Allylation of prochiral C-nucleophiles catalyzed by the Pd(0)-(S)-(-)-BINAP complex

Article abstract of DOI:10.1007/s11172-008-0239-9

The allylation of prochiral C-nucleophiles catalyzed by the Pd(0)-(S)-(-)-BINAP complex (BINAP is 2,2′-bis(diphenylphosphino)-1, 1′-binaphthyl) was studied. The enantioselectivity of the allylation was found to be low.

Full text of DOI:10.1007/s11172-008-0239-9

Russian Chemical Bulletin, International Edition, Vol. 57, No. 8, pp. 1787—1789, August, 2008
1787
Allylation of prochiral Cꢀnucleophiles catalyzed
by the Pd(0)—(S)ꢀ(–)ꢀBINAP complex
A. V. Lozanova, T. M. Ugurchieva, and V. V. Veselovsky
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: ves@ioc.ac.ru
The allylation of prochiral Cꢀnucleophiles catalyzed by the Pd(0)—(S)ꢀ(–)ꢀBINAP comꢀ
plex (BINAP is 2,2´ꢀbis(diphenylphosphino)ꢀ1,1´ꢀbinaphthyl) was studied. The
enantioselectivity of the allylation was found to be low.
Key words: allylation, Cꢀnucleophiles, palladium complexes, phosphines.
Palladiumꢀcatalyzed allylation of Cꢀnucleophiles is
an efficient tool for the formation of a new C—C bond
(see Ref. 1). Enantioselective versions of this reaction
using chiral ligands of diverse structure found wide use for
the formation of the (πꢀallyl)palladium complexes.2
It should be mentioned that the prochiral allylating agents
and achiral Cꢀnucleophiles (most frequently, malonic
esters) were combined in the most part of cases, and
the high degree of asymmetric induction was achieved.2
However, only several examples for the asymmetric
allylation of prochiral CHꢀacids with achiral allylic comꢀ
ponents are known.2
The present study deals with the allylation of prochiral
dialkylamides of substituted acetic acids 1 and 2, whose
allylation products 3 and 4 are promising precursors of
natural butanolides.3
Sulfones 1 and sulfides 2 were allylated in the presꢀ
ence of the catalyst prepared in situ from 1.25 mol.%
Pd2(dba)3•CHCl3 and 5.5 mol.% (S)ꢀ(–)ꢀBINAP
((S)ꢀ(–)ꢀ2,2´ꢀbis(diphenylphosphino)ꢀ1,1´ꢀbinaphthyl) (5).
PPh2
PPh2
SO2Ph
NR2
SO2Ph
NR2
i
O
O
5
1a,b
3a,b
For the metallation of sulfides 2, BunLi (solution in hexane,
1 equiv.) turned out to be appropriate, because at –70 °С
it does not almost add at the amide carbonyl. In the case
of sulfones 1, the standard deprotonation under the
action of NaH was used (cf. Ref. 3b) as well as the proceꢀ
dure of carbanion generation under the oneꢀpot condiꢀ
tions using diallyl carbonate as an allylating agent
(cf. Ref. 4). Sulfones 3 obtained in these reactions were
analyzed by HPLC on a column packed with the Kromasil
100ꢀ5ꢀTBB chiral phase. Sulfides 4 were transformed
into the corresponding sulfonyl derivatives 3 by oxidation
with H2O2 in AcOH prior to analysis, since we failed to
find conditions for the analysis of their enantiomeric comꢀ
position.
iii
SPh
SPh
NR2
ii
O
NR2
O
2a,b
4a,b
iii
2b
1b
NR2 = N(CH2)4 (a); NPri (b)
2
Reagents and conditions: i. (1) NaH, СН2Cl2, (2) Pd2(dba)3ꢀ
(CHCl3), (S)ꢀ(–)ꢀBINAP (5.5 mol.%), АllOAc, 20 °С or
Pd2(dba)3(CHCl3), (S)ꢀ(–)ꢀBINAP (5.5 mol.%), (AllO)2CO,
20 °С; ii. (1) BunLi, 2) Pd2(dba)3(CHCl3), (S)ꢀ(–)ꢀBINAP
(5.5 mol.%), АllOAc, СН2Cl2, –60 → 20 °С; iii. Н2O2, AcOH.
As found, in all studied examples of the allylation
of sulfones 1, the enantiomeric excess (ee) in obtained
products 3 does not exceed 3%. This value is at a level of
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1753—1755, August, 2008.
1066ꢀ5285/08/5708ꢀ1787 © 2008 Springer Science+Business Media, Inc.

1788
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
Lozanova et al.
IR (KBr), ν/cm–1: 640, 692, 728, 764, 808, 884, 948, 1044,
1084, 1144, 1160, 1212, 1236, 1308, 1316, 1344, 1380, 1416,
1452, 1472, 1584, 1640, 2880, 2972, 3004, 3024, 3060. 1H NMR,
δ: 1.25 and 1.32 (both d, 6 H each, 4 CH3, J = 6.7 Hz); 3.46 and
4.20 (both sept, 1 H each, 2 CH(СH3)2, J = 6.7 Hz); 4.22 (s, 2 H,
CH2S); 7.60 and 7.90 (both m, 5 H, Harom).
the error of the analytical method used. At the same time,
the reactions of sulfides 2, which are not characterized by
a high degree of asymmetric induction, afford scalemic
products 4 with the reliably measured values ee ≈ 10% for
4a and ee ≈ 20% for 4b. This difference can be explained,
in particular, by the racemization of products 3 under the
reaction conditions, taking into account that sulfones 3
have higher CHꢀacidity than sulfides 4 and, therefore, are
more prone to epimerization.
The structures of earlier unknown compounds 1b, 3b,
and 4b were confirmed by elemental analysis and spectral
characteristics. It should be mentioned that the 1Н NMR
spectra of the synthesized compounds are more compliꢀ
cated, which is especially pronounced as magnetic nonꢀ
equivalence of all methyl groups in the spectra of diisoꢀ
propyl amides 3b and 4b due to the hindered rotation
about the axis of the C—N amide bond and, in addition,
due to the presence of the asymmetric center in molecules
3 and 4.
Nꢀ(2ꢀPhenylsulfonylpentꢀ4ꢀenoyl)pyrrolidine (3a) and
N,Nꢀdiisopropylꢀ2ꢀphenylsulfonylpentꢀ4ꢀeneamide
(3b).
А. Sodium hydride (1.1 mmol, 43.3 mg of 60% dispersion
in mineral oil) was added to a stirred solution of sulfone 1a
(253 mg, 1 mmol) in CH2Cl2 (7 mL) at 20 °С under argon.
After 1 h, the catalyst, prepared by mixing for 30 min at 30 °С
(argon) of Pd2(dba)3(CHCl3) (13.5 mg, 0.0125 mmol) and
(S)ꢀ(–)ꢀBINAP (34.2 mg, 0.055 mmol) in CH2Cl2 (1 mL),
and allyl acetate (150 mg, 1.5 mmol) were consecutively added
to the mixture. The reaction mixture was stirred for 1.5 h at
20 °С, quenched with water, and extracted with CH2Cl2. The
extract was washed with water and a saturated solution of NaCl,
dried (Na2SO4), and concentrated in vacuo. The residue was
chromatographed on SiO2, eluting with a 10% MeOBut—CH2Cl2
mixture. Sulfone 3a (272 mg, 96%) was obtained as colorless
crystals with m.p. 102—104 °C (petroleum ether—EtOAc),
1
whose H NMR spectrum nearly coincided with that published
Experimental
earlier.3b
Sulfone 3b (313 mg, 97%) was obtained similarly as colorless
crystals with m.p. 79—80 °C (petroleum ether) from sulfone 1b
(226 mg, 0.8 mmol), NaH (0.9 mmol, 35.2 mg of 60% dispersion
in mineral oil), allyl acetate (120 mg, 1.2 mmol), Pd2(dba)3(CHCl3)
(10.8 mg, 0.01 mmol), and (S)ꢀ(–)ꢀBINAP (27.4 mg, 0.044 mmol)
in CH2Cl2 (6 mL). The reaction mixture was chromatographed
on SiO2 eluting with a petroleum ether—MeOBut (1 : 1) mixture.
Found (%): C, 63.09; H, 7.86; N, 4.34; S, 9.47. C17H25NO3S.
Calculated (%): C, 63.13; H, 7.79; N, 4.33; S, 9.91. MS, m/z
(Irel (%)): 323 [M+] (1), 308 (3), 223 (6), 217 (16), 216 (20), 183
(8), 182 (64), 166 (3), 155 (7), 143 (21), 141 (43), 140 (36), 128
(24), 125 (42), 119 (20), 112 (10), 101 (20), 100 (52), 98 (56), 97
(53), 86 (32), 85 (100), 83 (37), 80 (72), 76 (51), 70 (54), 56
(24), 55 (47). IR (KBr), ν/cm–1: 640, 696, 720, 764, 836, 916,
924, 1000, 1044, 1088, 1152, 1208, 1288, 1312, 1340, 1372,
IR spectra were recorded on a Specord Mꢀ80 instrument.
1H NMR spectra of solutions in CDCl3 were measured on a
Bruker ACꢀ200 spectrometer relative to the signals of the solvent
(δ 7.27). Mass spectra (EI, 70 eV) were obtained on a Finnigan
MAT ITDꢀ700 instrument. Column chromatography was carried
out on silicа gel 60 (0.04—0.06 mm, Fluka). The HPLC analysis
was performed on a column 3×250 mm packed with Kromasil
100ꢀ5ꢀTBB, eluting with a 0.5% (vol.) solution of PriOH in
hexane (elution rate 1 mL min–1) and using UVꢀdetection at
254 nm. The retention times of the enantiomers were 23 and
25 min for 3a; 6.0 and 7.0 min for 3b. The optical rotation of
the solutions in CHCl3 was measured with a Jasco DIPꢀ360
polarimeter. The solvents, including petroleum ether with b.p.
40—70 °С, were subjected to purification and drying according
to standard procedures. The following commercial reagents from
Acros Organics were used: Pd2(dba)3(CHCl3), (S)ꢀ(–)ꢀBINAP,
NaH, allyl acetate, and diallyl carbonate.
Sulfone 1a (see Ref. 3b) and sulfides 2a (see Ref. 3b) and 2b
(see Ref. 5) were synthesized according to known procedures.
N,NꢀDiisopropylꢀ2ꢀphenylsulfonylacetamide (1b). Hydrogen
peroxide (30%, 2.8 mL, ∼25 mmol) was added for 5 min
to a stirred suspension of sulfide 2b (1.26 g, 5 mmol) in AcOH
(7 mL) at 20 °С. The reaction mixture was kept for 1 h at 30 °С
and for 20 min at 100 °С. Then the mixture was cooled to 20 °С and
diluted with water (15 mL), and the products were extracted
with CHCl3. The extract was washed with water, a saturated
solution of NaHCO3, and a saturated solution of NaCl, dried
(Na2SO4), and concentrated in vacuo. Sulfone 1b was obtained
as colorless crystals with m.p. 144—145 °C (MeOBut) in a yield
of 1.42 g (∼100%). Found (%): C, 59.44; H, 7.97; N, 4.97;
S, 10.98. C14H21NO3S. Calculated (%): C, 59.34; H, 7.47;
N, 4.94; S, 11.31. MS, m/z (Irel (%)): 283 [M+] (2), 268 (29),
242 (3), 227 (4), 226 (25), 219 (25), 204 (5), 183 (10), 176 (12),
143 (14), 142 (45), 141 (45), 135 (7), 128 (22), 126 (9), 119 (48),
118 (19), 114 (22), 101 (18), 100 (27), 99 (25), 87 (25), 85 (100),
83 (38), 77 (16), 76 (67), 72 (20), 70 (27), 60 (7), 56 (12).
1
1388, 1448, 1472, 1636, 2940, 2980, 3012, 3068. H NMR, δ:
1.16, 1.25, 1.31 and 1.41 (all d, 3 H each, 4 CH3, J = 6.9 Hz);
2.70 (m, 2 H, H2C(3)); 3.45 and 4.26 (both sept, 1 H each,
2 HC(СH3)2, J = 6.9 Hz); 4.35 (dd, 1 H, HCS, J = 5.0 Hz,
J = 11.0 Hz); 5.05 (ddd, 1 H, HС(5), J = 1.0 Hz, J = 2.1 Hz,
J = 10.0 Hz); 5.10 (ddd, 1 H, H´С(5), J = 1.2 Hz, J = 2.5 Hz,
J = 17.0 Hz); 5.60 (m, 1 H, HС(4)); 7.50—7.90 (m, 5 H, Harom).
B. To a stirred at 30 °С under argon suspension of
Pd2(dba)3(CHCl3) (13.5 mg, 0.0125 mmol) in CH2Cl2 (1 mL)
was added (S)ꢀ(–)ꢀBINAP (34.2 mg, 0.055 mmol). After
30 min, a solution of sulfone 1a (253 mg, 1 mmol) and diallyl
carbonate (170 mg, 1.2 mmol) in CH2Cl2 (4 mL) was added.
The resulting solution was kept for 15 h at 20 °С, diluted with
MeOBut (20 mL), and filtered through a short layer of SiO2.
The filtrate was concentrated in vacuo, and the residue was
chromatographed on SiO2, eluting with a 10% CH2Cl2—MeOBut
mixture. Sulfone 3a (264 mg, 90%) was almost identical
(m.p., 1H NMR) to the sample described above.
Sulfone 3b (181 mg, 80%) was obtained analogously
from sulfone 1b (198 mg, 0.7 mmol), diallyl carbonate (121 mg,
0.85 mmol), Pd2(dba)3(CHCl3) (9.5 mg, 0.009 mmol), and
(S)ꢀ(–)ꢀBINAP (23.9 mg, 0.038 mmol) in CH2Cl2 (4 mL). The

Allylation of prochiral Cꢀnucleophiles
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1789
reaction mixture was chromatographed on SiO2 eluting with a
(17.5 mg, 0.0125 mmol) and (S)ꢀ(–)ꢀBINAP (46.0 mg,
0.074 mmol) in CH2Cl2 (1.5 mL). The reaction product was chroꢀ
matographed on SiO2 using gradient elution with a petroleum
ether—MeOBut mixture (up to 10% MeOBut) to give sulfide 4b
(196 mg, 50%) as colorless crystals with m.p. 48—49 °С
petroleum ether—MeOBut (1 : 1) mixture. Sulfone 3b obtained
1
was almost identical (m.p., H NMR) to the sample described
above.
C. Hydrogen peroxide (30%, 0.45 mL, ∼4 mmol) was added
to a stirred at 40 °С solution of sulfide 4a (104 mg, 0.4 mmol,
[α]D16 + 0.6) in AcOH (2 mL). The reaction mixture was kept for
20 h at 40 °С, then cooled to 20 °С, diluted with water
(10 mL), and extracted with CHCl3. The extract was washed
with water, a saturated solution of NaHCO3, and a saturated
solution of NaCl, dried (Na2SO4), and concentrated in vacuo.
The residue was chromatographed on SiO2 using gradient elution with
a petroleum ether—MeOBut (from 1 : 1 to 1 : 5) mixture. Sulfone
3a was obtained in a yield of 64 mg (55%) with [α]D – 0.8
(с 2.0, CHCl3, ее ≈ 10% (HPLC data)) and was almost i1d6entical
(m.p., 1H NMR) to the sample described above.
(petroleum ether), [α]D + 11.9 (с 2.0, CHCl3). Found (%): C,
16
69.71; H, 9.05; N, 4.76; S, 10.58. C17H25NOS. Calculated (%):
C, 70.06; H, 8.64; N, 4.81; S, 11.00. MS, m/z (Irel (%)): 291
[M]+ (3), 258 (11), 204 (5), 183 (4), 182 (42), 174 (3), 163 (10),
135 (8), 129 (10), 128 (46), 123 (4), 110 (8), 109 (23), 100 (16),
95 (10), 85 (100), 83 (35), 80 (47), 77 (13), 70 (66), 65 (22), 55
(48). IR (KBr), ν/cm–1: 640, 692, 748, 820, 920, 968, 1000,
1028, 1048, 1092, 1140, 1204, 1280, 1308, 1340, 1364, 1396,
1
1440, 1472, 1560, 1628, 2928, 2964, 3004, 3068. H NMR, δ:
1.07, 1.15, 1.35, and 1.37 (all d, 3 H each, 4 CH3, J = 6.7 Hz);
2.45 and 2.75 (both m, 1 H each, H2C(3)); 3.42 and 4.02 (both
sept, 1 H each, 2 HC(СH3)2, J = 6.7 Hz); 3.83 (dd, 1 H, HCS,
J = 5.7 Hz, J = 8.9 Hz); 5.05 (ddd, 1 H, HС(5), J = 0.5 Hz,
J = 1.8 Hz, J = 10.0 Hz); 5.09 (ddd, 1 H, H´С(5), J = 1.3 Hz,
J = 3.1 Hz, J = 17.0 Hz); 5.80 (dddd, 1 H, HС(4), J = 6.5 Hz,
J = 7.2 Hz, J = 10.0 Hz, J = 17.0 Hz); 7.25—7.60 (m, 5 H,
Harom).
Sulfone 3b was obtained analogously from sulfide 4b (192 mg,
0.66 mmol, [α]D16 + 11.9) and 30% H O2 (∼7 mmol, 0.8 mL) in
AcOH (3 mL). The reaction product2was chromatographed on
SiO2 using gradient elution with a petroleum ether—MeOBut
mixture (from 10% to 50% MeOBut) to give sulfone 3b (117 mg,
55%) with [α]D – 1.5 (с 2.0, CHCl3, ее ≈ 20% (HPLC data))
16
and was almost identical (m.p., 1H NMR) to the sample
described above.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 06ꢀ03ꢀ32238).
(+)ꢀNꢀ(2ꢀPhenylthiopentꢀ4ꢀenoyl)pyrrolidine (4a) and
(+)ꢀN,Nꢀdiisopropylꢀ2ꢀphenylthiopentꢀ4ꢀenamide (4b). A 2.5 М
solution of BunLi (0.44 mL, 1.1 mmol) in hexane was added
dropwise under argon to a stirred solution of sulfide 2a (221 mg,
1 mmol) in CH2Cl2 (5 mL) for 5 min at –70 °С. After 1 h, a
mixture of allyl acetate (130 mg, 1.3 mmol) and the catalyst,
prepared as described above from Pd2(dba)3(CHCl3) (13.0 mg,
0.0125 mmol) and (S)ꢀ(–)ꢀBINAP (34.2 mg, 0.055 mmol) in
CH2Cl2 (1 mL), was added to the resulting suspension at –60 °С.
The reaction mixture was stirred for 15 min at –60 °С and for
2 h at 20 °С, quenched with a saturated solution of NH4Cl, and
extracted with CH2Cl2. The extract was washed with water and
a saturated solution of NaCl, dried (Na2SO4), and concentrated
in vacuo. The residue was chromatographed on SiO2, eluting
with a petroleum ether—MeOBut (1 : 1) mixture. Sulfide 4a was
obtained in a yield of 112 mg (43%) as yellowish crystals with
References
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1
[α]D + 0.6 (с 2.0, CHCl ), whose H NMR spectrum almost
16
3
coincided with that described previously.3b
Sulfide 4b was synthesized analogously from sulfide 2b (339 mg,
1.35 mmol), CH2Cl2 (7 mL), a 2.5 М solution of BunLi in
hexane (0.60 mL, 1.5 mmol), allyl acetate (180 mg, 1.8 mmol), and
the catalyst prepared as described above from Pd2(dba)3(CHCl3)
Received April 1, 2008;
in revised form April 21, 2008