Regioselective palladium-catalysed prenylation of CH acids in the presence of diamidophosphite ligands and potassium carbonate

Article abstract of DOI:10.1016/j.mencom.2009.03.018

The palladium-catalysed prenylation of CH acids with 3-methylbut-1-en-3-yl or prenyl acetates under phase-transfer conditions affords high yield of the linear regioisomer provided by the use of diamidophosphite ligands.

Full text of DOI:10.1016/j.mencom.2009.03.018

Mendeleev
Communications
Mendeleev Commun., 2009, 19, 103–105
Regioselective palladium-catalysed prenylation of CH acids in the
presence of diamidophosphite ligands and potassium carbonate
Andrei A. Vasil’ev,*a Sergey E. Lyubimov,b Edward P. Serebryakov,a
Vadim A. Davankovb and Sergei G. Zlotina
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: vasiliev@ioc.ac.ru
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation
DOI: 10.1016/j.mencom.2009.03.018
The palladium-catalysed prenylation of CH acids with 3-methylbut-1-en-3-yl or prenyl acetates under phase-transfer conditions
affords high yield of the linear regioisomer provided by the use of diamidophosphite ligands.
The palladium-catalysed reaction of stabilised anions of CH
acids with allylic carboxylates is a good alternative to the use of
poorly accessible complex allylic halides and is widely used in
the fine synthesis.1 However, a drawback of this approach is
that it requires the preliminary conversion of CH acids into
carbanions by the treatment with strong and expensive bases,
e.g., NaH or BSA, which is a serious restriction in the large-
scale preparations. In the mid-1980s, Russian scientists found
that the application of phase-transfer concept in Pd-catalysed
allylation of CH acids allows one to use inexpensive safe bases,
such as metal carbonates or hydroxides.2 However, neryl acetate
was found to be inactive under the proposed conditions.2(a) To
the best of our knowledge, there is no other information about
the application of this approach to the Pd-catalysed allylation
with the involvement of (poly)prenyl acetates, although in a few
more recent publications3 describing mostly the asymmetric
allylation of CH acids with 1-acetoxy-1,3-diphenylprop-2-ene
in water or ionic liquids, the use of metal carbonates was
documented. It should be noted that this approach implies the
generation of both reacting species, viz., a CH-acid carbanion and
a Pd π-allylic complex, in low quasi-stationary concentrations.
In the present study, we have extended the scope of Pd-
catalysed allylation of certain CH acids, mostly of diethyl
malonate 1, under phase-transfer conditions (K2CO3 as the
base) and succeeded in performing this reaction with prenyl-
type acetates 2 and 2' (both these reagents generally form the
same intermediate π-allylic Pd complex, cf. refs. 4) with the use
of modern ligands† (Scheme 1, Table 1).
The reaction with the use of tertiary 3-methylbut-1-en-3-yl
acetate 2 and triphenylphosphine as the ligand afforded mostly
branched product 3' (Table 1, entries 1 and 2). More electron-
donating tributylphosphine did not improve the regioselectivity
(entries 3 and 4, cf. ref. 8). Surprisingly, the use of electron-rich
sterically hindered phosphines (entries 5 and 6) led to a serious
decrease in the reaction rate due, apparently, to the shielding
of the Pd atom in the activated complex. The BINOL-derived
phosphite and the amidophosphite ligands5–7 (L1 and L2)
proved to be essentially inactive (entries 7 and 8). Meanwhile,
to our great satisfaction, the next phosphite-type monodentate
ligand, viz., diamidophosphite7 L3, having a stronger coordina-
tion ability, allowed us to achieve the 68–77% fraction of linear
product 3 and the conversion of 100% (entries 9 and 10). Other
related diamidophosphites L4–L6 provided high yields, as well
as good 3/3' ratios (entries 11–14), whereas the regioselectivity
in the reaction with the use of the more sterically hindered
ligand L7 was much lower (entry 15). Variations of the nature
of the solvents and the use of Bu4NBr as the phase-transfer
catalyst (PTC) showed that DMF was the solvent of choice
(entries 9 and 10). Note that diprenylation of malonate 1 was
not observed in spite of the fact that a substantial excess of
reagent 2 was used.‡
†
Phosphine ligands were commercially available. Ligands L1–L3 were
prepared according to the literature procedures [see refs. 5, 6 and 7(a),
respectively]. Diamidophosphite ligands L4–L7 were prepared analogously
to the relative ligand L3 [see refs. 7(a),(b)] from the cheap L-glutamic
acid. Obviously, the chirality of these ligands thus prepared is not important
in this study dealing with non-chiral compounds.
(2R,5S)-2-Cyclohexyloxy-3-phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]-
octane L4: colourless oil. 31P NMR (CDCl3) d: 112.71 (50%, Sp), 128.92
2
(50%, Rp). 13C NMR (CDCl3) d: 145.6 (d, JC,P 16.1 Hz), 128.7, 118.3,
114.6 (d, 3JC,P 11.9 Hz), 72.1, 62.6, (d, 2JC,P 8.4 Hz), 54.1 (d, 2JC,P 7.0 Hz),
2
3
48.1 (d, JC,P 37.8 Hz), 34.4 (d, JC,P 44.4 Hz), 31.6, 25.9, 25.3, 24.2
2
(d, JC,P 11.5 Hz). Found (%): C, 67.20; H, 8.37; N, 9.01. Calc. for
C17H25N2OP (%): C, 67.08; H, 8.28; N, 9.20.
(2R,5S)-2-Phenoxy-3-cyclohexyl-1,3-diaza-2-phosphabicyclo[3.3.0]-
octane L5: colourless oil. 31P NMR (CDCl3) d: 127.01 (13%, Sp), 139.17
2
(87%, Rp). 13C NMR (major form, CDCl3) d: 153.2 (d, JC,P 12.1 Hz),
2
2
129.1, 119.3, 114.1, 57.2 (d, JC,P 9.1 Hz), 56.8, 52.2 (d, JC,P 6.1 Hz),
47.9 (d, 2JC,P 34.5 Hz), 32.7, 30.5, 27.8, 24.7, 23.2. Found (%): C, 67.28;
H, 8.41; N, 9.03. Calc. for C17H25N2OP (%): C, 67.08; H, 8.28; N, 9.20.
(2R,5S)-2-Cyclohexyloxy-3-(2-methylphenyl)-1,3-diaza-2-phosphabicyclo-
[3.3.0]octane L6: colourless oil. 31P NMR (CDCl3) d: 123.12 (17%, Sp),
134.2 (83%, Rp). 13C NMR (major form, CDCl3) d: 143.1 (d, 2JC,P 7.4 Hz),
2
132.5, 130.6, 128.0, 126.0, 123.0, 72.75 (d, JC,P 16.7 Hz), 63.18 (d,
2
2
2JC,P 7.7 Hz), 54.7, 49.0 (d, JC,P 35.6 Hz), 34.5 (d, JC,P 4.0 Hz), 34.3
(d, 2JC,P 4.0 Hz), 31.4, 26.4 (d, 3JC,P 4.0 Hz), 25.2, 24.0 (d, 3JC,P 3.9 Hz),
19.6 (d, 3JC,P 13.9 Hz). Found (%): C, 68.05; H, 8.69; N, 8.71. Calc. for
C18H27N2OP (%): C, 67.90; H, 8.55; N, 8.80.
(2R,5S)-2-tert-Butoxy-3-(2-methylphenyl)-1,3-diaza-2-phosphabicyclo-
[3.3.0]octane L7: colourless oil. 31P NMR (CDCl3): 112.71 (40%, Sp),
128.92 (60%, Rp). 13C NMR (R-form, CDCl3) d: 143.2 (d, 2JC,P 5.5 Hz),
132.2, 130.4, 125.9, 122.6, 122.3, 73.5 (d, 2JC,P 10.6 Hz), 63.6 (2JC,P 10.2 Hz),
54.0 (2JC,P 4 Hz), 49.37 (2JC,P 36.6 Hz), 31.3, 30.5 (2JC,P 9.1 Hz), 26.5
(d, 2JC,P 4.4 Hz), 19.5 (d, 3JC,P 15.0 Hz). 13C NMR (S-form, CDCl3): 143.7
(d, 2JC,P 9.1 Hz), 131.6, 130.5, 125.7, 122.2, 121.2, 72.7 (d, 2JC,P 7.0 Hz),
62.8 (2JC,P 7.3 Hz), 53.5 (2JC,P 5 Hz), 44.0 (2JC,P 2.2 Hz), 30.7, 30.7
3
(2JC,P 9.2 Hz), 28.2, 19.4 (d, JC,P 17.6 Hz). Found (%): C, 65.89; H,
8.79; N, 9.43. Calc. for C16H25N2OP (%): C, 65.73; H, 8.62; N, 9.58.
‡
Application of the conditions from Table 1 (except for PCy3 and S-PHOS
ligands) on the reaction between diethyl malonate and unsubstituted allyl
acetate (2.4 equiv.) afforded 100% of diallylation product.
– 103 –
© 2009 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2009, 19, 103–105
Table 1 Reaction of diethyl malonate 1 with 3-methylbut-1-en-3-yl (2) or
prenyl (2') acetates in the presence of various ligands.a
O
O
PCy2
OMe
Product, GC data
P
OCH(CF3)2
Allylic
MeO
Entry
Solvent PTC
Ligand
PPh3
acetate
Total
yield (%)
3:3'
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
DMF
none
100
53
16:84
6:94
S-PHOS
L1
CH2Cl2 Bu4NBr PPh3
DMF none PBu3
CH2Cl2 Bu4NBr PBu3
76
81
—
44:56
17:83
—
DMF
DMF
DMF
DMF
DMF
none
none
none
none
none
PCy3
S-PHOS
L1
L2
L3
L3
L4
L5
O
O
44
—
48:52
—
P
N
O
N
Ph
N Ph
N
N
P
—
—
P
100b
100
100
98
98
97
77:23
68:32
77:23
77:23
69:31
67:33
26:74
—
OPh
OCy
L4
DMSOc none
DMF
DMF
none
none
L2
L3
CH2Cl2 Bu4NBr L5
Me
Me
DMF
DMF
DMF
DMF
none
none
none
none
L6
L7
PPh3
PBu3
PBu3
L3
84
—
N
N
P
OBut
N
Cy
2'
2'
2'
2'
2'
N
N
N
P
P
57
98
18
94
40:60
43:57
77:23
71:29
DMSO none
OCy
OPh
DMF
DMF
none
none
L6
L7
L4
L5
aReaction conditions: 1.2 equiv. allylic acetate, 1.5 equiv. K2CO3, solvent
2 cm3 mmol–1, 2 mol% Pd(dba)2, 8 mol% phosphine or 4 mol% diamido-
phosphite, 10 mol% PTC, 20 °C, 18 h. bIsolated yield was 79%. cThe yields
in DMA and NMP were ~90%; in DMPU, 64% (3:3' ~ 70:30); by contrast,
the reaction in HMPA did not proceed.
CO2Et
CO2Et
OAc
CH2(CO2Et)2
3
+
1
2
Pd(dba)2, ligand
K2CO3, solvent, PTC
room temperature, 18 h
C
N
C
N
CO2Et
CO2Et
2
OAc
CO2Et
Pd(dba)2, phosphine
K2CO3, DMF
CO2Et
2'
3'
6
7
Scheme 1
37% (with PPh3
100% (with PBu3)
)
The use of linear prenyl acetate 2' gave lower yields (Table 1,
entries 16–20). This fact may be attributed to the fact that the
reaction of palladium species with the trisubstituted double bond
of this olefinic acetate is slower.
Scheme 3
In conclusion, we showed that the palladium-catalysed prenyla-
tion of CH acids can be efficiently performed in simple systems
containing potassium carbonate and diamidophosphite ligands.§
The ratios between linear and branched products were similar
to those reported earlier for technically difficult procedures
involving strong bases.4,9 The approach under study may promote
the development of advanced preparations of useful acyclic
terpenoids.1(a),10
The results obtained with C-substituted diethyl methylmalonate
4 are presented in Scheme 2. The reaction of the latter with
3-methylbut-1-en-3-yl acetate 2 afforded product 5 in high yield
only with the use of diamidophosphite ligand L4 (entry 4), the
branched isomer being never formed. Sterically hindered diethyl
cyclohexylmalonate did not undergo prenylation under the
conditions used. It should be noted that the reaction of the latter
compound even with active unsubstituted allyl acetate was
always incomplete.
§
Diethyl (3-methylbut-2-en-1-yl)malonate 3b (typical procedure). A Schlenk
CO2Et
tube equipped with a stirring magnet and charged with diethyl malonate 1
(80 mg, 0.5 mmol) and DMF (1 ml) was three times deaerated by evacua-
tion and filling with argon. Diamidophosphite L3 (12 mg, 0.04 mmol)
and Pd(dba)2 (6 mg, 0.01 mmol) were added and the mixture was stirred
for ca. 5 min until change in the colour occurred. 3-Methylbut-1-en-3-yl
acetate 2 (96 mg, ca. 108 μl, 1.5 mmol) was added, and the mixture was
stirred for 10 min, followed by finely powdered potassium carbonate
(138 mg, 1 mmol). Each opening of the Schenk tube was followed by
evacuation and filling with argon. The mixture was stirred at ambient
temperature for 18 h. A probe was treated with water, extracted with
hexane and analysed by gas chromatography, which showed the absence
of the starting malonate 1 and the presence of two products 3 and 3'
(77:23). To isolate the products, the reaction mixture was treated with
water, extracted with diethyl ether, the extracts were dried (Na2SO4)
and concentrated. The residue was subjected to column chromatography
(gradient 0®5% EtOAc in light petroleum) to afford 180 mg (79%) of
the mixture 3 and 3' (77:23 according to 1H NMR data). Chemical
CO2Et
2 or 2'
CO2Et
Pd(dba)2, ligand
K2CO3, solvent
Me
CO2Et
Me
4
5
Entry
Allylic acetate
Ligand
Solvent
Yield (%)
1
2
3
4
5
2
2
2
2
PPh3
PBu3
PBu3
L4
DMF
DMF
DMSO
DMF
DMF
0
0
36
94
0
2'
L4
Scheme 2
An important role of the nature of CH acids was confirmed
by the fact that the reaction of ethyl cyanoacetate 6 having a
higher CH acidity and a lower nucleophilicity of the corre-
sponding carbanion with acetate 2 gave only branched product 7
(Scheme 3).
1
shifts in the H and 13C NMR spectra were in good agreement with the
literature.4(b),9(a)
– 104 –

Mendeleev Commun., 2009, 19, 103–105
5
6
7
K. N. Gavrilov, S. E. Lyubimov, S. V. Zheglov, E. B. Benetsky and
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Received: 19th November 2008; Com. 08/3239
– 105 –