO, s), 1874 (υCO, s) cm–1. H NMR (400 MHz): δ = 1.55 (d, J =
6.5 Hz, 3 H, OCHCH3), 2.48–2.64 (m, 2 H, CH2CH=CH2), 4.38
(t, J = 6.5 Hz, 1 H, OCHCH2), 4.56 (q, J = 6.5 Hz, 1 H, OCHCH3),
5.05 (dd, J = 1.5, 17.0 Hz, 1 H, CH=CHЈH), 5.13 (dd, J = 1.4,
10.0 Hz, 1 H, CH=CHЈH), 5.02–5.46 (m, 8 H, CCrHϫ8), 5.69–5.80
(m, 3 H, CH=CH2, CCrHϫ2) ppm. 13C NMR (100 MHz, C6D6):
δ = 23.9 (OCHCH3), 42.5 (CH2CH=CH2), 73.8 (OCHCH3), 76.6
(OCHCH2), 90.1 (CCrH), 90.4 (CCrH), 90.9 (CCrϫ2), 91.6 (CCrH),
91.9 (CCrH), 92.1 (CCrH), 93.2 (CCrH), 93.6 (CCrH), 94.1 (CCrH),
111.5 (CCr), 113.4 (CCr), 119.0 (CH=CH2), 132.8 (CH=CH2),
233.47 (CϵOϫ3), 233.52 (CϵOϫ3) ppm. MS (EI): m/z (%) = 524
(19) [M+], 440 (9) [M+ – 3CO], 356 (35) [M+ – 6CO], 304 (88) [M+ –
6CO – Cr], 52 (100) [Cr+]. C24H20Cr2O7 (524.40): calcd. C 54.97,
(+)-(1R,1ЈR)-Hexacarbonyl{[1-(1,2-diphenylethyl)] [1-(1-phenylethyl)]
ether}dichromium(0) [(+)-18]: n-Butyllithium (0.18 mL, 2.50  in
hexane, 0.44 mmol) was added to a solution of the diamine (+)-2
(78 mg, 0.22 mmol) in THF (2 mL) at –78 °C. The solution was
warmed to room temperature over 30 min before recooling to
–78 °C. Heat gun-dried lithium chloride (10 mg, 0.22 mmol) in
THF (2 mL) was added and the reaction mixture was stirred for a
further 10 min before a precooled solution (–78 °C) of complex
(–)-17 (93 mg, 0.22 mmol) in THF (2 mL) was added. After stirring
for 40 min at –78 °C, benzyl bromide (0.08 mL, 0.66 mmol) was H 3.84; found C 54.97, H 3.85.
Eur. J. Org. Chem. 2008, 4963–4971
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4969

R. Felstead, S. E. Gibson, A. Rooney, E. S. Y. Tse
FULL PAPER
(–)-(1S,1ЈS)-Hexacarbonyl{[1-(1-phenylbut-3-enyl)] [1-(1-phenylethyl)]
continued at room temperature for 14 h. A saturated aqueous solu-
ether}dichromium(0) [(–)-19]: Complex (–)-19 was prepared from tion of ammonium chloride (5 mL) was added, the organic phase
(+)-17 (106 mg, 0.22 mmol) and (–)-2 (93 mg, 0.22 mmol) following was separated and the aqueous phase extracted with diethyl ether
the procedure described for (+)-19. 72% yield, yellow oil. [α]2D0
=
(3ϫ20 mL). The combined organic layers were washed with brine
–10 (c = 0.86, CHCl3). ee Ն 99%. All other analytical data were
identical to those obtained for (+)-19.
(60 mL), dried (MgSO4) and concentrated in vacuo to afford ether
22 (1.54 g, 99%) as a colourless oil. Rf = 0.71 (SiO2; hexane/diethyl
1
ether). IR (neat): ν = 1090 (υC–O–C, s) cm–1. H NMR (400 MHz):
˜
(+)-(1R,1ЈR)-[1-(1,2-Diphenylethyl)] [1-(1-Phenylethyl)] Ether [(+)-
20]: Complex (+)-18 (70 mg, 0.121 mmol) was dissolved in diethyl
ether (100 mL) and left for 24 h by the window. The solvent was
removed from the mixture under reduced pressure. Purification by
column chromatography (SiO2; hexane/diethyl ether, 98:2) gave a
colourless oil (30 mg, 81%). Rf = 0.18 (SiO2; hexane/diethyl ether,
δ = 1.34 [s, 18 H, C(CH3)3ϫ2], 4.55 (s, 4 H, OCH2ϫ2), 7.33 [d,
J = 8.0 Hz, 4 H, (OCH2CCArHϫ4)], 7.41 {d, J = 8.0 Hz, 4 H,
C
ArHC[C(CH3)3]ϫ4} ppm. 13C NMR (400 MHz): δ = 31.4
[C(CH3 )3 ϫ2], 34.6 [C(CH3 )3 ϫ2], 71.8 (CH2 ϫ2), 125.3
[CArHCArC(CH3)3ϫ4], 127.6 (OCH2CCArHϫ4), 135.4 (OCH2-
C
Arϫ2), 150.6 [CArC(CH3)3ϫ2] ppm. MS (EI): m/z (%) = 57 (100)
98:2). [α]2D0 = +111 (c = 1.00, CHCl ). IR (film): ν = 1090 (υ
,
˜
3
C–O–C
[C(CH3 )3 + ], 133 (34) [C6 H4 C(CH3 )3 + ], 147 (86) [M+
–
m) cm–1 1H NMR (400 MHz): δ = 1.36 (d, J = 6.5 Hz, 3 H,
.
OCH2C6H4C(CH3)3], 163 (47) [M+ – CH2C6H4C(CH3)3], 295 (38)
CHCH3), 2.87 (dd, J = 8.0, 13.5 Hz, 1 H, OCHCHHЈ), 3.08 (dd,
J = 5.5, 13.5 Hz, 1 H, OCHCHHЈ), 4.25 (q, J = 6.5 Hz, 1 H,
OCHCH3), 4.27 (dd, J = 5.5, 8.0 Hz, 1 H, OCHCHHЈ), 6.92–7.40
(m, 15 H, CArHϫ15) ppm. 13C NMR (100 MHz): δ = 24.8 (CH3),
45.3 (OCHCH2), 74.6 (OCHCH3), 79.9 (OCHCHHЈ), 126.0
(CArH), 126.3 (CArHϫ2), 126.9 (CArHϫ2), 127.1 (CArH), 127.5
(CArH), 127.9 (CArHϫ2), 128.2 (CArHϫ2), 128.3 (CArHϫ2), 129.8
(CArHϫ2), 138.6 (CAr), 142.4 (CAr), 143.7 (CAr) ppm. MS (CI): m/z
(%) = 320 (94) [M + NH4+], 198 (100) [M – C6H5CHCH3 + H+],
122 (54) [C6H5CHCH3+ + NH3]. C22H22O (302.41): calcd. C 87.38,
H 7.33; found C 87.33, H 7.31.
[M+ – CH3], 310 (3) [M+]. HRMS (EI): calcd. for C22H30
O
(310.2297); found 310.2297.
Hexacarbonyl[bis(4-tert-butyl)benzyl ether]dichromium(0) (23):
Bis(4-tert-butyl)benzyl ether 22 (1.24 g, 4.00 mmol), hexacarbon-
ylchromium(0) (2.64 g, 12.0 mmol), dry di-n-butyl ether (100 mL)
and THF (20 mL) were degassed 10 times and shielded from ambi-
ent light. The reaction mixture was heated under reflux for 48 h at
140 °C and then cooled to room temperature. The solvent was re-
moved under reduced pressure and the crude reaction mixture was
pre-absorbed onto silica (30 g). Purification was carried out via col-
umn chromatography (SiO2; hexane/ethyl acetate, 70:30) to yield
complex 23 (2.25 g, 97% yield) as a yellow solid; m.p. 86–87 °C. Rf
(–)-(1S,1ЈS)-[1-(1,2-Diphenylethyl)] [1-(1-Phenylethyl)] Ether [(–)-
20]: Ether (–)-20 was prepared from (–)-18 (70 mg, 0.121 mmol)
following the procedure described for (+)-20. 84% yield, colourless
oil. [α]2D0 = –116 (c = 1.00, CHCl3). All other analytical data were
identical to those obtained for (+)-20.
= 0.15 (SiO ; hexane/ethyl acetate, 80:20). IR (CHCl ): ν = 1958
˜
2
3
1
(υCO, s), 1874 (υCO, s) cm–1. H NMR (400 MHz): δ = 1.31 [s, 18
H, C(CH3)3ϫ2], 4.40 (s, 4 H, OCH2ϫ2), 5.31 [d, J = 6.0 Hz, 4 H,
(OCH2CCArHϫ4)], 5.59 {d, J = 8.0 Hz, 4 H, CArHC[C(CH3)3]ϫ4}
ppm. 1 3C NMR (400 MHz): δ = 31.1 [C(CH3 )3 ϫ2], 33.7
[C(CH3)3ϫ2], 71.1 (CH2ϫ2), 90.1 [CCrHCCrC(CH3)3ϫ4], 92.4
(OCH2CCCrHϫ4), 107.3 (OCH2CCrϫ2), 122.1 [CCrC(CH3)3ϫ2],
232.3 (CϵOϫ6) ppm. MS (EI): m/z (%) = 582 (30) [M+], 498 (19)
[M+ – 3CO], 414 (100) [M+ – 6CO], 362 (35) [M+ – Cr – 6CO].
C28H30Cr2O7 (582.53): calcd. C 57.73, H 5.19; found C 57.69, H
5.24.
(+)-(1R,1ЈR)-[1-(1-Phenylbut-3-enyl)] [1-(1-Phenylethyl)] Ether [(+)-
21]: Complex (+)-19 (120 mg, 0.23 mmol) was dissolved in diethyl
ether (100 mL) and left for 24 h by the window. The solvent was
removed from the mixture under reduced pressure. Purification by
column chromatography (SiO2; hexane/diethyl ether, 98:2) gave a
colourless oil (55 mg, 95%). Rf = 0.22 (SiO2; hexane/diethyl ether,
98:2). [α]2D0 = +193 (c = 1.00, CHCl ). IR (film): ν= 1089 (υ
,
˜
3
C–O–C
s) cm–1 1H NMR (400 MHz): δ = 1.41 (d, J = 6.5 Hz, 6 H,
.
(–)-(1R,1ЈR)-Hexacarbonyl(bis{1-[1-(4-tert-butylphenyl)ethyl]}
ether)dichromium(0) [(–)-24]: n-Butyllithium (0.56 mL, 2.50  in
hexane, 1.40 mmol) was added to a solution of the diamine (+)-2
(294 mg, 0.70 mmol) in THF (7 mL) at –78 °C. The solution was
warmed to room temperature over 30 min and the resulting deep
red solution was then recooled to –78 °C. Heat gun-dried lithium
chloride (30 mg, 0.70 mmol) in THF (4 mL) was added and the
reaction mixture was stirred for a further 5 min before a precooled
solution (–78 °C) of complex 23 (204 mg, 0.35 mmol) in THF
(7 mL) was added. After stirring for 60 min at –78 °C, iodomethane
(0.13 mL, 2.10 mmol) was added. Stirring was continued for a fur-
ther 1 h at –78 °C before MeOH (1 mL) was used to quench the
reaction. The solvent was removed in vacuo. Purification by col-
umn chromatography (SiO2; hexane/EtOAc, 100:0 Ǟ 80:20) yielded
complex (–)-24 (210 mg, 98%) as a yellow solid; m.p. 145–147 °C.
Rf = 0.49 (SiO2; hexane/ethyl acetate, 80:20). Enantiometric excess
was determined by HPLC analysis (Chiralcel AD, n-hexane/iPrOH,
90:10, 1.0 mL/min, 330 nm); (R)-enantiomer tr = 6.1 min (major);
CHCH3ϫ2), 2.34–2.01 (m, 1 H, CHHЈCH=CH2), 2.55–2.63 (m, 1
H, CHHЈCH=CH2), 4.15 (t, J = 6.0 Hz, 1 H, OCHCH2CH=CH2),
4.27 (q, J = 6.5 Hz, 1 H, OCHCH3), 4.95–4.98 (m, 1 H,
CH=CHHЈ), 4.98–5.02 (m, 1 H, CH=CHHЈ), 5.66–5.70 (m, 1 H,
CH=CH2) ppm. 13C NMR (100 MHz): δ = 24.7 (CH3), 43.0
(CH2CH=CH2), 74.6 (CHCH3), 78.5 (CHCH2CH=CH2), 116.7
(CH=CH2), 126.6 (CArHϫ2), 126.9 (CArHϫ2), 127.4 (CArH), 127.6
(CArH), 128.4 (CArHϫ4), 134.7 (CH=CH2), 142.4 (CAr), 143.8
(CAr) ppm. MS (CI): m/z (%) = 270 (100) [M + NH4+], 252 (30)
[M+ ], 148 (60) [M – C6 H5 CHCH3 + H+ ], 122 (72) [M –
CH(CH2 CH=CH2 )C6 H5 + H+ ]. HRMS (CI): calcd. for
C18H24NO+ (270.1851); found 270.1859.
(–)-(1S,1ЈS)-[1-(1-Phenylbut-3-enyl)] [1-(1-Phenylethyl)] Ether [(–)-
21]: Ether (–)-21 was prepared from (–)-19 (72 mg, 0.127 mmol)
following the procedure described for (+)-21. 92% yield, colourless
oil. [α]2D0 = –208 (c = 1.00, CHCl3). All other analytical data were
identical to those obtained for (+)-21.
Bis(4-tert-butyl)benzyl Ether (22): 4-tert-Butylbenzyl alcohol
(0.85 mL, 5 mmol) was added to a stirred and cooled (0 °C) suspen-
sion of sodium hydride (60% dispersion in mineral oil; 279 mg,
7 mmol, previously washed with hexane), in THF (20 mL). The
reaction mixture was warmed to room temperature and then heated
under reflux for 2 h. After cooling to room temperature, 4-tert-
butylbenzyl bromide (0.91 mL, 5 mmol) was added. Stirring was
(S)-enantiomer tr = 7.4 min (minor): ee Ն 99%, 97.4% de. [α]2D0
=
–22 (c = 1.00, CHCl ). IR (film): ν = 1957 (υCO, s), υCO 1874(s)
˜
3
cm–1. 1H NMR (400 MHz): δ = 1.32 [s, 18 H, C(CH3)3ϫ2], 1.53
(d, J = 6.5 Hz, 6 H, CHCH3ϫ2), 4.52 (q, J = 6.5 Hz, 2 H,
CHCH3ϫ2), 5.28 {dd, J = 7.0, 1.0 Hz, 2 H, CCr[C(CH3)3]
CCrHCCrHϫ2}, 5.50 {dd, J = 7.0, 1.0 Hz, 2 H, CCr[C(CH3)3]
C
CrHCCrHϫ2}, 5.55 {dd, J = 7.0, 1.0 Hz, 2 H, CCr[C(CH3)3]
4970
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4963–4971

A Stereocontrolled Approach to Ethers with Two α Stereocentres
CrHЈCCrHЈϫ2}, 5.63 {dd, J = 7.0, 1.0 Hz, 2 H, CCr[C(CH3)3]
[2]
[3]
C
a) M. P. Castaldi, S. E. Gibson, M. Rudd, A. J. P. White, An-
gew. Chem. Int. Ed. 2005, 44, 3432–3435; b) M. P. Castaldi,
S. E. Gibson, M. Rudd, A. J. P. White, Chem. Eur. J. 2006, 12,
138–148.
For highlights/reviews on C3-symmetrical molecules, see: a)
M. P. Castaldi, S. E. Gibson, Angew. Chem. Int. Ed. 2006, 45,
4718–4720; b) C. Moberg, Angew. Chem. Int. Ed. 2006, 45,
4721–4723; c) M. P. Castaldi, S. E. Gibson, Chem. Commun.
2006, 3045–3062; d) C. Moberg, Angew. Chem. Int. Ed. 1998,
37, 248–268.
A. R. E. Brewer, A. F. Drake, S. E. Gibson, J. T. Rendell, Org.
Lett. 2007, 9, 3487–3490.
S. J. Hughes, J. R. Moss, K. J. Naidoo, J. F. Kelly, A. S. Bats-
anov, J. Organomet. Chem. 1999, 588, 176–185.
K. Bambridge, M. J. Begley, N. S. Simpkins, Tetrahedron Lett.
1994, 35, 3391–3394.
M. Noji, T. Ohno, K. Fuji, N. Futaba, H. Tajima, K. Ishii, J.
Org. Chem. 2003, 68, 9340–9347.
F. Toda, K. Okuda, Chem. Commun. 2001, 1212–1214.
a) E. Licandro, S. Maiorana, A. Papagni, M. Pryce, A. Z.
Gerosa, Tetrahedron: Asymmetry 1995, 6, 1891–1894; b) E.
Licandro, S. Maiorana, C. Baldoli, L. Capella, D. Perdicchia,
Tetrahedron: Asymmetry 2000, 11, 975–980.
M. L. H. Green, M. Wagner, J. Chem. Soc., Dalton Trans. 1996,
2467–2473.
CC r HЈCC r HЈϫ2} ppm. 1 3 C NMR (100 MHz): δ = 23.7
(OCHCH3ϫ2), 31.1 [C(CH3)3ϫ2], 34.0 [C(CH3)3ϫ2], 71.1
( O C H ϫ 2 ) , 9 0 . 1 ( C C r H ϫ 4 ) , 9 2 . 4 ( C C r H ϫ 4 ) , 1 1 4 . 5
[CCrCH(CH3)ϫ2], 123.3 {CCr[C(CH3)3]ϫ2}, 233.7 (CϵOϫ6) ppm.
MS (EI): m/z (%) = 610 (44) [M+], 526 (35) [M+ – 3CO], 442 (100)
[M+ – 6CO], 390 (7) [M+ – 6CO – Cr]. C30H34Cr2O7 (610.58): calcd.
C 59.01, H 5.61; found C 59.07, H 5.57.
(+)-(1S,1ЈS)-Hexacarbonyl(bis{1-[1-(4-tert-butylphenyl)ethyl]}
ether)dichromium(0) [(+)-24]: Complex (+)-24 was prepared from
23 (150 mg, 0.26 mmol) and (–)-2 (219 mg, 0.52 mmol) following
[4]
[5]
[6]
[7]
the procedure described for (–)-24. 98% yield, yellow solid. [α]2D0
=
+22 (c = 2.72, CHCl3). ee Ն 99%, 96% de. All other analytical
data were identical to those obtained for (–)-24.
(+)-(1R,1ЈR)-Bis{1-[1-(4-tert-butylphenyl)ethyl]} Ether [(+)-25]:
Complex (–)-24 (159 mg, 0.26 mmol) was dissolved in DCM
(20 mL) and the solution was left in direct sunlight for 24 h. The
crude product mixture was filtered through a pad of Celite® and
neutral alumina. The pad was thoroughly washed with diethyl ether
and the filtrate was concentrated under reduced pressure to afford
ether (+)-25 (82 mg, 93%) as a white solid; m.p. 95–96 °C. Rf =
0.37 (SiO2; hexane/diethyl ether, 80:20). [α]2D0 = +184 (c = 1.00,
[8]
[9]
[10]
CHCl ). IR (film): ν = 1093 (υC–O–C, s) cm–1. 1H NMR (400 MHz):
˜
3
δ = 1.37 [s, 18 H, C(CH3)3ϫ2], 1.40 (d, J = 6.5 Hz, 6 H,
CHCH3ϫ2), 4.28 (q, J = 6.5 Hz, 2 H, CHCH3ϫ2), 7.24 {d, J =
[11] T. Mukaiyama, M. Ohshima, N. Miyoshi, Chem. Lett. 1987,
1121–1124.
8.0 Hz,
4 H, CCr[C(CH3)3]CCrHCCrHϫ2 and CCr[C(CH3)3]-
[12] M. A. Zolfigol, I. Mohammadpoor-Baltork, D. Habibi, B. F.
Mirjalili, A. Bamoniri, Tetrahedron Lett. 2003, 44, 8165–8167.
[13] K. Saramma, Ind. J. Chem. 1967, 522–523.
[14] P. O’Brien, J. Chem. Soc. Perkin Trans. 1 1998, 1439–1457.
[15] B. L. Feringa, Acc. Chem. Res. 2000, 33, 346–353.
[16] See, for example a) X. Teng, D. R. Cefalo, R. R. Schrock,
A. H. Hoveyda, J. Am. Chem. Soc. 2002, 124, 10779–10784; b)
A. B. Machotta, B. F. Straub, M. Oestreich, J. Am. Chem. Soc.
2007, 129, 13455–13463; c) M. Althaus, C. Becker, A. Togni,
A. Mezzetti, Organometallics 2007, 26, 5902–5911; d) K.
Namba, J. Wang, S. Cui, Y. Kishi, Org. Lett. 2005, 7, 5421–
5424.
C
CrHCCrHϫ2}, 7.29 {d, J = 8.0 Hz, 4 H, CCr[C(CH3)3]CCr
-
HЈCCrHЈϫ2 and CCr[C(CH3)3]CCrHЈCCrHЈϫ2} ppm. 13C NMR
(100 MHz): δ = 24.8 (OCHCH3ϫ2), 31.1 [C(CH3)3ϫ2], 34.5
[C(CH3)3ϫ2], 74.2 (OCHϫ2), 125.9 (CCrHϫ4), 126.0 (CCrHϫ4),
141.1 [CCrCH(O)CH3ϫ2], 150.1 {CCr[C(CH3)3]ϫ2} ppm. MS (EI):
m/z (%) = 338 (2) [M+], 177 {37} [M+ – CH(CH3)C6H4[C(CH3)3]],
161 {100} [M+ – OCH(CH3)C6H4[C(CH3)3]], 57 (39) [C(CH3)3+].
C24H34O (338.53): calcd. C 85.15, H 10.12; found C 85.21, H 10.13.
(–)-(1S,1ЈS)-Bis{1-[1-(4-tert-butylphenyl)ethyl]} Ether [(–)-25]: Ether
(–)-25 was prepared from (+)-24 (130 mg, 0.21 mmol), following
the procedure described for (+)-25. 62 mg, 86% yield, white solid.
[α]2D0 = –194 (c = 1.00, CHCl3). All other analytical data were iden-
tical to those obtained for (+)-25.
[17] D. F. Shriver, M. A. Drzdon, The Manipulation of Air Sensitive
Compounds, Wiley, Chichester, 1986.
[18] W. G. Kofron, L. M. Baclawski, J. Org. Chem. 1976, 41, 1879–
1880.
Received: June 26, 2008
Published Online: September 4, 2008
[1] E. L. M. Cowton, S. E. Gibson, M. J. Schneider, M. H. Smith,
Chem. Commun. 1996, 839–840.
Eur. J. Org. Chem. 2008, 4963–4971
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4971