The Journal of Organic Chemistry
Note
(C), 81.6* (C), 94.5 (C), 95.3* (C), 101.0 (C), 151.5 (C), 152.8*
(C), 199.6 (CH); IR (neat) 2981, 1739, 1709, 1370 cm−1; HRMS
(ESI) m/z calcd for [C11H19NO4+Na] 252.1207. Found 252.1194.
1,1-Dimethylethyl (S)-4-Hydroxymethyl-2,2-dimethyl-3-oxa-
zolidinecarboxylate [(S)-5]. NaBH4 (0.18 g, 4.83 mmol) was added
to a solution of aldehyde (R)-3 (0.79 g, 3.45 mmol) in MeOH (35
mL) at 0 °C. The solution was stirred at 0 °C for 1 h, quenched with
aq satd NH4Cl, warmed to rt, and extracted with EtOAc. The
combined organic layers were dried (MgSO4), filtered, and
concentrated in vacuo to give a colorless oil (0.67 g, 84%) that
lower temperatures (37 and 44 °C), lower catalyst loading
(1%), and higher concentration (1.2 M) resulted in erosion of
regioselectivity. Garner and co-workers have reported optical
rotation data for (R)-3 and (S)-3,7 but for more accurate data
enantioselectivities were determined by supercritical fluid
chromatography (SFC) of esters (R)-6 and (S)-6, prepared
by reduction of (R)-3 and (S)-3 with NaBH4 and acylation
with 4-bromobenzoyl chloride to provide a good chromophore
(Scheme 2). Absolute configuration was assigned on the basis
1
required no further purification: Rf 0.51 (50% EtOAc/hexane); H
NMR (300 MHz, CDCl3) δ 1.49 (br s, 12H), 1.55 (br s, 3H), 3.5−3.7
(m, 1H), 3.7−4.2 (m, 5H); 13C NMR (75 MHz, CDCl3, rotamer*)
23.2* (CH3), 24.7 (CH3), 26.9* (CH3), 27.3 (CH3), 28.6 (CH3),
58.5* (CH), 59.6 (CH), 63.1* (CH2), 65.2 (CH2), 65.4 (CH2), 80.2*
(C), 81.3 (C), 94.2 (C), 152.0* (C), 154.2 (C); IR (film) 3011, 1656,
1405 cm−1; HRMS (ESI) m/z calcd for [C11H21NO4 + Na] 254.1363,
found 254.1359.
Scheme 2. Preparation of 6 for Enantiopurity Analysis
1,1-Dimethylethyl (R)-4-(4-Bromobenzoyloxymethyl)-2,2-di-
methyl-3-oxazolidinecarboxylate [(R)-6]. To a solution of alcohol
(S)-5 (0.30 g, 1.30 mmol) in CH2Cl2 (3.0 mL) were added 4-
bromobenzoyl chloride (0.43 g, 1.95 mmol), DMAP (16 mg, 0.13
mmol), and Et3N (0.27 mL, 1.95 mmol), and the solution was stirred
overnight. The reaction mixture was diluted with CH2Cl2, washed with
satd aq NaHCO3, dried (MgSO4), and concentrated in vacuo. The
crude oil was purified by flash column chromatography (5% EtOAc/
hexane to 10% EtOAc/hexane) to give 0.38 g (70%) of a light yellow
to colorless oil that solidified with cold storage: mp 48−49 °C; Rf 0.53
(20% EtOAc/hexane); SFC (2% MeOH) 3.97 min (major
enantiomer), 5.31 min (minor enantiomer); 1H NMR (300 MHz,
CDCl3) δ 1.48 (s), 1.50 (s), 1.53 (s), 1.57 (s), 1.62 (s), 3.90−4.10 (m,
3H), 4.20−4.50 (m, 3H), 7.59 (m, 2H), 7.91 (d, J = 8.7 Hz, 2H); 13C
NMR (75 MHz, CDCl3, rotamer*) δ, 23.3* (CH3), 24.5 (CH3), 26.9*
(CH3), 27.8 (CH3), 28.6 (CH3), 55.8 (CH), 56.0* (CH), 64.2 (CH2),
65.3 (CH2), 65.5* (CH2), 77.5 (C), 80.5 (C), 80.8* (C), 93.9 (C),
94.5* (C), 128.3* (C), 128.5 (C), 129.0* (C), 129.1 (C), 131.4
(CH), 131.9* (CH), 132.0 (CH), 151.8* (C), 152.5 (C), 165.7* (C),
165.8 (C); IR (film) 2979, 1725, 1697, 1591 cm−1; HRMS (ESI) m/z
of SFC data for (S)-6 prepared from L-serine methyl ester
hydrochloride.
EXPERIMENTAL SECTION
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1,1-Dimethylethyl (S)-4-Formyl-2,2-dimethyl-3-oxazolidine-
carboxylate [(S)-3]. Under an inert atmosphere, (S,S,S)-BDP (2)
(174 mg, 0.133 mmol) and Rh(CO)2acac (27 mg, 0.106 mmol) were
dissolved in THF (3.64 mL) in a 40.5 cm long pressure bottle sealed
with a custom head (equipped with a pressure gauge, filling/venting
valve, and a septum-sealed valve) and pressurized to 140 psi with
syngas. The solution was stirred at 55 °C for 20 min, the pressure
reduced to about 15 psi, and alkene 4 (1.06 g, 5.32 mmol) added as a
solution in THF (7 mL) via syringe. The pressure was increased to
140 psi, and the reaction mixture was stirred at 55 °C for 3 d. After the
mixture was cooled to rt, the syngas was vented and the solution
concentrated in vacuo. The regioselectivity was determined to be 20:1
by comparison of the aldehyde peaks in the 1H NMR spectrum of the
crude oil (minor regiomeric aldehyde δ 9.76 (d, J = 1.2 Hz). The crude
oil was purified by flash column chromatography (20% EtOAc/
hexane) to give a colorless to yellow oil (0.85 g, 70%): Rf 0.35 (20%
EtOAc/hexane); 1H NMR (300 MHz, CDCl3) δ 1.44 (br s), 1.52 (br
s), 1.56 (s), 1.61 (s), 1.66 (s) 4.00−4.16 (m, 2H), 4.16−4.40 (m 1H)
9.55 (d, J = 2.4 Hz), 9.61 (d, J = 0.9 Hz, rotamer); 13C NMR (75
MHz, CDCl3, rotamer*) δ 24.0 (CH3), 24.9* (CH3), 26.0 (CH3),
26.9* (CH3), 28.5 (CH3), 63.7*(CH2), 64.1 (CH2), 64.9 (CH), 81.3
(C), 81.6* (C), 94.5 (C), 95.3* (C), 101.0 (C), 151.5 (C), 152.8*
(C), 199.6 (CH); IR (neat) 2981, 1739, 1709, 1370 cm−1; HRMS
(ESI) m/z calcd for [C11H19NO4 + Na] 252.1207, found 252.1194.
1,1-Dimethylethyl (R)-4-Formyl-2,2-dimethyl-3-oxazolidine-
carboxylate [(R)-3]. Under an inert atmosphere, (R,R,S)-BDP (1)
(160 mg, 0.122 mmol) and Rh(CO)2acac (25 mg, 0.097 mmol) were
dissolved in THF (2.74 mL) in a 40.5 cm long pressure bottle sealed
with a custom head (equipped with a pressure gauge, filling/venting
valve, and a septum-sealed valve) and pressurized to 140 psi with
syngas. The solution was stirred at 55 °C for 20 min, the pressure
reduced to about 15 psi, and alkene 4 (0.97 g, 4.87 mmol) added as a
solution in THF (7 mL) via syringe. The pressure was increased to
140 psi, and the reaction mixture was stirred at 55 °C for 3 d. After the
mixture was cooled to rt, the syngas was vented and the solution
concentrated in vacuo. The regioselectivity was determined to be 13:1
by comparison of the aldehyde peaks in the 1H NMR spectrum of the
crude oil (minor regiomeric aldehyde δ 9.76 (d, J = 1.2 Hz). The crude
oil was purified by flash column chromatography (20% EtOAc/
hexane) to give a colorless to yellow oil (0.79 g, 71%): Rf 0.35 (20%
EtOAc/hexane); 1H NMR (300 MHz, CDCl3) δ 1.44 (br s), 1.52 (br
s), 1.56 (s), 1.61 (s), 1.66 (s) 4.00−4.16 (m, 2H), 4.16−4.40 (m 1H)
9.55 (d, J = 2.4 Hz), 9.61 (d, J = 0.9 Hz, rotamer). 13C NMR (75
MHz, CDCl3, rotamer*) δ 24.0 (CH3), 24.9* (CH3), 26.0 (CH3),
26.9* (CH3), 28.5 (CH3), 63.7*(CH2), 64.1 (CH2), 64.9 (CH), 81.3
calcd for [C18H24BrNO5 + H] 414.0911, found 414.0919; [α]22
+31.3 (c = 1.0, CHCl3).
=
D
ASSOCIATED CONTENT
■
S
* Supporting Information
1
1H NMR spectrum for 4, H NMR spectra for crude AHF
1
reactions, H and 13C NMR spectra for (R)-6, and SFC traces
of (R)-6 and (S)-6. This material is available free of charge via
AUTHOR INFORMATION
■
Corresponding Author
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this research from the National Science
Foundation (NSF CHE 0848616) and from a Wisconsin
Distinguished Graduate Fellowship (A.J.L.C.) is gratefully
acknowledged.
REFERENCES
(1) For a recent review, see: Gual, A.; Godard, C.; Castillon
Claver, C. Tetrahedron: Asymmetry 2010, 21, 1135−1146.
(2) For recently reported AHF ligands, see: (a) Doro, F.; Reek, J. N.
■
́
, S.;
H.; van Leeuwen, B. W. N. M. Organometallics 2010, 29, 4440−4447.
(b) Gual, A.; Godard, C.; Castillon, S.; Claver, C. Adv. Synth. Catal.
́
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dx.doi.org/10.1021/jo300025t | J. Org. Chem. 2012, 77, 2983−2985