Hydroxyl-directed reductive cleavage of 3-oxetanols as an entry to diastereomerically pure 1,2-diols

Full text of DOI:10.1021/jo952235c

3900
J . Org. Chem. 1996, 61, 3900-3901
Sch em e 1
Hyd r oxyl-Dir ected Red u ctive Clea va ge of
3-Oxeta n ols a s a n En tr y to
Dia ster eom er ica lly P u r e 1,2-Diols
Thorsten Bach* and Kristian Kather
Sch em e 2
Organisch-Chemisches Institut der Westfa¨lischen
Wilhelms-Universita¨t Mu¨nster, D-48149 Mu¨nster, Germany
Received December 19, 1995
The polarity reversal of a carbonyl compound from an
a1 to a d1 synthon is a point of continuing interest in
organic synthesis.1 One of the most straightforward
solutions to this problem is the photoexcitation of an
Sch em e 3
3
aldehyde or a ketone. The nπ* state which is in many
cases the lowest lying excited state of these compounds
is electronically defined by an electrophilic oxygen and
a nucleophilic carbon atom. In particular, aromatic
carbonyl compounds which undergo a rapid intersystem
crossing from the 1nπ* to the 3nπ* level behave fairly
predictably and may undergo C-C bond formations with
suitable carbon nucleophiles. The most common reaction
in this context is the Paterno`-Bu¨chi reaction in which
photoexcited carbonyl compounds are quenched by alk-
enes to yield oxetanes.2 We have recently shown that
the photocycloaddition of silyl enol ethers 2 to aromatic
aldehydes, such as benzaldehyde (1), proceeds with
excellent diastereo- and regioselectivity (Scheme 1).3
Many functional groups (ketal, acetal, ester, ether, amide,
alkene, silane, chloride) either attached to the aldehyde
or to the enol ether are tolerated in this transformation.4
The decisive C-C bond between the umpoled carbonyl
and the (silyloxy)-substituted carbon is formed readily
despite the fact that the R-substituents of the silyl enol
ether are of considerable bulk.
Since the product oxetanes 3 can be envisaged as latent
1,2-diols we looked into the prospect of a selective SN2-
type ring opening at C-4. Our premier choice was a
reductive opening which would facilitate the formation
of diols in a stereochemically predictable manner. The
former methylene group of the enol ether 2 would end
up as a methyl substituent on the stereogenic tertiary
alcoholic center. However, all attempts to induce a
nucleophilic hydride displacement on the C-4 of oxetanes
3 encountered little success. Commonly used aluminum-
based hydride reagents5 failed, whereas catalytic hydro-
genolyses resulted in the expected benzylic cleavage
between C-2 and O.6 The best results were obtained with
the combination of lithium tris(tert-butoxy)aluminum
hydride (LTBA) and triethylborane (BEt3) in tetrahydro-
pyran (THP)7 the application of which gave access to the
monoprotected trimethylsilyl (TMS) diols 4a and 4b3b in
moderate yields (Scheme 2).
Obviously the bulky substituents at the C-3 carbon of
the oxetane nucleus prevent the approach of the incoming
nucleophile. Unfortunately, all attempts to increase the
electrophilicity of the four-membered heterocycle are
limited by a facile SN1-type ring opening at C-2 which
leads to rearranged material.8 An intramolecular deliv-
ery of the hydride occurred to us as a possible way to
overcome the described obstacles. Since the TMS group
of 3 can be readily cleaved in essentially quantitative
yield to furnish the corresponding 3-oxetanol9 we in-
tended to utilize the 3-hydroxyl substituent as a possible
control element. In a representative study we employed
the oxetanes depicted in Scheme 3 as starting materials.
After deprotection of the oxetanes 3 with K2CO3 in
methanol we were pleased to observe that treatment of
the crude oxetanol with LiAlH4 in THF lead cleanly to
the desired diols 5 as shown in Scheme 3. The reaction
proceeded smoothly at room temperature or for more
hindered substrates at reflux and yielded the products
in diastereomerically pure form (see Table 1).
Compared to the conventional addition of umpoled
carbanions to aldehyde electrophiles10 the described
methodology exhibits a more stereoselective approach to
1,2-diols which bear a secondary and a tertiary center.11
The preparation of the corresponding 1,2-diols by a
stereospecific dihydroxylation is certainly possible, even
in enantiomerically pure form.12 However, this route
(1) (a) Seebach, D. Angew. Chem. 1979, 91, 259; Angew. Chem., Int.
Ed. Engl. 1979, 18, 239. (b) Ager, D. J . In Umpoled Synthons; Hase,
T. A., Ed.; Wiley: New York, 1987; p 19.
(2) For recent reviews, see: (a) Mattay, J .; Conrads, R.; Hoffmann,
R. In Methoden der Organischen Chemie (Houben-Weyl); 4th ed.;
Helmchen, G., Hoffmann, R. W., Mulzer, J ., Schaumann, E., Eds.;
Thieme: Stuttgart, 1995, Vol. E 21c; p 3133. (b) Porco, J . A.; Schreiber,
S. L. In Comprehensive Organic Synthesis; Trost, B., Ed.; Pergamon
Press: Oxford, 1991; Vol. 5; p 151. (c) Carless, H. A. J . In Synthetic
Organic Photochemistry; Horspool, W. M., Ed.; Plenum Press: New
York, 1984; p 425. (d) J ones, G. In Organic Photochemistry; Padwa,
A., Ed.; Dekker: New York 1981; Vol. 5; p 1.
(7) Krishnamurthy, S.; Brown, H. C. J . Org. Chem. 1979, 44, 3678.
(8) Bach, T.; Kather, K. Tetrahedron 1994, 50, 12319. For related
migrations on 3-oxetanols, see: Kagan, J .; Przybytek, J . T. Tetrahedron
1973, 29, 1163.
(9) Shimizu, N.; Yamaoka, S.; Tsuno, Y. Bull. Chem. Soc. J pn. 1983,
56, 3853.
(3) (a) Bach, T. Tetrahedron Lett. 1991, 32, 7037. (b) Bach, T.;
J o¨dicke, K. Chem. Ber. 1993, 126, 2457.
(4) Bach, T. Liebigs Ann. 1995, 855.
(10) Sawyer, J . S.; Kucerovy, A.; Macdonald, T. L.; McGarvey, G. J .
J . Am. Chem. Soc. 1988, 110, 842.
(5) For previous applications of LiAlH4 and related reagents in
oxetane ring opening, see: (a) Searles, S., J r.; Pollart, K. A.; Lutz, E.
F. J . Am. Chem. Soc. 1957, 79, 948. (b) Seyden-Penne, J .; Schaal, C.
Bull. Soc. Chim. Fr. 1969, 3653. (c) Ruotsalainen, H.; Palosaari, V.;
Olavi, I. P. Suom. Kemistil. B 1972, 45, 40.
(6) (a) Bach, T. Tetrahedron Lett. 1994, 35, 1855. (b) Bach, T. Liebigs
Ann. 1995, 1045.
(11) (a) For the stereoselective addition of allylic metal compounds
to form this type of 1,2-diols, see: Hoffmann, R. W.; Metternich, R.
Liebigs Ann. Chem. 1985, 2390. (b) For aldol reactions, see: Mont-
gomery, S. H.; Pirrung, M. C.; Heathcock, C. H. Carbohydr. Res. 1990,
202, 13.
(12) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem.
Rev. 1994, 94, 2483.
S0022-3263(95)02235-3 CCC: $12.00 © 1996 American Chemical Society

Notes
J . Org. Chem., Vol. 61, No. 11, 1996 3901
Ta ble 1. Rin g Op en in g of Oxeta n es 3 u p on Dep r otection
a n d Su bsequ en t Tr ea tm en t w ith LiAlH4 in THF
(CDCl3) δ 16.8 (q), 17.8 (q), 19.1 (q), 33.3 (d), 77.0 (s), 78.4 (d),
127.8 (d), 127.9 (d), 128.1 (d), 140.9 (s). Anal. Calcd for C12H18O2
(194.273): C, 74.19; H, 9.34. Found: C, 73.97; H, 9.26.
(1RS,2SR)-1,2-Dip h en ylp r op a n e-1,2-d iol (5b): Yield 225
mg (99%) of a white solid with mp 102-104 °C (lit.15 mp 103-
104 °C); Rf ) 0.28 (CH/EtOAc ) 70/30); 1H NMR (CDCl3) δ 1.60
(s, 3 H), 2.55 (s, b, 2 H), 4.72 (s, 1 H), 6.99-7.02 (m, 2 H), 7.12-
7.23 (m, 8 H); 13C NMR (CDCl3) δ 25.5 (q), 76.8 (s), 80.9 (d),
126.0 (d), 126.9 (d), 127.4 (d), 127.5 (d), 127.5 (d), 127.6 (d), 139.4
(s), 143.6 (s). Anal. Calcd for C15H16O2 (228.290): C, 78.92; H,
7.06. Found: C, 78.96; H, 7.13.
(1RS,2SR)-1-P h en yl-2,3,3-tr im eth ylbu ta n e-1,2-d iol (5c).
After purification by flash chromatography (cyclohexane-ethyl
acetate ) 90:10) 156 mg (75%) of a white solid with mp 82-83
°C were obtained: Rf ) 0.60 (CH/EtOAc ) 50/50); 1H NMR
(CDCl3) δ 1.05 (s, 9 H), 1.11 (s, 3 H), 4.89 (s, 1 H), 7.24-7.41
(m, 5 H); 13C NMR (CDCl3) δ 18.0 (q), 26.4 (q), 37.8 (s), 77.1 (s),
77.3 (d), 127.7 (d), 127.9 (d), 128.1 (d), 142.1 (s). Anal. Calcd
for C13H20O2 (208.300): C, 74.96; H, 9.68. Found: C, 75.01; H,
9.66.
oxetane
R
ta (h)
T
diol
yieldb (%)
3a
3b
3c
3d
3e
3f
i-Pr
Ph
t-Bu
CH(OMe)2
C(OCH2)2Me
CMe2CHCH2
24
48
48
72
48
96
rt
rt
reflux
rt
reflux
rt
5a
5b
5c
5d
5e
5f
98
99
75
97
69
94
a
Time required for complete conversion at the designated
temperature. b Refers to isolated yield of analytically pure product.
requires a diastereoselective method for the carbonyl
olefination of aldehydes which yields highly congested
(Z)-alkenes and which therefore appears difficult to
devise.
The overall yield of diastereomerically pure diol 5 for
the three-step procedure, photocycloadditon, protective
group removal, and reductive ring opening, ranges
between 36 and 59% in the cases under scrutiny. Further
studies are under way to extend the scope of hydroxyl-
directed ring-opening reactions of oxetanes and will be
reported in due course.
(1RS,2RS)-3,3-Dim et h oxy-2-m et h yl-1-p h en ylp r op a n e-
1,2-d iol (5d ). After purification by flash chromatography
(cyclohexane-ethyl acetate ) 70:30) 220 mg (97%) of a white
solid with mp 70-71 °C were obtained: Rf ) 0.53 (CH/EtOAc )
1
10/90); H NMR (CDCl3) δ 1.16 (s, 3 H), 3.47 (s, 3 H), 3.55 (s, 3
H), 4.03 (s, 1 H), 4.72 (s, 1 H), 7.25-7.40 (m, 5 H); 13C NMR
(CDCl3) δ 17.8 (q), 57.5 (q), 58.7 (q), 75.8 (s), 76.8 (d), 109.7 (d),
127.5 (d), 127.7 (d), 127.8 (d), 139.8 (s). Anal. Calcd for C12H18O4
(226.272): C, 63.70; H, 8.02. Found: C, 63.86; H, 8.09.
Exp er im en ta l Section
(1RS,2RS)-2-(2-Met h yl-1,3-d ioxola n -2-yl)-1-p h en ylp r o-
p a n e-1,2-d iol (5e). After recrystallization from ethyl acetate
165 mg (69%) of a white solid with mp 123-124 °C were
obtained: Rf ) 0.45 (CH/EtOAc ) 30/70); 1H NMR (CDCl3) δ
1.12 (s, 3 H), 1.48 (s, 3 H), 3.99-4.18 (m, 4 H), 4.96 (s, 1 H),
7.26-7.37 (m, 3 H), 7.43-7.47 (m, 2 H); 13C NMR (CDCl3) δ 16.4
(q), 19.3 (q), 64.8 (t), 65.5 (t), 76.0 (d), 76.7 (s), 113.2 (s), 127.4
(d), 127.5 (d), 128.1 (d), 139.7 (s). Anal. Calcd for C13H18O4
(238.283): C, 65.53; H, 7.61. Found: C, 65.65; H, 7.58.
(1RS,2SR)-1-P h en yl-2,3,3-tr im eth yl-4-pen ten e-1,2-diol (5f).
After purification by flash chromatography (cyclohexane-ethyl
acetate ) 92:8) 206 mg (94%) of a white solid with mp 63-64
°C were obtained: Rf ) 0.67 (CH/EtOAc ) 50/50); 1H NMR
(CDCl3) δ 1.11 (s, 3 H), 1.13 (s, b, 1 H), 1.15 (s, 3 H), 1.22 (s, 3
H), 2.21 (s, b, 1 H), 5.09 (dd, J ) 10.9 Hz, J ) 1.4 Hz, 1 H), 5.14
(dd, J ) 17.7 Hz, J ) 1.4 Hz, 1 H), 6.21 (dd, J ) 17.7 Hz, J )
10.9 Hz, 1 H), 7.24-7.39 (m, 5 H); 13C NMR (CDCl3) δ 17.8 (q),
21.9 (q), 23.5 (q), 44.0 (s), 76.7 (s), 77.3 (d), 112.7 (t), 127.6 (d),
127.8 (d), 128.1 (d), 141.1 (s), 146.6 (d). Anal. Calcd for C14H20O2
(220.311): C, 76.33; H, 9.15. Found: C, 76.54; H, 9.20.
Gen er a l. For general remarks see ref 4. The oxetanes 3
were prepared as described previously.3b 13C NMR multiplicities
were obtained by DEPT experiments.
(1RS,2SR)-2,3-Dim eth yl-1-ph en yl-2-[(tr im eth ylsilyl)oxy]-
1-bu ta n ol (4a ). The ring opening of oxetane 3a with LTBA/
BEt3 in THP was carried out on a 1 mmol scale as previously
described for 3b.3b A total of 80 mg (30%) of 4a were obtained
as an oil after flash chromatography (cyclohexane-ethyl acetate
) 97:3): Rf ) 0.58 (CH/EtOAc ) 75/25); 1H NMR (CDCl3) δ 0.04
(s, 9 H), 0.80 (d, J ) 6.8 Hz, 3 H), 0.97 (d, J ) 6.8 Hz, 3 H), 1.25
(s, 3 H), 1.73 (sept, J ) 6.8 Hz, 1 H), 2.25 (s, b, 1 H), 4.60 (s, 1
H), 7.22-7.38 (m, 3 H), 7.39-7.42 (m, 2 H); 13C NMR (CDCl3) δ
2.5 (q), 17.7 (q), 18.1 (q), 19.0 (q), 34.7 (d), 79.3 (d), 80.9 (s), 127.4
(d), 127.6 (d), 128.3 (d), 141.5 (s). Anal. Calcd for C15H26O2Si
(266.457): C, 67.62; H, 9.84. Found: C, 67.67; H, 9.94.
Gen er a l P r oced u r e for th e Red u ctive Rin g Op en in g
w ith LiAlH4. The oxetanols were obtained in quantitative
yields from the corresponding oxetanes by treatment with K2-
CO3 in MeOH9 and were used without further purification. To
a suspension of 3 mmol LiAlH4 (114 mg) in 2 mL of THF was
added slowly a solution of 1 mmol crude oxetanol in 5 mL of
THF at 0 °C. After complete addition the mixture was stirred
for another hour at 0 °C and subsequently allowed to reach the
temperature indicated in Table 1. Stirring was continued until
the reaction was complete according to TLC (cf. Table 1).
Workup was carried out according to the standard protocol.13
The diols 5a and 5b proved to be analytically pure without
further purification. The other products were purified by flash
chromatography (cyclohexane-ethyl acetate mixture as eluent)
or by recrystallization.
Ack n ow led gm en t. This work was generously sup-
ported by the Deutsche Forschungsgemeinschaft (Ba
1372/1-2), by the Fonds der Chemischen Industrie, by
the Dr. Otto-Ro¨hm-Geda¨chtnisstiftung, and by the Ge-
sellschaft zur Fo¨rderung der Westfa¨lischen Wilhelms-
Universita¨t. We thank Prof. Dr. D. Hoppe for his
continuing support.
Su p p or tin g In for m a tion Ava ila ble: Further analytical
data (NMR assignments, IR, MS) for compounds 4a and 5a -
5f (7 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
(1RS,2SR)-2,3-Dim eth yl-1-p h en ylp r op a n e-1,2-d iol (5a ):
Yield 190 mg (98%) of a white solid with mp 125-126 °C (lit.14
mp 124-125 °C); Rf ) 0.22 (CH/EtOAc ) 80/20); 1H NMR
(CDCl3) δ 0.85 (d, J ) 6.9 Hz, 3 H), 0.93 (d, J ) 6.9 Hz, 3 H),
1.20 (s, 3 H), 1.52 (sept, J ) 6.9 Hz, 1 H), 2.10 (s, b, 2 H), 4.60
(s, 1 H), 7.26-7.36 (m, 3 H), 7.39-7.43 (m, 2 H); 13C NMR
J O952235C
(13) Micovic, V. M.; Mihailovic, M. L. J . Org. Chem. 1953, 18, 1190.
(14) Tiffeneau, M.; Levy, S. Bull. Soc. Chim. Fr. 1927, 41, 1351.
(15) Barnes, R. A.; J uliano, B. R. J . Am. Chem. Soc. 1959, 81, 6462.