Phosphites and diamidophosphites based on mono-ethers of BINOL: A comparison of enantioselectivity in asymmetric catalytic reactions

Article abstract of DOI:10.1016/j.tet.2011.11.092

Novel P-monodentate phosphite-type ligands have been synthesized in one step from BINOL mono-tosylate and BINOL mono-(-)-menthylcarbonate. The use of these ligands provides up to 96% ee in Pd-catalyzed asymmetric allylic substitution of (E)-1,3-diphenylal

Full text of DOI:10.1016/j.tet.2011.11.092

Tetrahedron 68 (2012) 1581e1589
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journal homepage: www.elsevier.com/locate/tet
Phosphites and diamidophosphites based on mono-ethers of BINOL:
a comparison of enantioselectivity in asymmetric catalytic reactions
,
a
a
a
Konstantin N. Gavrilov a , Sergey V. Zheglov , Mariya N. Gavrilova , Ivan M. Novikov ,
*
Marina G. Maksimova a, Nikolay N. Groshkin a, Eugenie A. Rastorguev b, Vadim A. Davankov b
a Department of Chemistry, Ryazan State University, 46 Svoboda Street, 390000 Ryazan, Russian Federation
b Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov Street, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel P-monodentate phosphite-type ligands have been synthesized in one step from BINOL mono-
tosylate and BINOL mono-(ꢀ)-menthylcarbonate. The use of these ligands provides up to 96% ee in
Pd-catalyzed asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate and up to 99% ee in Rh-
catalyzed asymmetric addition of phenylboronic acid to cyclohex-2-enone. The influence of the struc-
tural modules such as the nature of phosphorus-containing ring or exocyclic substituent on the enan-
tioselectivity is discussed.
Received 27 September 2011
Received in revised form 8 November 2011
Accepted 28 November 2011
Available online 6 December 2011
Keywords:
Asymmetric allylic substitution
Palladium
Ó 2011 Elsevier Ltd. All rights reserved.
Asymmetric addition
Rhodium
Phosphites
Diamidophosphites
1. Introduction
of novel chiral ligands with improved performance continue to
attract the interest of synthetic chemists.1b,5
Asymmetric metal complex catalysis is one of the most effective
and environmentally safe methods for the synthesis of enantiopure
organic and heteroorganic compounds, as reflected by the many
publications in this field and the award of the Nobel Prize in 2001 to
W. S. Knowles, R. Noyori, and K. B. Sharpless. In addition to the well-
known application in pharmaceutical chemistry, this method is
successfully used in the synthesis of enantiopure fragrance com-
pounds, plant protection chemicals, polymers, and liquid crystals.1
To achieve the highest levels of reactivity and selectivity in catalytic
enantioselective reactions, several reaction parameters must be
optimized, the most crucial of which is perhaps the design of ap-
propriate chiral ligands, among which phosphorus-containing
compounds are worth noting.1f,2 Since the early 1970s, an impres-
sive number of chiral phosphorus-based ligands have been applied
in many asymmetric catalytic reactions.1e3 Nevertheless, only
a handful of them (so-called privileged ligands), rooted in a few
core structures, can be regarded a truly successful in demonstrating
proficiency in various mechanistically unrelated reactions.4
Therefore, the tuning of existing ligands and/or the development
From a practical point of view, air-stable, inexpensive, and easily
accessible ligands are highly desirable.6 Optically active phosphite-
type compounds completely satisfy these criteria. Indeed, various
PeO and/or PeN bond containing phosphorus ligands may be
constructed in large quantities through the use of relatively simple
condensation processes, and from inexpensive starting materials.
Another advantage of phosphite-type ligands is that they are less
sensitive to air and other oxidizing agents than phosphines. Hence,
this makes it possible to develop protocols for the whole process,
including the ligand synthesis, that do not necessitate the use of
a glove box. Furthermore, they are amenable to parallel synthesis,
even in solid phase synthesis. Such key advantages allow synthesis
and screening of extensive libraries of chiral ligands aiming at high
activities and selectivities for each particular reaction. In addition,
phosphite-type ligands are characterized by pronounced p-acidity
and low cost. It should be noted, that phosphites are rather prone to
decomposition reactions such as hydrolysis or alcoholysis but, in
many instances, these side reactions can be suppressed when bulky
ligands (especially with aryl substituents) are used.1f,2,7
Herein, we report the synthesis of a small series of novel
phosphite-type ligands containing dissymmetric monoprotected
BINOL fragments and their evaluation in Pd-catalyzed asymmetric
allylation and Rh-catalyzed asymmetric addition. Note, that
* Corresponding author. Tel.: þ7 4912 280580; fax: þ7 4912 281435; e-mail
address: k.gavrilov@rsu.edu.ru (K.N. Gavrilov).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.092

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K.N. Gavrilov et al. / Tetrahedron 68 (2012) 1581e1589
enantioselective Pd-catalyzed allylic substitution has emerged as
a powerful synthetic tool, which is tolerant of various functional
groups in the substrate and operates with a wide range of C-, N-, O-,
S- and P-nucleophiles. As consequence, Pd-catalyzed allylic sub-
stitution is a novel and highly efficient strategy in the total synthesis
of enantiopure natural and unnatural products.1c,8 The asymmetric
of BINOL and (ꢀ)-menthyl chloroformate or tosyl chloride.12,13
Compounds 4 and 5 were obtained in moderate to good yields
(66e82%), reflecting their stability during the workup and sub-
sequent chromatographic purification. They also can be stored in
the solid form under dry conditions at room temperature over
several months without any degradation. Ligands 4 and 5 were fully
characterized by 1H, 13C, and 31P NMR spectroscopy, MALDI TOF/
TOF mass spectrometry as well as by elemental analysis.
All ligands are readily available and can be prepared on a gram
scale. Indeed, the phosphorylating agent 2 can easily be synthe-
sized in high yield from readily accessible (S)-glutamic acid ani-
lide.14 Furthermore, BINOL is commercially available in both
enantiomeric forms and is one of the cheapest chiral auxiliaries
currently on the market. As stated above, its transformation into
derivatives 1a and 1b (as well as into phosphorylating agent 3)
requires only one step.
conjugate addition of arylboronic acids to a,b-unsaturated carbonyl
compounds constitutes nowadays a very efficient method for the
stereoselective construction of CeC bonds.9 On the other hand, both
catalytic processes are a common benchmark tests for initial ligand
screening. From a functional point of view, the reached ees are the
simplest indexes for evaluating new chiral ligands.6,8g,h
The steric and electronic properties of the chiral ligands have
a tremendous effect on the performance of asymmetric metal
catalysts. A well-conceived stereoselector should possess one or
more structural features that may be varied readily in a systematic
fashion, in order to optimize the design for a given purpose. A de-
sign is informative to the extent that variations in the ligand fea-
tures can be correlated to changes in the reactivity or selectivity of
the catalyst. In particular, the nature of phosphocycle and the ste-
reochemistry of coordinating atom are crucial features for
obtaining satisfactory asymmetric induction.1b,3,4,5c,d Our novel
phosphite-type ligands 4, 5 give some new examples in this field.
The 31P NMR spectroscopic data for compounds 4 and 5 are
summarized in Table 1.
Table 1
31R NMR chemical shifts (CDCl3) and cone angles
(Sa)-5a,b, and (Ra)-5a,b
q (deg.) of ligands (Sa)-4, (Ra)-4,
Ligand
dR
q
(Sa)-4
(76%)a
(24%)
(78%)
(22%)
127.1
118.9
125.1
118.2
143.6
145.7
146.3
145.5
153
(Ra)-4
165
2. Results and discussion
(Sa)-5a
(Ra)-5a
(Sa)-5b
(Ra)-5b
152
149
171
142
The preparation of each ligand 4, 5 was a convenient single-step
operation (Scheme 1).
The appropriate enantiomer of monoacylated BINOL derivatives
1a or 1b reacted smoothly in toluene in the presence of Et3N as
a HCl scavenger and DMAP as catalyst with phosphorylating re-
agents 2 or 3, whose syntheses have been described in the litera-
ture.10,11 In turn, (Sa)- and (Ra)-2-hydroxy-20-(ꢀ)-menthyl-1,10-
binaphthyl carbonate (Sa)-1a and (Ra)-1a, (Sa)- and (Ra)-2-hydroxy-
20-tosyloxy-1,10-binaphthyl (Sa)-1b and (Ra)-1b were easily ob-
tained by direct interaction between the corresponding enantiomer
a
Percentage of R -epimers.
*
Diamidophosphites (Sa)-4 and (Ra)-4 are mixtures of epimers
with respect to the phosphorus stereocentre and contain 76% and
78% of the major R
4 and (Ra)-4 have the P
Indeed, the 13C NMR spectra of these compounds are characterized
*
-epimers, respectively. The major epimers of (Sa)-
*
-stereocentres with the (R) configuration.
Scheme 1. Synthesis of diamidophosphites (Sa)-4, (Ra)-4, and phosphites (Sa)-5a,b; (Ra)-5a,b.

K.N. Gavrilov et al. / Tetrahedron 68 (2012) 1581e1589
1583
bylarge spinespin coupling constants 2JC(8),P (34.7 and 36.9 Hz, see
Experimental section). These values suggest the anti-orientation of
the pseudoequatorial exocyclic substituent at the phosphorus atom
and the e(CH2)3e part of the pyrrolidine fragment of the phos-
phabicyclic skeleton and, consequently, the syn-orientation of the
phosphorus lone pair with respect to the C(8) atom (Fig. 1).
Table 2
Pd-catalyzed allylic sulfonylation and alkylation of (E)-1,3-diphenylallyl acetate (6)a
b
Entry
Ligand
L/Pd
Solvent
Conversion (%)
ee (%)
Allylic sulfonylation with sodium p-toluenesulfinatec
1
2
3
4
(Sa)-4
(Sa)-4
(Ra)-4
(Ra)-4
1
2
1
2
THF
THF
THF
THF
85
87
96
85
95 (S)
95 (S)
35 (S)
82 (S)
Fig. 1. Stereochemistry of the phosphabicyclic part in major epimers of dia-
midophosphites (Sa)-4 and (Ra)-4.
Allylic alkylation with dimethyl malonate (BSA, KOAc)d
5
6
7
8
9
10
11
12
(Sa)-4
(Sa)-4
(Sa)-4
(Sa)-4
(Ra)-4
(Ra)-4
(Ra)-4
(Ra)-4
1
2
1
2
1
2
1
2
CH2Cl2
CH2Cl2
THF
97
100
46
63
d
83 (S)
96 (S)
94 (S)
95 (S)
d
On the contrary, the minor epimers of (Sa)-4 and (Ra)-4 contain
asymmetric phosphorus atoms with the (S) configuration, as evi-
denced by the fact that their 13C NMR spectra have the small con-
stants 2JC(8),P (3.8 and 3.9 Hz, see Experimental section).10,14,15
In order to have an estimation of the steric demands of ligands 4
and 5, we calculated their Tolman cone angles16 by the reported
method using semi-empirical quantum-mechanical AM1 tech-
niques with full optimization of geometrical parameters.17 The
THF
CH2Cl2
CH2Cl2
THF
44
d
14 (R)
d
THF
23
43 (R)
a
All reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 at room temperature
for 48 h.
b
c
Isolated yield of 7a.
The ee of 7a was determined by HPLC (Daicel Chiralcel OJ, C6H14/i-PrOH¼4:1,
obtained results (Table 1) show that the steric parameters (q) of 4
0.5 mL/min, 254 nm).
and 5 vary within the interval of 142ꢁe171ꢁ, peaking at compounds
(Ra)-4 and (Sa)-5b. Compounds (Sa)-4, (Sa)-5a, (Ra)-5a, and (Ra)-5b
d
The conversion of substrate 6 and ee of 7b were determined by HPLC (Daicel
Chiralcel OD-H, C6H14/i-PrOH¼99:1, 0.6 mL/min, 254 nm).
are characterized by moderate steric demands (
q
¼142ꢁe153ꢁ),
while (Ra)-4 and (Sa)-5b appear to be rather bulky ligands (
q
¼165ꢁ
and 171ꢁ, respectively).16,18
With a view to examine the influence of the nature of phos-
phocycle, exocyclic substituent at the phosphorus atom, as well as
the stereochemistry of coordinating atom, we investigated the
ability of ligands 4 and 5 as stereoselectors for Pd-catalyzed
asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate 6
as a benchmark catalytic process (Tables 2e4). The reactions were
run in THF or CH2Cl2. Palladium complexes were prepared in situ
with [Pd(allyl)Cl]2 as the precatalyst and L/Pd molar ratio 1 or 2. In
general, the obtained results showed that the efficiency of novel
phosphite-type ligands differs dramatically. Beyond doubt, dia-
midophosphites (Sa)-4 and (Ra)-4 are most efficient chiral in-
ductors. Thus, the allylic sulfonylation of 6 with p-TolSO2Na as the
S-nucleophile proceeded smoothly to afford sulfone 7a in very good
yields and enantioselectivity (up to 95% ee for the S-enantiomer,
Table 2, entry 2). When the reaction was carried out using (Sa)-4 as
the ligand, the enantioselectivity was higher than in the case of
diastereomeric compound (Ra)-4 (Table 2, entries 1,2 and 3,4).
In the next step, diamidophosphites (Sa)-4 and (Ra)-4 were
studied in the Pd-catalyzed asymmetric allylic alkylation of sub-
strate 6 with dimethyl malonate. Again, the best result (quantita-
tive conversion and 96% ee) was obtained with ligand (Sa)-4 (Table
2, entry 6). Like the Pd-catalyzed allylic sulfonylation, the experi-
ments with the use of (Sa)-4 afforded the reaction product 7b
having the (S) configuration. It is clear that CH2Cl2 is the solvent of
choice; using THF led to a considerably decrease in conversion
(Table 2, entries 5e8). The molar ratio L/Pd¼2 was optimal in both
solvents. With ligand (Ra)-4, a diastereoisomer of (Sa)-4 with re-
spect to the axis of chirality, the degrees of asymmetric induction
and conversion were greatly reduced (43% ee, Table 2, entries
9e12). It is also noteworthy that the alkylation product 7b has the
opposite (R) configuration in contrast to the one observed with (Sa)-
4. It is possible to assume that the mismatched combination of the
(2R,5S)-stereocentres of the phosphabicyclic core with (Ra)-BINOL
fragment takes place.
Table 3
Pd-catalyzed allylic amination of (E)-1,3-diphenylallyl acetate (6)a
Entry
Ligand
L/Pd
Solvent
Conversion (%)
ee (%)
Allylic amination with dipropylamineb
1
2
3
4
5
6
7
8
(Sa)-4
(Sa)-4
(Sa)-4
(Sa)-4
(Ra)-4
(Ra)-4
(Ra)-4
(Ra)-4
1
2
1
2
1
2
1
2
CH2Cl2
CH2Cl2
THF
100
100
48
100
98
100
31
73
91 (þ)
87 (þ)
93 (þ)
95 (þ)
91 (þ)
84 (þ)
91 (þ)
95 (þ)
THF
CH2Cl2
CH2Cl2
THF
THF
Allylic amination with pyrrolidinec
9
(Sa)-4
(Sa)-4
(Sa)-4
(Sa)-4
(Ra)-4
(Ra)-4
(Ra)-4
(Ra)-4
1
2
1
2
1
2
1
2
CH2Cl2
CH2Cl2
THF
100
100
100
100
100
100
44
47 (R)
21 (R)
39 (R)
57 (R)
70 (R)
50 (R)
5 (R)
10
11
12
13
14
15
16
THF
CH2Cl2
CH2Cl2
THF
THF
46
31 (R)
a
All reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 at room temperature
for 48 h.
b
The conversion of substrate 6 and ee of 7c were determined by HPLC (Daicel
Chiralcel OD-H, C6H14/i-PrOH/HN(Et)2¼1000:1:1, 0.4 mL/min, 254 nm, tR(þ)¼
8.2 min, tR(ꢀ)¼9.1 min).
c
The conversion of substrate 6 and ee of 7d were determined by HPLC (Daicel
Chiralcel OD-H, C6H14/i-PrOH/HN(Et)2¼200:1:0.1, 0.9 mL/min, 254 nm).

1584
K.N. Gavrilov et al. / Tetrahedron 68 (2012) 1581e1589
Table 4
Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate (6) with 1-cyclohexenylpyrrolidinea,b
Entry
Ligand
L/Pd
Solvent
Conversion (%)
anti/sync,d
ee (%)
1
2
3
4
5
6
7
8
(Sa)-4
(Sa)-4
(Sa)-4
(Sa)-4
(Ra)-4
(Ra)-4
(Ra)-4
(Ra)-4
1
2
1
2
1
2
1
2
CH2Cl2
CH2Cl2
THF
100
100
30
100
98
98
25
96
56:44
52:48
55:45
52:48
59:41
52:48
61:39
62:38
84:84
59:56
43:40
49:51
81:84
76:77
71:70
92:94
THF
CH2Cl2
CH2Cl2
THF
THF
a
All reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 at room temperature for 48 h.
The conversion of substrate 6 and ee of 8a and 8b were determined by HPLC (Kromasil 5-CelluCoat, C6H14/i-PrOH¼96:4, 0.5 mL/min, 254 nm, tR(S,R)-8b¼14.0 min, tR(R,S)-
b
8b¼15.1 min; tR(S,S)-8a¼16.9 min, tR(R,R)-8a¼19.0 min).
c
Determined by 1H NMR.
d
The absolute configuration of the predominant enantiomers of anti- and syn-products was determined according to Ref. 19.
Ligands (Sa)-4 and (Ra)-4 were next evaluated in the Pd-
catalyzed allylic amination of (E)-1,3-diphenylallyl acetate 6 with
dipropylamine and pyrrolidine as N-nucleophiles. The asymmetric
amination with dipropylamine gives product (þ)-7c in high enan-
tioselectivities (84e95%) (Table 3, entries 1e8) regardless of the
absolute configuration of monoacylated BINOL fragment, the L/Pd
molar ratio and the nature of the solvent. As a rule, the highest
conversion was observed in CH2Cl2. The asymmetric amination of 6
with pyrrolidine showed a considerably smaller enantioselectivity
(ee is no higher than 70%, Table 3, entries 9e16). The resulting
product 7d proved to have the same (R) configuration in all cases. In
contrast to the substitution reactions stated above, dia-
midophosphite (Ra)-4 has been found to be more efficient stereo-
selector (Table 3, entry 13). With participation of ligand (Ra)-4, the
higher enantioselectivity was observed in CH2Cl2 at the molar ratio
L/Pd¼1, with participation of its diastereomer (Sa)-4din THF at the
molar ratio L/Pd¼2 (Table 3, entries 12 and 13).
1,3-diphenylallyl acetate 6. Indeed, these ligands gave no conver-
sion or enantioselectivity in the allylic sulfonylation of substrate 6
(Table S1 in Supplementary data, entries 1e8). Catalytic perfor-
mance in the allylic alkylation of 6 with dimethyl malonate fol-
lowed the same trend, excluding compounds (Sa)-5b and (Ra)-5b.
Nevertheless, these ligands afforded product (S)-7b with mediocre
enantiomeric purity (up to 57% ee, Table S1, entries 17e22). Besides,
in the allylic amination of 6 with pyrrolidine in the presence of
phosphites (Sa)-5a,b and (Ra)-5a,b the asymmetric induction was
poor (no more than 37% ee, Table S1, entries 25e40).
We evaluated the small phosphite-type ligands library 4 and 5
in the Pd-catalyzed desymmetrization of N,N0-ditosyl-meso-cyclo-
pent-4-ene-1,3-diol biscarbamate 10 (Table 5). Note that this pro-
cess has been successfully used in key steps during the synthesis of
mannostatin A and (ꢀ)-swainsonine.1c,8c The reaction was per-
formed in THF or CH2Cl2, in the presence of [Pd2(dba)3]$CHCl3 as
the catalytic precursor. In contrast to the Pd-catalyzed asymmetric
allylic substitution of (E)-1,3-diphenylallyl acetate 6, phosphites
(Sa)-5b and (Ra)-5b have been found to be the most efficient ster-
eoselectors (up to 67% and 65% ee, respectively; Table 5, entries 19
and 23). The use of both diastereomers of ligand 5b made it possible
to obtain product 11 with opposite absolute configurations (Table 5,
entries 17e20 and 21e24). We found that there was no obvious
trend in the influence of the nature of the solvent and the L/Pd
molar ratio on the chemical yield and asymmetric induction. When
the reaction was carried out using related phosphites (Sa)-5a and
(Ra)-5a, the chemical yields and enantioselectivities were consid-
erably lower (no more than 45% ee, Table 5, entries 9e16). In-
terestingly, an increase of the L/Pd molar ratio led to a significant
increase in chemical yield and enantioselectivity. Dia-
midophosphites (Sa)-4 and (Ra)-4 allowed the synthesis of product
11 with moderate enantioselectivity, and (Sa)-4 was shown to be
a better stereoselector than its diastereomer (Ra)-4 (57% and 38% ee,
respectively, Table 5, entries 4 and 8). The best chemical yields and
ee values were observed in THF.
We also screened diamidophosphites (Sa)-4 and (Ra)-4 in the Pd-
catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate 6 with
a pyrrolidine enamine of cyclohexanone as the C-nucleophile
(Table 4). Enamines can serve as good nucleophiles for Pd-catalyzed
asymmetric allylic alkylation, avoiding the use of unstablilized
ketone enolates formed by strong bases. Nevertheless, successful
examples of Pd-catalyzed asymmetric allylic substitution with en-
amines are very scarce,19 and this process remains a challenge for
synthetic chemists. As a whole, the new catalytic systems based on
(Sa)-4 and (Ra)-4 led to the expected product as a mixture of di-
astereomers 8a and 8b with excellent conversion, moderate to very
good enantioselectivity with both anti- and syn-configuration (up
to 94% ee, Table 4, entry 8) and moderate diastereomeric ratio. Both
(Sa)-4 and (Ra)-4 gave virtually equal conversion. However, dia-
midophosphite (Ra)-4 demonstrated higher anti/syn-ratio and
enantioselectivity than its diastereomer (Sa)-4 (70e94% and
40e84% ee, respectively; Table 4, entries 1e4 and 5e8). When the
reaction was carried out using (Sa)-4 as the ligand, the enantiose-
lectivity was higher in CH2Cl2 than in THF. At the same time, at the
molar ratio L/Pd¼1 (L¼(Ra)-4) the highest asymmetric induction
being observed in CH2Cl2, at the molar ratio L/Pd¼2din THF. To the
best of our knowledge, this is the first example of the use of
phosphite-type ligands in Pd-catalyzed asymmetric allylic alkyl-
ation with enamine nucleophiles.
The novel phosphite-type ligands 4 and 5 were applied in Rh-
catalyzed asymmetric addition of phenylboronic acid to cyclohex-
2-enone 12 using published mild highly practical protocol.20 The
reaction was performed in 1,4-dioxane/water medium in the
presence of Et3N at room temperature. In all cases the rhodium
catalysts were prepared in situ by treating [Rh(C2H4)2Cl]2 with 2 or
4 equiv of the corresponding monodentate ligand; the results are
summarized in Table 6. Overall, ligands 4e5 displayed mediocre to
Unfortunately, phosphites (Sa)-5a,b and (Ra)-5a,b are practically
inefficient in Pd-catalyzed asymmetric allylic substitution of (E)-

K.N. Gavrilov et al. / Tetrahedron 68 (2012) 1581e1589
1585
Table 5
Table 6
Pd-catalyzed desymmetrization of N,N0-ditosyl-meso-cyclopent-4-ene-1,3-diol bis-
carbamate (10)a
Rh-catalyzed asymmetric addition of phenylboronic acid to cyclohex-2-enone (12)a
Entry
Ligand
L/Rh
Yield (%)
ee (%)b,c
1
2
3
4
5
6
7
8
(Sa)-4
(Sa)-4
(Ra)-4
(Ra)-4
(Sa)-5a
(Sa)-5a
(Ra)-5a
(Ra)-5a
(Sa)-5b
(Sa)-5b
(Ra)-5b
(Ra)-5b
1
2
1
2
1
2
1
2
1
2
1
2
56
46
65
77
84
73
64
25
26
25
70
53
70 (II)
55 (II)
99 (I)
98 (I)
44 (I)
46 (I)
65 (II)
43 (II)
40 (II)
51 (II)
88 (I)
23 (I)
9
10
11
12
Entry
Ligand
L/Pd
Solvent
Yield (%)
ee (%)b,c
1
2
3
4
5
6
7
8
(Sa)-4
(Sa)-4
(Sa)-4
(Sa)-4
(Ra)-4
(Ra)-4
(Ra)-4
(Ra)-4
(Sa)-5a
(Sa)-5a
(Sa)-5a
(Sa)-5a
(Ra)-5a
(Ra)-5a
(Ra)-5a
(Ra)-5a
(Sa)-5b
(Sa)-5b
(Sa)-5b
(Sa)-5b
(Ra)-5b
(Ra)-5b
(Ra)-5b
(Ra)-5b
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
CH2Cl2
CH2Cl2
THF
53
57
69
73
29
34
46
42
59
78
38
42
59
70
59
64
83
92
89
75
88
85
91
83
20 (II)
35 (II)
47 (II)
57 (II)
4 (II)
a
All reactions were carried out with 1.8 mol % of [Rh(C2H4)2Cl]2 at room tem-
perature for 72 h.
b
The ee of 13 was determined by HPLC (Kromasil 5-CelluCoat, C6H14/i-
THF
PrOH¼99:1, 0.8 mL/min, 219 nm, tR(I)¼22 min, tR(II)¼24 min).
CH2Cl2
CH2Cl2
THF
s
The absolute configuration of the product 13 was not assigned.
3 (II)
30 (II)
38 (II)
2 (II)
35 (II)
8 (I)
THF
3. Conclusion
9
CH2Cl2
CH2Cl2
THF
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
We have successfully designed and synthesized a small series of
readily available phosphite-type ligands prepared from mono-
ethers of BINOL. The catalytic performance is highly affected by
the nature of phosphocycle and the stereochemistry of co-
THF
10 (I)
2 (II)
CH2Cl2
CH2Cl2
THF
17 (II)
10 (II)
45 (II)
53 (I)
64 (I)
67 (I)
50 (I)
63 (II)
52 (II)
65 (II)
61 (II)
THF
ordinating atom. Indeed, novel P -chiral diamidophosphites (Sa)-4
*
CH2Cl2
CH2Cl2
THF
and (Ra)-4 with 1,3,2-diazaphospholidine rings, as well as the
previously described15d,21 analogous ligands with TseBINOL and
PiveBINOL exocyclic moieties, yielded much higher conversion and
enantioselectivities in the Pd-catalyzed asymmetric allylic sub-
stitution of (E)-1,3-diphenylallyl acetate with various nucleophiles
than phosphites (Sa)-5a,b and (Ra)-5a,b with 1,3,2-
dioxaphosphepine rings. In addition, the first example of success-
ful Pd-catalyzed asymmetric allylic alkylation with enamine nu-
cleophiles (up to 94% ee) with participation of phosphite-type
ligands was found. Furthermore, (Sa)-4 and (Ra)-4 are better ster-
eoselectors than (Sa)-5a,b and (Ra)-5a,b in the Rh-catalyzed
asymmetric addition of phenylboronic acid to cyclohex-2-enone.
THF
CH2Cl2
CH2Cl2
THF
THF
a
All reactions were carried out with 5 mol % of [Pd2(dba)3]$CHCl3 at 35 ꢁC for
24 h.
b
The ee of 11 was determined by HPLC (Kromasil 5-CelluCoat, C6H14/i-PrOH¼9:1,
2 mL/min, 219 nm, tR(I)¼15 min, tR(II)¼18 min).
s
The absolute configuration of the product 11 was not assigned.
Hence, introducing the 1,3,2-diazaphospholidine rings with P -
*
good yields and moderate to high enantioselectivities. In particular,
diamidophosphite (Ra)-4 provided an excellent enantioselectivity
(98e99% ee, Table 6, entries 3 and 4) irrespective of the L/Rh molar
ratio. It should be noted that in the pair of diastereoisomers (Sa)-4
and (Ra)-4, (Ra)-4 is more efficient (Table 6, entries 1,2 and 3,4). It is
possible that this is a consequence of a matched (2R,5S) phosphorus
centre/(Ra)-BINOL combination and the much greater value of the
Tolman cone angle for (Ra)-4 (Table 1). With participation of
phosphites (Sa)-5a and (Ra)-5a, the medium enantioselectivity was
achieved (43e65% ee, Table 6, entries 5e8). In this diastereomeric
pair, phosphite (Ra)-5a is the best stereoselector: up to 65% ee at the
molar ratio L/Rh¼1. Among (Sa)-5b and (Ra)-5b, diastereoisomer
(Ra)-5b bearing a monoacylated (Ra)-BINOL fragment also produced
a significantly better asymmetric induction (Table 6, entries 9e12).
It is interesting, that in the case of (Ra)-5b the decrease of the L/Rh
molar ratio gave rise the dramatically growth of the enantiose-
lectivity (88% versus 23% ee, Table 6, entries 11 and 12). In all cases
the diastereomeric ligands 4 or 5a,b caused the formation of
product 13 with opposite absolute configurations, as a consequence
of the determining influence of the monoacylated BINOL fragment.
stereocentres into ligands (Sa)-4 and (Ra)-4 is advantageous. Such
compounds display balanced electronic characteristics since they
are both good
p
-acceptors (due to the accessibility of low-lying
p
*
orbitals) as well as good s
-donors.22 In their complexes, the
PN
asymmetric phosphorus atom bind directly to the metal atom and,
as consequence, it is as close as possible to the coordinated sub-
strate. This factor eliminates potentially inefficient secondary
transfer of chirality from the ligand backbone and, thus provides
a more efficient chiral environment at the site where the enantio-
selection originates.4,8b At the same time, in the Pd-catalyzed
intramolecular allylic substitution reaction such as desymmetri-
zation of N,N0-ditosyl-meso-cyclopent-4-ene-1,3-diol biscarbamate
BINOL-based phosphites (Sa)-5b and (Ra)-5b are preferable. In most
cases there is no direct correlation between the values of Tolman
cone angles of diastereomeric ligands 4 or 5a,b and the values of
the asymmetric induction. Thus, a less sterically demanding di-
astereomer may be a substantially better stereoselector. To sum up
the results obtained here in and published earlier,15d,21 we can
conclude that the presence of the (ꢀ)-menthyl substituent with an
additional C -stereocentres in the exocyclic BINOL fragment has no
*

1586
K.N. Gavrilov et al. / Tetrahedron 68 (2012) 1581e1589
positive effect on the stereochemical outcome of the catalytic re-
actions. Therefore, more accessible and cheap ligands with Ts-
BINOL and Piv-BINOL moieties should be widely used. Such in-
vestigations are currently in progress in our laboratories.
menthyl), 1.11e1.18 (m, 2H, menthyl), 1.26e1.39 (m, 3H, C(6)H2C(7)
H2), 1.45e1.56 (m, 2H, menthyl), 1.64e1.71 (m, 1H, C(6)H2C(7)H2),
1.84e1.93 (m, 1H, menthyl); 2.51e2.59 (m, 1H), 2.81e2.88 (m, 1H),
2.99e3.08 (m, 1H), 3.27e3.39 (m, 2H, C(4)H2, C(5)H, C(8)H2),
4.21e4.30 (m, 1H, menthyl), 6.77 (br d, J¼7.0 Hz, 2H, CH, aryl),
7.09e7.25 (m, 6H, CH, aryl), 7.30e7.53 (m, 5H, CH, aryl), 7.82e7.93
(m, 4H, CH, aryl). 13S{H} NMR (CDCl3, 25 ꢁC): dC¼16.3, 20.3, 22.0 (s,
CH3, menthyl), 23.6 (s, CH2, menthyl), 26.1 (s, CH, menthyl), 26.2 (d,
3J¼4.5 Hz, S(7)), 31.3 (s, CH, menthyl), 31.4 (s, C(6)), 34.1, 40.5 (s, CH2,
menthyl), 46.9 (s, CH, menthyl), 47.4 (d, 2J¼34.7 Hz, S(8)), 53.6 (d,
2J¼7.0 Hz, S(4)), 62.4 (d, 2J¼9.1 Hz, S(5)), 78.7 (s, CHO, menthyl),
115.1 (d, 3J¼12.8 Hz, CH, phenyl), 118.9 (s, CH, phenyl), 121.4 (s, CH,
binaphthyl), 122.7 (d, 3J¼3.0 Hz, C, binaphthyl), 123.0 (d, 3J¼5.3 Hz,
CH, binaphthyl), 124.3, 125.3 (s, CH, binaphthyl), 125.4 (s, C,
binaphthyl), 126.1, 126.2, 126.3, 126.9, 127.8, 127.9, 128.8, 128.9 (s, CH,
binaphthyl), 129.4 (s, CH, phenyl), 131.7, 133.6, 133.8, 133.9 (s, C,
binaphthyl), 145.1 (d, 2J¼16.5 Hz, C, phenyl), 147.1 (s, CO, binaphthyl),
150.2 (d, 2J¼5.6 Hz, CO, binaphthyl), 153.0 (s, CO3) (major epimer)
and 16.4, 20.4, 21.9 (s, CH3, menthyl), 23.5 (s, CH2, menthyl), 26.0 (s,
CH, menthyl), 27.5 (s, S(7)); 31.2 (s, CH, menthyl), 31.7 (s, C(6)), 34.0,
40.4 (s, CH2, menthyl), 43.4 (d, 2J¼3.8 Hz, S(8)), 46.8 (s, CH, menthyl),
51.2 (d, 2J¼6.0 Hz, S(4)), 65.5 (d, 2J¼10.6 Hz, S(5)), 79.0 (s, CHO,
menthyl), 117.1 (d, 3J¼13.6 Hz, CH, phenyl), 118.3 (s, CH, phenyl),
4. Experimental section
4.1. General comments
31P, 13C, and 1H NMR spectra were recorded with a Bruker AMX
400 instrument (162.0 MHz for 31P, 100.6 MHz for 13C and
400.13 MHz for 1H). Complete assignment of all the resonances in
13C NMR spectra was achieved by the use of DEPT techniques.
Chemical shifts (ppm) were given relative to Me4Si (1H and 13C) and
85% H3PO4 (31P NMR). IR spectra were recorded on a Specord M80
instrument. Mass spectra were recorded with a Bruker Daltonics
Ultraflex spectrometer (MALDI TOF/TOF). HPLC analyses were
performed on an Agilent 1100 and Stayer instruments using
ChiralcelÒ and KromasilÒ columns. Elemental analyses were per-
formed at the Laboratory of Microanalysis (Institute of Organoele-
ment Compounds, Moscow).
All manipulations were carried out under a dry argon atmosphere
in flame-dried glassware and in freshly dried and distilled solvents.
For example, toluene and tetrahydrofuran were freshly distilled from
sodium benzophenone ketyl before use; dichloromethane was dis-
tilled from NaH. Triethylamine, pyrrolidine, and dipropylamine were
distilled over KOH and then over a small amount of LiAlH4 before use.
Columnchromatography wasperformed using silicagelMNKieselgel
60 (230e400 mesh) and MN-Aluminum oxide, basic, Brockmann
Activity 1. Pd(allyl)Cl]2, starting substrate 6, and [Pd2(dba)3]$CHCl3
were prepared as published.23,24 Pd-catalyzed allylic substitution:
sulfonylation of substrate 6 with sodium para-toluene sulfinate, al-
kylation with dimethyl malonate, amination with dipropylamine and
pyrrolidine, alkylation with 1-cyclohexenylpyrrolidine were per-
formed according to the appropriate procedures.10,25,26,19 Pd-
catalyzed desymmetrization of N,N0-ditosyl-meso-cyclopent-4-ene-
1,3-diol biscarbamate and Rh-catalyzed asymmetric addition of
phenylboronic acid to cyclohex-2-enone 12 were performed as
published.27,20 DMAP (4-eimethylamino-pyridine), dimethyl malo-
nate, BSA (N,O-bis(trimethylsilyl) acetamide), sodium para-toluene
sulfinate, 1-cyclohexenylpyrrolidine, meso-cyclopent-4-ene-1,3-diol
9, tosyl isocyanate, cyclohex-2-enone 12, phenylboronic acid, and
[Rh(C2H4)2Cl]2 were purchased from Aldrich and Acros Organics and
used without further purification.
3
120.2 (d, J¼1.5 Hz, CH, binaphthyl), 121.5 (s, CH, binaphthyl), 122.5
(s, C, binaphthyl), 123.9, 125.4, 125.6 (s, CH, binaphthyl), 125.7 (s, C,
binaphthyl), 126.5, 126.6, 126.8, 127.7, 128.0, 128.9, 129.1 (s, CH,
binaphthyl), 129.7 (s, CH, phenyl), 131.9, 133.7, 133.9, 134.0 (s, C,
binaphthyl), 145.3 (d, 2J¼15.7 Hz, C, phenyl), 146.7 (s, CO,
binaphthyl), 150.5 (d, 2J¼5.2 Hz, CO, binaphthyl), 152.6 (s, CO3)
(minor epimer). IR, cmꢀ1
: n(CO) 1752 (KBr). MS (MALDI TOF/TOF): m/
z
(%)¼711 (12) [MþK]þ, 673 (100) [MþH]þ, 534 (9)
[MꢀmenthylþH]þ, 490 (13) [MꢀmenthylO2CþH]þ, 474 (48)
[MꢀmenthylO3CþH]þ. Anal. Calcd for C42H45N2O4P: C, 74.98; H,
6.74; N, 4.16. Found: C, 75.26; H, 6.64; N, 4.21.
4.2.2. (Ra)-2-[(2R,5S)-3-Phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]
oct-2-yloxy]-1,10-binaphthyl-20-yl (1R,2S,5R)-2-isopropyl-5-
methylcyclohexyl carbonate ((Ra)-4). Yield: 0.89 g (66%) as off-
white solid, mp 129e130 ꢁC. 1H NMR (CDCl3, 25 ꢁC):
d¼0.41e0.49
(m,1H, menthyl), 0.59e0.67 (m, 1H, menthyl), 0.68 (d, J¼6.6 Hz, 3H,
menthyl), 0.72 (d, J¼7.5 Hz, 3H, menthyl), 0.79 (d, J¼7.5 Hz, 3H,
menthyl), 1.14e1.22 (m, 3H, menthyl), 1.29e1.39 (m, 3H, C(6)H2C(7)
H2), 1.48e1.57 (m, 1H, menthyl), 1.61e1.75 (m, 2H, menthyl and 1H,
C(6)H2C(7)H2), 1.79e1.89 (m, 1H, menthyl); 2.84e2.95 (m, 2H),
3.24e3.31 (m, 2H), 3.36e3.48 (m, 1H, C(4)H2, C(5)H, C(8)H2);
4.15e4.25 (m, 1H, menthyl), 6.82 (br d, J¼6.1 Hz, 2H, CH, aryl),
7.08e7.24 (m, 7H, CH, aryl), 7.26e7.35 (m, 2H, CH, aryl), 7.38e7.47
(m, 1H, CH, aryl), 7.48 (d, J¼8.9 Hz, 1H, CH, aryl), 7.75 (d, J¼9.0 Hz,
1H, CH, aryl), 7.79 (d, J¼9.0 Hz, 1H, CH, aryl), 7.88e7.96 (m, 2H, CH,
4.2. General procedure for the preparation of ligands
A solution of the appropriate enantiomer of 1a or 1b (2 mmol) in
toluene (10 mL) was added dropwise to a vigorously stirred solu-
tion of the appropriate phosphorylating reagent (2 mmol), Et3N
(0.31 mL, 2.2 mmol), and DMAP (0.025 g, 0.2 mmol) in toluene
(10 mL). The mixture was then heated to the boiling point, stirred
for 20 min, and cooled to 20 ꢁC. Solid Et3N$HCl was removed by
filtration. The resulting solution was filtered through a short plug of
aluminum oxide, the solvent evaporated under reduced pressure
(40 Torr), and the residue was purified by careful trituration with
CHCl3/hexane (1:20) and then by flash chromatography on silica gel
(EtOAc/hexane, 1:1). The product was dried in vacuum (1 Torr) for
1 h.
13
aryl). S{H} NMR (CDCl3, 25 ꢁC): dC¼16.4, 20.6, 21.8 (s, CH3,
menthyl), 23.4 (s, CH2, menthyl), 25.8 (d, 3J¼4.5 Hz, S(7)), 26.0, 31.1
(s, CH, menthyl), 31.5 (s, C(6)), 34.0, 39.6 (s, CH2, menthyl), 46.4 (s,
CH, menthyl), 47.2 (d, 2J¼36.9 Hz, S(8)), 53.8 (d, 2J¼7.6 Hz, S(4)),
62.6 (d, 2J¼8.3 Hz, S(5)), 78.9 (s, CHO, menthyl), 115.1 (d,
3J¼12.8 Hz, CH, phenyl), 119.0 (s, CH, phenyl), 121.7 (s, CH,
binaphthyl), 122.5 (s, C, binaphthyl), 122.8 (d, 3J¼5.3 Hz, CH,
binaphthyl),124.3,125.2 (s, CH, binaphthyl),125.3 (s, C, binaphthyl),
126.0, 126.1, 126.5, 127.2, 127.7, 128.0, 128.9, 129.1 (s, CH,
binaphthyl), 129.4 (s, CH, phenyl), 130.4, 131.6, 133.7, 133.8 (s, C,
binaphthyl), 145.2 (d, 2J¼16.1 Hz, C, phenyl), 147.4 (s, CO,
binaphthyl), 150.2 (d, 2J¼5.5 Hz, CO, binaphthyl), 152.9 (s, CO3)
(major epimer) and 16.5, 20.4, 21.7 (s, CH3, menthyl), 23.5 (s, CH2,
menthyl), 25.9 (s, CH, menthyl), 27.8 (s, S(7)), 31.2 (s, CH, menthyl),
31.7 (s, C(6)), 34.1, 39.8 (s, CH2, menthyl), 42.7 (d, 2J¼3.9 Hz, S(8)),
46.5 (s, CH, menthyl), 51.4 (d, 2J¼5.3 Hz, S(4)), 65.5 (d, 2J¼10.6 Hz,
S(5)), 78.8 (s, CHO, menthyl), 117.5 (d, 3J¼12.8 Hz, CH, phenyl),118.9
4.2.1. (Sa)-2-[(2R,5S)-3-Phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]
oct-2-yloxy]-1,10-binaphthyl-20-yl (1R,2S,5R)-2-isopropyl-5-
methylcyclohexyl carbonate ((Sa)-4). Yield: 0.93 g (69%) as white
solid, mp 103e104 ꢁC. 1H NMR (CDCl3, 25 ꢁC):
3H, menthyl), 0.59 (d, J¼6.1 Hz, 3H, menthyl), 0.70e0.79 (m, 2H,
menthyl), 0.84 (d, J¼6.5 Hz, 3H, menthyl), 0.90e0.98 (m, 2H,
d
¼0.33 (d, J¼6.1 Hz,

K.N. Gavrilov et al. / Tetrahedron 68 (2012) 1581e1589
1587
(s, CH, phenyl), 120.4 (d, 3J¼1.9 Hz, CH, binaphthyl), 121.8 (s, CH,
binaphthyl), 122.6 (s, C, binaphthyl), 123.9 (s, CH, binaphthyl), 125.4
(s, C, binaphthyl),125.5,125.8,126.4, 126.6,126.7,127.9,128.3,129.2,
129.3 (s, CH, binaphthyl), 129.5 (s, CH, phenyl), 130.2, 131.9, 133.6,
133.9 (s, C, binaphthyl), 144.3 (d, 2J¼15.1 Hz, C, phenyl), 147.1 (s, CO,
binaphthyl), 150.4 (d, 2J¼5.3 Hz, CO, binaphthyl), 153.0 (s, CO3)
(CDCl3, 25 ꢁC):
d
¼2.04 (s, 3H, CH3), 6.30 (d, J¼8.1 Hz, 2H, CH), 6.72
(d, J¼8.0 Hz, 2H, CH), 7.07 (d, J¼7.9 Hz, 1H, CH), 7.13e7.24 (m, 6H,
CH), 7.25e7.32 (m, 2H, CH), 7.34e7.45 (m, 5H, CH), 7.69 (d, J¼8.0 Hz,
1H, CH), 7.81e7.90 (m, 5H, CH), 7.92e7.99 (m, 3H, CH), 8.12 (d,
13
J¼8.1 Hz, 1H, CH). S{H} NMR (CDCl3, 26 ꢁC): dC¼21.3 (s, CH3),
120.8 (d, 3J¼6.0 Hz, CH, aryl), 121.3, 121.7, 122.3 (s, CH, aryl), 123.3
123.8, 124.2, 124.5 (s, C, aryl), 124.9, 125.0, 125.2, 125.7, 125.8, 126.0,
126.1, 126.4, 126.7, 127.0 (s, CH, aryl), 127.1 (s, CH, tosyl), 127.4, 127.7,
127.9, 128.3, 128.5, 129.2 (s, CH, aryl), 129.4 (s, CH, tosyl), 129.6,
129.9, 130.0 (s, CH, aryl), 131.3, 131.7, 132.0, 132.6, 133.4, 133.5, 134.2
(s, C, aryl), 143.8, 146.3 (s, C, tosyl), 146.9 (s, CO, aryl), 147.4 (d,
2J¼4.3 Hz, CO, aryl), 147.6 (d, 2J¼7.5 Hz, CO, aryl), 148.8 (s, CO, aryl).
MS (MALDI TOF/TOF): m/z (%)¼793 (21) [MþK]þ, 777 (17)
[MþNa]þ, 755 (81) [MþH]þ, 600 (100) [MꢀTsþH]þ. Anal. Calcd for
C47H31O6PS: C, 74.79; H, 4.14; P, 4.10. Found: C, 75.02; H, 4.18; P,
3.89.
(minor epimer). IR, cmꢀ1
: n(CO) 1751 (KBr). MS (MALDI TOF/TOF):
m/z (%)¼711 (27) [MþK]þ, 673 (100) [MþH]þ, 534 (19)
[MꢀmenthylþH]þ, 490 (7) [MꢀmenthylO2CþH]þ, 474 (33)
[MꢀmenthylO3CþH]þ. Anal. Calcd for C42H45N2O4P: C, 74.98; H,
6.74; N, 4.16. Found: C, 75.13; H, 6.82; N, 4.19.
4.2.3. (Sa)-2-[(Sa)-Dinaphtho[2,1-d:10,20-f][1,3,2]dioxaphosphepin-4-
yloxy]-1,10-binaphthyl-20-yl (1R,2S,5R)-2-isopropyl-5-
methylcyclohexyl carbonate ((Sa)-5a). Yield: 1.28 g (82%) as white
solid, mp 172e173 ꢁC. 1H NMR (CDCl3, 25 ꢁC):
d¼0.18 (d, J¼7.2 Hz,
3H, menthyl), 0.50 (d, J¼7.2 Hz, 3H, menthyl), 0.66e0.75 (m, 1H,
menthyl), 0.79 (d, J¼6.5 Hz, 3H, menthyl), 0.80e0.88 (m, 1H,
menthyl), 0.91e1.0 (m, 1H, menthyl), 1.02e1.11 (m, 1H, menthyl),
1.21e1.29 (m, 2H, menthyl), 1.43e1.52 (m, 2H, menthyl), 1.79e1.87
(m, 1H, menthyl), 4.16e4.25 (m, 1H, menthyl), 7.16e7.24 (m, 6H, CH,
aryl), 7.24e7.32 (m, 4H, CH, aryl), 7.35e7.43 (m, 3H, CH, aryl),
7.44e7.51 (m, 2H, CH, aryl), 7.58 (d, J¼12.0 Hz, 1H, CH, aryl), 7.66 (d,
J¼12.0 Hz, 1H, CH, aryl), 7.83e7.91 (m, 5H, CH, aryl), 7.97 (d,
J¼8.0 Hz, 1H, CH, aryl), 8.09 (d, J¼8.1 Hz, 1H, CH, aryl). 13S{H} NMR
(CDCl3, 25 ꢁC): dC¼16.0, 20.3, 21.9 (s, CH3, menthyl), 23.4 (s, CH2,
menthyl)m 25.8, 31.3 (s, CH, menthyl), 33.9, 40.5 (s, CH2, menthyl),
46.7 (s, CH, menthyl), 79.0 (s, CHO, menthyl), 121.0, 121.1 (s, C, aryl),
121.6, 121.7, 121.8, 121.9 (s, CH, aryl), 122.5, 122.6 (s, C, aryl), 124.3,
124.8, 125.1, 125.2, 125.9, 126.1, 126.2, 126.3, 126.9, 127.0, 127.9,
128.2, 128.3, 128.4, 129.5, 129.8, 130.1, 130.2 (s, CH, aryl), 130.9, 131.1,
131.5, 131.8, 132.4, 132.8, 133.7(s, C, aryl), 147.0, 147.5 (s, CO, aryl),
147.7 (d, 2J¼6.0 Hz, CO, aryl), 147.9 (d, 2J¼8.0 Hz, CO, aryl), 152.9 (s,
4.2.6. (Ra)-2-[(Sa)-Dinaphtho[2,1-d:10,20-f][1,3,2]dioxaphosphepin-4-
yloxy]-1,10-binaphthyl-20-yl
4-methylbenzenesulfonate
5b). Yield: 1.19 g (79%) as white solid, mp 182e183 ꢁC. 1H NMR
(CDCl3, 25 ꢁC):
¼2.20 (s, 3H, CH3), 6.32 (d, J¼8.1 Hz, 1H, CH), 6.71
((Ra)-
d
(d, J¼8.0 Hz, 2H, CH), 6.93 (d, J¼12.0 Hz, 1H, CH), 7.06 (d, J¼7.8 Hz,
2H, CH), 7.12e7.23 (m, 5H, CH), 7.33e7.43 (m, 5H, CH), 7.74e7.90 (m,
10H, CH), 7.93 (d, J¼8.0 Hz, 1H, CH), 8.0 (d, J¼8.1 Hz, 1H, CH). 13S{H}
NMR (CDCl3, 26 ꢁC): dC¼21.4 (s, CH3), 121.2 (d, 3J¼6.2 Hz, CH, aryl),
121.3, 121.6, 122.3 (s, CH, aryl), 123.5 123.9, 124.1, 124.5 (s, C, aryl),
124.9, 125.2, 125.4, 125.5, 126.0, 126.2, 126.3, 126.4, 127.0, 127.2 (s,
CH, aryl), 127.5 (s, CH, tosyl),127.6, 127.7,127.9, 128.2, 128.5, 129.3 (s,
CH, aryl), 129.5 (s, CH, tosyl), 129.7, 130.1, 130.3, 130.5 (s, CH, aryl),
131.4,131.7,132.0, 132.5, 133.1,133.5,134.4 (s, C, aryl),143.5,146.4 (s,
C, tosyl), 147.2 (s, CO, aryl), 147.5 (d, 2J¼4.5 Hz, CO, aryl), 147.9 (d,
2J¼7.1 Hz, CO, aryl), 148.7 (s, CO, aryl). MS (MALDI TOF/TOF): m/z
(%)¼793 (43) [MþK]þ, 777 (3) [MþNa]þ, 755 (92) [MþH]þ, 600
(100) [MꢀTsþH]þ. Anal. Calcd for C47H31O6PS: C, 74.79; H, 4.14; P,
4.10. Found: C, 74.95; H, 4.22; P, 4.14.
CO3). IR, cmꢀ1
:
n
(CO) 1752 (KBr). MS (MALDI TOF/TOF): m/z (%)¼
805 (4) [MþNa]þ, 783 (14) [MþH]þ, 644 (100) [MꢀmenthylþH]þ,
600 (52) [MꢀmenthylO2CþH]þ. Anal. Calcd for C51H43O6P: C, 78.24;
H, 5.54; P, 3.96. Found: C, 78.49; H, 5.64; P, 3.88.
4.3. Catalytic reactions
4.2.4. (Ra)-2-[(Sa)-Dinaphtho[2,1-d:10,20-f][1,3,2]dioxaphosphepin-4-
yloxy]-1,10-binaphthyl-20-yl (1R,2S,5R)-2-isopropyl-5-
methylcyclohexyl carbonate ((Ra)-5a). Yield: 1.19 g (76%) as white
4.3.1. Pd-catalyzed allylic sulfonylation of (E)-1,3-diphenylallyl ace-
tate 6 with sodium para-toluene sulfinate. A solution of [Pd(allyl)
Cl]2 (0.0019 g, 0.005 mmol) and the appropriate ligand (0.01 mmol
or 0.02 mmol) in THF (1.5 mL) was stirred for 40 min. (E)-1,3-
Diphenylallyl acetate (0.05 mL, 0.25 mmol) was added and the so-
lution stirred for 15 min, then sodium para-toluene sulfinate
(0.089 g, 0.5 mmol) was added and the reaction mixture stirred for
further 48 h, quenched with brine (3 mL), and extracted with THF
(3ꢂ2 mL). The organic layer was washed with brine (2ꢂ2 mL) and
dried over MgSO4. The solvent was evaporated at reduced pressure
(40 Torr). Crystallization of the residue from EtOH, followed by
desiccation in vacuum (10 Torr, 12 h), gave (E)-1,3-diphenyl-3-
tosylprop-1-ene 7a as white crystals. The ee of 7a was de-
termined by HPLC.
solid, mp149e150 ꢁC.1H NMR (CDCl3, 25 ꢁC):
d¼0.25 (d, J¼7.3 Hz, 3H,
menthyl), 0.53 (d, J¼6.5 Hz, 3H, menthyl), 0.68e0.79 (m, 2H,
menthyl), 0.82 (d, J¼7.3 Hz, 3H, menthyl),1.01e1.15 (m, 2H, menthyl),
1.23e1.33 (m, 2H, menthyl), 1.43e1.55 (m, 2H, menthyl), 1.81 (br d,
J¼12.0 Hz, 1H, menthyl), 4.20e4.28 (m, 1H, menthyl), 7.15e7.25 (m,
6H, CH, aryl), 7.25e7.32 (m, 4H, CH, aryl), 7.33e7.43 (m, 4H, CH, aryl),
7.46e7.60 (m, 3H, CH, aryl), 7.74 (d, J¼8.0 Hz, 1H, CH, aryl), 7.83e7.91
(m, 3H, CH, aryl), 7.95 (d, J¼8.0 Hz,1H, CH, aryl), 8.04 (d, J¼8.1 Hz,1H,
CH, aryl), 8.11 (d, J¼8.1 Hz, 1H, CH, aryl). 13S{H} NMR (CDCl3, 25 ꢁC):
dC¼15.9, 20.2, 21.8 (s, CH3, menthyl), 23.1 (s, CH2, menthyl), 25.6, 31.1
(s, CH, menthyl), 33.8, 40.2 (s, CH2, menthyl), 46.4 (s, CH, menthyl),
78.9 (s, CHO, menthyl),120.9 (d, 3J¼7.0 Hz, CH, aryl),121.4,121.5,121.6
(s, CH, aryl), 122.3 (d, 3J¼2.1 Hz, C, aryl), 124.1, 124.2, 124.3 (s, C, aryl),
124.6, 124.9, 125.0, 125.7, 125.8, 125.9, 126.0, 126.4, 126.7, 126.8, 126.9,
127.8, 127.9, 128.0, 128.1, 129.1, 129.8, 130.0, 130.1 (s, CH, aryl), 131.3,
131.7,132.0,132.6,133.4,133.5 (s, C, aryl),146.9(d, 2J¼3.0 Hz, CO, aryl),
147.2,147.3 (s, CO, aryl),147.6 (d, 2J¼8.1 Hz, CO, aryl),152.8 (s, CO3). IR,
4.3.2. Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate
6 with dimethyl malonate. A solution of [Pd(allyl)Cl]2 (0.0019 g,
0.005 mmol) and appropriate ligand (0.01 mmol or 0.02 mmol) in
the appropriate solvent (1.5 mL) was stirred for 40 min. (E)-1,3-
Diphenylallyl acetate (0.05 mL, 0.25 mmol) was added and the so-
lution stirred for 15 min. Dimethyl malonate (0.05 mL, 0.44 mmol),
BSA (0.11 mL, 0.44 mmol), and potassium acetate (0.002 g) were
added. The reaction mixture was stirred for 48 h, diluted with
CH2Cl2 or THF (2 mL), and filtered through Celite. The filtrate was
evaporated at reduced pressure (40 Torr) and dried in vacuum
(10 Torr, 12 h) affording a residue containing (E)-dimethyl 2-(1,3-
diphenylallyl)malonate 7b. In order to evaluate ee and
cmꢀ1
:
n
(CO) 1755 (KBr). MS (MALDI TOF/TOF): m/z (%)¼783 (37)
[MþH]þ,
644
(100)
[MꢀmenthylþH]þ,
600
(49)
[MꢀmenthylO2CþH]þ. Anal. Calcd for C51H43O6P: C, 78.24; H, 5.54; P,
3.96. Found: C, 78.36; H, 5.49; P, 4.21.
4.2.5. (Sa)-2-[(Sa)-Dinaphtho[2,1-d:10,20-f][1,3,2]dioxaphosphepin-4-
yloxy]-1,10-binaphthyl-20-yl
4-methylbenzenesulfonate
((Sa)-
5b). Yield: 1.12 g (74%) as white solid, mp 155e156 ꢁC. 1H NMR

1588
K.N. Gavrilov et al. / Tetrahedron 68 (2012) 1581e1589
conversion, the obtained residue was dissolved in an appropriate
eluent mixture (8 mL) and a sample was taken for HPLC analysis.
(1.5 mL), MTBE (0.5 mL), and water (2 mL). The organic layer was
separated and washed with water (2 mL). The aqueous layers were
combined and extracted with MTBE/heptane (1:2, 2 mL). Combined
organic layers were filtered through Celite and concentrated in
vacuum (40 Torr). The residue was dissolved in heptane, filtered
through Celite, concentrated in vacuum (40 Torr), purified by flash
chromatography on a short plug of silica gel (CHCl3), and dried in
vacuum (1 Torr) for 1 h gave the desired product 13 as a colorless
oil. The ee of 13 was determined by HPLC.
4.3.3. Pd-catalyzed allylic amination of (E)-1,3-diphenylallyl acetate
6 with dipropylamine or pyrrolidine. A solution of [Pd(allyl)Cl]2
(0.0019 g, 0.005 mmol) and appropriate ligand (0.01 mmol or
0.02 mmol) in the appropriate solvent (1.5 mL) was stirred for
40 min. (E)-1,3-Diphenylallyl acetate (0.05 mL, 0.25 mmol) was
added and the solution stirred for 15 min, then freshly distilled
dipropylamine or pyrrolidine (0.75 mmol) was added and the re-
action mixture was stirred for further 48 h. The resulting solution
was filtered through Celite. The filtrate was evaporated at reduced
pressure (40 Torr) and dried in vacuum (10 Torr, 12 h) affording
a residue containing (E)-1,3-diphenyl-N,N-dipropylprop-2-en-1-
amine 7c or (E)-1-(1,3-diphenylallyl)pyrrolidine 7d. In order to
evaluate ee and conversion, the obtained residue was dissolved in
an appropriate eluent mixture (8 mL) and a sample was taken for
HPLC analysis.
Acknowledgements
We acknowledge the financial support from the Russian Foun-
dation for Basic Research (Grant No. 11-03-00347-a) and a grant
from the President of the Russian Federation for Young Candidates
of Sciences (No. MK-3889.2010.3).
Supplementary data
4.3.4. Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2011.11.092.
6
with 1-cyclohexenylpyrrolidine. A solution of [Pd(allyl)Cl]2
(0.0019 g, 0.005 mmol) and appropriate ligand (0.01 mmol or
0.02 mmol) in the appropriate solvent (1.5 mL) was stirred for
40 min. (E)-1,3-Diphenylallyl acetate (0.05 mL, 0.25 mmol) was
added and the solution stirred for 15 min, then 1-
cyclohexenylpyrrolidine (0.115 g, 0.75 mmol) was added and the
reaction mixture was stirred for further 48 h, quenched with sat-
urated NH4Cl solution (5 mL) for 2 h, and extracted with CH2Cl2
(3ꢂ3 mL). The combined organic extracts were washed with water
(3 mL), brine (3 mL), dried over Na2SO4, and concentrated under
reduced pressure (40 Torr) after filtration. The residue was dis-
solved in EtOAc/hexane (1:10) and filtered through a short plug of
silica gel. The filtrate was evaporated at reduced pressure (40 Torr)
and dried in vacuum (10 Torr, 12 h) affording a residue containing
(E)-2-(1,3-diphenylallyl)cyclohexanone of anti-configuration (8a)
and syn-configuration (8b). The ratio of anti- and syn-configuration
was determined by 1H NMR. In order to evaluate ee and conversion,
the obtained residue was dissolved in an appropriate eluent mix-
ture (8 mL) and a sample was taken for HPLC analysis.
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