A flexible route toward polypropylene model compounds of various tacticities

Article abstract of DOI:10.1055/s-0030-1258233

This paper reports the flexible synthesis of 2,4,6,8,10-pentamethylundecane (PMU) as well as a chromatographic method for the separation of its diastereoisomers. This strategy offers a unique opportunity to accede to three model compounds of polypropylene (PP) of different tacticities (i.e., isotactic, syndiotactic, and atactic PP). Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258233

PAPER
3755
A Flexible Route toward Polypropylene Model Compounds of Various
Tacticities
Polypropylene
Mo
a
del Compo
v
unds of
V
ario
i
us Ta
c
e
ticities r Drooghaag,1 Gaëtan Henry,1 Jacqueline Marchand-Brynaert*
Institute of Condensed Matter and Nanosciences (IMCN), Unité de Chimie organique et médicinale, Université catholique de Louvain,
Bâtiment Lavoisier, Place Louis Pasteur 1, 1348 Louvain-la-Neuve, Belgium
Fax +32(10)474168; E-mail: jacqueline.marchand@uclouvain.be
Received 12 July 2010
1) Mg
Abstract: This paper reports the flexible synthesis of 2,4,6,8,10-
pentamethylundecane (PMU) as well as a chromatographic method
for the separation of its diastereoisomers. This strategy offers a
unique opportunity to accede to three model compounds of polypro-
pylene (PP) of different tacticities (i.e., isotactic, syndiotactic, and
atactic PP).
OH
K2Cr2O7
H2SO4
O
2)
Br
O
70%
80%
OH
MeMgBr
93%
Key words: model hydrocarbons, polyolefins, total synthesis,
HPLC, NMR
I2
H2
80%
PMU
– H2O
Scheme 1 Synthesis of PMU according to Pino et al.3
Isotactic polypropylene modifications (i.e., grafting of po-
lar monomers, racemization, etc.) are very challenging in-
dustrial processes and the underlying chemical reactions
are barely established.2 The very high molecular weights
of the polymers and the low graft contents make the iden-
tification of reaction products and intermediates very del-
icate. As a consequence, small oligomers are commonly
used as model compounds to shed light on the functional-
ization mechanisms through the analytical tools of the or-
ganic chemist. This paper describes a flexible synthesis of
2,4,6,8,10-pentamethylundecane (PMU) and a chromato-
graphic method for the separation of its diastereoisomers
as a route to polypropylene model compounds with con-
trolled tacticities.
Weinreb amide with a view to directly forming the ketone
key intermediate, but without success. Therefore, we in-
vestigated another route to PMU based on Wittig-type
coupling reactions and using a flexible intermediate,
namely 2,4,8,10-tetramethyl-6-methyleneundecane, to
furnish either a mixture of PMU stereoisomers, or the in-
dividual stereoisomers by chromatographic separation of
more polar precursors.
Scheme 2 depicts the overall synthetic route to 2,4,6,8,10-
pentamethylundecane (PMU, 7) as a mixture of stereoiso-
mers. The first two steps were performed according to
known procedures.4 The unsaturated ester 1 was synthe-
sized from 4-methylpentan-2-one and triethyl phos-
phonoacetate, through a Horner–Wadsworth–Emmons
(HWE) reaction, as a mixture of regio- and stereoisomers
1¢, all of them led to ethyl 3,5-dimethylhexanoate (2) upon
catalytic hydrogenation; addition of methyl dimeth-
ylphosphonate in the presence of butyllithium led to the b-
ketophosphonate 3. The enone 4 was synthesized through
a second HWE reaction between 3 and isovaleraldehyde.
The subsequent addition of methylmagnesium bromide in
the presence of copper iodide allowed the insertion of the
missing methyl group in the polypropylene-like structure.
A simple Wittig reaction from ketone 5 led to the exo-
methylene compound 6 as a key intermediate in the syn-
thesis of the model compounds. Catalytic hydrogenation
of 6 gave PMU 7 (mixture of isomers) with an overall
yield of 42% for seven steps, including one purification by
distillation (for 1) and four purifications by flash chroma-
PMU synthesis was initially described about 40 years ago
and it has not been revisited since that time.3 Reaction of
3,5-dimethylhexanal with the Grignard reagent from 1-
bromo-2,4-dimethylpentane, followed by oxidation of the
alcohol intermediate, led to 2,4,8,10-tetramethylundecan-
6-one (Scheme 1). The central missing methyl group was
then introduced by addition of methylmagnesium bro-
mide, giving 2,4,6,8,10-pentamethylundecan-6-ol. Alco-
hol dehydration by distillation over iodine afforded a
mixture of isomeric olefins that was hydrogenated in the
presence of Raney nickel to yield PMU as a mixture of
stereoisomers, separable by fractional distillation with
low purity.
In our hands, this PMU synthesis was hardly reproducible
on a multigram scale, mainly because a competitive side
reaction that occurred during the first organometallic
coupling, auto-condensation of the alkyl bromide. We
tried to replace the aldehyde partner by the corresponding tography (for 3, 4, 5, and 6). Synthesis of 6 on a 250-mmol
scale was performed, without purification of the interme-
diates, in 65% yield for six steps (see Supporting Informa-
tion).
SYNTHESIS 2010, No. 21, pp 3755–3760
Advanced online publication: 30.08.2010
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DOI: 10.1055/s-0030-1258233; Art ID: P10910SS
© Georg Thieme Verlag Stuttgart · New York

3756
X. Drooghaag et al.
PAPER
O
P
O
O
EtOH, NaOEt
79%
+
EtO
O
OEt
O
OEt
EtO
1 + 1'
(MeO)2P(O)Me
n-BuLi
O
O
P
H2, 10% Pt/C
98%
OMe
OEt
83%
2
OMe
3
i-BuCHO
NaH
O
O
MeMgBr
CuI
97%
88%
5
4
Ph3P+MeBr–
t-BuOK
H2, 10% Pt/C
93%
81%
7 (PMU)
6
Scheme 2 High-yielding synthesis of PMU as a mixture of stereoisomers
thesized as a mixture of four stereoisomers in equivalent
amounts, two of them being enantiomers to each other.
The central peak of the chromatogram can unambiguously
be assigned to the mixture of enantiomers but without fur-
ther information it is impossible to ascribe the other peaks
to either of the two remaining diastereoisomers. These
must be isolated for accurate characterization. As no frac-
tion of pure isomer could be retrieved by distillation, we
turned to simple flash chromatography.
The chromatographic separation of hydrocarbons (and
more specially stereoisomers) is very delicate as there are
no functional groups to interact with the stationary phase.
Scheme 3 shows how olefin 6 was derivatized to insert
functional groups, i.e. a hydroxy 8 or a tosylate 9 group,
onto the main chain. PMU was then recovered through the
nucleophilic substitution of the tosylate moiety by hy-
dride.
The potential separation of the diastereoisomers of tosy-
late 9 was investigated using reverse-phase HPLC.
Figure 2 shows that a satisfactory separation could be ob-
tained, but the very long retention times (50–60 min)
make it difficult to scale up the separation to preparative
HPLC.
Figure 1 GC chromatogram of PMU synthesized as a mixture of
stereoisomers according to Scheme 2; {(Supelco Fused Silica capilla-
ry column, SLB 5ms, 30 m × 0.25 mm × 0.25 mm): tR =13.77
[(4R,6s,8S)-PMU], 14.03 [(4R,8R)- and (4S,8S)-PMU)], 14.22 min
[(4R,6r,8S)-PMU)]}.
GC analysis of the fractions collected during the flash
chromatography purification of alcohol 8 revealed that
many of them contained only one diastereoisomer (single
peak observed by GC whereas three peaks were observed
for the crude product). Fractions containing only one of
the three diastereoisomers were, therefore, collected sep-
Figure 1 shows the GC chromatogram of the mixture of
stereoisomers of PMU. It consists of three peaks in a 1:2:1
ratio. Since PMU has two asymmetric carbons (C4 and
C8) and one pseudo-asymmetric carbon (C6), it was syn-
H2, 10% Pt/C
100%
6
7
1) BH3⋅THF
66%
LiEt3BH, THF 100%
2) Na2CO3⋅1.5H2O2
OH
OTs
TsCl, Py
84%
8
9
Scheme 3 Derivatization of olefin 6 to introduce functional groups onto the PMU backbone for HPLC separation
Synthesis 2010, No. 21, 3755–3760 © Thieme Stuttgart · New York

PAPER
Polypropylene Model Compounds of Various Tacticities
3757
as Figure 3 (e) exhibits two sets of chemical shifts at d ~
1.06–1.22 and d ~ 0.95, such as those observed in iPP.
Figure 3 (d) exhibits all the resonances simultaneously
and is, therefore, coherent with the random conformation
of atactic PP.
13C NMR was also used to ascertain the assignments made
1
from H NMR data as the chemical shifts of the methyl
groups in polypropylenes are strongly dependent on the
tacticity. It was reported that 3,5,7,[9-13C],11,13,15-hep-
tamethylpentadecane (HMHD) can be used to assign the
triads centered on the 13C-enriched methyl group.7 The
chemical shifts of the HMHD methyl triads were very
close to those observed on polypropylene. 2,4,8,10-Tet-
ramethyl-[6-13C]-methylundecane (6-13CH3-PMU) was
therefore synthesized from 6-(13CH2)-6 in order to identi-
fy the 13C resonance of the central methyl group for each
stereoisomer of PMU (see Supporting Information).
Figure 4 (a) to (d) shows the 13C spectra of (4R,6s,8R)-
PMU, (4R,8R)- and (4S,8S)-PMU, (4R,6r,8S)-PMU, and
6-[13CH3]-PMU respectively.
Figure 2 Chromatographic separation of tosylate 9 {(Xterra RP-18,
5 mm, MeOH–H2O 85:15, 1 mL/min, 227 nm): tR = 53.82 [(4R,6r,8S)-
9], 56.15 [(4R,8R)- and (4S,8S)-9], 58.40 min [(4R,6s,8S)-9]}.
arately and converted into PMU 7 separately as well ac-
cording to Scheme 3. The correct stereochemistry of the
diastereoisomers of intermediates 8 and 9 was assigned a
posteriori based on NMR data of each PMU stereoisomer
independently prepared from their pure precursors.
As can be seen in Figure 3 (a) and (b), isotactic and syn-
diotactic polypropylene (iPP and sPP, respectively) can be
1
differentiated in H NMR on the basis of the chemical
shifts of their CH2 hydrogen atoms as their magnetic en-
vironment differs with respect to tacticity.5,6 These hydro-
gen atoms are magnetically equivalent in sPP and hence
have the same chemical shift at d ~ 1.1 [Figure 3 (b)].
Conversely, the two CH2 hydrogen atoms are magnetical-
ly non-equivalent in iPP and are exposed to different
shielding. Therefore these two hydrogen atoms have two
distinct chemical shifts at d ~ 1.3 and 0.9 [Figure 3 (a)].
The same principle also applies for small oligomers of
propylene and can, therefore, be used for the stereochem-
1
ical assignment of the models. H NMR spectra in
Figure 3 (c) to (e) show the three stereoisomers of PMU 7.
Figure 3 (c) clearly exhibits one set of resonances at
d = 0.9–1.14, very similar to that observed in sPP, where-
Figure 4 13C NMR spectrum (d, CDCl3, r.t.) of: (a) (4R,6s,8S)-
PMU, (b) (4R,8R)- and (4S,8S)-PMU, (c) (4R,6r,8S)-PMU, (d) 6-
[13CH3]-PMU.
Table 1 compares the chemical shifts of the methyl triads
of PMU to those of HMHD7 and polypropylene.5 The rule
of thumb ‘d isotactic > d atactic > d syndiotactic’ com-
monly observed for propylene oligomers and polymers
also applies in the case of PMU.
Each stereoisomer being clearly identified, it was there-
fore possible to assign the stereochemistry of each stereo-
isomer of intermediates 8 and 9 and to characterize them
correctly (see experimental section). The two remaining
peaks of PMU 7 of the GC chromatogram in Figure 1
could also be assigned accurately as reported in Table 2.
In conclusion, we have disclosed a practical and scalable
synthesis of PMU, the model compound of PP. The iso-
tactic stereoisomer could be isolated by flash chromatog-
raphy separation of the primary alcohol intermediate 8
Figure 3 1H NMR spectra (d) of (a) iPP, (b) sPP, (c) (4R,6r,8S)-
PMU, (d) (4R,8R)- and (4S,8S)-PMU, (e) (4R,6s,8S)-PMU. Condi-
tions: (a) and (b): o-dichlorobenzene, 150 °C, see ref. 6a; (c) to (e)
CDCl3, r.t.
Synthesis 2010, No. 21, 3755–3760 © Thieme Stuttgart · New York

3758
X. Drooghaag et al.
PAPER
Table 1 13C Chemical Shifts (d) of Isotactic, Atactic, and Syndiotac-
tic Triads in PMU 7, HMHD, and PP
methylpentan-2-one (14.29 g, 0.142 mmol) was added in 1 portion
and an exothermic reaction occurred. After 50 min, the mixture was
heated under reflux for 1.5 h. The mixture was then distilled under
atmospheric pressure to remove EtOH until the temperature of the
vapor reached 90 °C. The mixture was finally cooled to r.t and Et2O
(100 mL) and cold H2O (60 mL) were added. The aqueous layer was
extracted with Et2O (2 × 30 mL). The combined organic layers were
washed with H2O (3 × 50 mL) and dried (MgSO4). The crude prod-
uct was distilled under vacuum as a colorless oil; yield: 19.135 g
(112.4 mmol, 79%).
Structure
Isotactic
triad
Atactic
triad
Syndiotactic
triad
(4R,6s,8S)-PMU
(4R,8R)- and (4S,8S)-PMU
(4R,6r,8S)-PMU
HMHD7
20.99
–
–
–
20.43
–
–
–
19.65
20.17
1
The H NMR spectrum is very complicated because four isomers
21.55
20.85
were synthesized simultaneously. Only olefinic protons are present-
1
ed. Full H NMR assignment was done after catalytic hydrogena-
PP5
21.9–21.3 21.1–20.6 20.4–19.7
tion (vide infra, ethyl 3,5-dimethylhexanoate).
1H NMR (300 MHz, CDCl3): d = 5.63 (s, 1 H, E-a,b), 5.71 (s, 1 H,
Z-a,b), 5.10 (d, J = 9 Hz, 1 H, E-b,g), 5.15 (d, J = 9 Hz, 1 H, Z-b,g).
Table 2 GC/HPLC Retention Times (min) of Isotactic, Syndiotac-
tic, and Atactic Stereoisomers of Intermediates 8, 9, and PMU
GC 8a
21.6
22.0
21.9
GC PMU 7a HPLC 9b
Ethyl 3,5-Dimethylhexanoate (2)
Isomer
To a 3-neck round-bottomed flask was added the mixture of isomers
of unsaturated ester 1 (3.226 g, 18.9 mmol) and 10% Pt/C (1.221 g,
60 mmol). The atmosphere in the flask was purged with argon (3 ×)
and H2 (3 ×). The mixture was stirred vigorously at 30 °C under a
H2 atmosphere (~1 bar) for 30 h. The catalyst was then filtered and
washed with PE (3 × 50 mL). The pure product was recovered by
distillation of the solvent as a colorless oil; yield: 3.198 g (18.6
mmol, 98%).
1H NMR (300 MHz, CDCl3): d = 4.13 (q, J = 7 Hz, 2 H), 2.19–2.33
(m, 1 H), 1.93–2.12 (m, 2 H), 1.63 (m, 1 H), 1.26 (t, J = 7 Hz, 3 H),
1.01–1.18 (m, 2 H), 0.91 (d, J = 6 Hz, 3 H), 0.87 (2d, J = 6 Hz, 6 H).
Isotactic
13.8
14.2
14.0
58.4
53.8
56.1
Syndiotactic
Atactic (racemic mixture)
a Supelco fused silica capillary column, SLB 5ms, 30 m × 0.25
mm × 0.25 mm.
b Xterra RP-18, 5 mm, MeOH–H2O 85:15, 1 mL/min, 227 nm.
[obtained in 43% overall yield for 7 steps; recovery of
(4R,6s,8S)-8 = 30% of the initial content for the first run]
followed by tosylation and reduction with lithium trieth-
ylborohydride (yield of 84% for 2 steps). Knowing that
the initial content in (4R,6s,8S) stereoisomer is only 25%
and that the compound of interest has the highest retention
time, the final recovery of 6% of pure isotactic-PMU from
the initial mixture is acceptable. Moreover, the other dia-
stereoisomers are also accessible in pure forms. In the par-
ticular case of PMU, a molecule devoid of functional
group, our stereochemically noncontrolled synthesis was
preferred over asymmetric synthesis using the catalytic
methods recently developed in the field of biologically
Dimethyl 4,6-Dimethyl-2-oxoheptylphosphonate (3)
A 2-neck flask under argon containing 2.5 M BuLi in hexanes (9.3
mL, 23.2 mmol) and anhyd THF (13 mL) was cooled to –78 °C (dry
ice/i-PrOH). (MeO)2P(O)Me (2.881 g, 23.2 mmol) was then added
dropwise over 5 min; the colorless soln turned into a white gel. The
mixture was stirred at –78 °C for 30 min. A soln of ethyl 3,5-di-
methylhexanoate (2, 1 g, 5.8 mmol) in anhyd THF (3 mL) was add-
ed dropwise; the mixture turned into a colorless liquid again. The
temperature was then allowed to rise to –20 °C over 2 h. 18% aq
HCl (5 mL) was added to the mixture, the aqueous layer was sepa-
rated, and NaHCO3 was added until pH 8. The aqueous layer was
extracted with CH2Cl2 (15 mL). The organic layers were washed
with H2O (10 mL) and brine (10 mL), dried (MgSO4), filtered, and
relevant compounds featuring polydeoxypropionate concentrated. The crude product was purified by flash chromatog-
chains.8
raphy (silica gel, CH2Cl2–i-PrOH, 95:5, Rf = 0.6) to give a colorless
liquid; yield: 1.2 g (4.8 mmol, 83%).
IR (film): 2850–3000, 1716, 1469, 1386, 1259, 1032, 813, 545
All commercially available reagents were purchased from either
cm–1.
Aldrich or Acros Organics and used without further purification.
Unless specified, all solvents used in chemical reactions were of p.a.
1H NMR (300 MHz, CDCl3): d = 3.79 (d, J = 11 Hz, 6 H), 2.98–
3.18 (m, 2 H), 2.52–2.62 (dd, J = 5, 17 Hz, 1 H), 2.36–2.47 (dd,
J = 8, 17 Hz, 1 H), 2.09 (m, 1 H), 1.62 (m, 1 H), 1.00–1.16 (m, 2 H),
0.84–0.90 (m, 9 H).
13C NMR (75 MHz, CDCl3): d = 201.6, 52.9 (d, J = 6 Hz), 51.8,
46.3, 41.8 (d, J = 128 Hz), 26.7, 25.3, 23.2, 22.2, 19.8.
13P NMR (200 MHz, CDCl3, external reference: H3PO4 at d = 0):
d = 23.49.
grade, whereas solvents used for flash chromatography were tech-
nical grade. HPLC solvents were of HPLC grade. Technical petro-
leum ether (PE) was the fraction boiling in the range 40–65 °C.
1
Deuterated solvents were purchased from ROCC S.A. H and 13C
NMR spectra were recorded on a Bruker Avance II 300 MHz spec-
trometer. 31P NMR spectra were recorded on a Bruker Avance 500
MHz spectrometer. FTIR spectra were recorded on a BioRad FTS-
135 spectrophotometer. Mass spectra (APCI) were recorded on a
Finnigan LCQ Ion Trap. HRMS analyses were performed at the
‘Laboratoire de spectrometrie de masse de l'Université de Mons-
Hainaut’ (Prof. Flammang).
MS (APCI): m/z = 251 [M + H]+.
2,8,10-Trimethylundec-4-en-6-one (4)
NaH (0.80 g, 20 mmol, 60% in mineral oil) was washed in a 2-neck
flask under argon with PE (3 × 20 mL) and dried under vacuum.
Anhyd DME (20 mL) was then poured onto NaH and cooled down
to 0 °C. Phosphonate 3 (5 g, 20 mmol) was then added dropwise
over 15 min. When all the NaH had been consumed (NaH is not sol-
Ethyl (E)- and (Z)-3,5-Dimethylhex-2-enoate (1)
To a 3-neck round-bottomed flask under argon was added NaOEt
(53 mL, 21 wt% in EtOH, 142 mmol)), anhyd EtOH (100 mL), and
(EtO)2P(O)CH2CO2Et (32.83 g, 142 mmol) at r.t. After 5 min, 4-
Synthesis 2010, No. 21, 3755–3760 © Thieme Stuttgart · New York

PAPER
Polypropylene Model Compounds of Various Tacticities
3759
uble into DME), isovaleraldehyde (2.2 mL, 20 mmol) was slowly
added to the mixture. The mixture was stirred at 0 °C for 15 min.
H2O (40 mL) and Et2O (40 mL) were then added, and the aqueous
layer was extracted with Et2O (3 × 20 mL). The combined organic
layers were washed with brine (3 × 20 mL), dried (MgSO4), filtered,
and concentrated. The crude product was purified by flash chroma-
tography (silica gel, EtOAc, Rf = 0.9) to give a colorless liquid;
yield: 4.069 g (19.3 mmol, 97%). A fraction of the product still con-
tained an impurity that was removed on a short flash chromatogra-
phy (silica gel, CH2Cl2, Rf = 0.7).
fied by flash chromatography (silica gel, PE, Rf = 0.9) to give a
colorless liquid; yield: 1.822 g (8.1 mmol, 81%).
IR (film): 3071, 2913–2956, 2839–2869, 1641, 1437–1466, 1361–
1383, 892 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.71 (s, 2 H), 1.90–2.08 (m, 2 H),
1.58–1.80 (m, 6 H), 0.79–1.18 (m, 22 H).
13C NMR (75 MHz, CDCl3): d = 147.6, 111.9, 111.8, 47.2, 46.8,
44.5, 44.2, 28.4, 28.3, 25.4, 23.7, 23.6, 22.5, 22.3, 20.1, 19.8.
HRMS (EI): m/z [M + H]+ calcd for C16H33: 224.250401; found:
224.249788.
IR (film): 2930–2956, 2872–2902, 1696, 1671, 1629, 1457–1468,
1367–1386, 982 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.79 (dt, J = 7.5, 15 Hz, 1 H), 6.09
(dd, J = 2, 15 Hz, 1 H), 2.44–2.52 (dd, J = 6, 15 Hz, 1 H), 2.27–2.36
(dd, J = 7.5, 15 Hz, 1 H), 2.00–2.18 (m, 3 H), 1.78 (m, 1 H), 1.62
(m, 1 H), 1.01–1.8 (m, 2 H), 0.93 (d, J = 7 Hz, 6 H), 0.85–0.90 (m,
9 H).
13C NMR (75 MHz, CDCl3): d = 200.7, 146.1, 131.9, 48.2, 46.9,
41.9, 28.1, 27.8, 25.5, 23.5, 22.6, 22.4, 20.2.
6-(Hydroxymethyl)-2,4,8,10-tetramethylundecane (8)
A 2-neck round-bottomed flask under argon containing 6 (0.561 g,
2.5 mmol) was cooled to 0 °C. 1 M BH3·THF in THF (7.5 mL, 7.5
mmol) was then added dropwise and the mixture stirred at r.t. for 2
h. The mixture was then cooled again to 0 °C and H2O (7.5 mL) was
slowly added to neutralize the excess of hydride. Sodium percar-
bonate (2.777 g, ~13% H2O2 w/w, ~22.3 mmol H2O2) was slowly
added, and the mixture stirred at 50 °C for 1 h and at r.t. for 48 h.
The aqueous layer was then separated and extracted with Et2O
(3 × 10 mL). The combined organic layers were washed with brine
(10 mL), dried (MgSO4), filtered, and concentrated. The crude
product was purified by flash chromatography (silica gel, PE–
EtOAc 95:5, Rf = 0.21–0.55) as a colorless liquid; yield: 0.402 g
(1.7 mmol, 66%, all isomers considered).
HRMS (CI): m/z [M + H]+ calcd for C14H27O: 211.2062; found:
211.2069.
2,4,8,10-Tetramethylundecan-6-one (5)
CuI (0.146 g, 0.8 mmol) and anhyd Et2O (10 mL) were added to a
3-neck flask under argon. The flask was then cooled to 0 °C and 3.0
M MeMgBr in Et2O (5.0 mL, 15.0 mmol) was added dropwise over
10 min. The mixture was stirred at 0 °C for 30 min and then a soln
of enone 4 (1.530 g, 7.3 mmol) in anhyd Et2O (30 mL) was added
dropwise over 30 min. The mixture was stirred at 0 °C for a further
1 h and then aq 1 M HCl (10 mL) and H2O (60 mL) were added and
a white solid appeared. The aqueous layer was extracted with Et2O
(3 × 50 mL). The organic layers were washed with H2O (2 × 50 mL)
and brine (3 × 50 mL). The white solid then disappeared. The crude
product was recovered after drying (MgSO4), filtration, and evapo-
ration of the solvent. The crude product was purified by flash chro-
matography (silica gel, CH2Cl2, Rf = 0.8) to give a colorless liquid;
yield: 1.46 g (6.4 mmol, 88%).
(4R,6r,8S)-8
1H NMR (300 MHz, CDCl3): d = 3.51 (d, J3 = 5 Hz, 2 H), 1.46–1.72
(m, 5 H), 1.22–1.36 (m, 4 H), 0.89–1.16 (m, 4 H), 0.78–0.89 (m, 18
H).
13C NMR (75 MHz, CDCl3): d = 65.91, 47.31, 40.20, 35.29, 27.89,
25.38, 23.74, 22.38, 20.47.
(4R,6s,8S)-8
1H NMR (300 MHz, CDCl3): d = 3.51 (d, J = 5 Hz, 2 H), 1.48–1.75
(m, 5 H), 0.91–1.30 (m, 8 H), 0.74–0.91 (m, 18 H).
13C NMR (75 MHz, CDCl3): d = 66.97, 47.21, 40.10, 35.47, 27.96,
25.39, 23.77, 22.33, 20.51.
IR (film): 2931–2958, 2875–2900, 1711, 1454–1466, 1362–1385
cm–1.
1H NMR (300 MHz, CDCl3): d = 2.28–2.37 (dd, J = 5, 15 Hz, 2 H),
1.99–2.21 (m, 4 H), 1.61 (m, 2 H), 0.98–1.14 (m, 4 H), 0.83–0.90
(m, 18 H).
13C NMR (75 MHz, CDCl3): d = 211.3, 51.4, 51.3, 46.7, 46.6, 27.0,
25.4, 23.4, 22.3, 20.1.
(4R,8R)-8 and (4S,8S)-8
1H NMR (300 MHz, CDCl3): d = 3.50–3.60 (dd, J3 = 4.8 Hz,
J2 = 10.5 Hz, 1 H), 3.39–3.49 (dd, J3 = 5.7 Hz, J2 = 10.5 Hz, 1 H),
1.45–1.74 (m, 5 H), 0.74–1.34 (m, 26 H).
13C NMR (75 MHz, CDCl3): d = 66.47, 47.67, 47.56, 40.41, 39.30,
35.41, 27.93, 27.70, 25.35, 23.63, 23.59, 22.47, 20.22, 20.18.
HRMS (CI): m/z [M + H]+ calcd for C15H31O: 227.237491; found:
227.237145.
2,4,8,10-Tetramethyl-6-(tosyloxymethyl)undecane (9)
A 2-neck round-bottomed flask under argon containing 8 (0.292 g,
1.2 mmol) and anhyd pyridine (3.6 mL) was cooled to 0 °C. TsCl
(1.144 g, 6.0 mmol) was added and the mixture stirred at r.t. for 48
h. H2O (8 mL) was then added and the aqueous layer was separated
and extracted with Et2O (3 × 8 mL). The combined organic layers
were washed with 10% aq HCl (3 × 5 mL) and H2O (8 mL), dried
(MgSO4), filtered, and concentrated. The crude product was puri-
fied by flash chromatography (silica gel, CHCl3–cyclohexane,
60:40, Rf = 0.40–0.71) to give a colorless liquid; yield: 0.401 g (1.0
mmol, 84%).
2,4,8,10-Tetramethyl-6-methyleneundecane (6)
MePh3P+Br– (7.148 g, 20.0 mmol) and 1.0 M t-BuOK in THF (20
mL,20.0 mmol) were added to a 3-neck round-bottomed flask under
argon; the mixture was stirred at r.t. for 7 min. Ketone 5 (2.264 g,
10.0 mmol) was then added dropwise. The mixture was stirred at r.t.
for 2 h and then quenched by the addition of H2O (30 mL). The
aqueous layer was then extracted with EtOAc (2 × 60 mL). The
combined organic layers were washed with H2O (2 × 30 mL) and
brine (2 × 30 mL), dried (MgSO4), filtered, and concentrated. The
crystallization of Ph3PO occurred during evaporation of the solvent.
The solid was then triturated in pentane (40 mL) and filtered. This
procedure was repeated several times. The combined filtrates were
concentrated to give crude product (2.125 g). The remaining solid
was ground into a powder, poured into pentane (150 mL) and stirred
overnight. Additional crude product (0.25 g) was recovered after fil-
tration and distillation of the solvent. The crude product was puri-
(4R,6r,8S)-9
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J3 = 8 Hz, 2 H), 7.33 (d,
J3 = 8 Hz, 2 H), 3.91 (d, J3 = 4.5 Hz, 2 H), 2.44 (s, 3 H), 1.75 (m, 1
H), 1.57 (m, 2 H), 1.42 (m, 2 H), 1.18–1.30 (m, 2 H), 0.85–1.05 (m,
6 H), 0.74–0.85 (m, 18 H).
Synthesis 2010, No. 21, 3755–3760 © Thieme Stuttgart · New York

3760
X. Drooghaag et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 144.75, 133.32, 129.96, 128.07,
73.13, 47.09, 39.77, 32.62, 27.57, 25.25, 23.63, 22.32, 21.81, 20.09.
(4R,6s,8S)-7
1H NMR (300 MHz, CDCl3): d = 1.47–1.74 (m, 5 H), 0.79–1.22 (m,
29 H).
(4R,6s,8S)-9
13C NMR (75 MHz, CDCl3): d = 46.69, 46.06, 27.76, 27.35, 25.41,
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J3 = 8 Hz, 2 H), 7.33 (d,
J3 = 8 Hz, 2 H), 3.87 (d, J3 = 5 Hz, 2 H), 2.44 (s, 3 H), 1.75 (m, 1
H), 1.58 (m, 2 H), 1.39 (m, 2 H), 0.86–1.20 (m, 8 H), 0.83 (d, J3 = 6
Hz, 6 H), 0.76 (d, J3 = 6 Hz, 12 H).
24.01, 22.19, 20.98, 20.78.
(4R,8R)- and (4S,8S)-7
1H NMR (300 MHz, CDCl3): d = 1.47–1.74 (m, 5 H), 0.76–1.20 (m,
13C NMR (75 MHz, CDCl3): d = 144.75, 133.21, 129.90, 128.07,
74.01, 46.64, 39.49, 32.54, 27.55, 25.20, 23.68, 22.07, 21.71, 20.18.
29 H).
13C NMR (75 MHz, CDCl3): d = 48.06, 47.10, 46.73, 44.97, 27.72,
27.65, 27.39, 25.38, 25.32, 23.85, 23.42, 22.72, 22.36, 20.44, 19.83.
(4R,8R)- and (4S,8S)-9
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J3 = 9 Hz, 2 H), 7.33 (d,
J3 = 9 Hz, 2 H), 3.83–3.95 (m, 2 H), 2.44 (s, 3 H), 1.75 (m, 1 H),
1.57 (m, 2 H), 1.39 (m, 2 H), 0.85–1.25 (m, 8 H), 0.72–0.85 (m, 18
H).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
13C NMR (75 MHz, CDCl3): d = 144.75, 133.28, 129.84, 127.97,
73.57, 47.29, 46.90, 39.87, 38.73, 32.52, 27.50, 27.28, 25.11, 23.51,
23.42, 22.30, 22.16, 21.67, 19.82, 19.74.
Acknowledgment
The authors thank La Région Wallonne (programme ‘Recherche
d’initiative’) and FRIA for financial support. J.M.B. is a senior re-
search associate of the F.R.S.-FNRS (Belgium).
2,4,6,8,10-Pentamethylundecane (7)
From 6: To a 3-neck round-bottom flask was added 6 (0.617 g, 2.7
mmol) and 10% Pt/C (~0.5 g, ~24.5 mmol). The atmosphere in the
flask was purged with argon (3 ×) and H2 (3 ×). The mixture was
stirred vigorously at 25 °C under H2 (~1 atm) for 48 h. The catalyst
was then filtered and washed with PE (3 × 50 mL). The pure prod-
uct was recovered after distillation of the solvent as a colorless liq-
uid; yield: 0.577 g, (2.5 mmol, 93%). NMR spectra are of mixtures
of isomers.
1H NMR (300 MHz, CDCl3): d = 1.45–1.75 (m, 5 H), 0.75–1.22 (m,
29 H).
13C NMR (75 MHz, CDCl3): d = 48.08, 47.80, 47.13, 46.75, 46.20,
46.10, 45.01, 27.68–27.80, 27.40–27.43, 25.34–25.43, 24.00,
23.85, 23.54, 23.43, 22.72, 22.64, 22.37, 22.21, 21.01, 20.79,
20.43–20.46, 20.07, 19.85, 19.65.
References
(1) (a) Both authors have contributed equally to this work.
(b) Present address of G. Henry: Total Petrochemicals
Research, Zone industrielle C, B-7181 Feluy, Belgium.
(c) Present address of X. Drooghaag: 3B-Fibreglass, Route
de Maestricht, B-4651 Battice, Belgium.
(2) (a) Henry, G. R. P.; Drooghaag, X.; Rousseaux, D. D. J.;
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Sclavons, M.; Schanck, A.; Devaux, J.; Carlier, V.;
Marchand-Brynaert, J. J. Polym. Sci., Part A: Polym. Chem.
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From 9: In a 2-neck round-bottomed flask under argon atmosphere
containing 9 (0.086 g, 0.22 mmol) was added 1.0 M LiEt3BH in
THF (0.7 mL, 0.7 mmol) at r.t. The mixture was then stirred at 67
°C for 6 h. Aq 3 M NaOH (1.4 mL ) was then added dropwise at r.t.
The aqueous layer was then separated and extracted with PE (2 × 5
mL). The combined organic layers were washed with H2O (1 mL)
and brine (1 mL), dried (MgSO4), filtered, and concentrated to give
a colorless liquid; yield: 0.051 g (0.22 mmol, 100%). GC and NMR
measurements revealed that the product was pure and did not need
to be further purified.
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(4R,6r,8S)-7
1H NMR (300 MHz, CDCl3): d = 1.48–1.74 (m, 5 H), 0.90–1.13 (m,
8 H), 0.78–0.90 (m, 21 H).
13C NMR (75 MHz, CDCl3): d = 47.80, 46.19, 27.74, 27.42, 25.35,
23.55, 22.65, 20.70, 19.65.
Synthesis 2010, No. 21, 3755–3760 © Thieme Stuttgart · New York