Palladium-catalyzed enantioselective allylation in the presence of phosphoramidites derived from (Sa)-3-SiMe3-BINOL, (R,S)-semi-TADDOL, and (R,R)-TADDOL

Article abstract of DOI:10.1007/s11172-015-1047-7

P*- and P-monodentate phosphoramidites of a 1,3,2-dioxaphosphepine series were derived from (S_a)-3-trimethylsilyl-BINOL, (R,S)-semi-TADDOL, and (R,R)-TADDOL. Catalytic performance of the synthesized compounds were examined in the Pd-catalyzed a

Full text of DOI:10.1007/s11172-015-1047-7

Russian Chemical Bulletin, International Edition, Vol. 64, No. 7, pp. 1595—1601, July, 2015
1595
Palladiumꢀcatalyzed enantioselective allylation
in the presence of phosphoramidites derived from
(
S )ꢀ3ꢀSiMe ꢀBINOL, (R,S)ꢀsemiꢀTADDOL, and (R,R)ꢀTADDOL
a
3
K. N. Gavrilov,a S. V. Zheglov, I. M. Novikov, I. V. Chuchelkin, V. K. Gavrilov,
a
a
a
a
a
b
V. V. Lugovsky, and I. A. Zamilatskov
aS. A. Esenin Ryazan State University,
4
6 ul. Svobody, Russian Federation, 390000 Ryazan.
Fax: +7 (491 2) 28 1435. Eꢀmail: k.gavrilov@rsu.edu.ru
A. N. Frumkin Institute of Physical Chemistry and Electrochemistry of the Russian Academy of Sciences,
b
3
1 Leninsky prosp., 119071 Moscow, Russian Federation.
Fax: +7 (495) 952 0449. Eꢀmail: alex123.87@mail.ru
Novel P*ꢀ and Pꢀmonodentate phosphoramidites of a 1,3,2ꢀdioxaphosphepine series were
derived from (S )ꢀ3ꢀtrimethylsilylꢀBINOL, (R,S)ꢀsemiꢀTADDOL, and (R,R)ꢀTADDOL.
a
Catalytic performance of the synthesized compounds were examined in the Pdꢀcatalyzed asymꢀ
metric allylic substitution of (E)ꢀ1,3ꢀdiphenylallyl acetate: the reaction with dimethyl malonate
gave up to 92% ee. The effects of additives of 5,10,15,20ꢀtetraphenylporphyrin and its metal
complexes on conversion and enantioselectivity were studied.
Key words: chiral phosphoramidites, palladium catalysts, asymmetric allylation, 5,10,15,20ꢀ
tetraphenylporphyrin.
Asymmetric catalysis with metal complexes is an effiꢀ
cient approach to access enantiopure or, generally, enanꢀ
tioenriched products. These substances found applications
in the manufacturing of pharmaceuticals, vitamins, chemꢀ
icals for crop and forest protection, fragrances, food addiꢀ
tives, ferroelectric liquid crystals, and chiral polymers with
nonlinear optical properties.1
mance of the synthesized ligands was examined on the
example of the Pdꢀcatalyzed asymmetric allylic alkylation
and amination. These reactions are the reliable models for
the evaluation of the efficiency of novel chiral inductors
and are widely used in the asymmetric synthesis of valuꢀ
8
,26—29
able organic and natural compounds.
For instance,
—7
products of alkylation with dimethyl malonate can be
readily transformed into esters and amides of chiral unꢀ
saturated carboxylic acids under mild conditions, if their
Chiral phosphorusꢀcontaining compounds play an imꢀ
portant role in asymmetric catalysis.1
,2,4,7—12
However,
3
0
the vast majority of chiral phosphorus ligands have proven
to provide high enantiomeric control only in certain chemꢀ
ical transformations. Only a few ligands have a general
scope (so called privileged ligands), but high cost limits
their wide application. Therefore, the design of novel powꢀ
erful phosphorus ligands as chiral inductors, which can be
readily obtained from available enantiopure precursors, is
still challenging and appealing.1
C*ꢀchiral center remains untouched. Allylic amides,
especially chiral allylic amides, are the important precurꢀ
sors for the synthesis of ꢀ and ꢀamino acids, alkaloids,
carbohydrate derivatives, and azaheterocycles.3
1,32
Asymmetric metal catalysts are very sensitive to the
reaction conditions. For example, catalytic outcome and
sometimes enantioselectivity of the catalytic system can
be enhanced using small, comparable with catalytic,
3—17
33,34
Inexpensive phosphite and phosphoramidite ligands
showing robustness towards oxidation and excellent  acidꢀ
ity are of primary interest. Note also the accessibility
of phosphite and phosphoramidite ligands via condensaꢀ
tion reactions including parallel and solidꢀphase syntheꢀ
amounts of achiral additives.
In the present work,
we discuss the effects of additives of 5,10,15,20ꢀtetraꢀ
phenylporphyrin zinc and copper complexes on the outꢀ
come of the Pdꢀcatalyzed asymmetric allylic substitution
of (E)ꢀ1,3ꢀdiphenylallyl acetate as a substrate and phosꢀ
phoramidites as chiral inductors.
1
6,18—23
ses.
Phosphorusꢀcontaining chiral inductors with
stereogenic donor atoms are especially promising for asymꢀ
metric synthesis.2
4,25
Results and Discussion
In the present work, we describe synthesis of novel
P*ꢀ and Pꢀmonodentate phosphoramidites and their appliꢀ
cation for enantioselective catalysis. The catalytic perforꢀ
Enantiopure C symmetrical (S )ꢀ3ꢀSiMe ꢀBINOL
(1c) was synthesized by the reaction sequence (Scheme 1)
1
a
3
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1595—1601, July, 2015.
066ꢀ5285/15/6407ꢀ1595 © 2015 Springer Science+Business Media, Inc.
1

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Russ.Chem.Bull., Int.Ed., Vol. 64, No. 7, July, 2015
Gavrilov et al.
Scheme 1
+
Reagents and conditions: i. EtOCH=CH , H , CH Cl ; ii. BuLi, Me SiCl, THF; iii. HCl, CH Cl .
2
2
2
3
2
2
Scheme 2
Reagents and conditions: i. P(NEt ) , toluene; ii. PCl , NMP; iii. pyrrolidine (2.4 eqiuv.), toluene.
2
3
3
involving protection of (S )ꢀ1,1´ꢀbinaphthylꢀ2,2´ꢀdiol
amine in toluene in the presence of Et N produces ligands
a
3
(
1a, (S )ꢀBINOL) with ethyl vinyl ether to give comꢀ
4a,b (Scheme 3). Similarly to compounds 2a,b, phosphorꢀ
amidite 4a also contains asymmetric phosphorus atom
(epimer ratio is ~4.6 : 1, see Table 1).
a
pound 1b, selective orthoꢀlithiation of compound 1b, subꢀ
sequent reaction of the lithiated derivative with Me SiCl,
3
and deprotection by treatment with HCl in CH Cl .
2
2
Phosphorylation of diol 1c with P(NEt ) in toluene
proceeds with very high diastereoselectivity to give
2
3
Scheme 3
P*ꢀmonodentate phosphoramidite 2a (Scheme 2). Acꢀ
31
cording to the P NMR spectroscopy data, the ratio of
the P* epimers of 2a is 19 : 1 (Table 1). Compound 1c in
reactions with PCl and further with pyrrolidine gives phosꢀ
3
phoramidite 2b (a ~1.3 : 1 mixture of the P* epimers, see
Scheme 2 and Table 1).
Condensation of (R,S)ꢀsemiꢀTADDOL (3a) and
(
R,R)ꢀTADDOL (3b) with PCl followed by the reactions
3
of the corresponding intermediates with adamantanꢀ1ꢀ
Table 1. 31P NMR spectra (CDCl ) and the Tolman
3
cone angles of ligands 2a,b and 4a,b
Ligand
P
/deg
3, 4: R = H (a), Ph (b)
2
2
4
4
a
b
a
b
150.5 (95), 148.9 (5)
150.0 (44), 149.8 (56)
144.9 (82), 133.5 (18)
139.6
141
139
127
188
Reagents and conditions: i. PCl , NMP; ii. adamantanꢀ1ꢀamine,
3
Et N, toluene.
3
Phosphoramidites 2a,b and 4a,b are well soluble in
common organic solvents, relatively stable in air, and can
be stored for a longꢀterm under dry atmosphere. Sterical
Content (%) of P*ꢀepimers of compounds 2a,b and
a is given in parentheses.
4

Asymmetric allylic substitution
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 7, July, 2015
1597
demands of compounds 2a and 2b are nearly the same;
while, the pair of compounds 4a and 4b show dramatically
different sterical demands. This fact is confirmed by the
Tolman cone angles () (see Table 1) calculated for these
compounds using the AM1 semiꢀempirical quantum
Table 2. PdꢀCatalyzed asymmetric allylic alkylation of comꢀ
pound 5 with dimethyl malonatea
Entry
Ligand (L)
L : Pd
Conversion(%)
ee (%)b
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2b
2b
4a
4a
4a
4a
4a
4a
4a
4a
4b
4b
4b
4b
4b
4b
4b
4b
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
9
6
5
39 (R)
49 (R)
3
5,36
chemical method with the full geometry optimization.
It should be noted that few P*ꢀchiral phosphoramidite
c
30 (R)
26 (R)
40 (R)d
c
ligands synthesized from the C symmetrical BINOL deꢀ
3
1
rivatives and only one such ligand obtained from (R,S)ꢀ
17
25
31
28
62
39
18
33
28
44
38
52
75
100
46
72
47
79
62
99
85
95
88
78
54
86
98
92
96
97
37—40
d
49 (R)
25 (R)e
57 (R)
semiꢀTADDOL are known.
Stereodiscriminating ability of phosphoramidites 2a,b
and 4a,b were tested on the examples of two Pdꢀcatalyzed
asymmetric allylic substitutions involving (E)ꢀ1,3ꢀdiꢀ
phenylallyl acetate (5). Bis(allyl)dichlorodipalladium
e
f
21 (R)
1
1
0
1
49 (R)f
42 (R)
[
Pd(allyl)Cl] was used as a metal source (Scheme 4,
2
12
1
14
15
52 (R)
43 (R)d
53 (R)
42 (R)e
Tables 2 and 3). We also examined the effects of the addiꢀ
tives of porphyrin derivatives, i.e., 5,10,15,20ꢀtetrapheꢀ
nylporphyrin (TPP), 5,10,15,20ꢀtetraphenylporphyrin
zinc(II) complex (ZnꢀTPP), and 5,10,15,20ꢀtetraphenylꢀ
porphyrin copper(II) complex (CuꢀTPP). Achiral addiꢀ
tives of the porphyrin derivatives and chiral ligands were
used in equimolar amounts.
3
d
e
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
51 (R)
f
34 (R)
41 (R)f
44 (R)
51 (R)
34 (R)d
d
58 (R)
51 (R)e
Scheme 4
e
63 (R)
f
27 (R)
61 (R)f
90 (S)
91 (S)
91 (S)d
d
92 (S)
92 (S)e
e
91 (S)
92 (S)
f
92 (S)f
a
Reaction conditions: [Pd(allyl)Cl] (2 mol.%), CH Cl , 20 C,
2
2
2
Reagents and conditions: i. CH (CO Me) , BSA, AcOK, cataꢀ
lyst (see Table 2); ii. pyrrolidine, catalyst (see Table 3).
48 h.
b
2
2
2
Conversion of substrate 5 and enantiomeric excesses of prodꢀ
uct 6 were determined by HPLC (Daicel Chiralcel OD—H,
i
–1
C H —Pr OH (99 : 1), 0.3 mL min , 254 nm, t(R) = 28.0 min,
Both P*ꢀmonodentate phosphoramidites 2a and 2b
provide nearly equal enantioselectivity in allylic alkylation
of substrate 5 with dimethyl malonate (Cꢀnucleophile)
6
14
t(S) = 29.3 min).
In toluene.
In the presence of TPP.
In the presence of ZnꢀTPP.
c
d
(
up to 57 and 53% ee, respectively) and predominant
e
formation of (R)ꢀenantiomer of compound 6 (see Table 2,
f
In the presence of CuꢀTPP.
entries 1—18). This fact suggests that the (S )ꢀbinaphthyl
a
framework of compounds 2a,b substantially affects
the chiral induction. In virtually all cases, small chiral
induction is observed at the molar ratio L : Pd = 2. Simiꢀ
larly, catalytic transformations in the presence of P*ꢀchiral
phosphoramidite 4a yield compound (R)ꢀ6 with enantioꢀ
meric excess up to 63% ee; the optimum molar ratio
is L : Pd = 2. At the same time, ligand 4b provides
high enantioselectivity (90—92% ee) giving enantiomer
ly high steric demands of chiral ligand 4b ( = 188,
see Table 1).
Allylic alkylation of substrate 5 in the presence of ligand
2a in aromatic solvent, toluene, results in decrease in both
conversion and enantioselectivity (see Table 2, entries 1, 2
and 3, 4). However, achiral additives of porphyrin derivaꢀ
tives enhance conversions achieved in CH Cl in the presꢀ
2
2
(
S)ꢀ6 irrespectively to the reaction conditions (see Table 2).
ence of catalytic systems involving phosphoramidites 2a,b
and 4a,b. Conversion noticeably increases upon addition
Apparently, formation of (S)ꢀ6 is due to the sufficientꢀ

1
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Russ.Chem.Bull., Int.Ed., Vol. 64, No. 7, July, 2015
Gavrilov et al.
Table 3. PdꢀCatalyzed asymmetric amination of substrate 5 with
pyrrolidine
These chiral inductors provide up to 92% ee in alkylation
of (E)ꢀ1,3ꢀdiphenylallyl acetate (5) with dimethyl malꢀ
onate and up to 61% ee in amination of 5 with pyrrolidine.
Additives of achiral porphyrin complexes CuꢀTPP and
ZnꢀTPP enhance conversion and in some cases enantioꢀ
selectivity. Note that polyaromatic metalloporphyrin
molecule possessing a large surface can participate in the
formation of the key catalytic intermediate with the coorꢀ
dinated substrate. This process can involve — interacꢀ
tions between porphyrin derivative and aromatic substituꢀ
a
Entry
Ligand (L)
L : Pd
Conversion (%)
ee (%)b
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2b
2b
2b
2b
4a
4a
4a
4a
4b
4b
4b
4b
4b
4b
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
62
33
60
44
70
86
72
79
78
90
100
100
7
10
15 (S)
12 (S)
14 (S)c
12 (S)
13 (S)
c
c
10
41
ents of allylic substrate and/or phosphoramidite ligand.
14 (S)c
47 (S)
55 (S)
Presently, our research group carries out further studies of
the effects of metalloporphyrins on asymmetric metal
catalysis.
10
11
12
13
14
15
16
17
18
c
61 (S)
31 (S)c
22 (R)
14 (R)
37 (R)c
Experimental
8
41
100
0
31
P, H, and 13C NMR spectra were recorded using Bruker
Avance 400 (working frequencies of 161.98, 400.13, and
00.61 MHz, respectively) and Bruker Avance III 600 instruꢀ
1
c
35 (R)
1—
1—
d
1
d
0
ments (working frequencies of 242.94, 600.13, and 150.9 MHz,
respectively). The chemical shifts () are given relative to 85%
a
Reaction conditions: [Pd(allyl)Cl]2 (2 mol.%), CH Cl ,
0 C, 48 h.
Conversion of substrate 5 and enantiomeric excesses of prodꢀ
2
2
31
1
13
1
H PO in D O ( P) and Me Si ( H, C). The signals in H and
3
4
2
4
2
b
1
3
C NMR spectra were attributed using DEPT experiments
taking into account the published data.
4
2—44
Matrixꢀassisted laser
uct 7 were determined by HPLC (Daicel Chiralcel ODꢀH,
C H —Pr OH—HNEt (200 : 1 : 0.1), 0.9 mL min , 254 nm,
desorption ionization (MALDI TOF/TOF) mass spectrometry
was performed on a Bruker Daltonics Ultraflex instrument. Opꢀ
tical rotation was measured with an Atago APꢀ300 polarimeter.
i
–1
6
14
2

(R) = 5.0 min, (S) = 6.1 min).
In the presence of ZnꢀTPP.
In toluene.
c
Specific rotation values are quoted in deg mL g– dm , the
1
–1
d
–1
concentrations of the working solutions are given in g (100 mL)
.
Enantiomeric excesses of the products were measured with
a Staier HPLC system. Elemental analyses were carried out with
a Carlo Erba EA1108 CHNSꢀO analyzer.
of porphyrin compounds in the following order: TPP <
ZnꢀTPP < CuꢀTPP. These additives have no straightꢀ
forward and significant effect on chiral induction but the
effect of ZnꢀTPP is more pronounced (see Table 2).
The use of pyrrolidine as Nꢀnucleophile and P*ꢀchiral
<
All reactions were carried out under dry argon in anhydrous
4
5
solvents. (S )ꢀ2,2´ꢀBis(1ꢀethoxyethoxy)ꢀ1,1´ꢀbinaphthyl (1b)
(
,
a
42
43
R,S)ꢀsemiꢀTADDOL 3a, and (R,R)ꢀTADDOL 3b were synꢀ
thesized as reported. Porphyrin derivatives, TPP (C H N ),
4
4
30
4
ligands 2a,b derived from (S )ꢀ3ꢀSiMe ꢀBINOL leads to
a
3
ZnꢀTPP (C44H28N4Zn), and CuꢀTPP (C44H28CuN4), were
4
6—48
almost racemic product 7 (see Scheme 4, Table 3, 1—8).
In contrast, the reaction carried out in the presence of
P*ꢀmonodentate phosphoramidite 4a derived form
obtained following the published procedures.
Starting
(E)ꢀ1,3ꢀdiphenylallyl acetate (5) and complex [Pd(allyl)Cl]2
4
9
were synthesized as earlier described. Asymmetric allylation of
substrate 5 with dimethyl malonate and amination of 5 with
pyrrolidine, as well as the measurements of conversion of subꢀ
strate 5 and enantiomeric excesses of products 6 and 7 were
(
R,S)ꢀsemiꢀTADDOL proceeds with quantitative converꢀ
sion providing enantiomeric excess up to 61% (see Table 3).
Ligand 4b provides the opposite enantiomer of amine 7
although the enantioselectivity is lower (up to 37% ee).
The best results were achieved when the reactions were
carried out in CH Cl at molar ratio L : Pd = 1 (see Table 3,
5
0,51
performed as described.
n
(
S )ꢀBINOL 1a, Bu Li (1.6 M solution in hexane), Me SiCl,
a
3
P(NEt ) , Nꢀmethylpyrrolidone (NMP), dimethyl malonate,
2
3
2
2
bis(trimethylsilyl)acetamide (BSA), triethylamine, pyrrolidine,
and adamantanꢀ1ꢀamine were purchased from Fluka and
Aldrich.
entries 13—18). It should be noted that additives of
ZnꢀTPP to the catalytic system involving phosphoramidꢀ
ites 4a,b enhance conversion and, generally, enantioselecꢀ
tivity (see Table 3).
In summary, in the present work we described syntheꢀ
sis of novel P*ꢀ and Pꢀmonodentate phosphoramidites
(
Sa)ꢀ3ꢀTrimethylsilylꢀ1,1´ꢀbinaphthylꢀ2,2´ꢀdiol (1c). To
a vigorously stirred solution of compound 1b (1.68 g, 3.9 mmol)
n
in THF (10 mL), Bu Li (1.6 M solution in hexane, 3 mL,
4
.8 mmol) was added dropwise at 0 C over a period of 10 min.
The obtained mixture was stirred at 0 C for 40 min, then
2
a,b and 4a,b for the use as chiral inductors in asymmetric
precooled to 0 C chlorotrimethylsilane Me SiCl (0.55 mL,
3
catalysis. Phosphoramidites 2a,b and 4a,b in Pdꢀcatalyzed
asymmetric allylic substitution show high sensitivity to
both the nucleophile nature and the reaction conditions.
4
.29 mmol) was added dropwise over 5 min, and stirring was
continued for 15 min. Cooling was removed and the reaction
mixture was stirred at 20 C for 16 h, diluted with 6 M HCl

Asymmetric allylic substitution
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 7, July, 2015
1599
(
5 mL), stirred for 1 h, and diluted with CH Cl (15 mL).
powder, m.p. 110—111 C. Found (%): C, 71.09; H, 6.21;
2
2
The aqueous layer was separated and extracted with CH Cl2
N, 2.89. C H NO PSi. Calculated (%): C, 70.87; H, 6.17;
2
27 28
2
13
(
(
2×5 mL). The combined organic layers were washed with water
N, 3.06. C NMR (CDCl ), : 0.1 (s, CH Si); 0.2 (s, CH Si);
3
3
3
3
3
2×10 mL), saturated aqueous NaHCO (2×10 mL), dried with
25.7 (d, CH , J
= 4.2 Hz); 25.8 (d, CH , J
45.6 (d, CH N, J = 16.1 Hz); 45.7 (d, CH N, J = 18.0 Hz);
= 4.2 Hz);
3
2
C,P
2
C,P
2
2
MgSO , the drying agent was filtered off, and the filtrate was
4
2
C,P
2
C,P
concentrated in vacuo (40 Torr). Purification of the crude prodꢀ
120.7 (s, C ); 121.6 (s, CH ); 121.9 (s, CH ); 122.4 (s, C );
Ar Ar Ar Ar
uct by silica gel column chromatography (elution with CH Cl )
123.2 (s, C ); 124.3 (s, CHAr); 124.4 (s, CHAr); 125.7 (s, CH );
Ar Ar
2
2
followed by crystallization from hexane afforded the title product
125.8 (s, CHAr); 126.2 (s, CHAr); 126.7 (s, CHAr); 126.8
(s, CH ); 126.9 (s, CHAr); 128.1 (s, CHAr); 128.2 (s, CH );
128.3 (s, CH ); 128.9 (s, C ); 129.5 (s, CH ); 129.9 (s, CH );
Ar Ar Ar Ar
in the yield of 0.85 g (61%), white powder, m.p. 239—240 C,
Ar
Ar
2
9
[
]
–108.0 (c 1.0, THF). Found (%): C, 77.21; H, 6.23.
D
C H O Si. Calculated (%): C, 77.06; H, 6.19. HPLC (Kromaꢀ
130.0 (s, C ); 130.6 (s, C ); 130.7 (s, C ); 131.1 (s, C ); 132.7
Ar Ar Ar Ar
(s, C ); 132.9 (s, C ); 133.6 (s, CAr); 133.8 (s, CAr); 136.7
Ar Ar
2
3
22
2
i
–1
sil 5ꢀCelluCoat, C H —Pr OH (95 : 3), 0.3 mL min , 226 nm):
6
1
14
3

(S) = 19.2 min. C NMR (CDCl ), : –0.9 (s, CH ); 109.2
(s, CHAr); 149.6 (s, C O); 150.1 (s, C O); 153.7 (d, C O,
Ar Ar Ar
3
3
2
1
(
s, CAr); 111.1 (s, C ); 117.7 (s, CH ); 123.7 (s, CHAr); 123.9
JC,P = 7.0 Hz); 153.9 (s, C O). H NMR (CDCl ), : 0.44
Ar
Ar
Ar 3
(
s, CHAr); 124.0 (s, CH ); 124.3 (s, CH ); 127.4 (s, CHAr);
(br.s, 9 H, CH Si); 1.63—1.75 (m, 4 H, CH ); 2.79—2.88 (br.m,
3 2
Ar
Ar
1
1
27.6 (s, CHAr); 128.4 (s, CH ); 128.5 (s, CH ); 129.1 (s, CAr);
1 H, CH N); 2.89—2.98 (m, 1 H, CH N); 3.13—3.24 (m, 2 H,
2 2
CH N); 7.16—7.21 (m, 2 H, CH ); 7.22—7.27 (m, 2 H, CH );
2 Ar Ar
Ar
Ar
29.2 (s, C ); 129.5 (s, C ); 131.3 (s, CH ); 133.5 (s, C );
Ar
Ar
Ar
Ar
1
34.2 (s, C ); 137.9 (s, CH ); 152.8 (s, C O); 156.8 (s, CArO).
7.32—7.35 (m, 1 H, CHAr); 7.37—7.43 (m, 2 H, CHAr);
Ar
Ar
Ar
1
3
H NMR (CDCl ), : 0.46 (s, 9 H, Me); 5.12 (s, 1 H, OH); 5.23
7.89—7.94 (m, 2 H, CH ); 7.96 (d, 1 H, CH , J = 8.8 Hz);
3
Ar
Ar
3
(
s, 1 H, OH); 7.15 (d, 1 H, CH , J = 8.4 Hz); 7.20 (d, 1 H,
8.07 (br.s, 1 H, CH ). MS (MALDI TOF/TOF), m/z (I (%)):
Ar rel
Ar
3
+
+
CH , J = 8.4 Hz); 7.32—7.37 (m, 2 H, CH ); 7.38—7.43
496 [M + K] (100), 458 [M + H] (32).
Ar
Ar
(
m, 3 H, CHAr); 7.93 (t, 2 H, CHAr, 3J = 7.2 Hz); 8.0 (d, 1 H,
Synthesis of phosphoramidites 4a and 4b (general procedure).
To a vigorously stirred suspension of compound 3a or 3b (2 mmol)
in PCl3 (4 mL, 45.5 mmol), Nꢀmethylpyrrolidone (0.01 g,
0.1 mmol) was added and the mixture was refluxed for 5 min
until homogenous. The PCl3 excess was removed in vacuo
(40 Torr), the residue was dried in vacuo (30 min, 1 Torr) to
3
CH , J = 8.4 Hz); 8.14 (s, 1 H, CH ).
Ar
Ar
(
Sa)ꢀ4ꢀDiethylaminoꢀ2ꢀ(trimethylsilyl)dinaphtho[2,1ꢀd:1´,2´f]ꢀ
1,3,2]dioxaphosphepine (2a). A stirred solution of compound
c (0.72 g, 2 mmol) and P(NEt ) (0.55 mL, 2 mmol) in toluene
[
1
2
3
(
7 mL) was refluxed for 2 h, cooled to 20 C, and filtered through
a short alumina column. The filtrate was concentrated in vacuo
40 Torr). Purification of the crude product by silica gel flash
chromatography (elution with toluene) afforded the title comꢀ
pound in the yield of 0.79 (86%), white powder,
remove the PCl traces and then dissolved in toluene (12 mL).
3
(
The obtained vigorously stirred solution was treated with Et N
3
(0.56 mL, 4 mmol) and adamantanꢀ1ꢀamine (0.30 g, 2 mmol)
at 20 C. The reaction mixture was stirred at 20 C for 24 h
and filtered through a short alumina column. The solvent
was removed in vacuo (40 Torr), the products were purified by
silica gel column chromatography (elution with toluene—hexꢀ
ane (1 : 3)).
g
m.p. 180—181 C. Found (%): C, 70.81; H, 6.65; N, 3.17.
C H NO PSi. Calculated (%): C, 70.56; H, 6.58; N, 3.05.
2
7
30
2
1
3
C NMR (CDCl ), : 0.1 (s, CH Si); 15.1 (s, CH ); 40.2
3
3
3
2
(
d, CH , J = 27.6 Hz); 120.7 (s, C ); 121.9 (s, CH ); 123.9
2 C,P Ar Ar
(
(
1
1
1
s, CAr); 124.1 (s, CH ); 124.4 (s, CH ); 125.8 (s, CH ); 126.1
(3aR,8aS)ꢀ6ꢀ(1ꢀAdamantylamino)ꢀ2,2ꢀdimethylꢀ4,4ꢀdiphenꢀ
yltetrahydro[1,3]dioxolo[4,5ꢀe][1,3,2]dioxaphosphepine (4a).
Yield 0.73 g (74%), white powder, m.p. 87—88 C. Found (%):
C, 70.85; H, 7.28; N, 2.94. C H NO P. Calculated (%):
Ar
Ar
Ar
s, CHAr); 126.7 (s, CH ); 126.8 (s, CH ); 128.0 (s, CHAr);
Ar Ar
28.2 (s, CH ); 129.9 (s, C ); 130.0 (s, CH ); 131.2 (s, CAr);
Ar Ar Ar
32.3 (s, C ); 132.9 (s, C ); 133.6 (s, C ); 136.6 (s, CH );
Ar
Ar
Ar
Ar
29 36
4
2
1
13
49.5 (s, CArO); 153.7 (d, C O, JC,P = 7.7 Hz). H NMR
CDCl ), : 0.43 (s, 9 H, CH Si); 1.01 (t, 6 H, CH , J = 7.1 Hz);
C, 70.57; H, 7.35; N, 2.84. C NMR (CDCl ), , major epimer:
Ar
3
3
(
25.4 (s, Me); 27.4 (s, Me); 29.7 (s, C(3´), C(5´), C(7´)); 36.0
3
3
3
2
.91—2.97 (m, 4 H, CH ); 7.16—7.22 (m, 2 H, CH ); 7.24—7.29
2 Ar
(s, C(4´), C(6´), C(10´)); 46.2 (d, C(2´), C(8´), C(9´),
3
3
2
2
2
(
(
m, 1 H, CHAr); 7.33 (d, 1 H, CH , J = 8.0 Hz); 7.37—7.43
m, 2 H, CH ); 7.53 (d, 1 H, CH , J = 8.8 Hz); 7.91 (d, 2 H,
JC,P = 9.2 Hz); 50.9 (d, C(1´), J = 13.0 Hz); 65.7 (d, CH O,
C,P 2
Ar
3
3
JC,P = 10.4 Hz); 75.1 (d, CHO, J = 3.4 Hz); 81.5 (d, C(Ph ),
Ar
Ar
C,P 2
3
3
3
CH , J = 8.4 Hz); 7.96 (d, 1 H, CH , J = 8.8 Hz); 8.04 (s, 1 H,
CH ). MS (MALDI TOF/TOF), m/z (I (%)): 460 [M + H]
JC,P = 6.2 Hz); 85.9 (d, CHO, JC,P = 19.9 Hz); 110.7
Ar
Ar
+
(s, C(Me )); 126.7 (s, CHPh); 126.8 (s, CHPh); 127.1 (s, CHPh);
Ar
rel
2
+
(
100), 445 [M – Me + H] (79).
Sa)ꢀ4ꢀPyrrolidinoꢀ2ꢀ(trimethylsilyl)dinaphtho[2,1ꢀd:1´,2´f]ꢀ
1,3,2]dioxaphosphepine (2b). To a vigorously stirred suspension
127.3 (s, CHPh); 127.8 (s, CHPh); 128.6 (s, CHPh); 141.2
(s, CPh); 146.7 (s, CPh); minor epimer: 25.5 (s, Me); 27.2 (s, Me);
29.6 (s, C(3´), C(5´), C(7´)); 35.9 (s, C(4´), C(6´), C(10´)); 45.5
(
[
3
of compound 1c (0.72 g, 2 mmol) in PCl (4 mL, 45.5 mmol),
(d, C(2´), C(8´), C(9´), JC,P = 8.8 Hz); 50.1 (d, C(1´),
3
2
3
2
Nꢀmethylpyrrolidone (0.01 g, 0.1 mmol) was added and the mixꢀ
ture was refluxed for 5 min until homogeneous. Then the PCl3
excess was removed in vacuo (40 Torr), the residue was dried
JC,P = 14.3 Hz); 62.6 (d, CH O, J = 2.3 Hz); 75.6 (d, CHO,
2 C,P
2
JC,P = 7.3 Hz); 81.1 (d, C(Ph ), J = 5.5 Hz); 83.9 (d, CHO,
2
C,P
3J
= 5.3 Hz); 111.5 (s, C(Me )); 126.9 (s, CHPh); 127.0
2
C,P
in vacuo (30 min, 1 Torr) to remove the PCl traces, and disꢀ
solved in toluene (12 mL). To the obtained solution, pyrrolidine
(s, CHPh); 127.4 (s, CHPh); 127.5 (s, CHPh); 128.1 (s, CHPh); 128.5
3
3
(s, CHPh); 141.7 (d, CPh, JC,P = 3.3 Hz); 146.2 (s, CPh).
1
(
0.4 mL, 4.8 mmol) was added at 20 C under vigorous stirring.
H NMR (CDCl ), , major epimer: 0.63 (s, 3 H, Me); 1.44
3
The reaction mixture was refluxed for 15 min, cooled to 20 C,
and filtered through a short alumina column. The filtrate was
concentrated in vacuo (40 Torr). Purification of the crude prodꢀ
uct by silica gel flash chromatography (elution with toluene)
afforded the title product in the yield of 0.74 g (81%), white
(s, 3 H, Me); 1.57—1.67 (br.m, 6 H); 1.78 (br.s, 6 H); 2.02 (br.s, 3 H);
2
2.95 (br.d, 1 H, NH, J
= 4.4 Hz); 3.82—3.86 (m, 1 H);
H,P
3
4.09—4.13 (m, 1 H); 4.24—4.27 (m, 1 H); 4.94 (dd, 1 H, J
=
H,H
4
= 9.0 Hz, J = 3.6 Hz); 7.18—7.26 (m, 3 H, CHPh); 7.30—7.41
H,P
(m, 5 H, CHPh); 7.68 (d, 2 H, CHPh,
3J = 7.2 Hz); minor

1
600
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 7, July, 2015
Gavrilov et al.
epimer: 0.77 (s, 3 H, Me); 1.45 (s, 3 H, Me); 1.53 (br.s, 6 H);
This work was financially supported by the Russian
Science Foundation (Project No. 14ꢀ13ꢀ01383).
1
4
.57—1.67 (br.m, 6 H); 1.95 (br.s, 3 H); 4.14—4.19 (m, 2 H);
.28—4.33 (m, 1 H); 5.05 (d, 1 H, J = 9.0 Hz); 7.18—7.26
3
(
m, 3 H, CHPh); 7.30—7.41 (m, 3 H, CHPh); 7.43 (d, 2 H,
3
3
References
CHPh
, J = 7.2 Hz); 7.59 (d, 2 H, CHPh, J = 7.2 Hz).
+
MS (MALDI TOF/TOF), m/z (I (%)): 494 [M + H] (17),
1
rel
+
52 [C H N + H] (100).
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10
17
(
3aR,8aR)ꢀ6ꢀ(1ꢀAdamantylamino)ꢀ2,2ꢀdimethylꢀ4,4,8,8ꢀ
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ed (%): C, 76.26; H, 6.87; N, 2.17. 13C NMR (CDCl ), : 25.2
41
44
4
3
(
s, Me); 27.5 (s, Me); 29.8 (s, C(3´), C(5´), C(7´)); 36.1 (s, C(4´),
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C(6´), C(10´)); 46.2 (d, C(2´), C(8´), C(9´), J
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8
2
= 9.2 Hz);
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2
2
0.9 (d, C(1´), J = 11.8 Hz); 81.7 (d, C(Ph ), J = 4.2 Hz);
C,P 2 C,P
3
2.0 (s, CHO); 82.3 (d, CHO, J
= 5.0 Hz); 82.5 (d, C(Ph ),
C,P 2
JC,P = 3.5 Hz); 111.3 (s, C(Me )); 126.8 (s, CHPh); 126.9
2
(
(
1
(
(
(
s, CHPh); 127.1 (s, CHPh); 127.2 (s, CHPh); 127.3 (s, CHPh); 127.4
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Ph
1
s, CPh); 142.4 (s, CPh); 146.5 (s, CPh); 147.0 (s, CPh). H NMR
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3
br.m, 6 H); 1.81 (br.s, 6 H); 2.03 (br.s, 3 H); 2.94 (br.s, 1 H,
3
NH); 4.80 (d, 1 H, CHO, J = 8.8 Hz); 5.21 (dd, 1 H, CHO,
3
4
JH,H = 8.8 Hz, J
= 3.4 Hz); 7.18—7.22 (m, 2 H, CHPh);
H,P
7
(
7
.23—7.27 (m, 4 H, CHPh); 7.28—7.34 (m, 6 H, CHPh); 7.46
3
3
d, 2 H, CHPh, J = 7.8 Hz); 7.50 (d, 2 H, CH , J = 7.8 Hz);
Ph
.66 (d, 2 H, CHPh, 3J = 7.4 Hz); 7.79 (d, 2 H, CHPh, J = 7.8 Hz).
3
+
MS (MALDI TOF/TOF), m/z (I (%)): 684 [M + K] (10),
6
rel
+
+
46 [M + H] (15), 152 [C H N + H] (100).
10 17
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(
or 0.04 mmol) in the corresponding solvent (5 mL) was stirred
for 40 min and (E)ꢀ1,3ꢀdiphenylallyl acetate (0.1 mL, 0.5 mmol)
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Received February 24, 2015;
in revised form May 7, 2015