Asymmetric synthesis of dihydrofurans via a formal retro-Claisen photorearrangement

Article abstract of DOI:10.1021/ja043254j

Solution-phase irradiation of a series of syn-7-benzoylnorbornene derivatives is shown to lead to cis-fused dihydrofuran derivatives in low quantum but excellent chemical yields in what is formally a retro-Claisen rearrangement. In analogy to the well-kno

Full text of DOI:10.1021/ja043254j

Published on Web 02/04/2005
Asymmetric Synthesis of Dihydrofurans via a Formal
Retro-Claisen Photorearrangement
Wujiong Xia, Chao Yang, Brian O. Patrick, John R. Scheffer,* and Carl Scott
Contribution from the Department of Chemistry, UniVersity of British Columbia,
2036 Main Mall, VancouVer, B.C., Canada V6T 1Z1
Received November 9, 2004; E-mail: scheffer@chem.ubc.ca
Abstract: Solution-phase irradiation of a series of syn-7-benzoylnorbornene derivatives is shown to lead
to cis-fused dihydrofuran derivatives in low quantum but excellent chemical yields in what is formally a
retro-Claisen rearrangement. In analogy to the well-known Paterno-Bu¨chi reaction, the first step of the
rearrangement is suggested to involve (n,π*)3-mediated addition of the carbonyl oxygen to the norbornene
double bond, producing a triplet 1,4-biradical. This intermediate, rather than closing to the oxetane,
undergoes cleavage accompanied by intersystem crossing to form the dihydrofuran. To determine whether
the retro-Claisen photorearrangement could be carried out enantioselectively, the 7-benzoylnorbornene
reactant was equipped with a para-carboxylic acid substituent to which a series of optically pure amines
was attached ionically via salt bridges. Irradiation of these salts in the crystalline state followed by
diazomethane workup (the solid-state ionic chiral auxiliary method) was shown to afford the corresponding
dihydrofuran in optical yields as high as 93% at 95% conversion. X-ray crystallography revealed that the
enantioselectivity arises from crystallization of the reactant in a conformation in which the carbonyl oxygen
is more favorably oriented for bond formation to one end of the norbornene double bond than the other,
thus leading to a predominance of a single enantiomer.
Furans and partially reduced furans constitute a large class
of naturally occurring compounds1 that can be found in a variety
of commercially important pharmaceuticals,2 as well as in flavor
and fragrance additives.3 Consequently, efficient syntheses of
such compounds have attracted considerable interest from
organic chemists.4 Among the general synthetic routes to furans
are (i) regioselective introduction of substituents into simple
furans5 and (ii) cyclization reactions of appropriate acyclic
precursors.6,7 Despite these advances, room still exists for
developing alternative and environmentally friendly approaches
to the synthesis of such compounds. As part of a long-term
interest in solid-state organic photochemistry,8 we serendipi-
tously discovered a new approach to the asymmetric synthesis
of dihydrofurans via a novel retro-Claisen photorearrangement.
In this paper, we present what we have learned to date about
this unusual and interesting new reaction.
Our initial discovery in this area was made during the
synthesis of a series of 7-benzoylnorbornane derivatives, which
were subsequently shown to undergo diastereo- and enantio-
selective Yang photocyclization in the crystalline state.9 The
norbornane derivatives were synthesized via catalytic hydro-
genation of the corresponding norbornenes, an example of which
is keto-ester 1b (Scheme 1). In a spirit of curiosity, compound
1b was irradiated at >290 nm (Pyrex) in an acetonitrile solution
and, to our delight, found to give a single product in 91%
isolated yield. Based on its spectroscopic properties, in particular
its 1D and 2D 1H NMR spectra, this photoproduct was assigned
the cis-dihydrofuran-containing structure 5b.
The generality of this transformation, a formal retro-Claisen
rearrangement, was tested by photolyzing the ketones shown
in Table 1. Compounds 1a-1f, all of which are expected to
have lowest energy n,π* triplet states, formed the dihydrofuran
photoproduct 5 in excellent yield. In contrast, the p-methoxy-
phenyl derivative 1g, whose lowest triplet state is undoubtedly
π,π* in nature, failed to react, and the aliphatic ketone 1h
underwent inefficient formation of oxetane 4h upon irradiation.
The results suggest the mechanism shown in Scheme 1 in
which the (n,π*)3 state of the ketone undergoes initial carbon-
oxygen bonding to form triplet 1,4-biradical 3. This step is
(1) Gokel, G. W.; Korzeniowski, S. H. Macrocyclic Polyether Syntheses;
Springer-Verlag: Berlin, 1982.
(2) (a) Schulte, G.; Scheuer, P. J.; McConnel, O. J. HelV. Chim. Acta 1980,
63, 2159. (b) Hertz, W.; Kumar, N.; Blount, J. F. J. Org. Chem. 1981, 46,
1356.
(3) Chemistry of Heterocyclic Compounds in FlaVours and Aromas; Vernin,
G., Ed.; Halsted Press: New York, 1982.
(4) Dean, F. M. In AdVances in Heterocyclic Chemistry; Katrizky, A. R., Ed.;
Academic Press: New York, 1982; Vol. 30, p 167.
(5) (a) Nolan, S. M.; Cohen, T. J. Org. Chem. 1981, 46, 2473. (b) Tanis, S. P.
Tetrahedron Lett. 1982, 23, 3115.
(6) (a) Marshall, J. A.; DuBay, W. J. J. Am. Chem. Soc. 1992, 114, 1450. (b)
Okura, K.; Furuune, M.; Miura, M.; Nomura, M. J. Org. Chem. 1992, 57,
4754. (c) Katritzky, A. R.; Li, J.; Gordeev, M. F. J. Org. Chem. 1993, 58,
3038. (d) Frey, H. Synlett 1993, 905. (e) Tenaglia, A.; Brazidec, J. Y. Le;
Souchon, F. Tetrahedron Lett. 1995, 36, 4241. (f) Antonioletti, R.; Cecchini,
C.; Ciani, B.; Magnanti, S. Tetrahedron Lett. 1995, 36, 9019. (g) Hayashi,
T.; Yamasaki, K.; Mimura, M.; Uozumi, Y. J. Am. Chem. Soc. 2004, 126,
3036. (h) Hu, Y.; Nawoschik, K. J.; Liao, Y.; Ma, J.; Fathi, R.; Yang, Z.
J. Org. Chem. 2004, 69, 2235. (i) Iqbal, J.; Bathia, B.; Nayyar, N. K. Chem.
ReV. 1994, 94, 519.
(7) For the photochemical preparation of dihydrobenzofurans, see: (a) Pappas,
S. P.; Pappas, B. C.; Blackwell, J. E., Jr. J. Org. Chem. 1967, 32, 3066.
(b) Kraus, G. A.; Zhang, N. J. Org. Chem. 2000, 65, 5644.
(8) Gamlin, J. N.; Jones, R.; Leibovitch, M.; Patrick, B.; Scheffer, J. R.; Trotter,
J. Acc. Chem. Res. 1996, 29, 203.
(9) Patrick, B. O.; Scheffer, J. R.; Scott, C. Angew. Chem. 2003, 42, 3775.
9
10.1021/ja043254j CCC: $30.25 © 2005 American Chemical Society
J. AM. CHEM. SOC. 2005, 127, 2725-2730
2725

A R T I C L E S
Scheme 1
Xia et al.
Scheme 2
Wagner, and co-workers showed that such a process is operative
in the photochemistry of two γ,δ-unsaturated phenyl ketones
(1-phenyl-4-hexene-1-one and 1-phenyl-2-ethyl-4-pentene-1-
one).10 Ketones of general structure 1 are also γ,δ-unsaturated
aryl ketones, and it seems likely that quenching is occurring in
these cases as well.
Based on the product distribution, it is evident that path 3
(cleavage of bond a) is favored over path 2 (biradical closure),
which makes sense given the high strain energy of the oxetane.11
Only in the case of aliphatic ketone 1h was oxetane formation
observed, a reaction that is most likely singlet-mediated.12 The
failure of p-methoxyphenyl ketone 1g to react is also consistent
with the proposed mechanism. Such ketones have lowest π,π*
triplet excited states, which are known to form oxetanes
inefficiently.13 Because the retro-Claisen and oxetane-forming
reactions share the same first step, it is not surprising that neither
is formed in the case of reactant 1g.
Table 1. Irradiation of Norbornenes in Acetonitrile Solution
Thermal retro-Claisen rearrangements have been investigated
by Boeckman and others,14 and it was therefore of interest to
determine whether the 1 to 5 transformation could be initiated
thermally. However, as shown in Scheme 2, heating ketone 1b
at 210 °C for 52 h produced a 6:4 mixture of 1b and its epimer
6b. The same mixture was formed when pure ketone 6b was
thermolyzed. This reaction most likely takes place through
formation of the corresponding enol, although a mechanism
involving carbon-carbon bond rupture, rotation, and reclosure
cannot be ruled out completely.
The retro-Claisen photorearrangement of ketone 1 to dihy-
drofuran derivative 5 is suitable for asymmetric induction
studies, because it converts an achiral reactant to a chiral
product, and it was therefore decided to apply the solid-state
ionic chiral auxiliary approach to this problem.15 To this end,
keto-acid 1i (Scheme 3) was prepared and treated with a variety
of optically pure amines to form the corresponding ammonium
carboxylate salts 1j (Table 2). Such salts are required to
crystallize in chiral space groups, which provide the asymmetric
environment responsible for chiral induction. Crystals of the
isolated yield
compound
time (h)
conv. (%)
of product 5 (%)
1a
1.3
4.4
1.4
4.5
1.4
5.0
1.4
6.5
1.6
7.5
1.6
8.0
20
54
97
53
98
51
99
47
93
44
89
31
87
a
96
91
98
91
94
89
94
87
89
83
90
76
a
1b
1c
1d
1e
1f
1g
1h
0.5
5.0
4hb
a Trace amounts of several unidentified products formed according to
GC. b Identified by NMR as a mixture with starting material 1h. Prolonged
irradiation led to the formation of several additional unidentified byproducts.
identical to the first step of the triplet-mediated Paterno-Bu¨chi
reaction. Biradical 3 has three possible fates: (1) intersystem
crossing accompanied by cleavage of carbon-oxygen bond b
to regenerate ketone 1, (2) intersystem crossing accompanied
by biradical closure to form oxetane 4, and (3) intersystem
crossing accompanied by cleavage of carbon-carbon bond a
to produce dihydrofuran derivative 5. To get an indication of
the importance of pathway 1 (regeneration of starting ketone),
a quantum yield determination was carried out. In benzene, using
valerophenone actinometry, the quantum yield for formation of
dihydrofuran 5b from ketone 1b was found to be 0.021, a value
that suggests that reversion to starting material plays a significant
role in the partitioning of biradical 3. Another possible reason
for the low quantum yield is intramolecular charge-transfer
quenching of the triplet excited state. In 1975, Morrison,
(10) Morrison, H.; Tisdale, V.; Wagner, P. J.; Liu, K.-C. J. Am. Chem. Soc.
1975, 97, 7189. We thank a referee for bringing this paper to our attention.
(11) The difference in strain energy between oxetane 4b and compound 5b
calculated by molecular mechanics is 107.44 kcal/mol. The calculations
were performed using the HyperChem/ChemPlus software package (version
5.11/2.0).
(12) As a general rule, aliphatic aldehydes and ketones undergo stereospecific
oxetane formation through their (n,π*)1 excited states. See, for example:
Arnold, D. R.; Hinman, R. L.; Glick, A. H. Tetrahedron Lett. 1964, 1425.
Yang, N. C.; Eisenhardt, W. J. Am. Chem. Soc. 1971, 93, 1277.
(13) (a) Arnold, D. R. AdV. Photochem. 1968, 6, 301. (b) Turro, N. J. Modern
Molecular Photochemistry; Benjamin/Cummings: Menlo Park, CA, 1978;
Chapter 11.3.
(14) (a) Boeckman, R. K., Jr.; Reeder, M. R. J. Org. Chem. 1997, 62, 6456. (b)
Boeckman, R. K., Jr.; Flann, C. J.; Poss, K. M. J. Am. Chem. Soc. 1985,
107, 4359. (c) Boeckman, R. K., Jr.; Zhang, J.; Reeder, M. R. Org. Lett.
2002, 4, 3891.
(15) Scheffer, J. R. Can. J. Chem. 2001, 79, 349.
9
2726 J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005

Asymmetric Synthesis of Dihydrofurans
A R T I C L E S
Scheme 3
Table 2. Asymmetric Induction in the Irradiation of Salts 1j in the
Crystalline Statea
conversion
(%)b
amine
temp
ee (%)
Rc
Figure 1. ORTEP representation of the X-ray crystal structure of the (S)-
(-)-1-cyclohexylethylamine salt of keto-acid 1i with 50% probability
thermal ellipsoids.
(S)-(-)-1-p-tolylethylamine
-20 °C
95
68
97
47
53
89
100
59
90
68
72
100
85
72
86
43
83
90
74
60
82
59
60
77
93
90
75
91
91
88
71
90
57
80
72
62
95
53
35
74
71
37
60
58
57
28
43
42
+
+
+
-
-
-
+
+
+
-
-
-
+
+
+
+
+
+
-
-
-
-
-
-
room temp
room temp
-20 °C
(R)-(-)-1-aminoindan
(R)-(+)-1-phenylethylamine
(S)-(-)-1-phenylethylamine
L-prolinamide
room temp
room temp
-20 °C
room temp
room temp
-20 °C
room temp
room temp
-20 °C
room temp
room temp
Interestingly, lowering the photolysis temperature in the case
of the (1R,2R)-(-)-2-amino1-phenyl-1,3-propanediol salt actu-
ally decreased the ee slightly. At temperatures much below -20
°C, the solid-state photoreaction became impracticably slow.
To rationalize the enantioselectivity observed in the solid
state, the X-ray crystal structure of the (S)-(-)-1-cyclohexyl-
ethylamine salt was determined and is presented in Figure 1.
Under the influence of the ionic chiral auxiliary, the carboxylate
reactant crystallizes in a homochiral conformation in which the
carbonyl oxygen is significantly closer to Ca (2.95 Å) than to
Cb (3.29 Å). In addition, the n-orbital on oxygen, assumed to
lie in the plane of the carbonyl group, can be seen to be more
favorably oriented for bond formation with Ca than Cb.17 As a
result, the Ca-O bond is formed preferentially, affording a 1,4-
biradical that leads to one enantiomer of the final photoproduct.
The optical antipode of the photoproduct results from Cb-O
bond formation, which requires a large amplitude rotation of
the pendant aryl group that is topochemically and geometrically
disfavored in the crystalline state. The enantioselectivity is
therefore the result of preorganization of the reactant in a
homochiral conformation favorable for the formation of a single
enantiomer of the product.
(1S,2R)-(-)-cis-1-amino-indanol -20 °C
room temp
room temp
(S)-(-)-1-cyclohexyl-ethylamine -20 °C
room temp
room temp
-20 °C
room temp
room temp
(1R,2R)-(-)-2-amino-1-phenyl-
1,3-propanediol
a Samples were irradiated through Pyrex using a 450-W Hanovia
medium-pressure mercury lamp. b Conversion % based on GC. c Sign of
rotation of major enantiomer of photoproduct 5b at the sodium D-line.
salts (2-5 mg) were crushed between two Pyrex microscope
slides, sealed in polyethylene bags under nitrogen, and irradiated
with a 450 W medium-pressure mercury lamp.16 Following
photolysis, the samples were treated with ethereal diazomethane
(caution), and the resulting methyl esters were analyzed by chiral
HPLC to obtain the enantiomeric excess (ee) values and by GC
for the extent of conversion. As in solution, dihydrofuran
compound 5b was the sole GC-detectable photoproduct in the
solid state. The results of the enantiomeric excess determinations
are summarized in Table 2.
In summary, the present study reports a convenient approach
to the synthesis of highly enantiomerically enriched dihydrofuran
compounds via a novel retro-Claisen photorearrangement. We
are continuing to explore the scope and generality of this
interesting and unusual transformation.
Experimental Section
Synthesis of the Weinreb Amide of Bicyclo[2.2.1]hept-2-ene-syn-
7-carboxylate. The known carboxylic acid, bicyclo[2.2.1]hept-2-ene-
syn-7-carboxylate,18 was converted to its Weinreb amide by the general
As can be seen from the data in Table 2, the enantiomeric
excess values obtained for photoproduct 5b in the solid state
ranged from 28% to 95%. As expected for a well-behaved
system, the use of (R)-(+)- and (S)-(-)-1-phenylethylamine as
chiral auxiliaries led to the optical antipodes of dihydrofuran
5b. For the salts studied, there was a decline in photoproduct
ee with increasing conversion, which is presumably due to the
breakdown in order of the crystal lattice as product replaces
starting material. This could be compensated to a certain extent
by performing the photolyses at -20 °C, which had a
particularly strong effect in the case of the L-prolinamide salt.
1
procedure reported by Jones et al.,19,20 mp 64 °C (ether/pet ether). H
NMR (400 MHz, CDCl3): δ 5.96 (m, 2H), 3.64 (s, 3H), 3.15 (d, J )
1.5 Hz, 2H), 3.08 (s, 3H), 2.52 (s, 1H), 1.72 (m, 2H), 1.02 (m, 2H).
13C NMR (100 MHz, CDCl3): δ 182.3 (+), 132.4 (-), 62.3 (-), 62.3
(-), 60.9 (-), 44.3 (-), 24.8 (+). IR (KBr) νmax: 1646, 1479, 1387,
1175, 974, 877, 718, 511 cm-1. LRMS (EI): 181 [M+], 121, 103, 93,
(17) A rough estimate of the orientation of the n-orbital with respect to Ca and
Cb is given by the magnitude of the dihedral angle formed by the oxygen
atom, the carbonyl carbon, the R-carbon atom, and Ca or Cb. This angle is
-34.8° for Ca and -67.8° for Cb.
(16) Although not studied in the present instance, previous work from our group
has shown that the solid-state ionic chiral auxiliary procedure can be carried
out on scales as high as 500 mg and presumably even higher. For an
example, see: Scheffer, J. R.; Wang, K. Synthesis 2001, 1253.
(18) Beckman, S.; Geiger, H. Chem. Ber. 1961, 94, 48.
(19) Nahmn, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815.
(20) Jones, T. K.; Mills, S. G.; Reamer, R. A.; Askin, D.; Desmond, R.; Volante,
R. P.; Shinkai, I. J. Am. Chem. Soc. 1989, 111, 1157.
9
J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005 2727

A R T I C L E S
Xia et al.
79, 77, 65. Anal. Calcd for C10H15NO2: C, 66.27; H, 8.34; N, 7.73.
Found: C, 66.31; H, 8.33; N, 7.70.
(-), 133.4 (-), 129.4 (-), 128.8 (-), 68.2 (-), 46.0 (-), 25.6 (+). IR
(KBr) νmax: 2977, 2812, 1679, 1375, 1217, 1008, 861, 761, 687 cm-1
.
LRMS (EI): 198 [M+], 183, 120, 105, 91, 77, 51. Anal. Calcd for
C14H14O: C, 84.81; H, 7.12. Found: C, 84.77; H, 7.13.
Synthesis of Keto-Ester 1b. Methyl 4-iodobenzoate (0.365 g, 1.39
mmol) was dissolved in THF (50 mL) and cooled to -40 °C.
Isopropylmagnesium chloride (0.73 mL, 2 M, 1.46 mmol) was added,
and the solution was stirred for 1 h. A solution of the Weinreb amide
prepared above (0.24 g, 1.31 mmol) in THF (10 mL) was added, and
the mixture was stirred for 2 h, gradually warmed to -20 °C, stirred
for 2 h, and finally stirred overnight at room temperature. The reaction
was quenched by addition of a saturated solution of ammonium chloride
(25 mL), followed by removal of THF in vacuo and its replacement
with diethyl ether (25 mL). The ethereal solution was washed with
10% HCl (2 × 15 mL) and water (3 × 20 mL) before being dried over
magnesium sulfate. Removal of the solvent in vacuo gave a yellow
oil, which was purified by chromatography (10% ether/pet ether) to
give a white solid (0.101 g, 30%), mp 128-129 °C (ether/pet ether).
1H NMR (400 MHz, CDCl3): δ 8.06 (m, 2H), 7.85 (m, 2H), 5.95 (t,
J ) 1.8 Hz, 2H), 3.91 (s, 3H), 3.25 (m, 2H), 3.21 (brs, 1H), 1.91 (m,
2H), 1.11 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 199.2 (+), 166.2
(+), 146.6 (+), 133.3 (+), 132.7 (-), 129.6 (-), 127.9 (-), 67.7 (-),
52.4 (-), 45.2 (-), 25.1 (+). IR (KBr) νmax: 3061, 2958, 1716, 1405,
1116, 873, 770, 696 cm-1. LRMS (EI): 256 [M+], 197, 179, 164, 135,
103, 91, 77. Anal. Calcd for C16H16O3: C, 74.98; H, 6.29. Found: C,
75.15; H, 6.36.
1
Ketone 1c. Yield 88%, oil. H NMR (400 MHz, CD3CN): δ 7.89
(m, 2H), 7.17 (m, 2H), 5.89 (m, 2H), 3.28 (brs, 1H), 3.17 (d, J ) 1.2
Hz, 2H), 1.92 (m, 2H), 1.04 (m, 2H). 13C NMR (100 MHz, CD3CN):
δ 198.7 (+), 134.9 (+), 133.6 (-), 131.7 (-), 128.7 (+), 116.2 (-),
68.1 (-), 46.1 (-), 25.6 (-). IR (neat) νmax: 2987, 2863, 1673, 1436,
1216, 1014, 873, 770, 696 cm-1. LRMS (EI): 216 [M+], 201, 159,
138, 123, 95, 75, 51. HRMS (EI) calcd for C14H13FO: 216.2508.
Found: 216.2510.
1
Ketone 1d. Yield 64%, oil. H NMR (400 MHz, CD3CN): δ 8.06
(m, 2H), 7.84 (m, 1H), 7.62 (m, 1H), 5.87 (m, 2H), 3.35 (brs, 1H),
3.18 (d, J ) 1.6 Hz, 2H), 1.92 (m, 2H), 1.03 (m, 2H). 13C NMR (100
MHz, CD3CN): δ 199.2 (+), 139.0 (+), 133.7 (-), 132.7 (-), 131.4
(+), 130.6 (-), 129.8 (-), 123.7 (+), 125.3 (-), 68.2 (-), 46.04 (-),
25.6 (+). IR (neat) νmax: 2937, 2815, 1679, 1347, 1219, 997, 864,
753, 677, 593 cm-1. LRMS (EI): 266 [M+], 251, 225, 188, 173, 145,
93, 77, 51. HRMS (EI) calcd for C15H13F3O: 266.2583. Found:
266.2586.
1
Ketone 1e. Yield 78%, oil. H NMR (400 MHz, CD3CN): δ 7.76
(m, 2H), 7.52 (m, 1H), 7.42 (m, 1H), 5.88 (m, 2H), 3.26 (brs, 1H),
3.16 (d, J ) 1.4 Hz, 2H), 1.92 (m, 2H), 1.01 (m, 2H). 13C NMR (100
MHz, CD3CN): δ 199.0 (+), 140.0 (+), 135.2 (+), 133.6 (-), 133.2
(-), 131.2 (-), 128.5 (-), 127.4 (-), 68.2(-), 46.0 (-), 25.6 (+). IR
Synthesis of Carboxylic Acid 1i. 4-Iodobenzoic acid (1.30 g, 5.24
mmol) was dissolved in THF (50 mL) under nitrogen and cooled to
-30 °C. Isopropylmagnesium chloride (5.25 mL, 2 M, 10.5 mmol)
was added dropwise, and the resulting solution was stirred for 1 h. On
addition of the second Grignard equivalent, a light brown precipitate
began to form. The Weinreb amide prepared above (0.99 g, 5.47 mmol)
in THF (5 mL) was added dropwise, and the resulting mixture was
gradually warmed to -20 °C and stirred for 4 h during which time the
precipitate dissolved. The solution was allowed to stir at room
temperature overnight and then quenched with saturated ammonium
chloride. After acidification with 10% HCl, the THF was replaced by
ether and extracted with 10% HCl and water. The organic layer was
then washed with saturated sodium bicarbonate (3 × 50 mL), and the
combined aqueous portions were acidified with concentrated HCl
causing acid 1i to precipitate. The suspended precipitate was washed
with ether (2 × 50 mL), and the organic portions were washed with
water (3 × 50 mL) before being dried over magnesium sulfate. Removal
of the solvent gave an off-white solid composed of the desired acid
and benzoic acid that was purified by recrystallization from methanol
to give pure acid 1i as a white solid (0.58 g, 44%), mp 242 °C
(neat) νmax: 2969, 2779, 1643, 1412, 1216, 997, 861, 685, 597 cm-1
.
LRMS (EI): 234 [M+, {37Cl}], 232 [M+, {35Cl}], 217, 179, 154, 139,
111, 75, 51. HRMS (EI) calcd for C14H13ClO: 232.0654 {35Cl},
234.0673 {37Cl}. Found: 232.0655 {35Cl}, 234.0673 {37Cl}.
1
Ketone 1f. Yield 83%, mp 73 °C (ether/pet ether). H NMR (400
MHz, CD3CN): δ 7.62 (m, 2H), 7.34 (m, 2H), 5.88 (m, 2H), 3.27
(brs, 1H), 3.17 (d, J ) 1.2 Hz, 2H), 2.36 (s, 3H), 1.92 (m, 2H), 1.03
(m, 2H). 13C NMR (100 MHz, CD3CN): δ 200.3 (+), 139.4 (+), 138.4
(+), 134.1 (-), 133.7 (-), 129.3 (-), 129.2 (-), 126.1 (-), 68.3 (-),
46.1 (-), 25.7 (+), 21.4 (-). IR (KBr) νmax: 2979, 2814, 1681, 1345,
1219, 998, 867, 749, 673, 598 cm-1. LRMS (EI): 212 [M+], 197, 179,
134, 119, 91, 65, 51. Anal. Calcd for C15H16O: C, 84.87; H, 7.60.
Found: C, 84.77; H, 7.61.
1
Ketone 1g. Yield 73%, mp 76 °C (ether/pet ether). H NMR (400
MHz, CD3CN): δ 7.82 (d, J ) 8.8 Hz, 2H), 6.93 (d, J ) 8.8 Hz, 2H),
5.88 (d, J ) 1.4 Hz, 2H), 3.83 (s, 3H), 3.25 (brs, 1H), 3.17 (brs, 2H),
1.92 (m, 2H), 1.01 (m, 2H). 13C NMR (100 MHz, CD3CN): δ 198.4
(+), 164.0 (+), 133.6 (-), 131.3 (+), 131.2 (-), 114.5 (-), 68.1 (-),
56.2 (-), 46.2 (-), 25.7 (+). IR (KBr) νmax: 2930, 2834, 1673, 1356,
1207, 997, 867, 753, 677, 591 cm-1. LRMS (EI): 228 [M+], 213, 185,
150, 135, 107, 92, 77, 63. Anal. Calcd for C15H16O2: C, 78.92; H,
7.06. Found: C, 78.89; H, 7.09.
Ketone 1h. Yield 91%, oil. 1H NMR (400 MHz, C6D6): δ 5.76 (m,
2H), 2.96 (d, J ) 1.6 Hz, 2H), 1.95 (q, 2H), 1.84 (brs, 1H), 1.42 (m,
2H), 0.93 (m, 2H), 0.80 (m, 3H). 13C NMR (100 MHz, C6D6): δ 208.2
(+), 133.4 (-), 70.2(-), 44.1 (-), 35.2 (+), 25.2 (+), 7.7 (-). IR
(neat) νmax: 2922, 2813, 1672, 1217, 677, 591 cm-1. LRMS (EI): 150
[M+], 135, 121, 93, 72, 57. HRMS (EI) calcd for C10H14O: 150.1045.
Found: 105.1043.
1
(methanol). H NMR (400 MHz, DMSO): δ 8.01 (m, 2H), 7.90 (m,
2H), 5.89 (t, J ) 1.8 Hz, 2H), 3.39 (brs, 1H), 3.15 (m, 2H), 1.92 (m,
2H), 0.98 (m, 2H). 13C NMR (100 MHz, DMSO): δ 198.9 (+), 166.6
(+), 140.0 (+), 134.0 (+), 132.8 (-), 129.5 (-), 128.0 (-), 67.2 (-),
44.6 (-), 24.7 (+). IR (KBr) νmax: 3200-2700 (br), 2988, 2550, 1572,
1408, 1216, 1037, 985, 874, 786, 712 cm-1. LRMS (EI): 242 [M+],
227, 197, 179, 150, 149, 91, 77, 65, 50. Anal. Calcd for C15H14O3: C,
74.36; H, 5.82. Found: C, 74.35; H, 5.77.
General Procedure for Synthesis of Ketones 1a and 1c-h. To a
solution of the Weinreb amide prepared above (100 mg, 0.55 mmol)
in 3 mL of THF was added 3 equiv of the appropriate freshly prepared
Grignard reagent in THF. The mixture was refluxed until the amide
was consumed (checked by TLC), cooled to room temperature, poured
into 30 mL of 10% HCl, stirred for 30 min, and extracted with diethyl
ether (3 × 30 mL). The combined organic layer was washed with water
(2 × 30 mL) and dried over magnesium sulfate. The solvent was
removed in vacuo, and the residue was purified by silica gel column
chromatography (ether/pet ether) to give ketones 1a and 1c-h.
Irradiation of Keto-Ester 1b in Acetonitrile. Keto-ester 1b (100
mg, 0.39 mmol) was dissolved in acetonitrile (50 mL) and purged with
nitrogen for 15 min. The solution was then irradiated through Pyrex
with a 450 W medium-pressure mercury lamp for 3 h before the
acetonitrile was removed in vacuo. The residue was purified by silica
gel column chromatography (10% ether/pet ether) to give compound
1
5b as a white solid (91 mg, 91%), mp 58 °C. H NMR (400 MHz,
1
Ketone 1a. Yield 90%, mp 61 °C (ether/pet ether). H NMR (400
C6D6): δ 8.10 (m, 2H), 7.62 (m, 2H), 5.99 (m, 1H), 5.87 (t, J ) 1.8
Hz, 1H), 5.21 (d, J ) 2.8 Hz, 1H), 4.68 (d, J ) 8.8 Hz, 1H), 3.47 (s,
3H), 2.63 (m, 1H), 1.77 (m, 1H), 1.45 (m, 2H), 1.23 (m, 1H). 13C NMR
(100 MHz, C6D6): δ 166.3 (+), 155.4 (+), 135.8 (+), 132.7 (-), 130.3
MHz, CD3CN): δ 7.82 (m, 2H), 7.55 (m, 1H), 7.44 (m, 2H), 5.88 (m,
2H), 3.31 (brs, 1H), 3.18 (d, J ) 1.4 Hz, 2H), 1.93 (m, 2H), 1.04 (m,
2H). 13C NMR (100 MHz, CD3CN): δ 200.0 (+), 138.3 (+), 133.6
9
2728 J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005

Asymmetric Synthesis of Dihydrofurans
A R T I C L E S
(+), 129.9 (-), 125.4 (-), 125.2 (-), 103.4 (-), 77.2 (-), 51.5 (-),
41.4 (-), 26.0 (+), 23.2 (+). IR (KBr) νmax: 1716, 1679, 1225, 1219,
873, 770, 696 cm-1. LRMS (EI): 256 [M+], 241, 197, 178, 163, 147,
91. Anal. Calcd for C16H16O3: C, 74.98; H, 6.29. Found: C, 75.81; H,
6.33.
General Procedure for Irradiation of Ketones 1a and 1c-g in
Acetonitrile Solution. The solutions of ketones 1a and 1c-g (80 mg)
in acetonitrile (40 mL) were purged with nitrogen for 15 min and then
irradiated through Pyrex with a 450 W medium-pressure mercury lamp
for 1.3-20 h. The solvent was removed in vacuo and the residues were
purified by silica gel chromatography (ether/pet ether) to give dihy-
drofurans 5a and 5c-g.
(100 MHz, C6D6): δ 92.8 (+), 80.9 (-), 52.6 (-), 52.5 (-), 49.3 (-),
36.4 (-), 25.2 (+), 24.6 (+), 23.7 (+), 9.1 (-). GCMS (EI): 150 [M+],
135, 121, 108, 91, 79, 57.
General Procedure for the Preparation of Salts 1j. To keto-acid
1i (80 mg, 0.33 mmol) in 5 mL of diethyl ether was added 1 equiv of
optically pure amine. Upon addition, a precipitate formed immediately.
The resulting suspension was suction-filtered to give the salt, which
was recrystallized from methanol.
(S)-(-)-1-p-Tolylethylamine Salt. Mp 189-191 °C (methanol). 1H
NMR (400 MHz, CD3OD): δ 7.84 (d, J ) 8.4 Hz, 2H), 7.70 (d, J )
8.4 Hz, 2H), 7.19 (d, J ) 8.0 Hz, 2H), 7.11 (d, J ) 8.0 Hz, 2H), 5.78
(m, 2H), 4.27 (m, 1H), 3.25 (brs, 1H), 3.18 (m, 1H), 3.09 (brs, 2H),
Dihydrofuran 5a. Yield 91%, mp 56 °C (ether/pet ether). 1H NMR
(400 MHz, CD3CN): δ 7.54 (m, 2H), 7.32 (m, 3H), 6.13 (m, 1H),
5.96 (m, 1H), 5.51 (d, J ) 2.8 Hz, 1H), 4.78 (d, J ) 8.2 Hz, 1H), 3.00
(m, 1H), 2.12 (m, 1H), 1.89 (m, 2H), 1.29 (m, 1H). 13C NMR (100
MHz, CD3CN): δ 154.0 (+), 133.9 (-), 132.2 (+), 129.2 (-), 129.1
(-), 125.7 (-), 125.6 (-), 102.0 (-), 77.7 (-), 41.7 (-), 26.6 (+),
2.21 (s, 3H), 1.85 (m, 2H), 3.06 (d, J ) 6.8 Hz, 3H), 0.96 (m, 2H). 13
C
NMR (100 MHz, CD3OD): δ 202.0 (+), 174.0 (+), 140.2 (+), 139.8
(+), 136.9 (+), 133.3 (+), 133.8 (-), 130.8 (-), 130.2 (-), 128.7
(-), 127.6 (-), 68.9 (-), 52.0 (-), 46.5 (-), 25.9 (+), 21.1 (-), 20.8
(-). IR (KBr) νmax: 2945, 1677, 1516, 1091, 879, 779, 696, 517 cm-1
.
LRMS (ESI): 378 [M+ + 1], 360, 281, 243, 192. Anal. Calcd for
C24H27NO3: C, 76.36; H, 7.21; N, 3.71. Found: C, 76.67; H, 7.24; N,
3.65.
23.6 (+). IR (KBr) νmax: 1731, 1671, 1193, 1207, 893, 761, 689 cm-1
.
LRMS (EI): 198 [M+], 183, 141, 120, 105, 91, 77, 51. Anal. Calcd
for C14H14O: C, 84.81; H, 7.12. Found: C, 84.92; H, 7.07.
(R)-(-)-1-Aminoindan Salt. Mp 173-177 °C (methanol). 1H NMR
(400 MHz, CD3OD): δ 7.90 (d, J ) 8.4 Hz, 2H), 7.72 (d, J ) 8.4 Hz,
2H), 7.38 (d, J ) 7.6 Hz, 1H), 7.19 (m, 3H), 5.80 (d, J ) 1.6 Hz, 2H),
4.67 (m, 1H), 3.27 (brs, 1H), 3.19 (m, 2H), 3.05 (m, 3H), 2.88 (m,
1H), 2.48 (m, 1H), 1.98 (m, 1H), 1.87 (m, 2H), 0.99 (m, 2H). 13C NMR
(100 MHz, CD3OD): δ 201.9 (+), 173.1 (+), 145.4 (+), 141.6 (+),
140.2 (+), 139.8 (+), 133.8 (-), 130.7 (-), 130.3 (-), 128.7 (-),
128.2 (-), 126.4 (-), 125.5 (-), 69.0 (-), 56.9 (-), 46.5 (-), 31.6
(+), 31.0 (+), 25.9 (+). IR (KBr) νmax: 2978, 1691, 1573, 1291, 1013,
719, 687, 517 cm-1. LRMS (ESI): 376 [M+ + 1], 298, 267, 265, 243,
192, 179. Anal. Calcd for C24H25NO3: C, 76.77; H, 6.71; N, 3.73.
Found: C, 76.86; H, 6.63; N, 3.64.
1
Dihydrofuran 5c. Yield 89%, oil. H NMR (400 MHz, CD3CN):
δ 7.16 (m, 2H), 7.07 (m, 2H), 6.12 (m, 1H), 5.95 (m, 1H), 5.46 (d, J
) 2.8 Hz, 1H), 4.80 (d, J ) 8.8 Hz, 1H), 3.01 (m, 1H), 2.06 (m, 1H),
1.89 (m, 2H), 1.28 (m, 1H). 13C NMR (100 MHz, CD3CN): δ 155.1
(+), 134.8 (+), 134.0 (-), 128.7 (+), 127.8 (-), 127.7 (-), 125.5
(-), 116.1 (-), 115.9 (-), 101.8 (-), 77.8 (-), 41.7 (-), 26.6 (+),
23.6 (+). IR (neat) νmax: 1809, 1702, 1224, 1201, 879, 789, 654 cm-1
.
LRMS (EI): 216 [M+], 201, 183, 138, 95, 77, 51. HRMS (EI) calcd
for C14H13FO: 216.2508. Found: 216.2511.
1
Dihydrofuran 5d. Yield 87%, oil. H NMR (400 MHz, CD3CN):
δ 7.75 (m, 2H), 7.57 (m, 1H), 7.48 (m, 1H), 6.12 (m, 1H), 5.94 (m,
1H), 5.62 (d, J ) 2.8 Hz, 1H), 4.80 (d, J ) 8.8 Hz, 1H), 3.02 (m, 1H),
2.05 (m, 1H), 1.86 (m, 2H), 1.25 (m, 1H). 13C NMR (100 MHz, CD3-
CN): δ 153.7 (+), 134.2 (-), 131.1 (+), 130.9 (+), 129.4 (-), 126.0
(+), 125.6 (-), 125.4 (-), 122.3 (-), 104.2 (-), 78.0 (-), 41.8 (-),
26.5 (+), 23.6 (+). IR (neat) νmax: 1789, 1643, 1221, 1208, 897, 767,
657 cm-1. LRMS (EI): 266 [M+], 251, 238, 188, 173, 145, 91, 77, 51.
HRMS (EI) calcd for C15H13F3O: 266.2583. Found: 266.2584.
(R)-(+)-1-Phenylethylamine and (S)-(-)-1-Phenylethylamine Salts.
1
Mp 187-189 °C (methanol). H NMR (400 MHz, CD3OD): δ 7.93
(d, J ) 8.2 Hz, 2H), 7.78 (d, J ) 8.2 Hz, 2H), 7.37 (m, 2H), 7.30 (m,
1H), 5.89 (s, 2H), 4.32 (q, J ) 6.7 Hz, 1H), 3.37 (s, 1H), 3.15 (s, 2H),
1.93 (d, J ) 7.2 Hz, 2H), 1.46 (d, J ) 6.8 Hz, 2H), 0.96 (m, 2H). 13
C
NMR (100 MHz, CD3OD): δ 198.9 (+), 168.3 (+), 142.0 (+), 141.8
(+), 137.7 (+), 132.7 (-), 129.0 (-), 128.4 (-), 127.6 (-), 127.3
(-), 126.5 (-), 67.1 (-), 49.9 (-), 44.7 (-), 24.7 (+), 22.1 (-). IR
(KBr) νmax: 2942, 1677, 1387, 1291, 1091, 879, 826, 709, 696, 536
cm-1. LRMS (ESI): 364 [M+ + 1], 348, 297, 265, 243, 173. Anal.
Calcd for C23H25NO3: C, 76.01; H, 6.93; N, 3.85. Found: C, 76.23;
H, 6.99; N, 3.74.
1
Dihydrofuran 5e. Yield 83%, oil. H NMR (400 MHz, CD3CN):
δ 7.52 (m, 3H), 7.40 (m, 1H), 6.13 (m, 1H), 5.94 (m, 1H), 5.55 (d, J
) 2.8 Hz, 1H), 4.80 (d, J ) 8.8 Hz, 1H), 3.01 (m, 1H), 2.14 (m, 1H),
1.79 (m, 2H), 1.25 (m, 1H). 13C NMR (100 MHz, CD3CN): δ 154.7
(+), 134.2 (+), 137.1 (+), 134.1 (-), 130.9 (-), 128.9 (-), 125.5
(-), 125.4 (-), 124.2 (-), 77.9 (-), 41.8 (-), 26.5 (+), 23.6 (+). IR
(neat) νmax: 1717, 1679, 1224, 1218, 863, 769, 679 cm-1. LRMS (EI):
234 [M+, {37Cl}], 232 [M+, {35Cl}], 217, 178, 154, 139, 111, 91, 77,
51. HRMS (EI) calcd for C14H13ClO: 232.0654 {35Cl}, 234.0673 {37Cl}.
Found: 232.0655 {35Cl}, 234.0672 {37Cl}.
Dihydrofuran 5f. Yield 76%, mp 67 °C (ether/pet ether). 1H NMR
(400 MHz, CD3CN): δ 7.34 (m, 2H), 7.20 (m, 1H), 7.10 (m, 1H),
6.11 (m, 1H), 5.95 (m, 1H), 5.46 (d, J ) 2.8 Hz, 1H), 4.78 (d, J ) 8.0
Hz, 1H), 2.99 (m, 1H), 2.30 (s, 3H), 2.06 (m, 1H), 1.87 (m, 2H), 1.27
(m, 1H). 13C NMR (100 MHz, CD3CN): δ 153.7 (+), 138.9 (+), 133.9
(-), 132.2 (+), 129.9 (-), 129.2 (-), 126.3 (-), 125.7 (-), 122.9
(-), 101.9 (-), 77.7 (-), 41.7 (-), 26.7 (+), 25.0 (+), 21.3 (-). IR
(KBr) νmax: 1717, 1658, 1224, 1203, 873, 790, 676 cm-1. LRMS (EI):
212 [M+], 197, 165, 134, 119, 91, 77, 65. Anal. Calcd for C15H16O:
C, 84.87; H, 7.60. Found: C, 84.81; H, 7.66.
1
L-Prolinamide Salt. Mp 171-173 °C (methanol). H NMR (400
MHz, CD3OD): δ 7.88 (d, J ) 8.4 Hz, 2H), 7.73 (d, J ) 8.4 Hz, 2H),
5.80 (m, 2H), 4.13 (m, 1H), 3.21 (m, 4H), 3.11 (brs, 2H), 2.32 (m,
1H), 1.92 (m, 5H), 0.99 (m, 2H). 13C NMR (100 MHz, CD3OD): δ
202.0 (+), 173.3 (+), 172.4 (+), 141.7 (+), 140.2 (+), 133.8 (-),
130.3 (-), 128.8 (-), 68.9 (-), 61.0 (-), 47.3 (+), 46.5 (-), 31.2
(+), 25.9 (+), 25.3 (+). IR (KBr) νmax: 2951, 1637, 1521, 1224, 1087,
865, 773, 697, 552 cm-1. LRMS (ESI): 357 [M+ + 1], 297, 265, 229,
209, 137. Anal. Calcd for C20H24N2O4: C, 67.40; H, 6.79; N, 7.86.
Found: C, 64.88; H, 6.99; N, 7.57. Anal. Calcd for C20H24N2O4‚
0.75H2O: C, 64.94; H, 6.95; N, 7.57.
(1S,2R)-(-)-cis-1-Aminoindanol Salt. Mp 175-178 °C (methanol).
1H NMR (400 MHz, CD3OD): δ 7.86 (d, J ) 8.4 Hz, 2H), 7.70 (d, J
) 8.4 Hz, 2H), 7.34 (d, J ) 7.2 Hz, 1H), 7.20 (m, 3H), 5.78 (d, J )
1.4 Hz, 2H), 4.59 (m, 1H), 4.44 (d, J ) 6.0 Hz, 1H), 3.26 (brs, 1H),
3.19 (m, 2H), 3.09 (m, 3H), 2.91 (m, 1H), 1.86 (m, 2H), 0.98 (m, 2H).
13C NMR (100 MHz, CD3OD): δ 202.0 (+), 173.9 (+), 142.8 (+),
142.7 (+), 139.9 (+), 138.2 (+), 133.8 (-), 130.9 (-), 130.3 (-),
128.7 (-), 128.4 (-), 126.7 (-), 126.2 (-), 71.9 (-), 69.0 (-), 58.6
(-), 46.5 (-), 40.1 (+), 25.9 (+). IR (KBr) νmax: 3300, 2968, 1689,
1574, 1293, 1201, 1013, 773, 689, 573 cm-1. LRMS (ESI): 392 [M+
Irradiation of Ketone 1h. A solution of ketone 1h (30 mg) in C6D6
(3 mL) was purged with nitrogen for 5 min and then irradiated with a
450 W medium-pressure mercury lamp equipped with a quartz filter
for 0.5 h. The solution was then analyzed directly by NMR to obtain
1
the spectral data for oxetane 5h. H NMR (400 MHz, C6D6): δ 4.14
(brs, 1H), 2.88 (m, 1H), 2.71 (brs, 1H), 2.61 (m, 1H), 2.52 (m, 1H),
1.70 (m, 2H), 1.35 (m, 2H), 0.94 (m, 2H), 0.82 (m, 3H). 13C NMR
9
J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005 2729

A R T I C L E S
Xia et al.
+ 1], 300, 299, 265, 150. Anal. Calcd for C24H25NO4: C, 73.64; H,
6.44; N, 3.58. Found: C, 73.62; H, 6.47; N, 3.48.
2-propanol ) 90:10) to give the enantiomeric excesses, and GC analysis
(HP-35 column) to give the conversions.
(S)-(-)-1-Cyclohexylethylamine Salt. Mp 189-191 °C (methanol).
1H NMR (400 MHz, DMSO): δ 7.91 (d, J ) 8.4 Hz, 2H), 7.91 (d, J
) 8.4 Hz, 2H), 5.88 (d, J ) 1.7 Hz, 2H), 3.36 (s, 1H), 3.14 (brs, 2H),
2.96 (q, J ) 6.4 Hz, 1H), 1.92 (m, 2H), 1.70 (m, 2H), 1.68 (brs, 2H),
1.59 (m, 1H), 1.45 (m, 1H), 1.12 (d, J ) 6.7 Hz, 3H), 1.11 (m, 3H),
0.97 (m, 2H), 0.96 (m, 2H). 13C NMR (100 MHz, DMSO): δ 198.9,
168.5, 143.1, 137.2, 132.7, 128.9, 127.1, 67.1, 50.7, 49.7, 41.1, 28.6,
27.0, 25.7, 25.6, 25.5, 24.7, 15.8. IR (KBr) νmax: 2929, 1681, 1377,
1350, 1192, 1060, 1032, 985, 816, 781, 553 cm-1. LRMS (ESI): 370
[M+ + 1], 313, 277, 243, 139. Anal. Calcd for C23H31NO3: C, 74.76;
H, 8.46; N, 3.79. Found: C, 75.01; H, 8.46; N, 3.81.
Thermal Reaction of Ketone 1b. Ketone 1b (40 mg, 0.16 mmol)
was placed in a sealed tube and heated at 210 °C in a sand bath for 52
h. The reaction mixture was separated on a silica gel column to afford
starting material (23 mg) and the isomeric product 6b (16 mg), mp
1
113-115 °C. H NMR (400 MHz, C6D6): δ 8.00 (m, 2H), 7.67 (m,
2H), 5.89 (t, J ) 1.8 Hz, 2H), 3.45 (s, 3H), 2.92 (d, J ) 1.6 Hz, 2H),
2.19 (m, 1H), 1.85 (m, 2H), 0.87 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 198.1 (+), 165.9 (+), 140.0 (+), 136.0 (+), 133.8 (-),
129.9 (-), 128.3(-), 65.5 (-), 51.8 (-), 44.4 (-), 22.6(+). IR (KBr)
ν
max: 3059, 2948, 1716, 1400, 1106, 874, 770, 696 cm-1. LRMS (EI):
256 [M+], 241, 225, 178, 163, 135, 93, 77. Anal. Calcd for C16H16O3:
C, 74.98; H, 6.29. Found: C, 75.13; H, 6.36.
(1R,2R)-(-)-2-Amino-1-phenyl-1,3-propanediol Salt. Mp 147-
1
150 °C (methanol). H NMR (400 MHz, DMSO): δ 7.96 (d, J ) 8.4
Quantum Yield Determination. The quantum yield for formation
of furan 5b in benzene was determined using valerophenone actinometry
(Φ ) 0.33)21 and a merry-go-round apparatus22 according to the
standard procedure used in our group.23 n-Tetradecane and n-nona-
decane were used as internal standards for valerophenone and furan
5b, respectively. Quantum yields were determined at varying conver-
sions and plotted against conversion; the reported quantum yield of
0.021 represents the value extrapolated to 0% conversion.
Hz, 2H), 7.79 (d, J ) 8.4 Hz, 2H), 7.38 (m, 4H), 7.29 (m, 1H), 5.89
(t, J ) 1.6 Hz, 2H), 4.65 (d, J ) 8.6 Hz, 1H), 3.38 (m, 2H), 3.22 (dd,
J ) 11.7, 5.7 Hz, 1H), 3.15 (brs, 2H), 3.07 (m, 1H), 1.93 (m, 2H),
0.98 (m, 2H). 13C NMR (100 MHz, DMSO): δ 198.9, 169.2, 142.3,
141.3, 137.8, 132.7, 129.1, 128.1, 127.5, 127.3, 126.8, 71.1, 67.1, 59.3,
58.6, 44.7, 24.7. IR (KBr) νmax: 1680, 1584, 1531, 1293, 1040, 837,
780, 700, 543 cm-1. LRMS (ESI): 410 [M+ + 1], 373, 279, 253, 177.
Anal. Calcd for C23H31NO3: C, 70.40; H, 6.65; N, 3.42. Found: C,
70.34; H, 6.66; N, 3.67.
General Procedure for Solid-State Irradiation of Chiral Salts
1j. The salt (2-5 mg) was crushed between two Pyrex microscope
slides and sealed in a polyethylene bag under a positive pressure of
nitrogen. The sample was irradiated from both sides with a 450 W
medium-pressure mercury lamp. After irradiation, the salt crystals were
suspended in an excess of ethereal diazomethane solution (caution:
poisonous and explosive) and allowed to stand until dissolution was
complete. Ether and excess diazomethane were removed in vacuo, and
the residue was taken up in methylene chloride and passed through a
short plug of silica gel to remove the chiral auxiliary. This afforded
furan 5b as a colorless solid, which was then submitted to HPLC
analysis (Chiralcel OJ column with eluting solution of hexanes:
Acknowledgment. We thank the Natural Sciences and
Engineering Research Council of Canada for financial support.
Supporting Information Available: Crystallographic data for
the (S)-(-)-1-cyclohexylethylamine salt of keto-acid 1i in CIF
format. This material is available free of charge via the Internet
at http://pubs.acs.org.
JA043254J
(21) Wagner, P. J.; Kochevar, I. E.; Kemppainen, A. E. J. Am. Chem. Soc. 1972,
94, 7489.
(22) Moses, F. G.; Liu, R. S. H.; Monroe, B. H. Mol. Photochem. 1969, 1, 245.
(23) Leibovitch, M.; Olovsson, G.; Scheffer, J. R.; Trotter, J. J. Am. Chem.
Soc. 1998, 120, 12755.
9
2730 J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005