Stereoselective Synthesis of Exocyclic Phosphine Oxides
(101 MHz, CDCl3) δ: 204.2, 203.9, 141.5, 141.2, 135.5,
135.4, 134.1, 133.6, 133.1, 132.6, 131.6, 131.5, 131.4,
131.3, 130.9, 130.8, 130.7, 130.6, 130.5, 130.4, 128.6,
128.5, 128.5, 128.4, 123.3, 123.2, 59.2, 41.0, 40.1, 40.0,
39.2, 39.1, 38.2, 38.1, 28.8 (d, J=72.0 Hz), 14.7; 31P
NMR (162 MHz, CDCl3) δ: 31.80, 30.72. HRMS (ESI):
m/z calculated for C27H25O3P [M+H]+: 429.1614, found
429.1616.
MHz, CDCl3) δ: 31.47, 30.68. HRMS (ESI): m/z calcu-
lated for C28H29O3P [M+H]+: 445.1927, found 445.1930.
((4-Methyl-1-tosylpyrrolidin-3-yl)methyl)diphenyl-
1
phosphine oxide (3ka) (79%) White solid; H NMR
(400 MHz, CDCl3) δ: 7.75-7.66 (m, 4H), 7.62 (t, J=
9.0 Hz, 2H), 7.58-7.41 (m, 6H), 7.30-7.24 (m, 2H),
3.36 (m, 2H), 3.11-2.60 (m, 2H), 2.49-2.36 (m, 3H),
2.30-2.12 (m, 2H), 2.11-1.91 (m, 2H), 0.82 (dd, J=
49.8, 6.5 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ:
143.3, 133.7, 133.1, 132.2, 132.0, 131.9, 130.6, 130.5,
129.6, 128.8, 128.7, 128.6, 128.5, 127.4, 127.4, 54.1,
53.7, 53.5, 51.4, 51.3, 40.2, 39.7, 36.2, 36.1, 35.8, 35.7,
32.6, 28.4, 27.7, 21.5, 15.7, 13.2; 31P NMR (162 MHz,
CDCl3) δ: 30.45, 29.90. MS (ESI) m/z calculated for
C25H28NO3PS [M+H]+: 454.1600, found 454.1.
Diethyl 3-((diethoxyphosphoryl)methyl)-4-meth-
yl-cyclopentane-1,1-dicarboxylate (3ab) Colorless
oil; 1H NMR (400 MHz, CDCl3) δ: 4.17 (dd, J=14.2,
7.1 Hz, 4H), 4.14-4.01 (m, 4H), 2.59-2.32 (m, 2H),
2.25 (m, 1H), 2.13 (dd, J=13.6, 9.8 Hz, 1H), 2.05-
1.94 (m, 1H), 1.88 (d, J=16.6 Hz, 1H), 1.84-1.54 (m,
2H), 1.38-1.28 (m, 6H), 1.24 (t, J=7.1 Hz, 6H),
0.93-0.75 (m, 3H); 13C NMR (101 MHz, CDCl3) δ:
172.7, 61.5, 61.4, 58.7, 41.0, 38.8, 38.7, 37.0, 36.9, 36.6,
36.5, 26.7, 25.3, 16.5, 16.4, 14.8, 14.0; 31P NMR (162
MHz, CDCl3) δ: 31.62, 30.89. MS (ESI) m/z calculated
for C17H31O7P [M+H]+: 379.1880, found 379.1.
2-((Diphenylphosphoryl)methyl)-3-methylspiro-
1
[4.5]decane-6,10-dione (3ga) (80%) White solid; H
NMR (400 MHz, CDCl3) δ: 7.82-7.64 (m, 4H), 7.60-
7.34 (m, 6H), 2.75-2.43 (m, 4H), 2.41-2.29 (m, 1H),
2.28-2.02 (m, 6H), 2.00-1.87 (m, 2H), 1.87-1.70
(m, 1H), 0.90 (d, J=6.5 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ: 208.4, 207.6, 134.1, 133.4, 133.1, 132.4,
131.7, 131.6, 131.5, 130.8, 130.7, 130.6, 130.5, 128.7,
128.6, 128.6, 128.5, 71.8, 38.9, 38.9, 38.2, 38.1, 37.9,
37.5, 37.4, 37.3, 36.1, 28.8 (d, J=72.1 Hz), 17.5, 15.0;
31P NMR (162 MHz, CDCl3) δ: 31.94, 31.16. HRMS
(ESI): m/z calculated for C24H27O3P [M+H]+: 395.1771,
found 395.1770.
Dibenzyl-3-((diphenylphosphoryl)methyl)-4-meth-
yl-cyclopentane-1,1-dicarboxylate (3ha)
(66%)
White solid; 1H NMR (400 MHz, CDCl3) δ: 7.84-7.64
(m, 4H), 7.46 (m, 6H), 7.34-7.24 (m, 6H), 7.23-7.09
(m, 4H), 5.18-4.90 (m, 4H), 2.39 (m, 3H), 2.33-2.27
(m, 1H), 2.19 (m, 3H), 2.01 (dd, J=13.8, 5.0 Hz, 1H),
0.84 (d, J=7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ:
172.2, 172.0, 135.4, 133.8, 132.8, 131.5, 130.7, 130.6,
130.5, 130.4, 128.6, 128.4, 128.3, 128.0, 127.8, 127.7,
67.0, 67.0, 58.8, 41.0, 39.1, 39.0, 37.0, 36.9, 36.6, 36.5,
30.2, 29.5, 14.9; 31P NMR (162 MHz, CDCl3) δ: 30.97.
HRMS (ESI): m/z calculated for C35H35O5P [M+H]+:
567.2295, found 567.2299.
Results and Discussion
At the onset of our studies, we chose diethyl
2,2-diallylmalonate (1a) and diphenylphosphine oxide
(2a) as our model substrates. Firstly, the reaction was
investigated in the presence of Ag2CO3 (10 mol%) and
Mg(NO3)2•6H2O (1.0 equiv.) in CHCl3 at 60 ℃ for 6 h.
To our delight, the desired product 3aa was isolated in
40% yield with good stereoselectivity (trans/cis=11∶1)
(Table 1, Entry 1). Motivated by this result, other nitrate
additives such as Zr(NO3)4•5H2O, Y(NO3)3•6H2O,
Bi(NO3)2•5H2O, La(NO3)3•6H2O, AgNO3, and
Cu(NO3)2•3H2O were also examinated and performed
with moderate to good stereoselectivity in this reaction
except Cu(NO3)2•3H2O (Table 1, Entries 2-7). Then,
the screening of different solvents (MeCN, DMF, tolu-
ene, DCE, dioxane, DME) and silver salts (AgOAc,
Ag2O, AgClO4, AgCl, AgTFA) illustrated that DCE and
Ag2CO3 were optimal with an improved yield of 65%
with excellent stereoselectivity (trans/cis=10∶1) (Ta-
ble 1, Entries 8-18). Moreover, as the changing of the
1a∶2a=1∶2, the yield of the target product 3aa in-
creased to 79% (Table 1, Entry 19). Also, when the
temperature was dropped to 40 ℃, the yield increased
to 85% and was improved further to 90% with reducing
the loading of Mg(NO3)2•6H2O to 0.5 equiv. (Table 1,
Entries 20-21). The yield of 3aa decreased to 77%
when the reaction was carried out under air (Table 1,
Entry 22). Finally, with 10 mmol% Ag2CO3, 0.5 equiv.
Mg(NO3)2•6H2O, we got the product in the best yield of
3'-((Diphenylphosphoryl)methyl)-4'-methyl-2H-
spiro[benzofuran-3,1'-cyclopentan]-2-one
(3ia)
1
(45%) White solid; H NMR (400 MHz, CDCl3) δ:
7.91-7.70 (m, 4H), 7.63-7.38 (m, 6H), 7.26-7.15
(m, 1H), 7.05 (m, 3H), 3.07-2.75 (m, 1H), 2.67-2.31
(m, 3H), 2.21-2.00 (m, 3H), 1.94 (dd, J=13.4, 6.6 Hz,
1H), 1.10 (d, J=7.0 Hz, 1H); 13C NMR (101 MHz,
CDCl3) δ: 181.9, 152.1, 135.2, 134.0, 133.6, 133.0,
132.6, 131.8, 130.9, 130.8, 130.7, 130.6, 128.7, 128.6,
128.2, 124.6, 122.5, 110.3, 51.1, 46.7, 44.6, 44.5, 38.8,
38.7, 38.1, 38.0, 29.8, 29.1, 15.0; 31P NMR (162 MHz,
CDCl3) δ: 31.17, 30.27. HRMS (ESI): m/z calculated for
C26H25O3P [M+H]+: 417.1614, found 417.1617.
1-(1-Benzoyl-3-((diphenylphosphoryl)methyl)-4-
methylcyclopentyl)ethanone (3ja)
(56%): White
1
solid; H NMR (400 MHz, CDCl3) δ: 7.83-7.69 (m,
6H), 7.59-7.41 (m, 7H), 7.37 (m, 2H), 2.50 (ddd, J=
28.0, 13.3, 6.6 Hz, 2H), 2.29 (m, 3H), 2.20-2.12 (m,
2H), 2.09 (dd, J=13.3, 5.7 Hz, 1H), 1.92 (s, 3H), 0.89
(d, J=6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ:
205.9, 196.6, 134.8, 134.0, 133.7, 133.1, 133.0, 132.7,
131.7, 131.6, 131.5, 130.9, 130.8, 130.7, 130.6, 129.3,
128.7, 128.6, 128.5, 128.4, 71.4, 39.0, 37.7, 37.6, 37.5,
37.4, 36.9, 36.9, 29.9, 29.2, 27.4, 15.0; 31P NMR (162
Chin. J. Chem. 2017, XX, 1—7
© 2017 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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