V. V. Nesterov, O. I. Kolodiazhnyi / Tetrahedron: Asymmetry 17 (2006) 1023–1026
1025
O
NaBH4/( R,R)-TA
ClCH2C(O)Cl
BuLi
(MntO)2P(O)
Cl
(MntO)2P(O)CH2Cu
(MntO)2P(O)Me
Cu2I2
2a, 70%
7
OH
OH
+
OH
H
1) crystallization
Cl
Me3N/H2O
-
H2O3P
Cl
HO(O )(O)P
NMe3
(MntO)2P(O)
2) H3O+
H
H
(
S )-3a, 96% de
(S
)
-
4,~ 100% ee
(R )-8
Scheme 3. Synthesis of phospho-carnitine (R)-8.
10. General methodology of reduction of ketophosphonates with
chiral reagent 1. Tartaric acid (7.16 mmol) was added to a
suspension of NaBH4 (7.16 mmol) in 25 ml of THF and the
reaction mixture refluxed with stirring for 4 h. The mixture
was cooled to ꢀ30 °C, at which point a solution of
ketophosphonate (1.79 mol) in 8 ml THF was added and
the mixture left overnight at ꢀ30 °C with stirring. 15 ml of
ethyl acetate and 25 ml of 1 M hydrochloric acid were then
added consecutively to the mixture. The organic layer was
separated and the aqueous layer extracted with ethyl acetate.
The combined extracts were washed out with a saturated
solution of sodium carbonate and dried over Na2SO4. The
solvent was removed under vacuum and the residue was
recrystallized in acetonitrile or purified by column
chromatography.
3. Conclusion
In conclusion, we have developed a simple method for the
asymmetric hydroboration of ketophosphonates and their
conversion to hydroxyphosphonates. This methodology
can as well be applied for the hydroboration of organic
ketones.
References
1. Procter, G. Asymmetric Synthesis; Oxford University:
Oxford, 1996.
2. Seyden-Penne, J. Reductions by the Alumino- and Boro-
hydrides in Organic Synthesis, 2nd ed.; Wiley-VCH: New
York, 1997; p 6.
3. Gribble, G. W. Chem. Soc. Rev. 1998, 27, 395–404.
4. Compound 1: Mp > 200 °C. 1H NMR (DMSO): d 1.7 m
(CH2C); 3.29 br (OH); 3.7 m (CH2O); 4.5 m (CHOH). IR
(KBr, cmꢀ1) 1720, 1740 (C@O), 2550 (B–H), 2970 (CH), 3525
(OH). The 1 contains solvated THF: 0.75 equiv (dried under
vacuum at 20 °C) or 0.5 equiv (dried under vacuum at
+50 °C). Anal. calcd for C7H11BNaO6.75: C, 35.48, H, 4.68;
found C, 35.56, H, 4.97.
11. The ee values of compounds 3 were estimated by 31P NMR-
{1H}, using dimenthylchlorophosphite as derivatizing
agent12a or cinchonidine12b as a chiral solvating agent.
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19. Compounds 3a: Mp 86.2 °C; 3c: mp 76 °C; 3e: mp 113 °C;
3f: mp 139 °C; 3g: mp 138.5 °C; 3h: mp 117 °C; 3i:
mp 96 °C.
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HO
OH
O
Na+
O
.
(THF)x
H
O
O
-
B
H
1
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21. The (S)-phospho-carnitine was described as an oil,
20
½aꢂD ¼ ꢀ24 (c 2.3, MeOH–H2O), 100% ee13 as a crystalline
20
product, mp 270°, ½aꢂD ¼ ꢀ17:4 (c 1.15, H2O), 100% ee22 and
20
as a solid, ½aꢂD ¼ ꢀ15 (c 2.1, H2O), 100% ee.23
22. Wroblewski, A. E.; Halajewska-Wosik, A. Tetrahedron:
Asymmetry 2003, 14, 3359–3363.
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24. Phospho-carnitine (R)-8 was purified by column chromato-
graphy with silica gel using methanol–water as eluent. Yield