New synthesis of Evans chiral oxazolidinones by using Sharpless AA reaction

Article abstract of DOI:10.1039/a801404c

Optically pure new Evans auxiliary analogs, (4R)- and (4S)-4-(2-naphthyl)oxazolidin-2-one, have been synthesized by using the Sharpless catalytic asymmetric aminohydroxylation reaction (Sharpless AA). The concise two-step synthesis involves a unique solution-to-solid Sharpless AA process and new neat cyclization conditions.

Full text of DOI:10.1039/a801404c

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New synthesis of Evans chiral oxazolidinones by using Sharpless AA
reaction
Guigen Li,* Robert Lenington, Steven Willis and Sun Hee Kim
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA
Optically pure new Evans auxiliary analogs, (4R)- and
(4S)-4-(2-naphthyl)oxazolidin-2-one, have been syn-
thesized by using the Sharpless catalytic asymmetric amino-
6
hydroxylation reaction (Sharpless AA). The concise two-
step synthesis involves a unique solution-to-solid Sharpless
AA process and new neat cyclization conditions.
O
K2OsO2(OH)4
2%
BnO
NClNa
Evans chiral auxiliaries have been successfully used in many
asymmetric organic reactions,1–5 such as the aldol condensation
reaction,2 Diels–Alder reaction,3 alkylation,4 Michael add-
ition,5 etc. These auxiliaries can be synthesized from optically
pure - or -α-amino acids,6 amino alcohols,7 glycidol8 and
carboxylic acid derivatives.9 Chiral oxazolidinones can also be
synthesized from diols10 and allylic alcohols.11 Modifying the
R group on position 4 of the oxazolidinone ring can conceiv-
ably improve diastereoselectivities in some cases,12–14 especially
when the R group is replaced by rigid and extended aromatic
moieties. So far, the synthesis of unnatural 4-aryl- or 4-alkyl-
oxazolidin-2-one is limited by the availability of the unnatural
precursors and their trivial preparations. Here, we would like to
report a novel method for the synthesis of Evans auxiliaries,
especially the new ‘unnatural’ (4R)- and (4S)-4-(2-naphthyl)-
oxazolidin-2-one by using the Sharpless asymmetric amino-
hydroxylation reaction.15,16
2.5% (DHQD)2PHAL
HNZ
2.5% (DHQ)2PHAL
HNZ
Solution-to-Solid Process
OH
OH
R
S
9
7
91.5% ee, 61%
94% ee, 70.6%
neat, 94 °C
30–45 min
neat, 94 °C
30–45 min
K2CO3
K2CO3
O
O
Solid-to-Solid Process
HN
HN
O
O
R
S
10
93–99% ee, 89%
8
Our synthetic procedures and results are described in Scheme
1 and Scheme 2. Common petroleum olefins, styrene and
2-vinylnaphthalene, were subject to the carbamate-based
99% ee, 93%
Scheme 2 Solution-to-solid AA/neat cyclization for the synthesis of
4-(2-naphthyl)oxazolidin-2-one
Sharpless asymmetric aminohydroxylation reaction16 and fol-
lowed by a neat cyclization process in which no solvent was
needed. Benzyl carbamate/styrene-based Sharpless AA was
applied to the synthesis of (4R)- and (4S)-4-phenyloxazolidin-
1
O
K2OsO2(OH)2
1
2-one of which the H and 13C NMR spectra are identical to
4%
BnO
NClNa
those of the commercially available authentic samples. They
were also confirmed by HPLC co-injection determinations.17
Ethyl carbamate was also used as the nitrogen source for
styrene-based AA with 4 mol% of K2OsO2(OH)4 and 5 mol%
of phthalazine ligands. This modification resulted in only a
little improvement in enantiomeric selectivity [94% ee for
(DHQ)2PHAL and 92% ee for (DHQD)2PHAL respectively],
but gave lower yields (50–55%) than the benzyl carbamate-
based AA process. The synthesis of (4R)- and (4S)-4-(2-
naphthyl)oxazolidin-2-one was achieved by using benzyl
carbamate/2-vinylnaphthalene-based AA in which 2 mol% of
K2OsO2(OH)4 and 2.5 mol% of (DHQ)2PHAL and (DHQD)2-
PHAL ligands were employed. The reduced load of potassium
osmate and phthalazine ligands gave almost identical yields to
the original catalyst loading conditions, but resulted in amino
alcohol benzyl carbamates with lower enantiomeric excesses
(91.5–93.5% ee). Interestingly, these N-Z protected amino
alcohols with their lower enantiomeric excesses gave optically
pure (4R)- and (4S)-4-(2-naphthyl)oxazolidin-2-one after
cyclization processes.17
5% (DHQD)2PHAL
HNCOOBn
5% (DHQ)2PHAL
HNCOOBn
OH
OH
R
S
4
2
90% ee, 56%
93% ee, 61%
neat K2CO3
neat K2CO3
O
O
HN
O
HN
O
R
S
5
3
90% ee, 90%
93–99% ee, 95%
The ethyl carbamate derivatives of vicinal amino alcohols,
which were synthesized from the reduction of amino esters, can
Scheme 1 Asymmetric synthesis of (4R)- and (4S)-4-phenyloxazolidin-
2-one
J. Chem. Soc., Perkin Trans. 1, 1998
1753

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be cyclized to oxazolidinones by reacting them with potassium
carbonate at ca. 110 ЊC in a boiling toluene solution.18 We
found that the amino alcohol benzyl carbamates of Sharpless
AA reactions can be easily cyclized to oxazolidinones by a new
solid-to-solid process without using any solvent. In this process,
the N-Z protected amino alcohols were mixed with well
ground dry potassium carbonate and then heated at 94 ЊC in a
hot water bath. A vacuum was imposed on the reaction vessel
so that the benzyl alcohol produced from the cyclization could
be distilled off. The cyclization reaction took ca. 45 minutes to
complete. No racemization was observed in this basic solid-to-
solid cyclization process.
Purification was conducted by flash silica gel filtration by which
less polar impurities were washed away by EtOAc–hexane (1:9,
v/v), the remaining polar (4S)-4-(2-naphthyl)oxazolidin-2-one
was washed out by ethyl acetate, and then condensed by rotary
evaporation to give the pure product (2.73 g, 99% ee, 93%)21 as
a colorless solid; mp 164–167 ЊC; [α]D25 ϩ41.8 (c = 0.39 in 95%
EtOH); δH(200 MHz, CDCl3) 4.27 (dd, J 8.60 Hz, 6.7 Hz, 1 H),
4.80 (t, J 8.7 Hz, 1 H), 5.12 (t, J 7.03 Hz, 1 H), 5.89 (s, 1 H),
7.42–7.93 (m, 7 H); δC(50 MHz, CDCl3) 56.5, 72.3, 123.1, 125.4,
126.6, 126.8, 127.8, 127.9, 129.4, 133.1, 133.3, 136.6, 159.7; m/z
(EI) 214.20 (214.16 calc. for C13H11NO2).
Acknowledgements
We gratefully acknowledge financial support from the Robert
A. Welch Foundation (grant no. D-1361) and thank Dr
Han-Xun Wei for his assistance.
Conclusion
The solution-to-solid Sharpless AA and the new neat solid-to-
solid cyclization process provide a very convenient and concise
route to the synthesis of chiral 4-phenyloxazolidin-2-ones and
4-(2-naphthyl)oxazolidin-2-ones. The described method can be
applied for the synthesis of many other 4-aryloxazolidin-2-one
analogs. (4R) and (4S)-(2-naphthyl)oxazolidin-2-one, the novel
Evans auxiliary analogs, could be very efficient in controlling
stereochemistry in the asymmetric induction processes because
of the rigid and extended aromatic moiety on the 4-position of
the oxazolidinone ring. The applications of (4R)- and (4S)-4-
(2-naphthyl)oxazolidinone as chiral auxiliaries to asymmetric
reactions, such as Baylis–Hillman related processes, will be
carried out in this laboratory in the future.
References and notes
1 D. J. Ager, I. Prakash and D. Schaad, Aldrichimica Acta, 1997, 30, 3.
2 D. A. Evans, J. Bartroli and T. L. Shih, J. Am. Chem. Soc., 1981, 103,
2127.
3 (a) D. A. Evans, K. T. Chapman, D. T. Hung and A. T. Hawaguchi,
Angew. Chem., Int. Ed. Engl., 1987, 26, 1184; (b) I. W. Davies, C. H.
Senanayake, L. Castonguay, R. D. Larsen, T. R. Verhoeven and
P. J. Reider, Tetrahedron Lett., 1995, 36, 7619.
4 M. A. Walker and C. H. Heathcock, J. Org. Chem., 1991, 56, 5747.
5 (a) D. A. Evans, M. T. Bilodeau, T. Somers, J. Clardy, D. Cherry and
Y. Kato, J. Org. Chem., 1991, 56, 5750; (b) G. Li, K. C. Russell,
M. A. Jarosinski and V. J. Hruby, Tetrahedron Lett., 1993, 34, 2565.
6 (a) J. R. Cage and D. A. Evans, Org. Synth., 1990, 68, 77; (b)
M. Sudharshan and P. G. Hultin, Synlett, 1997, 2, 171.
7 (a) W. Lubell and H. Rapoport, J. Org. Chem., 1989, 54, 3824; (b)
T. P. Curren, M. P. Pollastri, S. M. Ablelleira, R. J. Messier, T. A.
McCollum and C. G. Rowe, Tetrahedron Lett., 1994, 35, 5409.
8 S. Iwama and S. Katsumura, Bull. Chem. Soc. Jpn., 1994, 67, 3363.
9 J. Takacs, M. R. Jaber and A. S. Vellekoop, Abstracts of Papers,
214th ACS National Meeting, Las Vegas, September 7th–11th,
1997, ORG 206.
10 D. Xu and K. B. Sharpless, Tetrahedron, 1993, 34, 951.
11 J. D. Blas, J. C. Carretero and E. Domingurez, Tetrahedron Lett.,
1994, 35, 4603.
12 E. Nicolas, K. C. Russell and V. J. Hruby, J. Org. Chem., 1993, 58,
766.
13 A. K. Ghosh and W. Liu, J. Org. Chem., 1996, 61, 6175.
14 M. P. Sibi, D. Rutherford and R. Sharma, J. Chem. Soc., Perkin
Trans. 1, 1994, 1675.
15 (a) G. Li, H.-T. Chang and K. B. Sharpless, Angew. Chem., Int. Ed.
Engl., 1996, 35, 451; (b) J. Rudolph, P. C. Sennhenn, C. P. Vlaar and
K. B. Sharpless, Angew. Chem., Int. Ed. Engl., 1996, 35, 2810.
16 G. Li, H. H. Angert and K. B. Sharpless, Angew. Chem., Int. Ed.
Engl., 1996, 35, 2813.
17 HPLC determinations for 4-aryloxazolidin-2-ones [chiralcel OD-
H, PriOH–hexane (3:7), 0.7 ml minϪ1]: 12.98 min (3, S), 12.18 min (5,
R); 21.97 min (9, S), 26.91 min (10, R).
18 N. Lewis, A. McKillop, R. J. K. Taylor and R. J. Watson, Synth.
Commun., 1995, 25, 561.
19 HPLC determinations for ethyl carbamate/styrene-based AA
products: chiralcel OD-H, PriOH–hexane (3:17), 0.7 ml minϪ1, 8.44
min (S), 10.70 min (R). The enantiomeric excesses of benzyl
carbamate-based AA products (2, 4, 7 and 9) were determined by
using the HPLC conditions as described in ref. 16.
20 The neat cyclization can be conducted by using a catalytic amount
of K2CO3 (10 mol%) and gave a lower yield of 82%.
Experimental
Sharpless AA
To a stirred solution of benzyl carbamate (4.69 g, 31.0 mmol)
in n-propanol (37 ml) was added a freshly prepared solution of
sodium hydroxide (1.22 g, 30.5 mmol) in water (37 ml), followed
by recently prepared tert-butyl hypochlorite (3.31 g, 30.5 mmol,
ca. 3.5 ml). Then the (DHQ)2PHAL ligand (400 mg, 0.5 mmol,
2.5 mol%) was added into the above solution. The resulting
mixture should be vigorously stirred until a homogeneous
solution is obtained. The reaction vessel was immersed in a
0 ЊC ice-bath, and 2-vinylnaphthalene 6 (1.54 g, 10 mmol) was
added, followed by K2OsO2(OH)4 (147 mg, 0.4 mmol, 2 mol%).
The green homogeneous solution was stirred at 0 ЊC with
appearance of a colorless slurry in about 2 h. The second
portion of 2-vinylnaphthalene 6 (1.54 g, 10 mmol) was added
to the above mixture when the green color almost disappeared.
The reaction mixture was stirred at 0 ЊC for another 4 hours to
completion. The product precipitates were obtained simply by
filtration. The solid was then washed with cold (ca. 5 ЊC) n-
propanol–H2O (1:1, 15 ml) and dried in a vacuum to yield the
1
product that was determined by H NMR spectroscopy to be
nearly pure (S)-8 (4.67 g, 94% ee, 70.6%).19 The dried product
was directly subjected to the following cyclization reaction.
Neat cyclization
To the above crude AA product (S)-8 (4.54 g, 13.8 mmol, 94%
ee), well ground potassium carbonate powder (1.91 g, 13.8
mmol) was added.20 The resulting mixture was ground together
thoroughly and then transferred to a 50 ml round bottom flask
equipped with a vacuum adapter which was connected to a
vacuum system. The vial was immersed in a boiling water bath
for ca. 20 min at which time benzyl alcohol, the side product of
the cyclization reaction, started to appear as the liquid. The
heating was then continued for 20 more min to completion. The
reaction was monitored by TLC (EtOAc–hexane, 1:1, v/v).
21 99% ee indicates that only one enantiomer was observed in HPLC
analysis.
Paper 8/01404C
Received 17th February 1998
Accepted 15th April 1998
1754
J. Chem. Soc., Perkin Trans. 1, 1998