Synthesis and Reactivity of Optically Active Spiroketals by Ring-Expansion of Chromium Carbene Complex-Derived Cyclobutanones

Article abstract of DOI:10.1021/jo971665v

Photolysis of cyclic chromium alkoxycarbene complexes with an optically active ene-carbamate gave spirofused, optically active cyclobutanones. Baeyer-Villiger ring expansion followed by further functionalization gave optically active spiroketals. Photochemical ring expansion of these spirofused cyclobutanones in the presence of acetic acid or thiophenol gave 2-acetoxy- or 2-(thiophenoxy)-4- spirofused tetrahydrofurans. Elimination of the thiophenoxy group gave a 3,4-dihydrofuran that underwent Heck arylation and photochemical cycloaddition with chromium carbene complexes to give cyclobutanones.

Full text of DOI:10.1021/jo971665v

684
J . Org. Chem. 1998, 63, 684-690
Syn th esis a n d Rea ctivity of Op tica lly Active Sp ir ok eta ls by
Rin g-Exp a n sion of Ch r om iu m Ca r ben e Com p lex-Der ived
Cyclobu ta n on es
Ana B. Bueno and Louis S. Hegedus*
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523
Received September 8, 1997
Photolysis of cyclic chromium alkoxycarbene complexes with an optically active ene-carbamate
gave spirofused, optically active cyclobutanones. Baeyer-Villiger ring expansion followed by further
functionalization gave optically active spiroketals. Photochemical ring expansion of these spirofused
cyclobutanones in the presence of acetic acid or thiophenol gave 2-acetoxy- or 2-(thiophenoxy)-4-
spirofused tetrahydrofurans. Elimination of the thiophenoxy group gave a 3,4-dihydrofuran that
underwent Heck arylation and photochemical cycloaddition with chromium carbene complexes to
give cyclobutanones.
The spiroketal unit is a widespread substructure in
tion into butyrolactones were recently reported by these
laboratories (eq 1).3,4
many natural products with biological activity, such as
avermectins, milbemycins, steroidal saponins, insect
pheromones, polyether ionophores, and toxic metabolites
from algae and fungi. As a consequence, much effort has
been focused on the development of general methods for
the synthesis of spiroketals.1 Most of the chemistry in
this area is focused on the [4,4], [4,5], and [5,5] ring
systems, because most natural products fall into one of
these structural categories. Despite the variety of gen-
eral methods existing for the construction of the spiroket-
al moiety, the control of the stereochemistry at the
anomeric center is, almost exclusively, based on the
thermodynamically favored isomer in the acid-catalyzed
spiroketalization.1b When all factors that control the
spirocyclization (maximum anomeric effect, minimum
steric interactions, possible hydrogen bonding) are rein-
forcing, a major isomer is produced.1c The stereoselec-
tivity is lower when some of these preferences must be
compromised.1d In general, high stereoselectivity is
observed in the acid-catalyzed spirocyclization of [5,5]-
spiroketals mainly controlled by the anomeric effect,1c but
mixtures are usually observed in the spirocyclization of
[4,5]-spiroketals1e and especially [4,4]-spiroketals,1f where
the anomeric effect is almost nonexistant. Only a few
examples of enantioselective syntheses of [4,4]-spiroket-
als have been described.2
The photochemical reaction was general for a variety
of R and R′ groups, including R ) R′ ) (CH2)4. The
reaction was very stereoselective, resulting in the syn
disposition of large groups in the major isomer and
having a predictable configuration at the two new
centers, depending on the configuration of the starting
ene-carbamate.
Despite the existence of a large number of five- and
six-membered oxacyclic carbene complexes of the Fisher-
type in the literature, only a few synthetic applications
of them have been described.5 The easy accessibility of
cyclic chromium carbene complexes and the high stereo-
selectivity of the reaction of chromium carbene complexes
with olefins prompted the study of a new approach to
the synthesis of [4,4]- and [4,5]-spiroketals consisting of
the ring-expansion of spirocyclobutanones with a prees-
tablished configuration at the spirocyclic center.
An efficient synthesis of chiral 2-alkyl-2-alkoxycyclobu-
tanones by photochemical reaction of chromium alkoxy-
carbene complexes with optically active ene-carbamates
derived from phenylglycine as well as their transforma-
The viability of this strategy was assesed by the
synthesis of simple spiroketals such as A (basic structure
units of spiroketal enol ether polyacetylenes1 and inter-
mediate in the synthesis of more functionalized spiroket-
als6) and B, pheromones of insects (eq 2).1a In addition,
unsaturated spiroketal C was generated and its reaction
chemistry briefly examined.
(1) For a review see: (a) Perron, F.; Albizati, K. F. Chem. Rev.
(Washington, D.C.) 1989, 89, 1617. (b) Pothier, N.; Goldstein, S.;
Deslongchamps, P. Helv. Chim. Acta 1992, 75, 604 and references
therein. (c) Iwata, C.; Masahire, F.; Moritani, Y.; Hattori, K.; Imanishi,
T. Tetrahedron Lett. 1987, 28, 3135. (d) Ireland, R. E.; Thaisrvongs,
S.; Dussault, P. H. J . Am. Chem. Soc. 1988, 110, 5768. (e) Mori, K.;
Watanabe, H. Tetrahedron Lett. 1984, 25, 6025. (f) Rosini, G.; Ballini,
R.; Petrini, M.; Marotta, E. Angew. Chem., Int. Ed. Engl. 1986, 25,
941.
(3) Hegedus, L. S.; Bates, R. W.; Soderberg, B. C. J . Am. Chem. Soc.
1991, 113, 923.
(4) Miller, M.; Hegedus, L. S. J . Org. Chem. 1993, 58, 6779.
(5) Schmidt, B.; Kocienski, P.; Reid, G. Tetrahedron 1996, 52, 1617.
(6) Kocienski, P.; Fall, Y.; Whitby, R. J . Chem. Soc., Perkin Trans.
1 1989, 841.
(2) Solladie´, G.; Huser, N.; Fischer, J .; Decian, A. J . Org. Chem.
1995, 60, 4988 and references therein.
S0022-3263(97)01665-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/22/1998

Synthesis of Optically Active Spiroketals
J . Org. Chem., Vol. 63, No. 3, 1998 685
clobutanones 4a and 4b obtained by photoreaction (eq
4) were epimers at that center.
Resu lts a n d Discu ssion
Carbene complexes 17,8 and 2 were obtained in a single
step by allowing K2Cr(CO)5 to react with commercially
available 4-chlorobutyryl chloride and 5-bromovaleryl
chloride, respectively (eq 3).
The elimination of the carbamate moiety with LHMDS
provided the butenolides 8 and 9 in good yield. The
enantiomeric purity of these systems was determined by
the use of chiral shift lanthanide reagents to be >96%.
Spiroketals 8 and 9 can be versatile starting materials
for the synthesis of other spiroketals since 4-alkoxy-4-
alkyl-disubstituted butenolides display a very rich chem-
istry.9 Hydrogenation of 9 in the presence of a catalytic
amount of Et3N gave rise to compound 10 in 90% yield.
In the absence of base, complete racemization was
observed. Compound 10 has been previously used in its
racemic form as an intermediate in the synthesis of
pheromones of the common wasp and the olive fruit fly.10
The enantiomers of 8-10 could be easily synthesized by
using 6b and 7b as starting materials in eq 7.
Both the five-membered and the six-membered com-
plexes underwent the photochemical reaction with the
ene-carbamate under the described reaction conditions,3
in CH3CN under 90 psi of CO pressure after 48 h of
irradiation (eq 4).
1
Complete stereoselectivity was observed by H NMR
spectroscopy for the reaction of 2, whereas a 86:14
mixture of isomers was obtained for the [3,4]-spiro
compound. These two isomers were easily separated by
flash chromatography, 4a being obtained in an 83%
isolated yield. The absolute configuration for 4 and 5 was
assigned on the basis of the previous work (see eq 1).
The first ring-expansion attempted was the Baeyer-
Villiger oxidation since it had been successfully used in
related systems for the synthesis of butenolides.3 Thus,
the treatment of 4a or 5 with m-CPBA gave the corre-
sponding [4,4]- and [4,5]-spiroketals in excellent yield (eq
5).
A different ring-expansion of the spirocyclobutanones
was also explored. The irradiation of a cyclobutanone
in the presence of a nucleophile and a source of protons
affords 2-substituted tetrahydrofurans.11 When a solu-
tion of 4a or 5 in degassed solvent was irradiated in the
presence of a nucleophile (AcOH, PhSH, or H2O), the
corresponding spiroketals were obtained as inseparable
mixtures of epimers at C-2 (eq 8).
Transformation of spiroketals 12 and 13 was ac-
complished by oxidation of the thioether moiety. The use
of 1 equiv of m-CPBA provided the corresponding sul-
foxides, whose pyrolysis in benzene at reflux12 afforded
the allylic carbamates 15 and 16 in good yield. Reaction
Treatment of spiroketals 6a or 7a with acid produced
equilibration at the spiranic center (eq 6). Spiroketal 6b
was identical with that obtained by Baeyer-Villiger
oxidation of 4b , confirming that the two [3,4]-spirocy-
(9) Reed, A.; Hegedus, L. S. J . Org. Chem. 1995, 60, 3787.
(10) DeShong, P.; Rybczynski, P. J . J . Org. Chem. 1991, 56, 3207.
(11) Lee-Ruff, E.; Wan, W.-Q.; J iang, J .-L. J . Org. Chem. 1994, 59,
2114.
(7) Semmelhack, M. F.; Lee, G. R. Organometallics 1987, 6, 1839.
(8) Betschart, C.; Hegedus, L. S. J . Am. Chem. Soc. 1992, 114, 5010.
(12) Danishefsky, S. J .; Armistead, D. M.; Wincott, F. E.; Selnick,
H. G.; Hungate, R. J . Am. Chem. Soc. 1989, 111, 2967.

686 J . Org. Chem., Vol. 63, No. 3, 1998
Bueno and Hegedus
of spirothioether 13 with 2 equiv of m-CPBA gave rise
to the corresponding sulfone as a mixture of epimers.
Reductive cleavage with Li/NH3 removed the sulfone and
cleaved the carbamate in one step to the free amine 17,
which was characterized as its acetyl derivative 18 (eq
9).
possibility of allylic substitution15 catalyzed by Pd(0).
Although a vast range of allylic groups can be used for
this chemistry, to our knowledge urethanes have not been
utilized as leaving groups. However, other functionalities
based on nitrogen, such as ammonium salts,16 disubsti-
tuted aliphatic amines,17 indolines,18 aziridines,19 and
sulfonamides20 have been shown to be active for this
reaction. A study on a model system 2321 was first
undertaken.
Allyloxazolidinone 23 did not react with Pd(0) under
a variety of conditions (different sources of Pd, ligands,
solvents, and temperatures), although it could be easily
transformed in the trimethylammonium salt 25, the
tosylamine 28, or the triflamide 29, which were substi-
tuted by malonate in the presence of Pd(0) (Scheme 1,
eq 12).
Compounds 15 and 16 were further functionalized.
The Heck reaction of the olefin 16 was attempted. When
16 was treated with iodobenzene in the presence of Pd-
(OAc)2 in CH3CN under reflux,13 the product of coupling
19 was obtained as a single isomer tentatively assigned
as depicted in eq 10. Under the same reaction conditions
1-iodohexene failed to react with 16.
With these results in hand, direct coupling of 16 with
Pd(0) was first attempted, although, as for the model
system, reaction did not occur under a variety on condi-
tions. The reaction of 16 with LiOH at 100 °C22 did not
produce amino alcohol after 48 h. When the temperature
was raised to 115 °C, only decomposition was observed.
Variations in these conditions (use of LiOOH or Cs2CO3)
were undertaken but in no case was the product of
opening of the oxazolidinone observed. Ring opening was
tried with a thiolate.23 Unfortunately, opening of the
carbamate moiety of 16 with ethylthiolate provided the
amino thioether in only a 30% yield.
(15) Lewis acid assisted allylic substitution on 15 with allyl trim-
ethylsilane in the presence of TMSOTf (see: Haraguchi, K.; Tanaka,
H.; Itoh, Y.; Yamaguchi, K.; Miyasaka, T. J . Org. Chem. 1996, 61, 851)
generated a mixture of at least three different isomers of allylated
compound identified by NMR spectroscopy. Only ring opening and
reclosure of the spiroketal can explain the presence of more than two
isomers in the reaction.
(16) Hirao, T.; Yamada, N.; Ohshiro, Y.; Agawa, T. J . Organomet.
Chem. 1982, 236, 409.
(17) Atkins, K. E.; Walker, W. E.; Manyik, R. M. Tetrahedron Lett.
1970, 3821.
(18) Zhang, D.; Liebeskind, L. S. J . Org. Chem. 1996, 61, 2594.
Bailey, W. F.; J iang, X.-L. J . Org. Chem. 1996, 61, 2596.
(19) Satake, A.; Shimizu, I.; Yamamoto, A. Synlett 1995, 64. Ma-
tano, Y.; Yoshimune, M.; Suzuki, H. J . Org. Chem. 1995, 60, 4663.
(20) J ung, M. E.; Rhee, H. J . Org. Chem. 1994, 59, 4719.
(21) Le Coz, S.; Mann, A. Synth. Commun. 1993, 23, 165.
(22) Dyen, M. E.; Swern, D. Chem. Rev. (Washington, D.C.) 1967,
67, 197.
Reaction of 15 with methoxymethylchromium carbene
complex 20 in the presence of light and under CO
pressure provided the spirocyclobutanone 21 as a single
isomer. The configuration of 21 was assigned on the
basis of previous work14 and was confirmed by NOE
studies. Ring expansion of 21 under Baeyer-Villiger
reaction conditions provided the highly functionalized
lactone 22 having five adjacent chiral centers (eq 11).
The presence of a carbamate, a relatively good leaving
group, in an allylic position in 15 and 16 suggested the
(13) Chen, J . J .; Walker, J . A., II; Liu, W.; Wise, D. S.; Townsend,
L. B. Tetrahedron Lett. 1995, 36, 8363.
(14) Soderberg, B. C.; Hegedus, L. S.; Sierra, M. A. J . Am. Chem.
Soc. 1990, 112, 4364.
(23) Corey, E. J .; Weigel, L. O.; Floyd, D.; Bock, M. G. J . Am. Chem.
Soc. 1978, 100, 2916.

Synthesis of Optically Active Spiroketals
J . Org. Chem., Vol. 63, No. 3, 1998 687
Sch em e 1a
a
Key: (a) LiOH, EtOH, 100 °C; (b) EtSLi, HMPA, rt; (c) MeI, KHCO3, MeOH, 30 °C; (d) Pd(PPh3)4, CH2(CO2Et)2, NaH, THF, ref; (e)
TsCl, Et3N, CH2Cl2, rt; (f) Tf2O, CH2Cl2, -78 °C.
Sch em e 2a
purified by SiO2 chromatography, eluting with 4:1 hexane/
ethyl acetate to give 2.53 g (48% yield) of 2 as an orange solid.
The product was stored in the freezer under argon to minimize
decomposition. Its spectroscopic data are consistent with those
described in the literature.25
Gen er a l P r oced u r e for th e P r ep a r a tion of Sp ir ocy-
clobu ta n on es. In an Ace pressure tube were placed under
an argon atmosphere the ene-carbamate 3 (1 equiv) and the
carbene complex (1.5 equiv) in dry degassed acetonitrile. The
vessel was saturated with CO (three cycles to 90-100 psi of
CO) and irradiated at 25 °C for 48 h under 90 psi of CO. The
solvent was removed, and the residue was purified by flash
chromatography (SiO2). The first yellow band was concen-
trated, placed in a Ace tube dissolved in methanol, and stirred
under 90 psi of CO for 24 h. It was filtered through Celite to
recover the Cr(CO)6.
(3S,4R,5′S)-1-Oxo-3-(4-p h en yl-1,3-oxa zolid in -3-yl)-5-
oxa sp ir o[3.4]octa n e (4). Carbene complex 1 (1.90 g, 7.20
mmol) and ene-carbamate 3 (0.91 g, 4.82 mmol) were photo-
lyzed in 24 mL of CH3CN according to the general procedure.
a
Key: (a) Ac2O, Et3N, CH2Cl2, rt, 83% from 16; (b) TsCl, Et3N,
rt, 60% from 16.
Flash chromatography of the crude reaction (eluent hexane/
Reductive cleavage of the oxazolidinone 16 with Li in
liquid ammonia24 provided the free amine 30. When the
crude reaction was treated with an excess of Ac2O, the
acetamide 31 was formed in good yield. Treatment of
the amine 30 with excess TsCl gave rise to the tosylamine
32. Neither the tosyl derivative 32 nor the acetamide
31 were reactive toward Pd(0). All attempts to introduce
a second withdrawing group in the amine (a tosyl or a
acetyl group) led to formation of mixtures of many
unidentified compounds. Attempts to synthesize a tri-
flamide or a quaternary ammonium salt from 30 were
also unfruitful (Scheme 2, eq 13).
In conclusion, enantiomerically pure [4,4]- and [4,5]-
spiroketals have been synthesized for the first time by
two stereoselective ring expasions of spirocyclobutanones.
These reactions provide a lactone or a thioketal moiety
that has been used for further functionalization of the
spiroketals.
ethyl acetate 1.5:1) gave 1.16 g of 4a and 0.18 g of 4b as white
solids (97% yield in cyclobutanones, 83% yield of the major
isomer). Data for 4a : mp 115-117 °C; 1H NMR (CDCl3) δ
7.42-7.24 (m, 5H), 4.81 (dd, 1H, J ) 5.3, 8.7 Hz), 4.68 (t, 1H,
J ) 8.7 Hz), 4.26 (dd, 1H, J ) 5.3, 8.7 Hz), 3.96 (t, 1H, J ) 9.7
Hz), 3.77 (dt, 1H, J ) 4.5, 7.5 Hz), 3.59 (dd, 1H, J ) 8.4, 17.9
Hz), 3.38 (q, 1H, J ) 8.0 Hz), 2.69 (dd, 1H, J ) 10.2, 17.9 Hz),
2.15-1.75 (m, 4H); 13C NMR (CDCl3) δ 207.9, 156.7, 138.2,
128.6 (2C), 128.5, 126.2 (2C), 98.8, 69.4, 69.0, 61.1, 50.8, 41.9,
27.9, 25.1; IR (CHCl3) 1791, 1750 cm-1; [R]25 ) +62° (c ) 1,
D
CH2Cl2). Anal. Calcd for C16H17NO4: C, 66.89, H, 5.96, N,
4.87. Found: C, 66.90, H, 6.14, N, 4.86. Spectroscopic data
for 4b: mp 137-139 °C; 1H NMR (CDCl3) δ 7.41-7.25 (m, 5H),
4.99 (dd, 1H, J ) 5.8, 9.1 Hz), 4.67 (t, 1H, J ) 9.1 Hz), 4.36 (X
part of ABX system, 1H), 4.10 (dd, 1H, J ) 5.8, 9.1 Hz), 3.99
(m, 2H), 2.90 and 2.51 (AB part of ABX system, 2H), 2.20-
1.70 (m, 4H); 13C NMR (CDCl3) δ 209.1, 159.4, 140.2, 129.4
(2C), 128.9, 126.4 (2C), 97.7, 71.6, 70.8, 58.9, 52.3, 44.8, 34.1,
25.4; IR (CHCl3) 1786, 1746 cm-1; [R]25D ) +82° (c ) 1, CHCl3).
(3S,4R,5′S)-1-Oxo-3-(4-p h en yl-1,3-oxa zolid in -3-yl)-5-
oxa sp ir o[3.5]n on a n e (5). Carbene complex 2 (1.07 g, 3.90
mmol) and ene-carbamate (0.49 g, 2.60 mmol) were photo-
lyzed in 26 mL of CH3CN according to the general procedure.
Purification via flash chromatography (eluent hexanes/EtOAc
2:1) gave 0.50 g (76% yield) of 5 as a white solid. Its data
were consistent with those reported previously in the litera-
ture.3
Exp er im en ta l Section
Silica gel was neutralized by passing through it the corre-
sponding eluent with 5% of Et3N followed by washing several
times with the eluent before loading the product.
P en ta ca r bon yl[tetr a h yd r op yr a n yl-1-ca r ben e]ch r om i-
u m (0) (2). A solution of K2Cr(CO)5 (37.80 mmol) in 350 mL
of THF was prepared by standard methods7 and cooled at -78
°C under argon. A solution of 5-bromobutyryl chloride (2.50
mL, 18.90 mmol) in 50 mL of THF was added by cannula to
the dianion. After 10 min, the reaction was allowed to warm
to rt and stirred for 1 h. The crude reaction was filtered
through Celite eluting with ether. Celite was added to the
liquid layer, and solvents were evaporated. The residue was
Gen er a l P r oced u r e for th e Ba eyer -Villiger Oxid a tion
of th e Cyclobu ta n on es. The cyclobutanone (1.0 equiv),
m-CPBA (50-60% in water) (1.50 equiv), and Li2CO3 (0.30
equiv) in CH2Cl2 were stirred at 25 °C overnight. The crude
reaction was poured in a separatory funnel, washed with Na2-
SO3 (satd) (10 mL) and with NaHCO3 (3 × 10 mL), and dried
(25) Landtrada, L.; Licandro, E.; Maiorana, S.; Papagri, A. In
Advances in Metal Carbene Chemistry; Schubert, U., Ed.; Kluver
Academic: Dordrecht, The Netherlands, 1989; pp 149-151.
(24) Evans, D. A.; Sjogren, B. E. Tetrahedron Lett. 1985, 26, 3783.

688 J . Org. Chem., Vol. 63, No. 3, 1998
Bueno and Hegedus
over MgSO4. Trituration of the residue with hexanes/EtOAc
3:1 followed by filtration gave most of the butyrolactones.
Concentration of the mother liquor and flash chromatography
gave the rest of the pure lactone.
by chromatography on silica gel. Solvent was removed on a
rotatory evaporator at 0 °C.
(S)-2-Oxo-1,6-d ioxa sp ir o[4.4]n on -3-en e (8). The reaction
of compound 6a (0.06 g, 0.21 mmol) with LHMDS (0.21 mL,
1.0 M in hexanes) in 4 mL of THF under the general reaction
conditions gave, after purification by chromatography (eluent
ether/pentane 2:1) and removal of the solvents at 0 °C, 0.02 g
(79% yield) of 8 as a colorless oil: 1H NMR (CDCl3) δ 7.10 (d,
1H, J ) 5.8 Hz), 6.13 (d, 1H, J ) 5.8 Hz), 4.28-4.21 (m, 1H),
4.11-4.02 (m, 1H), 2.32-2.05 (m, 4H); 13C NMR (CDCl3) δ
(4S,5S,5′S)-2-Oxo-4-(4-p h en yl-1,3-oxa zolid in -3-yl)-1,6-
d ioxa sp ir o[4.4]n on a n e (6a ). Cyclobutanone 4a (1.49 g, 5.20
mmol), m-CPBA (2.20 g, 7.80 mmol), and Li2CO3 (0.12 g, 1.50
mmol) in 50 mL of CH2Cl2 were subjected to the Baeyer-
Villiger reaction. Trituration of the crude reaction with
hexanes/EtOAc gave 1.46 g (93% yield) of 6a as a white solid:
mp 129-130 °C; 1H NMR (CDCl3) δ 7.44-7.27 (m, 5H), 4.72-
4.58 (m, 3H), 4.22 (dd, 1H, J ) 4.2, 8.0 Hz), 4.05 (dt, 1H, J )
4.5, 7.9 Hz), 3.91 (c, 1H, J ) 7.6 Hz), 2.82 (dd, 1H, J ) 8.5,
18.2 Hz), 2.34-2.0 (m, 5H); 13C NMR (CDCl3) δ 173.3, 157.9,
138.8, 129.6, 129.5, 126.7, 117.3, 70.8, 69.4, 59.2, 57.4, 32.5,
31.8, 23.4; IR (CHCl3) ν 1780, 1753 cm-1; [R]25D ) +87° (c ) 1,
CHCl3). Anal. Calcd for C16H17NO5: C, 63.36; H, 5.65, N, 4.62.
Found: C, 63.26, H, 5.69, N, 4.61.
169.8, 151.8, 124.2, 114.4, 70.5, 35.2, 24.1; [R]25 ) +159° (c
D
) 1.11, CHCl3). Its other data were consistent with those
reported previously in the literature.26
(S)-2-Oxo-1,6-d ioxa sp ir o[4.5]d ec-3-en e (9). The reaction
of compound 7a (0. 10 g, 0.31 mmol) with LHMDS (0.31 mL,
0.31 mmol) in 6 mL of THF gave, after purification by
chromatography (eluent ether/pentane 1:1) and removal of the
solvents at 0 °C, 0.04 g (81% yield) of pure butenolide 9: 1H
NMR (CDCl3) δ 7.12 (d, 1H, J ) 5.5 Hz), 6.09 (d, 1H, J ) 5.5
Hz), 4.05-3.85 (m, 2H, CH2O), 2.0-1.60 (m, 6H); 13C NMR
(4S,5S,5′S)-2-Oxo-4-(4-p h en yl-1,3-oxa zolid in -3-yl)-1,6-
d ioxa sp ir o[4.5]d eca n e (7a ). Cyclobutanone 5 (0.59 g, 1.96
mmol), m-CPBA (1.0 g, 2.90 mmol), and Li2CO3 (0.04 g, 0.60
mmol) in 20 mL of CH2Cl2 were subjected to the Baeyer-
Villiger reaction. Trituration of the crude reaction with
hexane/ethyl acetate gave 0.56 g of pure lactone 7a . Flash
cromatography of the residue obtained by concentration of the
mother liquor (hexane/ethyl acetate 1:1) gave 0.04 g of 7a (97%
yield): mp 162-164 °C; 1H NMR (CDCl3) δ 7.50-7.27 (m, 5H),
4.69-4.61 (m, 2H,), 4.41 (d, 1H, J ) 8.3 Hz), 4.21 (m, 1H),
3.83 (m, 1H), 3.71 (m, 1H), 2.84 (dd, 1H, J ) 8.5, 18.2 Hz),
1.96 (d, 1H, J ) 18.2 Hz), 1.93-1.55 (m, 6H); 13C NMR (CDCl3)
δ 174.0, 158.0, [139.2, 129.4, 126.5 (6C)], 108.3, 70.7, 63.1, 59.0,
(CDCl3) δ 170.5, 154.1, 122.8, 106.8, 64.8, 31.9, 23.9, 18.8; [R]25
D
) +123° (c ) 1.07, CHCl3). Its other data were consistent with
those reported previously in the literature.26
(S)-2-Oxo-1,6-d ioxa sp ir o[4.5]d eca n e (10). Compound 7a
(0.03 g, 0.30 mmol) was dissolved in 3 mL of dry CH2Cl2. Pd
on carbon (10%, 0.02 g) and Et3N (0.01 mL, 0.06 mmol) were
added, and the mixture was stirred under 1 atm of H2 for 3 h
at room temperature. The crude reaction mixture was filtered
through Florisil, washing with ether. The solvent was re-
moved with a rotatory evaporator at 0 °C to give 0.03 g of 10
(90% yield) as a colorless oil: 1H NMR (CDCl3) δ 3.88 (dt, 1H,
J ) 4.0, 11.6 Hz), 3.77 (m, 1H), 2.76 and 2.48 (AB part of ABX
system, 2H), 2.20 and 2.02 (AB part of ABX system, 2H), 2.0-
1.55 (m, 6H); 13C NMR (CDCl3) δ 176.5, 107.7, 63.3, 34.6, 33.8,
58.3, 31.7, 28.4, 24.0, 18.8; IR (CHCl3) ν 1785, 1751 cm-1; [R]25
D
) +79° (c ) 1, CH2Cl2). Anal. Calcd for C17H19NO5: C, 64.34,
H, 6.03, N, 4.41. Found: C, 64.32, H, 5.90, N, 4.41.
Gen er a l P r oced u r e for th e Ep im er iza tion of 2-Ox-
osp ir ok eta ls. The spiroketal (0.16 mmol) was dissolved in 4
mL of CHCl3, and 5 drops of HCl (concentrated) were added.
After 1.5 h, NaHCO3 (satd) was added dropwise. The reaction
mixture was poured into 20 mL of CH2Cl2 and washed with
NaHCO3 (satd) (2 × 10 mL). The combined organic layers
were dried over MgSO4, filtered, and concentrated.
28.2, 24.3, 19.3; IR (neat) 1777 cm-1; [R]25 ) +40° (c ) 1.2,
D
CHCl3).
Gen er a l P r oced u r e for th e P h otoch em ica l Rin g Ex-
p a n sion of Cyclobu ta n on es. The cyclobutanone (1.0 mmol)
was dissolved in 20 mL of degassed solvent under argon in a
Pyrex test tube. The X-H component (5.0 mmol) was added.
The sample was immersed in a bath at 0 °C, and it was
irradiated until consumption of the starting material by TLC
was complete. The subsequent treatment of the crude reaction
is indicated in each case.
(4S,5S,5′S)-2-Oxo-4-(4-p h en yl-1,3-oxa zolid in -3-yl)-1,6-
d ioxa sp ir o[4.4]n on a n e (6b). Compound 6a (0.04 g) was
epimerized under the general conditions to give 0.04 g of a
80:20 mixture of epimers. Column chromatography on neu-
tralized silica gel (eluent 2:1 hexane:ethyl acetate) gave 0.03
g (72% yield in this isomer) of 6b as a white solid: mp 151-
(2S,4S,5S,5′S)- a n d (2R,4S,5S,5′S]-2-Acetoxy-4-(4-p h en -
yl-1,3-oxa zolid in -3-yl)-1,6-d ioxa sp ir o[4.5]d eca n e (11). Cy-
clobutanone 5 (0.17 g, 0.60 mmol) and dry acetic acid (0.18
mL, 3.20 mmol) were irradiated in 12 mL of THF for 24 h.
The solvent was removed with a rotary evaporator, and acetic
acid was eliminated on the vacuum line. The residue was
purified by a rapid chromatography (hexane/ethyl acetate 3:1)
using neutralized silica gel, affording 0.17 g (84% yield) of 11
as a 70:30 oily mixture of epimers: 1H NMR (mixture 70:30
of epimers) (CDCl3) δ 7.48-7.22 (m, 5H), 6.11 (dd, 0.3H, J )
2.2, 7.0 Hz), 6.03 (dd, 0.7H, J ) 4.6, 6.6 Hz), 5.03 (dd, 0.3H, J
) 1.8, 8.1 Hz), 4.76 (dd, 0.7H, J ) 3.6, 8.8 Hz), 4.65-4.55 (m,
1.7H), 4.45 (dd, 0.3H, J ) 1.6, 9.2 Hz), 4.28-4.02 (m, 1H),
3.90-3.60 (m, 2H), 2.58 (m, 0.3 H), 2.30 (ddd, 0.7H, J ) 4.7,
8.3, 13.0 Hz), 2.04 (s, 3H), 1.90-1.50 (m, 7H); 13C NMR (CDCl3)
δ [170.3, 169.0] (1C), [158.8, 158.4] (1C), [129.4, 129.1, 128.4,
125.9, 125.5] (5C), [108.4, 108.1] (1C), [97.3, 96.6] (1C), [71.0,
70.7] (1C), [61.7, 61.5] (1C), [61.2, 58.8, 58.1, 57.7] (2C), [33.0,
31.6] (1C), [28.6, 28.3] (1C), [24.5, 19.3] (1C), [21.1, 20.9] (1C);
1
153 °C; H NMR (CDCl3) δ 7.45-7.35 (m, 3H), 7.35-7.20 (m,
2H), 5.21 (dd, 1H, J ) 3.8, 8.7 Hz), 4.88 (dd, 1H, J ) 8.6, 11.2
Hz), 4.64 (t, 1H, J ) 8.7 Hz), 4.20 (dt, 1H, J ) 4.9, 8.3 Hz),
4.07 (c, 1H, J ) 7.6 Hz), 2.40-1.95 (m, 6H); 13C NMR (CDCl3)
δ 171.6, 158.6, 140.2, 129.5 (2C), 129.2, 126.0 (2C), 115.9, 71.0,
70.1, 58.2, 53.3, 33.9, 31.6, 23.6; IR (CHCl3) 1785, 1746 cm-1
;
[R]25 ) +34° (c ) 1, CHCl3).
D
(4S,5S,5′S)-2-Oxo-4-(4-p h en yl-1,3-oxa zolid in -3-yl)-1,6-
d ioxa sp ir o[4.5]d eca n e (7b). 7a (0.07 g) was epimerized to
give 0.07 g of a 85:15 mixture of epimers. Column chroma-
tography on neutralized silica gel (eluent 3:1 hexane:ethyl
acetate) gave 0.05 g (76% yield in this isomer) of 7b as a white
solid: mp 153-155 °C; 1H NMR (CDCl3) δ 7.45-7.30 (m, 3H),
7.24-7.20 (m, 2H), 5.25 (dd, 1H, J ) 3.6, 8.7 Hz), 4.67 (t, 1H,
J ) 8.6 Hz), 4.54 (X part of ABX system, 1H), 4.13 (dd, 1H, J
) 3.6, 8.6 Hz), 3.90 (m, 2H), 2.32 and 2.09 (AB part of ABX
system, 2H), 2.04-1.60 (m, 6H); 13C NMR (CDCl3) δ 171.9,
158.4, 140.2, 129.3 (2C), 128.9, 125.4 (2C), 107.6, 70.7, 63.4,
IR (neat) 1751, 1741 cm-1
.
(2S,4S,5S,5′S)- a n d (2R,4S,5S,5′S)-2-(P h en ylsu lfen yl)-
4-(4-p h e n y l-1,3-o x a zo lid in -3-y l)-1,6-d io x a s p ir o [4.4]-
n on a n e (12). Cyclobutanone 4a (0.20 g, 0.70 mmol) was
reacted with PhSH (0.36 mL, 3.50 mmol) at 0 °C in 14 mL of
CH2Cl2. After 2 days, the crude reaction was diluted with 20
mL of CH2Cl2 and washed with NaOH (10%) (3 × 10 mL). The
aqueous layer was extracted with CH2Cl2, the combined
58.3, 55.8, 31.0, 30.4, 24.1, 18.6; IR (CHCl3) 1785, 1746 cm-1
;
[R]25 ) +47° (c ) 1.02, CHCl3).
D
Gen er a l P r oced u r e for th e Con ver sion of γ-La cton es
to Bu ten olid es. To a solution of γ-lactone in dry THF at -78
°C was added by syringe under Ar atmosphere LHMDS (1.0
equiv, 1 M in THF). T he solution was stirred at the same
temperature for 15 min. Most of the solvent was removed
under vacuum at 0 °C. Without going to dryness, ether was
added, and the mixture was stirred and filtered. The ether
filtrate was evaporated at 0 °C, and the residue was purified
(26) Fukuda, H.; Takeda, M.; Sato, Y.; Mitsunobu, O. Synthesis
1979, 368.

Synthesis of Optically Active Spiroketals
J . Org. Chem., Vol. 63, No. 3, 1998 689
organic layers were dried over MgSO4 and filtered, and the
solvent was eliminated in vacuo. Purification by a rapid flash
chromatography on neutralized SiO2 (eluent hexane/EtOAc
2:1) provided 0.13 g of 12 as an oil consisting of a 70:30 mixture
of epimers (63% yield based on 78% conversion): 1H NMR
(CDCl3) δ 7.45-7.15 (m, 10H), 5.28 (t, 0.3H, J ) 7.9 Hz), 4.99
(t, 0.7H, J ) 7.6 Hz), 4.96 (dd, 0.3H, J ) 2.4, 8.3 Hz), 4.77 (dd,
0.7H, J ) 4.3, 8.9 Hz), 4.66 (d, 0.7H, J ) 7.0 Hz), 4.64-4.52
(m, 1.3H), 4.10-3.85 (m, 3H), 2.50 (ddd, 0.3H, J ) 8.0, 8.9,
16.8 Hz), 2.32 (td, 0.7H, J ) 7.6, 14.9 Hz), 2.20-1.90 (m, 4.7H),
1.82 (ddd, 0.3H, J ) 4.6, 7.9, 14.6 Hz); 13C NMR (CDCl3) δ
158.5 (1C), 140.6, 140.4 (1C), 136.0, 134.9 (1C), 130.5-126.0
(8C), 117.1, 117.0 (1C), 85.6, 81.9 (1C), 71.1, 70.8 (1C), 67.8,
67.5 (1C), 59.9, 58.9 (1C), 58.3, 58.2 (1C), 35.5, 32.8 (1C), 31.3,
141.4, 129.0 (2C), 128.4, 126.0 (2C), 117.6, 99.8, 70.7, 68.5, 61.6,
58.3, 30.8, 23.8; IR (CHCl3) ν 1743, 1618, 1404, 1040 cm-1
;
[R]25 ) +368° (c ) 1, CHCl3). Anal. Calcd for C16H17NO4:
D
C, 66.87, H, 5.96, N, 4.87. Found: C, 66.70, H, 6.11, N, 4.87.
(4S ,5S ,5′S )-4-(4-P h e n y l-1,3-o x a z o li d i n -3-y l)-1,6-
d ioxa sp ir o[4.5]d ec-2-en e (16). Thioether 13 (0.67 g, 1.70
mmol) dissolved in 34 mL of CH2Cl2 was allowed to react under
the general reaction conditions and purified via flash chro-
matography (eluent hexane/EtOAc 4:1) to provide 0.40 g (77%
yield) of 16 as a white solid: mp 123-127 °C; 1H NMR (CDCl3)
δ 7.50-7.35 (m, 5H), 4.67 (dd, 1H, J ) 2.5, 8.5 Hz), 4.54 (t,
1H, J ) 8.5 Hz), 4.43 (d, 1H, J ) 7.6 Hz), 4.34 (m, 1H), 4.07
(dd, 1H, J ) 2.5, 8.5 Hz), 3.79 (dt, J ) 3.3, 11.6 Hz), 3.65 (m,
1H), 3.60 (m, 1H), 2.80 (tdd, 1H, J ) 2.5, 8.0, 17.1 Hz), 2.10-
1.60 (m, 7H); 13C NMR (CDCl3) δ 158.1, 147.6, 141.9, 129.1
(2C), 128.3, 125.9 (2C), 108.5, 100.1, 70.6, 63.7, 62.9, 58.4, 28.4,
30.9 (1C), 23.9, 23.8 (1C); IR (NaCl) 1748 cm-1
.
(2S,4S,5S,5′S)- a n d (2R,4S,5S,5′S)-2-(P h en ylsu lfen yl)-
4-(4-p h e n y l-1,3-o x a zo lid in -3-y l)-1,6-d io x a s p ir o [4.5]-
d eca n e (13). Cyclobutanone 5 (1.0 g, 3.30 mmol) and PhSH
(1.70 mL, 16.50 mmol) were reacted 48 h in 64 mL of CH2Cl2.
The reaction was worked up as for compound 12 and purified
by flash chromatography on neutral SiO2 (eluent hexane/ethyl
acetate 4:1) to give 1.06 g (83% yield, 90% based on 91%
conversion) of 13 as a solid: 1H NMR (mixture 65:35 of
epimers) (CDCl3) δ 7.50-7.20 (m, 10H), 5.31 (t, 0.6H, J ) 7.6
Hz), 5.22 (dd, 0.4H, J ) 7.0, 7.9 Hz), 5.0 (dd, 0.4H, J ) 2.1,
8.3 Hz), 4.76 (dd, 0.6H, J ) 3.7, 8.9 Hz), 4.61-4.52 (m, 1.6H),
4.47 (dd, 0.4H, J ) 3.4, 9.2 Hz), 4.08-3.99 (m, 1.6H), 3.77-
3.61 (m, 1.4H), 2.55 (ddd, 0.4H, J ) 5.8, 6.7, 15.0 Hz), 3.22
(dt, 0.6H, J ) 6.7, 14.7 Hz), 1.97 (dd, 0.6H, J ) 7.3, 14.3 Hz),
1.90-1.40 (m, 6.4H); 13C NMR (CDCl3) δ [158.2, 158.1] (1C),
[140.8, 140.7] (1C), [136.4, 134.8] (1C), 129.6-125.4 (11C),
[108.0, 107.6] (1C), [86.1, 82.2] (1C), [70.7, 70.3] (1C), [61.3,
60.6, 60.0, 57.6, 57.3] (3C), [33.7, 32.1] (1C), [28.4, 28.3] (1C),
[24.5, 24.3] (1C), [19.3, 19.2] (1C); IR (CHCl3) ν 1746, 1413,
24.5, 19.1; IR (CHCl3) ν 1746, 1618, 1091, 1042 cm-1; [R]25
)
D
+468° (c ) 0.60, CHCl3). Anal. Calcd for C17H19NO4: C, 67.76,
H, 6.35, N, 4.65. Found: C, 67.49, H, 5.99, N, 4.64.
Op en in g of th e Oxa zolid in on e w ith Li/NH3. In a flame-
dried three-neck round-bottom flask provided with a dry ice
condenser and cooled at -78 °C was dissolved a shiny piece of
Li in liquid NH3. A solution of the oxazolidinone in a 10:1
mixture of THF/t-BuOH was added via cannula. After 2 min,
NH4Cl was added until the blue color disappeared. The
reaction was allowed to warm to rt while passing through a
flow of Ar to remove the excess NH3.
(4S,5S)-4-(N-Acet yla m in o)-1,6-d ioxa sp ir o[4.5]d eca n e
(18). A round-bottom flask equipped with an addition funnel
was charged with 13 (0.22 g, 0.55 mmol) dissolved in 5 mL of
CH2Cl2, NaHCO3 (0.41 g, 4.88 mmol) was added, and the
mixture was cooled to -78 °C. The addition funnel was
charged with 50-86% m-CPBA (0.42 g, 50-60% in water)
dissolved in 6 mL of CH2Cl2 and added dropwise to the first
solution. After the addition was complete, the reaction was
allowed to warm to 0 °C and stirred for 2 h. The crude reaction
was poured into a separatory funnel, washed with Na2SO3 (2
× 10 mL) and NaHCO3, dried over MgSO4, filtered, and
concentrated. The corresponding sulfones were obtained (0.23
g, 97% yield) as white solids, which were used for the next
reaction without purification.
1086, 992 cm-1
.
(2S,4S,5S,5′S)- a n d (2R,4S,5S,5′S)-2-Hyd r oxy-4-(4-p h en -
yl-1,3-oxa zolid in -3-yl)-1,6-d ioxa sp ir o[4.5]d eca n e (14). Cy-
clobutanone 5 (50 mg, 0.2 mmol) and water (0.09 mL, 0.9
mmol) in 5 mL of THF were reacted 24 h. Solvents were
removed, giving the hemiketal 14 as a mixture 71:29 of
epimers: 1H NMR (from the crude reaction) (CDCl3 + D2O) δ
7.50-7.20 (m, 5H), 5.43 (dd, 0.21H, J ) 1.8, 6.7 Hz), 5.16 (dd,
0.79H, J ) 4.6, 6.1 Hz), 4.91 (dd, 0.21H, J ) 6.4, 8.8 Hz), 4.73
(dd, 0.79H, J ) 3.7, 8.9 Hz), 4.66 (t, 0.21 H, J ) 8.8 Hz), 4.56
(t, 0.79H, J ) 8.9 Hz), 4.25 (dd, 0.21H, J ) 6.1, 8.9 Hz), 4.07
(dd, 0.79H, J ) 3.7, 8.5 Hz), 3.93 (dt, 0.79H, J ) 3.3, 11.0 Hz),
3.77 (dt, 0.21H, J ) 3.1, 11.6 Hz), 3.64 (m, 0.79H), 3.43 (m,
0.21H), 2.70 (ddd, 0.21H, J ) 7.0, 9.7, 16.8 Hz), 2.10-1.20 (m,
The crude mixture of sulfones (0.11 g, 0.25 mmol) and Li
(0.04 g, 6.3 mmol) was allowed to react according to the general
procedure. After quenching of the reaction with NH4Cl and
elimination of the excess of ammonia, the crude reaction
mixture was dissolved in CH2Cl2, Ac2O (0.59 mL, 6.50 mmol)
and Et3N (0.87 mL, 6.50 mmol) were added, and the mixture
was allowed to react at rt overnight. The reaction was washed
with NaHCO3, dried over MgSO4, filtered, and concentrated.
The residue was purified by chromatography on neutralized
SiO2 (eluent acetone/CH2Cl2 1:6), providing 0.02 g (44% yield)
of 18 as a white solid: mp 120-124 °C; 1H NMR (CDCl3) δ
5.60 (bd, 1H, J ) 8.6 Hz), 4.39 (ddd, 1H, J ) 1.8, 7.3, 9.5 Hz),
3.96 (dt, 1H, J ) 6.1, 8.6 Hz), 3.86 (dt, 1H, J ) 5.6, 8.9 Hz),
3.74 (dt, 1H, J ) 3.3, 11.3 Hz), 3.61 (m, 1H), 2.52 (m, 1H),
1.98 (s, 3H), 1.75-1.45 (m, 7H); 13C NMR (CDCl3) δ 169.3,
106.0, 64.4, 61.4, 56.0, 31.3, 28.3, 25.0, 23.3, 19.7; IR (neat) ν
7.21H); IR (CHCl3) 3413, 1742 cm-1
.
Gen er a l P r oced u r e for th e Con ver sion of th e Th io-
eth er s to Olefin s. In a flask equipped with a pressure-
equalizing addition funnel was dissolved the thioether (1.0
equiv) in CH2Cl2. NaHCO3 (4.0 equiv) was added, and the
suspension was cooled at -78 °C. The funnel was charged
with a solution of m-CPBA (50-85%) (1.0 equiv) in CH2Cl2,
which was added dropwise to the flask. The reaction was
monitored by TLC. When all the starting material was
consumed, a solution of Na2S2O3 (10% in water) was added,
and the mixture was allowed to warm to rt. The layers were
separated, and the organic layer was washed with NaHCO3,
dried over MgSO4, and evaporated to dryness. The crude
residue was dissolved in benzene, Et3N was added, and the
mixture was heated at reflux for 30 min. Elimination of the
solvent and purification of the residue by chromatography on
neutralized SiO2 gave the pure dihydrofurans.
3421, 1650 cm-1; [R]25 ) +57° (c ) 1, CHCl3). Anal. Calcd
D
for C10H17NO3: C, 60.28; H, 8.60; N, 7.03. Found: C, 60.28;
H, 8.43; N, 7.15.
(2R,5S,5′S)-4-(4-P h en yl-1,3-oxa zolid in -3-yl)-2-p h en yl-
1,6-d ioxa sp ir o[4.5]d ec-3-en e (19). In a flame-dried round-
bottom flask provided with a reflux condenser Pd(OAc)2 (0.002
g, 0.01 mmol) and AsPh3 (0.006 g, 0.02 mmol) was stirred in
3 mL of dry CH3CN for 30 min. Iodobenzene (0.02 mL, 0.16
mmol), Et3N (0.07 mL, 0.52 mmol), and 16 (0.04 g, 0.13 mmol)
were added, and the mixture was stirred at 75 °C for 48 h.
Elimination of the solvent and purification of the residue by
flash chromatography in neutralized silica gel (eluent hexanes/
EtOAc 5:1) provided 0.05 g (92% yield) of 19 as a white solid:
mp 159-161 °C; 1H NMR (CDCl3) δ 7.45-7.20 (m, 10H), 6.20
(d, 1H, J ) 1.8 Hz), 5.65 (d, 1H, J ) 1.8 Hz), 5.34 (dd, 1H, 3.4,
8.3 Hz), 4.66 (t, 1H, J ) 8.3 Hz), 4.15 (dd, 1H, J ) 3.4, 8.6
Hz), 3.95 (dt, 1H, J ) 2.5, 11.3 Hz), 3.71 (m, 1H), 1.90-1.15
(m, 6H); 13C NMR (CDCl3) δ 156.7, 141.0, 140.7, 135.9, 129.2,
(4S ,5S ,5′S )-4-(4-P h e n y l-1,3-o x a z o li d i n -3-y l)-1,6-
d ioxa sp ir o[4.4]n on -2-en e (15). Compound 12 (0.50 g, 1.74
mmol) dissolved in 34 mL of CH2Cl2 was subjected to the
general reaction conditions. Pyrolysis of the sulfoxide was
performed in 20 mL of benzene and 2 mL of Et3N. Purification
of the residue (eluent hexane/ethyl acetate 3:1) gave 0.31 g
1
(86% yield) of 15 as a white solid: mp 137-141 °C; H NMR
(CDCl3) δ 7.40-7.15 (m, 5H), 6.24 (dd, 1H, J ) 1.5, 2.8 Hz),
4.96 (m, 1H), 4.59 (m, 2H), 4.37 (t, 1H, J ) 3.1 Hz), 4.11-4.0
(m, 3H), 2.30-2.0 (m, 4H); 13C NMR (CDCl3) δ 158.0, 147.6,

690 J . Org. Chem., Vol. 63, No. 3, 1998
Bueno and Hegedus
128.6, 128.4, 127.9, 126.8, 126.2, 120.0, 107.5, 83.9, 71.0, 62.7,
concentrating, the crude acetamide. Column chromatography
on neutralized SiO2 (eluent EtOAc) provided 0.08 g (83% yield)
of the acetamide 31 as a colorless oil: 1H NMR (CDCl3) δ 6.53
(dd, 1H, J ) 1.2, 2.8 Hz), 5.32 (bs, 1H), 5.00 (t, 1H, J ) 2.7
Hz), 4.83 (ddd, 1H, J ) 1.5, 2.7, 8.9 Hz), 3.93 (m, 1H), 3.72
(m, 1H), 2.00 (s, 3H), 1.85-1.50 (m, 6H); 13C NMR (CDCl3) δ
170.0, 147.9, 108.4, 100.9, 62.8, 59.3, 28.1, 24.4, 22.9, 19.0; IR
59.8, 32.9, 24.3, 19.2; IR (CHCl3) 1757 cm-1; [R]25 ) +229° (c
D
) 0.75, CHCl3). Anal. Calcd for C23H23NO4: C, 73.19; H, 6.14;
H, 3.71. Found: C, 73.24; H, 6.21; N, 3.76.
Com p ou n d 21. In a dry Ace pressure tube, spiroketal 15
(0.10 g, 0.35 mmol) was dissolved in 4 mL of CH2Cl2 and
methylmethoxychromium carbene complex 2027 (0.13 g, 0.52
mmol) was added. The mixture was degassed, charged with
CO (80 psi), and irradiated with visible light at 35 °C for 36
h. The solvent was removed, and the residue was purified by
chromatography on neutralized SiO2 to give 90 mg (70% yield)
of the spiroketal 21 obtained as a white solid: mp 118-121
°C; 1H NMR (CDCl3) δ 7.42-7.28 (m, 5H), 4.70-4.65 (m, 2H),
4.56 (t, 1H, J ) 8.6 Hz), 4.08 (dd, 1H, 4.3, 8.2 Hz), 3.95-3.80
(m, 3H), 3.48 (d, 1H, J ) 6.4 Hz), 3.11 (s, 3H), 2.12-1.90 (m,
4H), 1.21 (s, 3H); 13C NMR (CDCl3) δ 201.9, 158.0, 139.6, 129.3
and 126.3 (5C), 119.2, 96.3, 80.0, 70.8, 68.1, 64.4, 60.8, 58.3,
(neat) 3280, 1651 cm-1; [R]25 ) +179° (c ) 1.81, CHCl3).
D
(4S,5S)-4-[N-(p-Tolu en esu lfon yl)am in o]-1,6-dioxaspir o-
[4.5]d ec-2-en e (32). Compound 16 (0.15 g, 0.50 mmol) was
reacted with Li (0.03 g, 5.0 mmol) in 15 mL of NH3, 2.50 mL
of THF, and 0.50 mL of t-BuOH. Treatment of the residue
obtained with TsCl (0.48 g, 2.50 mmol) and Et3N (0.70 mL,
10.0 mmol) overnight followed by washing with NaHCO3 (3 ×
10 mL), drying over MgSO4, and concentrating of the solvents
provided 88 mg (60% yield) of the tosylamine 32 as a colorless
oil: 1H NMR (CDCl3) δ 7.35 and 7.31 (AA′BB′ system, 2H),
6.39 (dd, 1H, J ) 1.5, 2.5 Hz), 4.59 (t, 1H, J ) 2.6 Hz), 4.35
(bd, 1H, J ) 9.2 Hz), 4.08 (ddd, 1H, J ) 1.5, 2.9, 9.6 Hz), 3.90
(dt, 1H, J ) 3.3, 11.4 Hz), 3.71 (m, 1H), 2.43 (s, 3H), 1.90-
1.50 (m, 6H); 13C NMR (CDCl3) δ 148.3, 143.6, 137.6, 129.8,
127.0, 108.8, 100.6, 63.9, 63.3, 29.2, 24.6, 21.5, 19.4; IR (neat)
52.3, 31.2, 24.3, 10.5; IR (neat) 1787, 1751 cm-1; [R]25 ) +88
D
(c ) 1, CHCl3). Anal. Calcd for C20H23NO6: C, 64.33, H, 6.21,
N, 3.75. Found: C, 64.50C, H, 6.17, N, 3.75.
Com p ou n d 22. Cyclobutanone 21 (0.03 g, 0.09 mmol) was
ring-expanded following the general procedure for the Baeyer-
Villiger reaction to provide 0.03 g (98% yield) of 22 as a
colorless oil. Trituration with ether/hexanes provided 0.01 g
of 22 as a white solid: 1H NMR (CDCl3) δ 7.50-7.30 (m, 5H),
4.77 (bs, 1H), 4.76 (dd, 1H, J ) 4.9, 8.8 Hz), 4.60 (t, 1H, J )
8.6 Hz), 4.11 (dd, 1H, J ) 4.9, 8.6 Hz), 3.96 (d, 1H, J ) 6.4
Hz), 3.95-3.82 (m, 2H), 3.16 (s, 3H), 2.98 (d, 1H, J ) 6.4 HZ),
2.15-1.85 (M, 4H), 1.47 (S, 3H); 13C NMR (CDCl3) δ 173.9,
157.9, 139.4, 129.6, 129.5, 126.4, 117.3, 110.3, 84.4, 70.7, 68.5,
63.4, 58.8, 50.0, 48.8, 31.0, 24.3, 16.7; IR (neat) 1774, 1755
ν 3267, 1161 cm-1; [R]25 ) +91° (c ) 0.94, CHCl3).
D
Ack n ow led gm en t. Support for this research by
National Science Foundation Grant No. CHE-9224489
is gratefully acknowledged. Mass spectra were obtained
on instruments supported by the National Institutes of
Health shared instrumentation Grant No. GM49631.
A.B.B. would like to thank the Ministerio de Educacio´n
y Ciencia of Spain for a postdoctoral fellowship.
cm-1; [R]25 ) +55° (c ) 1, CHCl3).
D
(4S,5S)-4-(N-Acet yla m in o)-1,6-d ioxa sp ir o[4.5]d ec-2-
en e (31). Reaction of 16 (0.15 g, 0.50 mmol) with Li (0.03 g,
5.0 mmol) in 15 mL of NH3, 2.5 mL of THF, and 0.5 mL of
t-BuOH and treatment of the residue obtained with Ac2O (0.78
mL, 8.25 equiv) and Et3N (0.91 mL, 6.60 mmol) in 20 mL of
CH2Cl2 for 4 h provided, after washing the crude reaction with
NaHCO3 (3 × 20 mL), drying over MgSO4, filtering, and
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
compounds 4b, 6b, 7b, 10, 11a ,b, 12a ,b, 13a ,b, 14, 21, 22,
and 30-32 and 13C NMR spectra for compounds 4b, 6b, 7b,
10, 11a ,b, 12a ,b, 13a ,b, 22, 31, and 32 (27 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.
(27) Bao, J .; Wulff, W. D.; Dominy, J . B.; Fumo, M. J .; Grant, E. B.;
Rob, A. C.; Whitcomb, M. C.; Yeung, S.-M.; Ostrander, R. L.; Rheingold,
A. L. J . Am. Chem. Soc. 1996, 118, 3392.
J O971665V