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Organic & Biomolecular Chemistry
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J = 3.3 Hz, 1H), 4.55 (ddd, J = 9.0, 9.0, 9.0 Hz, 1H), 4.21 (dd, J = 31P NMR (121 MHz, CDCl3), δ(ppm) = 33.6; 13C NMR (75 MHz,
9.2, 3.4 Hz, 1H), 3.77 – 3.61 (m, 3H), 3.55 (s, 3H), 3.35 – 3.30 CDCl3), δ(ppm) = 159.8 (d, J = 4.4 Hz, C)D, O1I3: 140.7.10(3d9,/CJ5=OB50.2132H3zB,
(m, 4H), 2.26 (s, 3H); 31P NMR (121 MHz, CDCl3), δ(ppm) = 35.9; CH), 134.0 (d, J = 99.6 Hz, C), 133.7 (d, J = 2.1 Hz, CH), 131.2 (d,
13C NMR (75 MHz, CDCl3), δ(ppm) = 161.3 (d, J = 4.9 Hz, C), J = 2.8 Hz, CH), 130.7 (d, J = 9.5 Hz, 2 x CH), 128.2 (d, J = 11.8
142.8 (C), 137.1 (C), 137.0 (C), 134.5 (d, J = 1.7 Hz, CH), 133.7 Hz, 2 x CH), 121.2 (d, J = 10.6 Hz, CH), 120.3 (d, J = 99.9 Hz, C),
(d, J = 5.7 Hz, CH), 133.0 (d, J = 11.2 Hz, 2 x CH), 132.1 (d, J = 110.7 (d, J = 6.6 Hz, CH), 55.2 (CH3), 22.2 (d, J = 74.2 Hz, CH2),
2.9 Hz, CH), 130.2 (d, J = 136.7 Hz, C), 129.4 (2 x CH), 129.4 5.6 (d, J = 5.4 Hz, CH3). Chiral HPLC (Chiralpack Heptane/IPA
(CH), 128.3 (2 x CH), 127.7 (d, J = 13.5 Hz, 2 x CH), 127.6 (2 x 85/15
1 mL/min): (R)-enantiomer, Rt = 12.2 min, (S)-
CH), 126.7 (2 x CH), 120.5 (d, J = 12.5 Hz, CH), 119.0 (d, J = enantiomer, Rt = 18.7 min. The NMR data are in agreement
143.4 Hz, C), 111.6 (d, J = 8.3 Hz, CH), 102.3 (CH), 100.6 (CH), with the literature.31
80.7 (d, J = 5.2 Hz, CH), 71.4 (d, J = 5.8 Hz, CH), 69.1 (CH2), 62.6
Characterization
of
enriched
(S)-
(CH), 57.7 (CH), 56.1 (CH3), 55.8 (CH3), 21.7 (s, CH3). HRMS ethylmethylphenylphosphine oxide SP-10. Colorless oil in 99%
[M+H]+ C34H37NO9PS calcd 666.1921 found 666.1927. [α]25
+16.9 (c = 1.05, CHCl3).
=
yield with 94% e.e. from RP-6 [P(V)-strategy]. Rf = 0.15
(AcOEt/MeOH 95/5). 1H NMR (300 MHz, CDCl3), δ(ppm) = 7.70
(ddd, J = 11.2, 7.6, 1.6 Hz, 2H), 7.57 – 7.40 (m, 3H), 2.07 – 1.77
D
General procedure for the cleavage of P-O bond from P(V)- or (m, 2H), 1.68 (d, J = 12.7 Hz, 3H), 1.11 (dt, J = 17.4, 7.7 Hz, 3H);
P(III)-strategy. In a dried and inert schlenk, the appropriate 31P NMR (121 MHz, CDCl3), δ(ppm) = 39.0; 13C NMR (75 MHz,
phosphinate (0.14 mmol) was placed. The commercially CDCl3), δ(ppm) = 133.5 (d, J = 95.4 Hz, C), 131.6 (d, J = 2.7 Hz,
available organomagnesium (6.0 eq) was then added CH), 130.1 (d, J = 9.1 Hz, 2 x CH), 128.6 (d, J = 11.4 Hz, 2 x CH),
dropwise. The resulting mixture was stirred for 15 minutes and 24.7 (d, J = 71.3 Hz, CH2), 15.4 (d, J = 69.5 Hz, CH3), 5.7 (d, J =
the temperature was then increased to 40°C. The reaction was 5.0 Hz, CH3). Chiral HPLC (Cellulose OD-H Heptane/IPA 95/5 1
carried out overnight. After completion of the reaction, the mL/min): (R)-enantiomer, Rt = 12.6 min, (S)-enantiomer, Rt =
reaction mixture was diluted with dichloromethane (5 mL), 13.9 min. The NMR and HPLC data are in agreement with the
quenched with saturated ammonium chloride (5 mL). After literature.12
extraction, the organic phase was dried over Na2SO4, and
Characterization
of
enriched
(S)-i-
concentrated. Purification was performed by column propylmethylphenylphosphine oxide SP-11. Colorless oil in
chromatography on silica gel using first dichloromethane / 34% yield with 90% e.e. from RP-6 [P(V)-strategy]. Rf = 0.17
EtOAc (9/1) and then EtOAc / MeOH (95/5) as eluent. D- (AcOEt/MeOH 95/5). 1H NMR (300 MHz, CDCl3), δ(ppm) = 7.75
Glucosamine derivative
enantiomeric purity, and could be used again for the synthesis (d, J = 12.4 Hz, 3H), 1.19 (dd, J = 16.3, 7.1 Hz, 3H), 1.06 (dd, J =
of the phosphinate derivatives with the same 16.4, 7.2 Hz, 3H); 31P NMR (121 MHz, CDCl3), δ(ppm) = 43.3; 13
diastereoselectivity (based on 31P NMR).
NMR (75 MHz, CDCl3), δ(ppm) = 132.6 (d, J = 92.8 Hz, C), 131.5
Characterization of enriched (S)-o- (d, J = 2.7 Hz, CH), 130.5 (d, J = 8.6 Hz, 2 x CH), 128.5 (d, J =
1 was recovered without loss of the – 7.63 (m, 2H), 7.57 – 7.42 (m, 3H), 2.10 – 1.90 (m, 1H), 1.69
C
(R)-
and
anisylmethylphenylphosphine oxide RP- and SP-8. Colorless oil 11.1 Hz, 2 x CH), 29.6 (d, J = 71.5 Hz, CH), 15.5 (d, J = 2.5 Hz,
in 75% yield with 90% e.e. from SP-5 [P(V)-strategy], in 84% CH3), 15.3 (d, J = 2.5 Hz, CH3), 12.9 (d, J = 67.7 Hz, CH3). Chiral
yield with 98% e.e. from RP-6 [P(V)-strategy], and in 75% yield HPLC (Cellulose OD-H Heptane/IPA 95/5 1 mL/min): (R)-
with 96% e.e. from RP-5 [P(III)-strategy]. Rf = 0.15 (AcOEt). 1H enantiomer, Rt = 23.6 min, (S)-enantiomer, Rt = 28.3 min. The
NMR (300 MHz, CDCl3), δ(ppm) = 7.96 (ddd, J = 13.1, 7.5, 1.5 NMR and HPLC data are in agreement with the literature.32
Hz, 1H), 7.73 (ddd, J = 12.4, 7.9, 1.3 Hz, 2H), 7.54 – 7.34 (m,
4H), 7.09 (dddd, J = 7.5, 7.5, 1.8, 0.9 Hz, 1H), 6.88 (dd, J = 8.2,
5.4 Hz, 1H), 3.72 (s, 3H), 2.07 (d, J = 14.0 Hz, 3H); 31P NMR (121
MHz, CDCl3), δ(ppm) = 28.6; 13C NMR (75 MHz, CDCl3), δ(ppm)
= 160.0 (d, J = 4.2 Hz, C), 135.1 (d, J = 103.9 Hz, C), 134.1 (d, J =
4.2 Hz, CH), 134.0 (d, J = 5.9 Hz, CH), 131.4 (d, J = 2.7 Hz, CH),
130.4 (d, J = 10.1 Hz, 2 x CH), 128.3 (d, J = 12.1 Hz, 2 x CH),
121.6 (d, J = 100.0 Hz, C), 121.2 (d, J = 11.1 Hz, CH), 111.0 (d, J
= 6.6 Hz, CH), 55.4 (CH3), 16.3 (d, J = 75.3 Hz, CH3). Chiral HPLC
(Chiralpack AD Heptane/IPA 85/15 1 mL/min): (R)-enantiomer,
Rt = 13.2 min, (S)-enantiomer, Rt = 17.7 min. The NMR and
HPLC data are in agreement with the literature.12,14
Acknowledgements
L.C. deeply acknowledges the French Ministry of Higher
Education (MESR) for financial support.
References
1
Phosphorus (III) Ligands in Homogeneous Catalysis: Design
and Synthesis, P.C. J. Kamer, P. W. N. M. van Leeuwen (Eds),
2012, Wiley.
2
3
4
P-Stereogenic Ligands in Enantioselective Catalysis, A.
Grabulosa (Ed.), 2011, RSC Catalysis Series No.7.
B. D. Vineyard, W. S. Knowles, M. J. Sabacky, G. L. Bachman
and D. J. Weinkauff, J. Am. Chem. Soc. 1977, 99, 5946.
Resolution of racemic and diasteromeric mixtures in P-
Stereogenic Ligands in Enantioselective Catalysis, A.
Grabulosa (Ed.), 2011, RSC Catalysis Series No.7, pp. 21-113.
A. R. Muci, K. R. Campos and D. A. Evans, J. Am. Chem. Soc.
1995, 117, 9075.
Characterization
of
enriched
(S)-o-
anisylethylphenylphosphine oxide SP-9. Colorless oil in 85%
yield with 92% e.e. from SP-5 [P(V)-strategy]. Rf = 0.14 (AcOEt).
1H NMR (300 MHz, CDCl3), δ(ppm) = 8.00 (ddd, J = 12.7, 7.5,
1.8 Hz, 1H), 7.77 (ddd, J = 11.7, 7.9, 1.6 Hz, 2H), 7.47 – 7.30 (m,
4H), 7.04 (dd, J = 7.2, 7.2 Hz, 1H), 6.82 (dd, J = 8.2, 5.1 Hz, 1H),
3.69 (s, 3H), 2.43 – 2.24 (m, 2H), 1.16 (dt, J = 18.2, 7.7 Hz, 3H);
5
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