Catalytic cyclometallation of allylbenzenes by EtAlCl2 and Mg as new route to synthesis of dibenzyl butane lignans

Article abstract of DOI:10.1016/j.jorganchem.2014.09.033

The cyclometallation of allylbenzenes (Ar = Ph, 4-MeO-Ph, 3,4-(MeO)₂-Ph) with EtAlCl₂ (Et₂AlCl) and Mg in the presence of Zr and Ti catalysts (Dzhemilev reaction) has been studied. The reaction run with high diastereoselectivity and gives cyclic organoaluminum compounds, which deuterolysis or hydrolysis gave 2R(S), 3R(S)-dibenzyl butanes with yield of 48-69%. The study of catalyst structure effect on the substrate conversion, reaction chemo- and stereoselectivity showed that the best results were obtained in the case of Cp₂ZrCl₂ among the tested complexes. The enantioselectivity of neomenthylindenyl or neomenthyltetrahydroindenyl zirconium catalysts in the reaction did not exceed 20%ee. The trans-configuration of the substitutes in the metallacycles formed in the reaction has been proved by X-ray analysis of the hydrolysis product - 2R(S), 3R(S)-dimethyl-1,4-bis[(4′- methoxyphenyl)methyl]-butane. The proposed method could be used for the one-pot diastereoselective synthesis of dibenzyl butane lignans from readily available allylbenzenes.

Full text of DOI:10.1016/j.jorganchem.2014.09.033

Accepted Manuscript
Catalytic cyclometallation of allylbenzenes by EtAlCl and Mg as new route to
2
synthesis of dibenzyl butane lignans
Lyudmila V. Parfenova, Tatyana V. Berestova, Pavel V. Kovyazin, Aydar R. Yakupov,
Ekaterina S. Mesheryakova, Leonard M. Khalilov, Usein M. Dzhemilev
PII:
S0022-328X(14)00460-4
10.1016/j.jorganchem.2014.09.033
JOM 18738
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 4 June 2014
Revised Date: 15 September 2014
Accepted Date: 24 September 2014
Please cite this article as: L.V. Parfenova, T.V. Berestova, P.V. Kovyazin, A.R. Yakupov, E.S.
Mesheryakova, L.M. Khalilov, U.M. Dzhemilev, Catalytic cyclometallation of allylbenzenes by EtAlCl
and Mg as new route to synthesis of dibenzyl butane lignans, Journal of Organometallic Chemistry
(2014), doi: 10.1016/j.jorganchem.2014.09.033.
2
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
The cyclometallation of allylbenzenes (Ar= Ph, 4-MeO-Ph, 3,4-(MeO)2-Ph) with
EtAlCl2 (Et2AlCl) and Mg in the presence of Zr and Ti catalysts (Dzhemilev
reaction) has been studied. The reaction runs with high diastereoselectivity and
provides 2R(S),3R(S)-dibenzyl butanes with yield of 48-69%.

ACCEPTED MANUSCRIPT
Ar
Ar
Ar
Ar
H3O+ (D3O+)
Mg, [Zr]
Ar
Ar
(D)
(D)
H
H
EtAlCl2
(Et2AlCl)
Et Al
+
THF, 200C, 72h
97-99%
48-69%
OMe
>99%de
Ar=
OMe
OMe

1
ACCEPTED MANUSCRIPT
Catalytic cyclometallation of allylbenzenes by EtAlCl2 and Mg as new route to
synthesis of dibenzyl butane lignans
Lyudmila V. Parfenova, Tatyana V. Berestova, Pavel V. Kovyazin, Aydar R.
Yakupov, Ekaterina S. Mesheryakova, Leonard M. Khalilov, Usein M.
Dzhemilev
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences,
450075, Ufa, prospect Oktyabrya, 141, Russian Federation
Abstract:
The cyclometallation of allylbenzenes (Ar= Ph, 4-MeO-Ph, 3,4-(MeO)2-Ph) with
EtAlCl2 (Et2AlCl) and Mg in the presence of Zr and Ti catalysts (Dzhemilev
reaction) has been studied. The reaction run with high diastereoselectivity and
gives cyclic organoaluminum compounds, which deuterolysis or hydrolysis gave
2R(S),3R(S)-dibenzyl butanes with yield of 48-69%. The study of catalyst structure
effect on the substrate conversion, reaction chemo- and stereoselectivity showed
that the best results were obtained in the case of Cp2ZrCl2 among the tested
complexes.
The
enantioselectivity
of
neomenthylindenyl
or
neomenthyltetrahydroindenyl zirconium catalysts in the reaction did not exceed
20%ee. The trans-configuration of the substitutes in the metallacycles formed in
the reaction has been proved by X-ray analysis of the hydrolysis product –
2R(S),3R(S)-dimethyl-1,4-bis[(4′- methoxyphenyl)methyl]-butane. The proposed
method could be used for the one- pot diastereoselective synthesis of dibenzyl
butane lignans from readily available allylbenzenes.
Keywords: cyclometallation, metallocenes, dibenzyl butanes, lignans,
terameprocol, MTPA, (R)- 2- phenylselenopropanoic acid
1. Introduction
Corresponding author. Tel.: +7 347 2843527; fax: +7 347 2842750.
E-mail address: luda_parfenova@mail.ru (L.V. Parfenova).

2
ACCEPTED MANUSCRIPT
Catalytic alkene cycloalumination (Dzhemilev’s reaction) is an effective and
stereoselective method for the synthesis of a variety of organic compounds [1].
Thus, it was shown that a reaction of terminal alkenes with organoaluminum
compounds
(OAC)
and
Mg,
catalyzed
by
Cp2ZrCl2,
provides
aluminacyclopentanes, which hydrolysis gives racemic 2,3- disubstituted butanes
at high diastereselectivity [2].
H3O+
Cp2ZrCl2
Mg
R'AlCl2
2
THF, r.t.
-MgCl2
R= n-Pr, i-Bu, n- C5H11, n- C8H17, Ph;
R'= Et, Cl, OEt, OBu, Et2N, C5H10N
99%de
>
The use of methoxy-substituted allylbenzenes in the reaction opens a way to
the one-pot diastereoselective synthesis of dibenzyl butane-type lignans [3] − a
group of natural products, which are being considered as potential drugs due to a
wide range of their biological activity. Thus, 2,3-dibenzylbutanes (for example,
nordihydroguaiaretic acid (NDGA), dihydroguaiaretic acid (DGA), terameprocol
and austrobailignan-5) show anti-tumor, antiviral, anti-inflammatory, antioxidant
and other activity [4]. Despite the presence of numerous methods for their
preparation in the literature [5,6], the development of new stereoselective synthetic
routes is still of interest.
In order to find a novel approach to the synthesis of the dibenzyl butane
lignans we have studied a reaction of methoxy-substituted allylbenzenes with
EtAlCl2 (Et2AlCl) and Mg in the presence of Zr and Ti catalysts. The effect of the
catalyst structure and the reaction conditions on the alkene conversion and reaction
chemo-, regio- and enantioselectivity has been considered.
2. Results and discussion
We have studied the cyclometallation reaction of substituted allylbenzenes 1a-
c (Ar = Ph, 4-methoxyphenyl, 3,4-dimethoxyphenyl) by EtAlCl2 (Et2AlCl) and Mg
in the presence of catalytic amounts of Zr and Ti complexes (2a-i) (Scheme 1) in
ethereal solvents (THF, Et2O) at a room temperature. The reaction runs with high
diastereoselectivity (>99%de) and gives racemic 3R(S),4R(S)-dibenzylsubstituted

ACCEPTED MANUSCRIPT
3
Scheme 1
Mg, [Zr] (2a-i)
Et
EtAlCl2
(Et2AlCl)
Et
THF, 200C
6a-c
7a-c
1a-c
3a-c
4a-c
5a-c
H3O+ (D3O+)
H3O+ (D3O+)
H3O+ (D3O+)
H3O+ (D3O+)
Ar=
(D)
(D)
(D)
(D)
(D)
(D)
1a
1b
1c
14a-c
D-15a-c
8a-c
D-9a-c
10a-c
D-11a-c
12a-c
D-13a-c
ZrCl
4
2a
2b
2c
2j
2d
2e
2g
2f
2h
2i

4
ACCEPTED MANUSCRIPT
aluminacyclopentanes
as the major products Moreover, we have identified
.
3а-с
regioisomers
, acyclic organoaluminum compounds with double bond
,
4а-с
5a-c
hydroalumination products
and alkenes with shifted double bond
. The
6а-с
structure of the obtained organoaluminum compounds has been proved by the
analysis of deuterolysis products
7a-c
,
,
,
.
9a-c 11a-c 13a-c 15a-c
It has been found that the conversion of allylbenzenes
in the reaction
1a-c
with EtAlCl and Mg, catalyzed with Cp ZrCl ( ), in THF at a room temperature
2с
2
2
2
for 72 h reaches 97-99%. The reaction gives expected cycloalumination products
with yield of 48-69% according to GC analysis of deuterolysis products
3a-c
(Table 1, entries 4, 14, 23). Catalysts ZrCl ( ) and CpZrCl ( ) showed lower
2a 2b
4
3
activity, chemo- and regioselectivity than complex
in the reaction (Table 1,
2с
entries 1 and 2). Further, the application either of Et2O solvent or of Et2AlCl
significantly reduces the conversion of the alkenes to 45-79% (see, for example,
entries 3, 11, 13, 24 in Table 1). Increasing the reaction temperature accelerates the
side hydroalumination reaction (Table 1, entries 5, 15, 22).
<Table 1>
Ansa-zirconocenes rac-2e,f show good activity in the reaction; however, they
increase the relative content of regioisomer 4a-c in the product mixture (Table 1,
entries 7, 8, 17, 18, 25). Moreover, catalyst rac-2f speeds up the hydroalumination
process.
It should be noted that the byproducts
and
are formed due to C-H
7a-c
5a-c
activation in the reaction intermediates. Typically, in catalytic systems based on
zirconocenes, the C-H activation process could be slowed down by an introduction
of sterically hindered η5- ligands into the metal complex [7]. This approach to the
catalyst design could improve the reaction regioselectivity as well. Thus, for the
further search for active, chemo- and stereoselective catalysts for allylbenzene
cyclometallation reaction we have studied the catalytic effect of complexes
containing bulky ligands, including enantiomerically pure: Cp* ZrCl ( ),
2d
2
2
CpInd*ZrCl (Ind*- 1-neomenthylindenyl) ( ), Ind* ZrCl ( ), Cp′ ZrCl (Cp′-
2g 2h
2
2
2
2
2
1-neomenthyl-4,5,6,7-tetrahydroindenyl) ( ). Unfortunately, the tested complexes
2i

5
ACCEPTED MANUSCRIPT
showed lower activity, chemo- and regioselectivity than . The enantiomeric
2c
excess was determined for oxidation product 2R(S),3R(S)-2-benzyl-3-methyl-4-
phenyl-1-butanol ( ) using derivatization reagents R-MTPA (Mosher’s reagent)
16a
[8] and (R) - 2 - phenylselenopropanoic acid (R-PSPA) [9]. The alcohol
was
16a
isolated after the oxidation of the reaction mixture with tBuOOH for 24 h.
Ph
Al
Et
3a
Ph
tBuOOH
Ph
Ph
Ph
Ph
Ph
O
O
1
5
2
MeO
F C
R-
PSPA
R-
HO
MTPA
O
O
3
3
Ph
SePh
4
6
Ph
18a
17a
16a
Thus, the enantioselectivity of complexes
in the cyclometallation reaction
2g-i
did not exceed 20%ee. It should be noted that the increasing of steric hindrances in
catalysts improved the reaction enantioselectivity, but dramatically decreased
2g-i
the alkene conversion.
Further, replacing of transition metal atom in the metallocene from Zr to Ti
(Cp2TiCl2 (2j)) changed the reaction so that it resulted in C-H activation product 7
with a shifted double bond; this is generally characteristic to the Ti complexes.
During the isolation of the reaction products, we have obtained compound 8b
in the crystalline form suitable for the X-ray diffractometry analysis [10] (Table 2).
Its ORTEP diagram is presented in Fig. 1. The geometric parameters of non-
hydrogen bonds and angles observed in 8b are summarized in Table 3. The torsion
angle between the vicinal methyl groups of 169° proves their trans- configuration.
The twist angle between the planes of the two phenyl groups is 78°. The distance
between the centers of parallel phenyl groups of adjacent molecules in a crystal
(Fig. 2) is 5.290 Å; this excludes the existence of π – π interactions between the
molecules.

6
ACCEPTED MANUSCRIPT
<Figure 1>
<Figure 2>
<Table 2>
<Table 3>
Conclusions
Finally, the proposed method of catalytic cycloalumination of methoxy-
substituted allylbenzenes by EtAlCl2 and Mg provides an effective way to an one-
pot synthesis of dibenzyl butane lignans. The study of catalyst structure effect on
the activity and selectivity of the catalytic system showed that the best results were
obtained in the case of zirconocene dichloride among the tested complexes. The
asymmetric induction of enantiomerically pure neomenthylindenyl or
neomenthyltetrahydroindenyl zirconium complexes did not exceed 20%ee.
The present work will be continued towards the search of new active and
selective catalysts for these reactions, as well as the methods for the synthesis of
dibenzylbutanediols, which could be obtained in the reaction via the oxidation of
organoaluminum products.
Experimental
All operations with organometallic compounds were carried out under argon
using Schlenk techniques. Solvents were dried and distilled under argon prior to
use. THF, Et2O was freshly distilled from sodium/benzophenone. Allylbenzenes
(1а-c) were purchased from Aldrich. Commercially available EtAlCl2 (85%) and
Et2AlCl (82%) were involved in the reactions. Tert-butyl hydroperoxide solution
(5.5 M) in decane (Aldrich) was used for the oxidation of the reaction products.
Complex 2c was prepared from ZrCl4 (99.5%, Aldrich) [11]. Catalysts 2d-f
(98%, Strem) and 2i (99.5%, Aldrich) were purchased and used as received
.
Catalysts 2g,h were prepared from (+)-3-[(1'S,2'S,5'R)-2'-isopropyl-5'-
methylcyclohexyl]indene (3-neomenthylindene) and ZrCl4 (2a) (99.5%, Aldrich)
[12] or CpZrCl3 (2b) [13]. Complex 2i was prepared from TiCl4 (99.0%, Aldrich)
[14].

7
ACCEPTED MANUSCRIPT
1
13
The H and C NMR spectra were recorded on “Bruker AVANCE-400”
spectrometer (400.13 MHz (1H), 100.62 MHz (13C)). The samples were prepared in
standard tubes of 5 mm diameter. One and two-dimensional NMR spectra (COSY,
HSQC, HMBC, NOESY) were measured using standard pulse sequences.
Elemental analyses of compounds 8,9b,c were carried out on CHNO analyzer
Carlo Erba-1106.
The hydrolysis and deuterolysis products of the reaction mixture were
analyzed on Carlo Erba gas chromatograph (He, column 50,000 x 0.32 mm, fixed
phase ‘Ultra-1’, flame ionization detector). GC-MS analysis was carried out on
spectrometer QP 2010 Ultra (Shimadzu). The yields of reaction products and
alkene conversion were determined using internal standard.
MTPA ester 17a was synthesized as described in Ref. [8]. PSPA ester 18a
was prepared according to Ref. [9].
The single crystal of 8b was prepared by slow evaporation of benzene
solution at the room temperature. X-ray diffraction data was collected on a
XCalibur Eos diffractometer with graphite monochromated Mo-Kα radiation (λ =
0.71073 Å). Collection and processing of data performed with using the program
CrysAlisPro Oxford Diffraction Ltd., Version 1.171.33.66. The structure was
refined by a full-matrix least-square technique using anisotropic thermal
parameters for non-hydrogen atoms and a riding model for hydrogen atoms in the
program SHELXS-97 [10]. Crystallographic data for the structure of 8b have been
deposited in the Cambridge Crystallographic Data Centre as a CIF deposition with
file number CCDC 909400. Copies of these data can be obtained free of change on
application to CCDC, 12, Union Road, Cambridge, CB2 1EZ, UK (fax: +44 1223
336033,
e-mail:
deposit@ccdc.cam.ac.uk)
or
from
http://www.ccdc.cam.ac.uk/data_request/cif.
Reaction of allylbenzenes (1a-c) with EtAlCl2 (Et2AlCl) and Mg in the
presence of complexes 2a-j.

8
ACCEPTED MANUSCRIPT
A 10 ml flask equipped with a magnetic stirrer and filled with argon was
loaded with 0.2 mmol of complexes (2a-j), 4 mmol of Mg (powder), 3 ml of a
solvent (THF or Et2O) and 4 mmol of allylbenzene (1a-c). The mixture was cooled
o
to 0 C and 5 mmol of EtAlCl2 or Et2AlCl was added dropwise. The reaction
mixture was stirred for 72 h at 20–30oC. Further, the mixture was decomposed
with 10% HCl or DCl at 0oC. The products were extracted with Et2O; the organic
layer was dried over Na2SO4 and analyzed by GC and GC–MS. The products 8,9a-
c were isolated by column chromatography on silica gel (hexane/Et2O 5:1). NMR
characteristics and mass-spectral data of 8a, 9a were identical to the literature data
[2d].
t
The oxidation of the reaction mixture with BuOOH for 24 h, subsequent
hydrolysis with 10% HCl and extraction with Et2O gave alcohol 16a, which was
isolated by column chromatography on silica gel (hexane/ethyl acetate 97:3).
2R(S),3R(S)-dimethyl-1,4-bis[(4′- methoxyphenyl)methyl]butane (8b).
Isolated as white crystals with a purity of 98%, 324 mg (1.09 mmol, 54%); m/z
(EI) 298 (M+, %), 298 (9), 121 (75), 77 (9), 65 (10), 31 (100). Anal. Calcd. for
C20H26O2 (%): C, 80.50, H, 8.78, O, 10.72. Found (%): C, 80.53; H, 8.81; O, 10.66.
3
1H NMR (CDCl3) δ 0.87 (d, J = 6.4 Hz, 6Н, СН3), 1.72-1.88 (m, 2Н, СН), 2.45
(dd, 2J = 13.6 Hz, 3J = 8.4 Hz, 2H, CHСНH), 2.65 (dd, 2J = 13.2 Hz, 3J = 6.6 Hz,
2H, CHСHH); 3.83 (s, 6H, OCH3) 6.85 (d, 3J = 8.4 Hz, 4Н, m-H (Ph)), 7.06 (d, 3J
= 8.4 Hz, 4Н, o-H (Ph)). 13C NMR (CDCl3) δ 13.9 (C1), 38.2 (C2), 40.5 (C3), 55.8
(OCH3), 113.6 (C6), 129.9 (C5), 133.8 (C4); 157.7 (C7).
2R(S),3R(S)-2,3-bis[(4′-methoxyphenyl)methyl]butane-1,4-d2 (9b): m/z
(EI) 300 (M+, %), 300 (4), 121 (100), 89 (2), 78 (11), 65 (3), 51 (2). Anal. Calcd.
for C20H24D2O2 (%): C, 79.96; (H+D), 9.39; O, 10.65. Found (%): C, 81.01;
1
(H+D), 9.47; O, 9.52. H NMR (CDCl3) δ 0.82-0.91 (4H, СН2D), 1.77-1.87 (m,
2H, СН), 2.43 (dd, 2J = 13.6 Hz, 3J = 8.4 Hz, 2Н, CHCHH), 2.65 (dd, 2J = 13.6 Hz,
3
3J = 5.8 Hz, 2Н, CHCHH), 3.84 (s, 6Н, OCH3), 6.86 (d, J = 8.4 Hz, 4Н, m-H
(Ph)), 7.07 (d, 3J = 8.4 Hz, 4H, o-H (Ph)). 13C NMR (CDCl3) δ 13.6 (t, JC-D = 19.1

9
ACCEPTED MANUSCRIPT
Hz, C1), 38.2 (C2), 40.5 (C3), 55.3 (OCH3), 113.6 (C6), 129.9 (C5), 133.8 (C4),
157.7 (C7).
2R(S),3R(S)-bis[(3′,4′-dimethoxyphenyl)methyl]butane
((±)-
terameprocol) (8c). Isolated as colorless oil with a purity of 97%, 261 mg (0.73
mmol, 36%); m/z (EI) 358 (M+, %), 358 (19), 179 (3), 165 (2), 151 (100), 137 (3),
135 (4), 121 (4), 107 (14), 91 (8), 78 (5), 77 (5), 73 (2), 65 (5), 40 (13). Anal.
Calcd. for C22H30O4 (%): C, 73.71, H, 8.44, O, 17.85. Found (%): C, 73.77; H,
1
3
8.49; O, 17.27. H NMR (CDCl3) δ 0.86 (d, J = 6.4 Hz, 6H, СН3), 1.72-1.82 (m,
2H, СН), 2.42 (dd, 2J = 13.4 Hz, 3J = 8.0 Hz, 2H, CHCHH), 2.58 (dd, 2J = 13.6 Hz,
3J = 6.8 Hz, 2H, CHCHH), 3.84 (s, 6H, OCH3), 3.87 (s, 6H, OCH3), 6.61 (s, 2Н,
3
3
CCHC (Ph)), 6.64 (d, J = 8.0 Hz, 2H, CCHCH (Ph)), 6.78 (d, J = 8.0 Hz, 2Н,
13
CCHCH (Ph)). C NMR (CDCl3) δ 13.9 (C1), 37.6 (C2), 41.0 (C3), 55.77, 55.80
(OCH3), 111.0 (C8), 112.1 (C5), 120.9 (C9), 134.3 (C4), 147.0 (C7), 148.7 (C6).
2R(S),3R(S)-bis[(3′,4′-dimethoxyphenyl)methyl]butane-1,4-d2 (9c): m/z
(EI) 360 (M+, %), 360 (9), 180 (2), 151 (100), 107 (14), 78 (7), 77 (7), 73 (8), 65
(5). Anal. Calcd. for C22H28D2O4 (%): C, 73.30, (H+D), 8.95, O, 17.75. Found (%):
1
3
C, 73.79; (H+D), 8.86; O, 17.35. H NMR (CDCl3) δ 0.82 (d, J = 6.8 Hz, 4H,
СН2D), 1.71-1.80 (m, 2H, СН), 2.40 (dd, 2J = 13.6 Hz, 3J = 8.0 Hz, 2H, CHCHH),
2
3
2.56 (dd, J = 13.6 Hz, J = 6.8 Hz, 2H, CHCHH), 3.81 (s, 6H, OCH3), 3.85 (s,
3
6H, OCH3), 6.59 (s, 2Н, CCHC (Ph)), 6.62 (d, J = 8.2 Hz, 2H, CCHCH (Ph)),
3
13
6.75 (d, J = 8.2 Hz, 2Н, CCHCH (Ph)). C NMR (CDCl3) δ 13.6 (t, JC-D = 21.5
Hz, C1), 37.5 (C2), 41.0 (C3), 55.73, 55.78 (OCH3), 111.0 (C8), 112.1 (C5), 120.9
(C9), 134.2 (C4), 147.0 (C7), 148.7 (C6).
1-Methoxy-4-[5′-(4′′-methoxyphenyl)-2′-(methyl-d)-pentyl-4′-d]benzene
(11b).
9
14
13
1
2
8
6
4
11
12
10
7
5
3
m/z (EI) 300 (M+, %), 300 (8), 207 (3), 179 (2), 135 (2), 121 (100), 105 (2), 92 (2),
91 (5), 78 (4), 77 (6), 65 (7), 40 (29). 1H NMR (CDCl3) δ 0.93 (d, 3J= 7.0 Hz, 2H,

10
ACCEPTED MANUSCRIPT
СН2D), 1.20–1.32 (m, 1Н, CHСНHСН), 1.41–1.52 (m, 1Н, CHСНHСН), 1.60–
1.80 (m, 1Н, СНD), 1.72–1.81 (m, 1Н, СНСH2D), 2.39 (dd, 2J = 13.4 Hz, 3J = 7.8
Hz, 1H, CHCHHPh), 2.54–2.67 (m, 2Н, CHDСН2Ph), 2.59–2.68 (m, 1Н,
CHCHHPh), 3.85 (s, 6H, OCH3), 6.86- 6.94 (m, 4H, Ph(m-H)), 7.07- 7.10 (m, 4H,
Ph(o-H)). 13C NMR (CDCl3) δ 19.2 (t, JC-D = 19.0 Hz, C9), 29.0 (t, JC-D = 19.0 Hz,
C6), 35.1 (C8), 35.3 (C5), 36.2 (C7), 42.9 (C10), 55.2 (OMe), 113.6, 113.7 (С2, C13),
129.9, 130.0 (C3, C12), 133.6, 135.0 (C4, C11), 157.7 (C1, C14).
4-[5′-(3′′,4′′-Dimethoxyphenyl)-2′-(methyl-d)-pentyl-4′-d]-1,2-dimethoxy-
benzene (11c).
6
17
16
18
5
11
1
10
8
15
13
2
4
9
14
3
12
7
m/z (EI) 360 (M+, %), 360 (35), 165 (2), 151 (100), 152 (17), 135 (3), 136 (2), 137
1
(3), 121 (3), 107 (9), 91 (4), 78 (4), 77 (4), 65 (2), 40 (4). H NMR (CDCl3) δ
0.91–0.95 (m, 2H, СН2D), 1.16–1.26 (m, 1Н, CHСНHСН), 1.38–1.46 (m, 1Н,
CHСНHСН), 1.54–1.61 (m, 1Н, СНD), 1.67–1.76 (m, 1Н, СНСH2D), 2.34 (dd, 2J
3
= 13.4 Hz, J = 8.1 Hz, 1H, CHCHHPh), 2.48–2.61 (m, 2Н, CHDСН2Ph), 2.54–
2.63 (m, 1Н, CHCHHPh), 3.85 (s, 6H, OCH3), 3.88 (s, 6H, OCH3), 6.52 – 6.95 (m,
6Н, Ph). 13C NMR (CDCl3) δ 19.1 (t, JC-D = 19.0 Hz, C11), 28.9 (t, JC-D = 19.0 Hz,
C8), 35.0 (С10), 35.8 (С7), 36.2 (С9), 43.3 (С12), 111.8, 111.9 (С6, С17), 112.3 (С14),
115.5 (С3), 121.2, 121.6 (C5, С18), 134.2 (C13), 135.5 (C4), 147.4 (C1), 148.8 (C2,
C16), 148.9 (C15).
1-Methoxy-4-[(E)-5′-(4′′-methoxyphenyl)-4′-(methyl-d)-pent-1′-en-1′-
yl]benzene (13b).
9
14
1
2
6
13
8
4
11
12
7
5
3
10
m/z (EI) 297 (M+, %), 297 (42), 207 (15), 176 (11), 180 (2), 150 (18), 149 (11),
148 (16), 147 (100), 134 (60), 121 (99), 115 (19), 103 (8), 91 (38), 77 (19), 65 (8),
40 (99). 1H NMR (CDCl3) δ 0.95 (d, 3J=6.8 Hz, 2Н, СН2D), 1.90 (sept, 1Н, 3J=6.4

11
ACCEPTED MANUSCRIPT
Hz, СН), 2.04-2.14 (m, 1Н, CHHCH=), 2.25-2.36 (m, 1Н, CHHCH=), 2.45 (dd,
3
2
3
2J= 13.4 Hz, J= 6.2 Hz, 1H, CHHPh), 2.70 (dd, J= 13.4 Hz, J= 8.4 Hz, 1H,
CHHPh), 3.84 (s, 6Н, OCH3), 6.08-6.20 (m, 1H, СН=СНPh), 6.38 (d, 1Н, 3J= 16.0
3
Hz, СН=СНPh), 6.78-6.93 (m, 4H, Ph(m-H)), 7.14 (d, 2H, J=8.2 Hz, CH2Ph(o-
H)), 7.34 (d, 2Н, 3J= 8.6 Hz, CHPh(o-H)). 13C NMR (CDCl3) δ 19.1 (t, JC-D = 18.7
Hz, C9), 35.6 (C8), 40.1 (C7), 42.3 (C10), 55.2 (OMe), 113.7 (C13), 113.9 (С2), 127.1
(C3), 127.2 (C5), 129.3 (C4), 130.1 (C12), 130.6 (C5), 133.4 (C11), 157.8 (C14), 158.7
(C1).
1,2-Dimethoxy-4-[(E)-5′-(3′′,4′′-dimethoxyphenyl)-4′-(methyl-d)-pent-1′-
en-1′-yl]benzene (13c).
6
17
MeO
D
OMe
16
18
5
11
1
10
8
15
13
2
4
MeO
OMe
9
14
3
12
7
m/z (EI) 357 (M+, %), 357 (74), 219 (5), 207 (17), 206 (16), 193 (10), 180 (13),
179 (8), 177 (69), 164 (21), 159 (4), 151 (100), 152 (35), 147 (11), 146 (28), 137
(11), 131 (12), 121 (22), 115 (12), 107 (17), 103 (10), 91 (18), 90 (5), 77 (14), 73
(11), 65 (8), 40 (72). 1H NMR (CDCl3) δ 0.95 (d, 2Н, 3J=6.8 Hz, СН2D), 1.83–1.95
(m, 1Н, СН), 1.99-2.11 (m, 1Н,CHHCH=), 2.22-2.32 (m, 1Н,CHHCH=), 2.42
2
3
2
3
(dd, J= 13.6 Hz, J=5.6 Hz, 1H, CHHPh), 2.65 (dd, J= 13.6 Hz, J=6.4 Hz, 1H,
CHHPh), 3.88 (s, 6Н, OCH3), 3.89 (s, 6H, OCH3), 6.04-6.16 (m, 1H, СН=СНPh),
3
3
6.34 (d, 1Н, J= 15.6 Hz, СН=СНPh), 6.61 (s, 1H, CH2Ph(o-H)), 6.64 (d, 1H, J=
3
3
8.0 Hz, CH2Ph(o-H)), 6.78 (d, 1H, J=8.0 Hz, CH2Ph(m-H)), 6.82 (d, 1Н, J= 8.4
Hz, CHPh(m-H)), 6.90 (d, 1Н, 3J= 8.4 Hz, CHPh(o-H)), 6.92 (s, 1Н, CHPh(o-H)).
13C NMR (CDCl3) δ 19.2 (t, JC-D = 18.7 Hz, C11), 35.7 (C11), 40.1 (C9), 42.9 (C12),
55.8, 56.0 (OMe), 108.7 (C3), 111.1 (С6), 111.2 (С17), 112.5 (C14), 118.9 (C5),
121.1 (C18), 127.4 (C8), 130.9 (C7), 131.0 (C4), 133.9 (C13), 147.2 (C16), 148.4 (C2),
148.7 (C15), 149.1 (C1).
2R(S),3R(S)-2-benzyl-3-methyl-4-phenyl-1-butanol (16a). Anal. Calcd. for
C20H26O2 (%): C, 84.99, H, 8.72, O, 6.29. Found (%): C, 84.88; H, 8.80; O, 6.32.
3
1H NMR (CDCl3) δ 0.94 (d, 3Н, J=6.8 Hz, СН3), 1.84-1.94 (m, 1H, OCH2CH),

12
ACCEPTED MANUSCRIPT
1.97-2.09 (m, 1H, CH3CH), 2.47 (dd, 2J=13.2 Hz, 3J=9.0 Hz, 1H, CH3CHСННPh),
3
2
3
2.73 (d, J=7.6 Hz, 2H, СН2Ph), 2.84 (dd, J= 13.2 Hz, J= 5.6 Hz, 1H,
2
3
2
CH3CHСННPh), 3.64 (dd, J= 10.8 Hz, J= 6.0 Hz, 1Н, СННОН), 3.73 (dd, J=
3
3
10.8 Hz, J= 5.6 Hz, 1Н, СННОН), 7.12 (d, J= 7.2 Hz, 2H, Ph(o-H)), 7.15-7.34
13
(m , 8H, Ph). C NMR (CDCl3) δ 15.8 (C6), 35.2 (C3), 35.4 (C5), 40.7 (C4), 46.7
(C2), 62.9 (C1), 125.8, 125.9, 128.2, 128.4, 129.0, 129.1, 141.1, 141.4 (Ph).
(R)-MTPA ester of 2R(S),3R(S)-2-benzyl-3-methyl-4-phenyl-1-butanol
3
(17a). 1H NMR (CDCl3) δ 0.77 (d, J= 6.8 Hz, 3H, CH3CH); 1.78-1.95 (m, 1H,
CH3CH); 1.88-2.05 (m, 1H, OCH2CH); 2.18-2.31 (m, 1H, CH3CHCHHPh); 2.56-
2.70 (m, 1H, CH3CHCHHPh); 2.53, 2.58 (d, 3J= 7.6 Hz, 2H, CH2Ph); 3.495, 3.507
(s, 3H, OMe); 4.09 (dd, 2J= 11.0 Hz, 3J= 5.6 Hz, 1Н, СННОН), 4.27 (qd, 2J= 11.2
Hz, 3J=3J= 5.7 Hz, 1Н, СН2ОН), 4.41 (dd, 2J= 11.0 Hz, 3J= 5.2 Hz, 1Н, СННОН);
13
6.50-7.80 (m, 15H, Ph). C NMR (CDCl3) δ 15.20, 15.16 (C6); 34.82, 35.01 (C3);
35.2 (C5); 40.5 (C4); 42.83, 43.04 (C2), 55.1 (OMe), 66.03, 66.07 (C1), 84.9 (q, 2JC-
F= 27.5 Hz, CCF3), 123.3 (q, JC-F=288 Hz, CF3), 125.9, 126.0, 126.1-129.1, 139.9,
140.7, 140.8 (Ph), 166.4 (C=O) .
(R)-PSPA ester of 2R(S),3R(S)-2-benzyl-3-methyl-4-phenyl-1-butanol (18a). 1H
3
NMR (CDCl3) δ 0.87 (d, J= 6.0 Hz, 3H, CH3CH); 1.553, 1.557 (s, 3H,
CH3CHSe); 1.85-1.95 (m, 1H, CH3CH); 1.91-1.99 (m, 1H, OCH2CH); 2.37-2.47
(m, 1H, CH3CHCHHPh); 2.54-2.72 (m, 2H, CH2Ph); 2.71-2.80 (m, 1H,
CH3CHCHHPh); 3.75 (q, 3J=7.2 Hz, CHSe), 3.78 (q, 3J= 6.8 Hz, CHSe); 3.93-4.07
2
3
(m, 1Н, СННОН), 4.159 (dd, J= 11.2 Hz, J= 5.6 Hz, 1Н, СННОН), 4.168 (dd,
3
13
2J= 11.2 Hz, J= 6.00 Hz, 1Н, СННОН); 7.01-7.74 (m, 15H, Ph). C NMR
(CDCl3) δ 15.4 (C6); 17.7 (CH3CHSe); 35.09, 35.21 (C3); 35.34, 35.40 (C5); 37.27,
37.52 (CHSe); 40.66, 40.69 (C4); 43.1 (C2); 65.1 (C1); 125.7, 125.8, 127.9, 128.0,
128.2, 128.8, 129.1, 135.3, 135.4, 140.3, 140.9 (Ph); 173.54, 173.59 (C=O). 77Se
NMR (CDCl3) δ 451.5, 453.2.
Acknowledgements

13
ACCEPTED MANUSCRIPT
The authors thank the Russian Foundation of Basic Research (Grant No. 12-
03-00363-а) for financial support.
References
1. (a) U.M. Dzhemilev, A.G. Ibragimov, Russ. Chem. Rev. 69 (2000) 121;
(b) V.A. D’yakonov, Dzhemilev Reaction in Organic and Organometallic
Synthesis (Chemistry Research and Applications), Nova Science Pub., New York,
2010.
2. (a) U.M. Dzhemilev, A.G. Ibragimov, A.B. Morozov, L.M. Khalilov,
R.R. Muslukhov, G.A. Tolstikov, Russ. Chem. Bull. 40 (1991) 1022; (b) U.M.
Dzhemilev, A.G. Ibragimov, A.B. Morozov, Mend. Comm. 1 (1992) 26; (c)
U.M. Dzhemilev, A.G. Ibragimov, A.B. Morozov, R.R. Muslukhov, G.A.
Tolstikov, Russ. Chem. Bull., 40 (1991) 1425; (d) U.M. Dzhemilev, A.G.
Ibragimov, A.B. Morozov, R.R. Muslukhov, G.A. Tolstikov, Russ. Chem. Bull. 41
(1992) 1089; (i) U.M. Dzhemilev, A.G. Ibragimov, V.N. Azhgaliev, R.R.
Muslukhov, Russ. Chem. Bull. 44 (1995) 1501; (f) A.G. Ibragimov, L.O.
Khafizova, L.G. Yakovleva, E.V. Nikitina, K.G. Satenov, L.M. Khalilov, U.M.
Dzhemilev, Russ. Chem. Bull. 48 (1999) 774.
3. (a) D.C. Ayres, J.D. Loike, Lignans: Chemical, biological and clinical
properties, Cambridge University Press, Cambridge, 1990; (b) R.S. Ward, Nat.
Prod. Rep. (1993) 1; (c) R.S. Ward, Nat. Prod. Rep. (1993) 183; (d) R.S. Ward,
Nat. Prod. Rep. (1997) 43; (e) R.S. Ward, Nat. Prod. Rep. (1999) 75; (f) G.P.
Moss, Pure Appl. Chem. 72 (2000) 1493.
4. (a) J.D. Lambert, R.T. Dorr, B.N. Timmermann, Pharm. Biol. 42 (2004)
149; (b) M. Saleem, H.J. Kim, M.S. Ali, Y.S. Lee, Nat. Prod. Rep. 22 (2005) 696.
5. (a) G. Schroeter, L. Lichtenstadt, D. Irineu, Ber. 51 (1918) 1587; (b) R.D.
Haworth, C.R. Mavin, G. Sheldrick, J. Chem. Soc. (1934) 1423; (с) R.D.
Haworth, T. Richardson, J. Chem. Soc. (1935) 120; (d) S.V. Lieberman, G.P.
Mueller, E.T. Stiller, J. Am. Chem. Soc. 69 (1947) 1540; (e) Y. Sakakibara,
Nippon kagaku zasshi 73 (1952) 235; (f) M.P. Gerchuk, V.M. Ivanova, Khim.

14
ACCEPTED MANUSCRIPT
Nauka i Prom. 3 (1958) 685; (g) C.W. Perry, M.V. Kalnins, K.H. Deitcher, J. Org.
Chem. 37 (1972) 4371; (h) T. Biftu, B.G. Hazra, R. Stevenson J. Chem. Soc.,
Perkin Trans. (1979) 2276; (i) A. Minato, K. Tamao, K. Suzuki, M. Kumada,
Tetrahedron Lett. 21 (1980) 4017; (j) T. Takeya, T. Okubo, S. Nishida, S.
Tobinaga, Chem. Pharm. Bull. 33 (1985) 3599; (k) K.V. Rao, S.K. Chattopadhyay,
J. Org. Chem. 55 (1990) 1427; (l) A.R. Carroll, A.S. Krauss, W.C. Taylor, Aust. J.
Chem. 46 (1993) 277; (m) R. Dhal, Y. Landais, A. Lebrun, J.-P. Robin,
Tetrahedron 50 (1994) 1153; (n) A.R. Carroll, W.C. Taylor, Aust. J. Chem. 47
(1994) 937; (o) W.X. Gu, A.X. Wu, Q. Gao, X.F. Pan, Chin. Chem. Lett. 11
(2000) 15; (p) M.H. Gezginci, B.N. Timmermann, Tetrahedron Lett. 42 (2001)
6083; (q) Y.M. Xia, X.P. Cao, K. Peng, X.F. Ren, X.F. Pan, Chin. Chem. Lett. 4
(2003) 359; (r) J.-K. Son, S.H. Lee, L. Nagarapu, Y. Jahng, Bull. Korean Chem.
Soc. 26 (2005) 1117; (s) Q. Wang, Y. Yang, Y. Li, W. Yu, Z. J. Hou, Tetrahedron
62 (2006) 6107; (t) Y.-M. Xia, Q. Wang, Y.-N. Din, F.-K. Yang, X.-P. Cao, Chin.
J. Org. Chem. 28 (2008) 1040; (u) S. Yamauchi, T. Masuda T. Sugahara, Y.
Kawaguchi, M. Ohuchi, T. Someya, J. Akiyama, Sh. Tominaga, M. Yamawaki,
T. Kishida, K. Akiyama, M. Maruyama, Biosci., Biotechnol., Biochem. 72 (2008)
2981; (v) Y. Xia, Y. Zhang, W. Wang, Y. Ding, R. He, J. Serb. Chem. Soc. 75
(2010) 1325;
6. (a) G.P. Mueller, E.T. Stiller, S.V. Lieberman, U.S. Patent 2,456,443,
1948; (b) I.A. Pearl U.S. Patent 2,644,822, 1949; (c) C.V. Perry, U.S. Patent
3,906,004, 1975; (d) R.M. Parkhurst, R.S. Pardini, U.S. Patent 4,562,298, 1985; (e)
Ch. Quingqi, J. A. Blomberg, WO 2010/014936, 2010.
7. (a) P.J. Chirik, M.W. Day, J.A. Labinger, J.E. Bercaw J. Am. Chem. Soc.
121 (1999) 10308; (b) P.J. Chirik, J.E. Bercaw, Organometallics 24 (2005) 5407
.
8. (a) J.A. Dale, D.L. Dull, H.S. Mosher, J. Org. Chem. 34 (1969) 2543; (b)
J.A. Dale, H.S. Mosher, J. Am. Chem. Soc. 95 (1973) 512.
9. N.V. Orlov, V.P. Ananikov, Chem. Commun. 46 (2010) 3212.
10. SHELXS, G.M. Sheldrick, Acta Cryst. A64 (2008) 112.

15
ACCEPTED MANUSCRIPT
11. R.Kh. Freidlina, E.M. Brainina, A.N. Nesmeyanov, Dokl. Acad. Nauk
SSSR 138 (1969) 1369.
12. G. Erker, M. Aulbach, M. Knickmeier, D. Wingbermuhle, C. Krueger, M.
Nolte, S. Werner, J. Am. Chem. Soc. 115 (1993) 4590.
13. (a) L. Bell, R.J. Whitby, R.V.H. Jones, M.C.H. Standen, Tetrahedron
Lett. 37 (1996) 7139; (b) L.V. Parfenova, T.V. Berestova, T.V. Tyumkina, P.V.
Kovyazin, L.M. Khalilov, R.J. Whitby, U.M. Dzhemilev, Tetrahedron: Asymmetry
21 (2010) 299.
14. G. Wilkinson, J.M. Birmingham, J. Am. Chem. Soc. 76 (1954) 4281.

ACCEPTED MANUSCRIPT
Table 1. Reaction of allylbenzenes 1a-с with EtAlCl2 (ClAlEt2) and Mg,
catalyzed by Zr and Ti complexes (2a-j) (mole ratio Cp2ZrCl2 : Mg : EtAlCl2 :
allylbenzene = 1: 20:25:20, 22ºC, 72 h).
Product yield, % (ee%)b
Alkene
Entry Substrate [Zr]
OAC
Solvent
conversion,
%
9
11
13
7
15
1
2
3
4
5
6
7
8
EtAlCl2
EtAlCl2
Et2AlCl
EtAlCl2
ТHF
ТHF
ТHF
ТHF
83
85
66
98
96
31
70
96
83
65
79
13
62
99
99
27
82
99
97
51
96
98
97
45
99
31
43
65
27
21
29
58
37
16
47
35
21 (13)
34 (16)
30
6 (20)
27
69
26
19
40
34
19
12 (9)
31
22
48
19
50
18
21
16
2
8
3
22
10
9
23
9
1
5
8
7
-
-
2
12
14
7
-
6
8
4
-
17
9
19
5
5
-
-
-
29
10
2
4
-
2
3
24
3
2
-
-
3
20
-
13
9
14
6
42
5
1
26
18
13
2
-
16
2
44
-
9
30
19
-
27
58
3
11
17
-
-
9
2a
2b
2c
EtAlCl2 ТHF (30о)
EtAlCl2
EtAlCl2
EtAlCl2
EtAlCl2
EtAlCl2
EtAlCl2
EtAlCl2
Et2AlCl
EtAlCl2
ТHF
ТHF
ТHF
ТHF
ТHF
Et2O
ТHF
ТHF
ТHF
6
2d
2e
2f
1а
13
23
14
16
45
5
5
9
1
7
17
21
8
11
8
2
8
3
9
2g
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
2h
2i
2c
EtAlCl2 ТHF (30о)
EtAlCl2
EtAlCl2
EtAlCl2
EtAlCl2
EtAlCl2
EtAlCl2
ТHF
ТHF
ТHF
ТHF
ТHF
ТHF
2d
2e
2f
2g
2h
1b
8
4
48
27
11
5
18
6
2
3
6
56
EtAlCl2 ТHF (30о)
2c
a
EtAlCl2
Et2AlCl
EtAlCl2
EtAlCl2
EtAlCl2
EtAlCl2
ТHF
ТHF
ТHF
ТHF
ТHF
ТHF
1c
23
10
12
-
2e
2f
2h
2j
25
-
-
a Twofold excess of EtAlCl2. bGC yield of deuterolysis products.

ACCEPTED MANUSCRIPT
Table 2. Crystal data and structure refinement for 8b
8b
Empirical formula
Formula weight
C20H26O2
298.41
Crystal system
Space group
monoclinic
I2/a
a/Å
b/Å
c/Å
α/°
13.1601(7)
7.8740(4)
16.9944(7)
90.00
β/°
γ/°
107.993(5)
90.00
Volume/Å3
Z
1674.89(14)
4
ρcalcmg/mm3
1.183
0.074
µ/mm‑1
2Θ range for data collection
Data/restraints/parameters
Goodness-of-fit on F2
Final R indexes [I>=2σ (I)]
Final R indexes [all data]
5.04 to 62.26°
2362/0/152
1.061
R1 = 0.0480, wR2 = 0.1260
R1 = 0.0555, wR2 = 0.1327
Table 3. Bond lengths and angles in compound 8b.
Label
O1–C3
O1–C11
C2–C4
C2–C5
C3–C5
C3–C8
C4–C6
C4–C7
C6–C10
C7–C8
C9–C10
C10–C101
Length(Å)
1.3738(13)
1.4290(15)
1.3887(16)
1.3937(16)
1.3906(15)
1.3966(15)
1.5091(15)
1.4037(16)
1.5415(15)
1.3842(17)
1.5261(15)
1.544(2)
Label
Angle (˚)
116.83(9)
C3–O1–C11
C4–C2–C5
O1–C3–C5
O1–C3–C8
C5–C3–C8
C2–C4–C6
C2–C4–C7
C7–C4–C6
C3–C5–C2
C4–C6–C10
C8–C7–C4
C7–C8–C3
C6–C10–C101
C9–C10–C6
C9–C10–C101
122.17(10)
124.61(10)
116.01(10)
119.37(11)
121.30(10)
117.15(10)
121.53(10)
119.60(10)
113.77(9)
121.64(10)
120.06(10)
112.59(7)
110.27(9)
112.09(11)

ACCEPTED MANUSCRIPT
Fig. 1. ORTEP diagram of 8b.
Fig. 2. ORTEP diagram: Crystal packing in compound 8b.

ACCEPTED MANUSCRIPT
Highlights
We studied catalytic cyclometallation of allylbenzenes with EtAlCl2 (Et2AlCl) and Mg
The one- pot diastereoselective synthesis of dibenzyl butane lignans is developed
The trans-configuration of the substitutes in the products is proved by X-ray analysis

ACCEPTED MANUSCRIPT
Catalytic cyclometallation of allylbenzenes by EtAlCl2 and Mg as new route to
synthesis of dibenzyl butane lignans
Lyudmila V. Parfenova, Tatyana V. Berestova, Pavel V. Kovyazin, Aydar R.
Yakupov, Ekaterina S. Mesheryakova, Leonard M. Khalilov, Usein M.
Dzhemilev
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences,
450075, Ufa, prospect Oktyabrya, 141, Russian Federation
Supporting Information

ACCEPTED MANUSCRIPT
NMR 1H of 2R(S),3R(S)-dimethyl-1,4-bis[(4′- methoxyphenyl)methyl]butane (8b).

ACCEPTED MANUSCRIPT
NMR 13C of 2R(S),3R(S)-dimethyl-1,4-bis[(4′- methoxyphenyl)methyl]butane (8b).

ACCEPTED MANUSCRIPT
NMR 1H of 2R(S),3R(S)-bis[(3′,4′-dimethoxyphenyl)methyl]butane ((±)-terameprocol) (8c).

ACCEPTED MANUSCRIPT
NMR 13C of 2R(S),3R(S)-bis[(3′,4′-dimethoxyphenyl)methyl]butane ((±)-terameprocol) (8c).

ACCEPTED MANUSCRIPT
NMR 1H of 2R(S),3R(S)-2-benzyl-3-methyl-4-phenyl-1-butanol (16a).

ACCEPTED MANUSCRIPT
NMR 13C of 2R(S),3R(S)-2-benzyl-3-methyl-4-phenyl-1-butanol (16a).

ACCEPTED MANUSCRIPT
NMR 1H of (R)-MTPA ester of 2R(S),3R(S)-2-benzyl-3-methyl-4-phenyl-1-butanol (17a).