S. A. Said, A. Fiksdahl / Tetrahedron: Asymmetry 12 (2001) 893–896
895
accurate and gives lower results than the more precise
GLC method.
tively. The homochiral phenyl and 2-naphthyl ethers 3a
and 3b were prepared alternatively from the corre-
sponding chiral alcohol via the TFA ester with 100%
inversion of configuration. Phenyl ether 3a has also
been synthesised8 via a benzyne route with complete
retention of configuration.
Based on previous experience,7 we have made the fol-
lowing observations regarding the effect of the leaving
group, the substrate and the attacking nucleophile on
the degree of inversion in nucleophilic substitution reac-
tions of N,N-disulfonylimides:
1. Higher stereoselectivity was observed for the
reported ether formation from the cyclic disul-
fonylimides relative to the corresponding azide and
alcohol formation previously reported.7 The 1,2-
naphthalenedisulfonylimide leaving group affords
only a slightly lower degree of inversion than the
corresponding 1,2-benzene leaving group in the for-
mation of aryl ethers 3a and 3b. This is in contrast
to our previous observations for the formation of
azide and alcohol products,6,7 which showed 20–
25% lower stereoselectivity for the 1,2-naphthalene
intermediate.
2. In the formation of the azide and alcohol products,
alkyl substrates generally afford 5–15% higher
stereoselectivity than benzylic substrates,7 caused by
the carbocation stabilising effect of the latter. For
aryl ether formation, higher stereoselectivity would,
therefore, have been expected for non-benzylic
substrates.
3. The reactions were carried out at ambient tempera-
ture overnight. As observed previously, both 2a and
2b were more easily substituted than the corre-
sponding ditosyl-, dimesyl- and dinosylimides.1–7
This is demonstrated by the lower reaction tempera-
tures required for the formation of ethers from 2a
and 2b. The ethers were formed in 39–68% yield,
which is higher than in our previous nucleophilic
substitution reactions of N,N-disulfonylimides.1–7
All studies were focused on the degree of inversion
for the reactions and no attempts were made to
optimise the yields.
4. Experimental
(S)-N,N-1,2-Benzenedisulfonyl-1-phenylethylamine 2a
and (S)-N,N-1,2-naphthalenedisulfonyl-1-phenylethyl-
amine 2b were prepared from (S)-phenylethylamine 1
and benzene 1,2-disulfonyl chloride and naphthalene
1,2-disulfonyl chloride, respectively, as described else-
where.6,7 Phenol and 2-napthol were obtained from
Merck, (R)-phenylethanol from Acros, TFA anhydride
from Fluka, and NaH (>95%) from Aldrich. THF was
distilled (N2) from the sodium ketyl of benzophenone
and was used immediately, while DMF was dried over
,
activated molecular sieve (4 A). All solvents were pro
analysi quality. Chiral GLC analysis: Chrompack CP-
CHIRADEX-CB fused silica WCOT (25 m, 0.32 mm;
0.32 mm), carrier gas pressure 5–5.5 psi. H/13C NMR:
1
Bruker Avance DPX 300/75.47 MHz spectrometer;
chemical shifts are reported in ppm downfield from
TMS. MS: MAT 95 XL. IR: Nicolet 20SXC FT-IR
spectrometer.
4.1. Preparation of (R)-1-phenylethyl phenyl ether 3a
from (S)-N,N-1,2-naphtalenedisulfonyl-1-phenylethyl-
amine 2b
The preparation of (R)-3a from (S)-2b and the charac-
terisation of (R)-3a has been published elsewhere.8
HRMS calcd for C14H14O: 198.1045; obsvd: 198.1042.
Chiral GLC indicated a degree of inversion of 83%
(R:S ratio 83:17).
4. Two methods are presented for the formation of
ethers 3a and 3b from amine and alcohol deriva-
tives, respectively, by nucleophilic substitution with
ArO− to give inversion of configuration. Higher
stereoselectivity is observed for the oxygen leaving
group, -O-TFA (100% for substrate 6), compared
with the cyclic N,N-disulfonylimides (70–87% for
substrates 2a and 2b). The O-TFA leaving group,
having higher electron withdrawing character and
lower nucleophilic power, therefore seems to favour
an SN2 reaction even when a less ionising solvent
(THF versus DMF) and less vigorous reaction con-
ditions (room temperature compared to 100°C) are
used for the disulfonylimide reactions, which occur
with partial racemisation.
4.2. Preparation of (R)-1-phenylethyl 2-naphthyl ether
3b from (S)-N,N-1,2-naphthalenedisulfonyl-1-phenyl-
ethylamine 2b
The reaction was carried out as described elsewhere8 for
(R)-3a using 2-naphthol (33 mg, 0.23 mmol), NaH
(16.5 mg, 0.69 mmol, 3 equiv.) in dry THF (5 mL) and
(S)-N,N-1,2-naphthalenedisulfonyl-1-phenylethylamine
(2b, 85 mg, 0.20 mmol) in dry THF (5 mL). The oily
product (38.6 mg, 68% yield) was obtained after flash
1
chromatography. H NMR (300 MHz, CDCl3): l 1.69
(d, J=6.4 Hz, 3H), 5.46 (q, J=6.4 Hz, 1H), 6.9 (d,
J=2 Hz, 1H), 7.18 (dd, J=8.1 and 2 Hz, 1H), 7.30 (m,
5H), 7.42 (m, 2H), 7.58 (d, J=8.1 Hz, 1H), 7.71 (dd,
J=8 and 1.8 Hz, 2H); 13C NMR (75.47 MHz, CDCl3):
l 24.6, 76.2, 109.0, 119.7, 123.7, 125.8, 126.1, 126.4,
127.0, 127.6, 127.7, 128.9, 129.5, 134.6, 143.2, 156.5;
MS [m/z (% rel. int.)]: 248 (M, 6%), 145 (9%), 144
(100%), 127 (3%), 105 (57%), 104 (33%), 77 (15%); IR
(neat film, cm−1): 3058 (w), 3028 (w), 2972 (w), 2869
(w), 1628 (s), 1600 (s), 1510 (m), 1485 (s), 1386 (m),
1258 (s), 1217 (s), 1181 (m), 1103 (m), 837 (m), 747 (m),
700 (s). HRMS calcd for C18H16O: 248.1201; obsvd:
248.1203. [h]D +87 (c=0.2, CHCl3). Comparison of
3. Conclusion
Nucleophilic attack on N,N-1,2-benzenedisulfonyli-
mides 2a and N,N-1,2-naphthalenedisulfonylimides 2b
by aryloxide anions afforded (R)-1-phenylethyl phenyl
ether 3a and 2-naphthyl ether 3b in 39–68% yield with
83–87 and 70–79% inversion of configuration, respec-