Diastereoselective addition of radicals to chiral 1,3-dioxin-4-ones

Article abstract of DOI:10.1002/(SICI)1099-0690(199905)1999:5<1057::AID-EJOC1057>3.0.CO;2-A

Intermolecular addition of radicals to the 1,3-dioxin-4-ones 1a,b and 2a,b with (-)-menthone incorporated as chiral auxiliary in 2-position were investigated. Photochemically generated radicals from 1,3-dioxolane, oxolane, and 2-propanol were added with h

Full text of DOI:10.1002/(SICI)1099-0690(199905)1999:5<1057::AID-EJOC1057>3.0.CO;2-A

FULL PAPER
Diastereoselective Addition of Radicals to Chiral 1,3-Dioxin-4-ones
Heiner Graalfs,[a][°] Roland Fröhlich,[b] Christian Wolff,[a] Jochen Mattay*[a,c]
Keywords: Free radicals / Stereoselective addition / Chiral 1,3-dioxin-4-ones / Photoreactions / Spirocycles
Intermolecular addition of radicals to the 1,3-dioxin-4-ones
1a,b and 2a,b with (–)-menthone incorporated as chiral
auxiliary in 2-position were investigated. Photochemically
generated radicals from 1,3-dioxolane, oxolane, and 2-
propanol were added with high facial selectivity from the
an unsaturated side chain were attacked by radicals at the
terminal double bond. In the case of irradiation of 32b in 1,3-
dioxolane a cyclization followed the intermolecular addition
of a 1,3-dioxolan-2-yl radical and the dispiro compound 36
was formed. However, the formation of dispiro compound 40
more exposed a-side. Intramolecular addition of 1,3- required two reaction steps starting with irradiation of 32b
dioxolan-2-yl radicals to chiral dioxinones proceeded less and bromotrichloromethane. The achiral 1,3-dioxin-4-one 44
efficiently and with lower selectivity also from the a-side. possessing an unsaturated side chain at C-2 was attacked by
Nevertheless, it was possible to form the new spirocyclic 1,3-dioxolan-2-yl radicals preferentially at C-6.
compounds 22–27. The 1,3-dioxin-4-ones 32a,b possessing
Introduction
The efficient use of 1,3-dioxin-4-ones as versatile syn-
thons in organic synthesis has been well documented but
there is still an increasing interest in mechanistic aspects
because the facial selectivity in addition reactions to the
CϭC bond of chiral dioxinones depends on the type of re-
action (Scheme 1).[1] Sato et al. reported that cuprate ad-
dition to dioxinone 1a occurred preferentially on the face
opposite the isopropyl group (b-side).[2] The same b-side
preference was observed in catalytic hydrogenation of 1a.[2]
This is in accordance with results of Seebach et al. who
investigated conjugate addition reactions with dialkyl cup-
rates and catalytic hydrogenations of chiral dioxinone 3a.[3] Scheme 1. Chiral 1,3-dioxin-4-ones
Lange et al. have found that dialkyl cuprate addition to 3b
also takes place from the b-side with complete selectivity.[4]
for ground-state [4ϩ2] cycloadditions. Demuth et al. de-
Corresponding facial selectivity of two types of dioxinones
(2-tert-butyl- and 2-spiro-substituted) was also reported for
DielsϪAlder reactions with cyclopentadiene which proceed
from the opposite side (a-side).[5] An attack from the a-side
has also been proposed for the DielsϪAlder reaction of N-
phenylmaleimide and spirodioxinones 1 and 2 (R ϭ alk-
enyl).[6] The addition of molecular fluorine to spirodioxi-
nones is another type of ground-state reaction. The ap-
proach of fluorine proceeds with high selectivity also from
the a-side.[7]
scribed the a-side preference in the reaction of 1b and 2b
for the first time.[8] Later, Sato et al. reported that 1a and 2a
were attacked also preferentially from the a-side.[2] Lange et
al. have used 2-tert-butyldioxinones 3. High facial selec-
tivity was only obtained in the photoaddition of 3b with
preferred approach from the a-side.[4] However, 3a shows
only poor facial selectivity in photoaddition with alkenes.
The selectivity in intramolecular photocycloaddition of al-
kenes to chiral dioxinones depends on the length of the side
chain.[9] In some cases addition proceeds preferentially
from the b-side, which is explained by a distortion of the
conformation in the triplet excited state.[10]
Intermolecular [2ϩ2] photocycloadditions of alkenes to
dioxinones occur preferentially from the same side as found
The addition of alkyl radicals to enones is an efficient
route for the formation of CϪC bonds.[11] However, only
little work has been reported on the behaviour of dioxi-
nones in radical reactions. This report deals with the ad-
dition of radicals to chiral 1,3-dioxin-4-ones. Since radicals
should be influenced by similar stereochemical and stereoe-
lectronic effects as nucleophiles it would be interesting to
know whether alkyl radical addition takes place on the
same face as preferred, for example, by cuprates (b-side).
On the other hand, radical additions may be compared to
New address: Merck KGaA, Darmstadt, Germany.
[a]
Institut für Organische Chemie der Universität Kiel,
Olshausenstraße 40, D-24098 Kiel, Germany
[b]
Organisch-Chemisches Institut der Universität Münster,
Corrensstraße 40, D-48149 Münster, Germany
[c]
New address: Fakultät für Chemie, Organische Chemie I,
Universität Bielefeld,
Postfach 10 01 31, D-33501 Bielefeld,Germany
Fax: (internat.) ϩ 49(0)521/106-6417
E-mail: mattay@uni-bielefeld.de
[°] Taken in part from the Ph. D. thesis, University of Münster,
1997.
Eur. J. Org. Chem. 1999, 1057Ϫ1073
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
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H. Graalfs, R. Fröhlich, C. Wolff, J. Mattay
FULL PAPER
other types of reactions showing a-side preference like tri- the attack of a 1,3-dioxolan-2-yl radical on the a-side. Be-
plet reactions in the excited state. For example, the intramo- sides, an addition took place on the b-side which led to the
lecular photoaddition of alkenes to dioxinones are two-step minor adducts 8a and 10a. The structure of 8a was verified
reactions involving a diradical intermediate. In the first step by X-ray-crystallographic analysis (Figure 1).[17]
a bond is formed at C-6.[12] If the intramolecular radical
addition gives the same facial selectivity as the photocy-
cloaddition the conformation of excited-state and ground-
state spirodioxinones should be comparable.
Results and Discussion
Intermolecular Addition
The addition reactions of photochemically generated rad-
icals to dioxinones 1 and 2 were performed by irradiation
at 350 nm.[13][14] The reaction of 1a in 2-propanol using
benzophenone as triplet sensitizer gave only one adduct 4
(28%) after chromatographic workup (Scheme 2). Sensi-
tized irradiation of 2a in 2-propanol gave 5 in 17% yield as
a sole product. Compound 5 was converted to 6 by acid
hydrolysis. The optical rotation of 6 is almost identical with
the value of the known (S)-6.[15] Therefore the configura-
Scheme 3. Photoaddition of 1,3-dioxolane to 1 and 2
tion of 5 must be the same. Accordingly the addition of the
hydroxypropyl radical has taken place from the a-side. In
the absence of the sensitizer no adducts were formed.
Figure 1. Crystal structure of 8a
Table 1. Photoaddition of 1,3-dioxolan-2-yl radicals to 1,3-dioxin-
4-ones
Scheme 2. Photoaddition reactions of 1,3-dioxin-4-ones
Entry Compound Irradiation Products (yield)[a] Conversion
time
Irradiation of 1a or 2a in methanol was not successful.
Only small amounts were converted even after ten days and
1
2
3
4
1a
2a
1b
2b
44 h
27 h
12 d
12 d
7a (75%)/8a (3%)
100%
we were not able to separate the complex mixture. Investi-
gations with cyclohexane/methanol mixtures as solvents led
to the formation of by-products which may result from
cycloaddition reactions. There were no adducts observed
when 1b or 2b were irradiated in 2-propanol under the same
conditions as for the 6-unsubstituted 1,3-dioxin-4-ones.
9a (56%)/10a (6%) 83%
7b (23%)
9b (42%)
80%
82%
[a]
Yields of isolated products.
Dioxinones 1b and 2b show lower reactivities in the ad-
The photoaddition reactions of 1,3-dioxolane were car- dition to 1,3-dioxolan-2-yl radicals. Thus, irradiation must
ried out without a sensitizer.[16] The product ratio was be maintained for twelve days in order to obtain the same
1
measured by H-NMR spectroscopy from samples of the extent of conversion as in the case of the 6-unsubstituted
crude products. Irradiation of 1a and 2a in 1,3-dioxolane dioxinones. The photoaddition reaction of 1b and 1,3-diox-
afforded two adducts each in a ratio of 96:4 and 90:10 olane gave only one adduct 7b after chromatography.[18]
(Scheme 3 and Table 1). The stereochemistry of the major Due to the stereochemical information obtained by a NOE
adducts 7a and 9a were determined by NOE difference experiment of 7b the radical addition had occurred from the
experiments (Scheme 3). Thus, both isomers resulted from a-side (Scheme 3). The same a-side preference was observed
1058
Eur. J. Org. Chem. 1999, 1057Ϫ1073

Diastereoselective Addition of Radicals to Chiral 1,3-Dioxin-4-ones
FULL PAPER
Figure 2. Crystal structure of 9b
when 2b was used. The sole adduct was 9b of which the
structure was determined by X-ray-crystallographic analysis
(Figure 2).[17]
Scheme 4. Photoaddition of tetrahydrofuran to 1 and 2
The photoaddition reaction of dioxinones and 1,3-diox-
olane afforded only adducts which can be explained by the
attack of a 1,3-dioxolan-2-yl radical. However, cleavage of
a CϪH bond at the acetal center should be preferred by the
two neighbouring oxygen atoms. Surprisingly, no adduct
was observed resulting from the reaction of a 1,3-dioxolan-
4-yl radical and dioxinone. In order to test the possibility
of a reaction at an α-ether rather than acetal center the
photoaddition of THF (oxolane) was investigated.
Table 2. Photoaddition of oxolan-2-yl radicals to 1,3-dioxin-4-ones
Entry Compound Irradiation Products (yield)[a] Conversion
time
1
2
3
4
1a
2a
1b
2b
5 d
11a (41%/22%)
12a (22%/22%)
11b (6%/3%)
12b (10%)[b]
100%
> 95%
30%
4 d
12 d
12 d
30%
Irradiations of dioxinones in THF were carried out under
the same conditions as for the irradiations in 1,3-dioxo-
lane.[16] Because of the lower reactivity of the 2-oxolanyl
radicals irradiation of 1a and 2a was maintained twice as
[a]
Yields of isolated isomers, ratio of the products was determined
[b]
by NMR to be 2:1. Ϫ Isomers not separated.
long (Table 2). In each case two adducts were formed in a enone moiety.[3][4] The addition occurs preferentially from
ratio of 65:35 and 50:50, respectively. They were separated the b-side, i.e. from the direction into which the centers are
by HPLC and the polar product was the major isomer in pyramidalized. On the other hand, Sato et al. have con-
case of 11a. NOE experiments of both isomers 11 showed sidered that hyperconjugation causes the facial selectivity in
correlations between 11-H and the proton at the new stere- conjugate addition.[19] The lone-pair electrons of O-1
ogenic center in the dioxanone ring for both compounds should interact with the antibonding orbital of the incipient
(Scheme 4). Thus, the oxolan-2-yl radical attacked the diox- bond. Since the nucleophilic attack occurs at an obtuse an-
inones from the a-side. Because of the generation of an ad- gle the unfavourable 1,3-diaxial interaction is small and
ditional chiral center in the oxolanyl moiety two isomers stereoelectronic effects predominate steric demand.
were formed. We were not able to assign the structure of
(2ЈR) and (2ЈS) isomers.
In radical addition reactions a stereoelectronic effect may
also compensate a steric demand and, therefore, selectivity
The irradiation of the dioxinones 1b and 2b in THF was in acyclic radical reactions where steric effects are small is
stopped after twelve days. Two isomers were produced in a often explained by electronic interactions.[20][21] A radical
ratio of 2:1 [(2ЈS)-11b/(2ЈR)-11b] which were separated by approaches an enone along a trajectory similar to that of a
HPLC. The separation of the isomers (2ЈS)-12b and (2ЈR)- nucleophile and because of its comparable steric and stereo-
12b failed. There is no proof of the relative configurations electronic demand the ionic and radical addition should
of isomers 11b and 12b but it can be assumed that the at- show the same selectivity.[22][23] Nevertheless, radicals at-
tack of the oxolan-2-yl radicals to 6-methyl-substituted di- tack dioxinones from the opposite side as shown above.
oxinones shows the same selectivity mentioned for the pho- Thus, the influence of hyperconjugation or non-planar en-
toaddition reactions before. In trimethyl orthoformate the one portion is less important. Obviously, the addition oc-
CϪH bond is activated by three oxygen atoms. However, to curs preferentially from the more exposed a-side of the sofa
our surprise we did not observe any product formation conformation as found by X-ray analyses of the dioxinones
upon photolysis of dioxinones in the presence of this ortho- 1a[2] and 2b.[8] Only in the case of the addition of reactive
ester.
1,3-dioxolan-2-yl radicals to the 6-unsubstituted dioxinones
The groups of Seebach and Lange have correlated the 1a and 2a an attack from the b-side was observed as the
stereoselectivity of conjugate addition of cuprates to 2-tert- minor pathway of the reaction. The diverse facial selectivity
butyl-1,3-dioxin-4-ones 3 with the pyramidalization of the in the reaction of ionic nucleophiles and radicals with cyclic
Eur. J. Org. Chem. 1999, 1057Ϫ1073
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H. Graalfs, R. Fröhlich, C. Wolff, J. Mattay
FULL PAPER
enones was already described by Fraser-Reid and Giese as may result from remaining oxygen in the solution. We as-
well.[24]
sume that the intermediate adduct radical is trapped by
oxygen followed by hydrogen transfer. The produced hydro-
peroxide should be unstable under the photochemical con-
ditions and the alcohol 23 is formed.[32] In contrast to the
intermolecular reaction of 1,3-dioxolanes the cyclization re-
action takes place only in the presence of a sensitizer. Un-
fortunately, the yields were unsatisfactory in comparison
with the former reactions.
Intramolecular Addition
Since so far all attempts failed to use other precursors
than alcohols, acetals, and ethers in intermolecular radical
addition reactions with dioxinones we were interested in
radical cyclizations in order to gain more information on
the behaviour of dioxinones in radical reactions. Earlier re-
ports already showed that it is possible to form spiro sys-
tems using 1,3-dioxin-4-ones bearing an appropriate side
chain at C-6.[25][26] Here a favoured process should be the
well-known 5-exo cyclization of 5-hexenyl radicals. As a
first approach we chose the 1,3-dioxolane as a unit for cycli-
zation reactions of 1,3-dioxin-4-ones.
Two procedures to synthesize 6-substituted dioxinones
are known[28], i.e. γ-alkylation of the dioxinones 1b or 2b[29]
and treatment of appropriate tert-butyl β-oxo esters with
ketones under acidic conditions.[30] Attempts to synthesize
the achiral dioxinone 14 according to the latter method
failed so far because of the lability of the dioxolane moiety
under acidic conditions. Interestingly, the tert-butyl 6-oxo-
1-cyclohexenecarboxylate was not formed as expected from
the reaction of 20 in acetic acid.[31] The hexahydrobenzofu-
ran derivative 21 was the only isolated product. Thus, the
dioxinones 14Ϫ16 were prepared by γ-alkylation of the cor-
responding dioxinones. In all cases α-alkylated dioxinones
17؊19 were also formed in smaller amounts (Scheme 5).
Figure 3. Crystal structure of 22b
Irradiation of the chiral dioxinones were carried out un-
der the same conditions as for the achiral ones. Reaction of
15 (5 m) gave two diastereoisomers 24 and 25 after sepa-
ration by HPLC in yields of 14% and 9%, respectively. The
relative configuration of the major product 24 was deter-
mined by X-ray analysis of single crystals (Figure 4).[17]
From these data it is obvious that the addition of the 1,3-
dioxolan-2-yl radical has taken place from the a-side lead-
ing to 24. Thus, the minor product 25 (5 m) should be
formed by an attack from the b-side. The cyclization reac-
tion of 16 yielded two products in a ratio of 10:9 which
could be separated by HPLC. Though the spectroscopic
data correspond to the trispiro compounds 26 and 27, we
were not able to assign the structures to the isolated prod-
ucts because of the lack of certain structure determination.
In summary, radicals generally attack chiral dioxinones in
intermolecular addition reactions as well as in cyclization
reactions preferentially from the a-side. The latter agrees
with a recent investigation on cascade cyclizations of poly-
alkenyl-substituted chiral dioxinones by photoinduced elec-
tron transfer.[33]
In order to get further information on the relative reactiv-
ities of intra- versus intermolecular photoadditions under
the conditions used in this study the dioxinone 14a (20 m)
Scheme 5. γ-Alkylation of dioxinones
Irradiation of the achiral dioxinones 14a,b (40 m) and was irradiated for five days in 1,3-dioxolane in the presence
acetone as sensitizer in cyclohexane at 350 nm for 2 d gave of acetone (Scheme 8). After chromatography, 28 was iso-
the cyclized products 22a and 22b in yields of 11% and 17%, lated as the major adduct in 8% yield. There was no hints
respectively. The structure of the dispiro compound 22b was of cyclized products but the bis-1,3-dioxolanyls 29 and 30
verified by X-ray-crystallographic analysis (Figure 3).[17] were formed in large amounts indicating that the primary
The intramolecular photoaddition of dioxolane to acrylate H abstraction mainly results from 1,3-dioxolane rather than
has already been reported leading to five-membered ring 14a. Unlike the intermolecular addition, dimerization be-
products in only very small amounts.[27] In some cases we comes the favoured reaction because of the efficient sensi-
observed the formation of by-products of type 23 which tization of acetone and the low reactivity of 6-subtituted
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Diastereoselective Addition of Radicals to Chiral 1,3-Dioxin-4-ones
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Scheme 8. Competition between inter- and intramolecular pho-
toaddition
Chemoselectivity
It is known that 1,3-dioxolane adds to terminal olefins
under UV irradiation in the presence of a triplet sensi-
tizer.[34] In order to obtain information about the reactivity
of dioxolanyl radicals against 1,3-dioxin-4-ones provided
with a terminal olefin unit we envisaged the synthesis of
compounds 32a,b. They were prepared from the β-oxo ester
31 and (Ϫ)-menthone in acetic anhydride under acid cataly-
sis.[30a] The yield of the dioxinones 32a,b range from 14%
to 19%. In both cases a second isomer 33a,b was formed in
smaller amounts which was separated chromatographically.
Irradiation of dioxinone 32a (10 m) and acetone in 1,3-
dioxolane for 24 hours gave the two adducts 34 and 35 in
yields of 35% and 6%, respectively. Obviously, 1,3-dioxolan-
2-yl radicals preferentially attacks the terminal olefin lead-
ing to 34 rather than the double bond of the dioxinone. The
by-product 35 results from the addition of 1,3-dioxolan-4-
yl radicals to the terminal double bond as well. The CϭC
bond in the dioxinone ring cannot compete with the ter-
minal olefin for both types of radicals.
Figure 4. Crystal structure of 24
1,3-dioxin-4-ones. This latter process, i.e. the addition of
1,3-dioxolan-2-yl radicals to the CϭC double bond of 14a
followed by hydrogen transfer is only observed as a side
reaction. The final product 28 is probably formed by H ab-
straction from the internal acetal center. Alternatively, 28
could be formed by 1,6-H shift followed by ring opening of
the 1,3-dioxolane and H abstraction.[34]
Irradiation of the dioxinone 32b (13 m) and acetone in
1,3-dioxolane was carried out for 48 hours. After chroma-
tographic workup, 36 was isolated as the main product in a
yield of 14%. The structure of 36 was assigned on the basis
of NMR analyses [1H-1H COSY, 1J(CH) correlated,
NOESY]. The NOE experiment shows a correlation be-
tween 15-Ha (located at the a-side of the dioxanone) and
a proton of the 1,3-dioxolan-2-ylmethyl group (Figure 5).
Therefore, the methylene group C-15 and the 1,3-dioxolan-
2-ylmethyl group are cis-fused at the new generated cyclo-
pentane. This is in agreement with the NOE observed be-
tween the isopropyl and dioxolanylmethyl group.
Scheme 6. Photocyclization of 14
Figure 5. NOE effects of 36 and preferred formation of intermedi-
ate A
As found for the 6-butenyl-substituted dioxinone 32a the
dioxolanyl radicals attack the terminal olefin with high
preference leading to the intermediate A. The following 5-
exo cyclization under formation of 36 occurs from the a-
side. Since four-membered rings are disfavoured no cyclized
Scheme 7. Photocyclization of 15 and 16
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H. Graalfs, R. Fröhlich, C. Wolff, J. Mattay
FULL PAPER
products were detected next to 34 and 35 in the reaction
of 32a. To explain the configuration of the newly formed
cyclopentane moiety in 36 a closer look at the transition
state is helpful. A pseudoequatorial position of the dioxo-
lanylmethyl group in a chair-like transition state leads to 36
(Figure 5). Alternative transition states involving an a-side
attack of the radical are unfavourable because of the steric
effect of the isopropyl group.
Polyhalogenated compounds can also be added to olefins
in photoreactions.[35] The addition of bromotrichlorometh-
ane to olefins by a chain reaction is achieved by bromine
atom transfer. Irradiation of the dioxinone 32b in bromotri-
chloromethane gave the two products 37 and 38 in a ratio
of 9:1. The trichloromethyl radical reacts only with the ter-
minal olefin. Because of the electrophilic nature of the
trichloromethyl radical no addition occurs even with 6-un-
substituted dioxinones. In contrast to the reaction of 32b in
dioxolane the radical A is trapped by abstraction of a bro-
mine atom indicating that cyclization is too slow to com-
pete. Thus, under the used reaction conditions trapping of
secondary radical A by BrCCl3 is much faster than hydro-
gen transfer from 1,3-dioxolane. To construct spiro systems
a reaction would be needed in which radical A leading to 32
has a longer lifetime so that cyclization becomes possible.
Dioxinone 37 can be converted to such a radical of type
A by reduction. In a nonoptimized photoinitiated reaction
of 37 and tri-n-butyltin hydride the reductive removal of
bromine was performed and the dioxinone 39 was found as
the main product beside other dehalogenated products. The
only cyclized product which could be isolated after chroma-
tographic workup was the dispirocyclic compound 40
whose structure was determined by X-ray analysis (Figure
6).[17] The configuration of 40 is in accordance with the
structure of 36 showing that both cyclizations proceed pref-
erentially from the a-side probably via chair-like transition
states (Figure 5). Since an excess of tin hydride was used
the cyclization reaction of 40 is followed by a reduction of
the trichloromethyl to the dichloromethyl group. The for-
mation of the dispirocyclic compound 36 starting with the
alkenyl-substituted dioxinone 32b is a one-pot reaction
which is more favourable than the two-step reaction leading
to 40. From these results it can be concluded that in gen-
eral, 6-haloalkyl-substituted dioxinones should be versatile
precursors for spirocyclic compounds in radical cycliza-
tions.
Figure 6. Crystal structure of 40
Scheme 9. Synthesis and photoaddition reactions of 32 and 33
In the same way aryl or vinyl bromides could be used.
Therefore we investigated the photoinitiated reaction of tri-
n-butyltin hydride with achiral dioxinone 41 which was pre-
pared from tert-butyl acetoacetate in two steps (Scheme
11)[30a,36] Besides the non-cyclized product 43 (6%) the in-
dane 38 was formed in 29% yield.
The results of irradiation of the dioxinones 32a,b in 1,3-
dioxolane show that the double bond in the dioxinone ring
cannot compete with that of the terminal olefin as radical
trap. Radicals prefer the addition to less substituted carbon
atoms in double bonds. The unfavourable effect of a sub-
stituent at C-6 also requires the ten times longer reaction
times in additions of 1,3-dioxolane to dioxinones 1b and 2b Scheme 10. Free-radical reaction of 32b and 37
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Diastereoselective Addition of Radicals to Chiral 1,3-Dioxin-4-ones
FULL PAPER
involved in intermolecular radical addition reactions next
to a 6-substituted 1,3-dioxin-4-one.
Conclusion
We have shown that in general 1,3-dioxin-4-ones are at-
tacked by radicals from the a-side in both inter- and intra-
molecular reactions. Therefore radicals behave like dienes
and alkenes in DielsϪAlder reactions and photochemical
[2ϩ2] cycloadditions, respectively, rather than nucleophiles
in cuprate additions. The origin of this behaviour which
may not be expected when considering the often observed
similarities of polar and radical reactions are not yet known
in detail.[11] Both SeebachЈs concept of pyramidalization of
the enone[3][4] and SatoЈs hyperconjugation model[19] may
not be applicable to radical reactions since diverse stereo-
selectivities would have been predicted. On the other hand,
our free radical reactions resemble photochemical [2ϩ2]
cycloadditions via enone triplets. In both reactions open-
shell-type intermediates are involved. Therefore, steric ef-
fects which were derived from X-ray analyses of 1a and 2b
to rationalize the facial selectivity may operate as well.
Studies on the chemoselectivities of unsubstituted and 6-
alkyl-substituted 1,3-dioxin-4-ones on the one side and ter-
minal alkenes on the other side were carried out as well. In
general, the highest reactivity in radical additions is ob-
served for the unsubstituted 1,3-dioxin-4-one followed by
the terminal olefin reflecting the balance of stereoelec-
tronic effects.
Scheme 11. Synthesis and free-radical reaction of 41
Scheme 12. Photoreaction of 44 in the presence of 1,3-dioxolane
compared to the additions to the 6-unsubstituted dioxi-
nones 1a and 2a.
To establish whether 6-unsubstituted dioxinones are bet-
ter radical traps for 1,3-dioxolan-2-yl radicals than terminal
olefins the dioxinone 44 was prepared by refluxing 5-for-
myl-2,2-dimethyl-1,3-dioxane-4,6-dione in xylene.[37] Ir-
radiation of dioxinone 44 (12 m) and acetone in 1,3-diox-
olane afforded a mixture of two products. After chromatog-
raphic workup two dioxabicyclo[3.2.2]nonanones 46 were
separated in yields of 8% and 12%, respectively. Further
separation gave one isomer of the dioxabicyclo[4.2.2]de-
canone 45 in a yield of 14%. The second isomer 45 was
only enriched.
Experimental Section
General Remarks: Melting points are uncorrected. Ϫ Optical ro-
tations: PerkinϪElmer Polarimeter 241. Ϫ IR: PerkinϪElmer
FTIR-Spektrometer 1600. Ϫ 1H and 13C NMR: Varian EM 390;
Bruker AC 200 P, WM 300, AM 360 or DRX 500 with TMS as
internal standard. Multipicities of 13C resonances were determined
by gated decoupling or by DEPT experiments. Ϫ Mass spectra:
Finnigan MAT C 312 or MAT 8230, CI with isobutane. Ϫ HPLC:
Kontron Pump 420 or Merck Pump L-6000, RI detector Bischoff
RI 8110, column 250 ϫ 20 mm, Merck LiChrosorb Si 60-5 or Si
The products 45 and 46 arise from addition of the 1,3-
dioxolan-2-yl radical to C-6 of 1,3-dioxin-4-one followed by
a cyclization reaction via the butenyl substituent. In com-
parison with the reactions of 1a and 2a the attack of the
radical should proceed with lower facial selectivity because 60-7. Ϫ CC: Merck silica gel 60, 40Ϫ63 µm and 63Ϫ200 µm. Ϫ
DC: Merck tin foil, silica gel 60 F 254 and Macherey and Nagel
SIL G/UV254. Ϫ GC: Siemens Sichromat 3 and 1-4, HewlettϪPack-
ard Ultra 2 (25 m, 0.2 mm) and Macherey and Nagel SE 30 (25 m,
0.2 mm). Ϫ Elemental analyses: PerkinϪElmer DIA CHN 240 and
Heraeus CHN-O-Rapid. Ϫ All crystal data sets were collected with
an Enraf Nonius CAD4 diffractometer. Programs used: data re-
duction MolEN, structure solution SHELXS-86, structure refine-
ment SHELXL-93, graphics (with unsystematical numbering
schemes) DIAMOND.
of the conformative flexibility of 44. Then in both inter-
mediates the newly formed radical is trapped by the ter-
minal olefin. If this intramolecular addition to the side
chain proceeds in an 8-endo mode the dioxabicyclo[4.2.2]de-
canone 45 is formed. The alternative 7-exo mode cyclization
leads to the dioxabicyclo[3.2.2]nonanones 46. The 7-exo
mode cyclization should give four possible isomers but only
two were detected.
Unsubstituted dioxinones are better radical traps for nu-
cleophiles like the dioxolanyl radical than terminal olefins
reflecting the influence of the electron-withdrawing group
next to the double bond in the dioxinone ring. An alkyl
substituent at C-6 of the dioxinone decreases the reactivity
with dioxolanyl radicals in such a way that terminal olefins
General Procedure A (Intermolecular Photoaddition): The solutions
were distributed in Pyrex tubes (volume 12 mL) and deoxygenated
with argon (15 min). The tubes were sealed and irradiated in a
Rayonet Photochemical Reactor (model RPR-100, Southern New
England) fitted with a merry-go-round apparatus and with 350-nm
lamps. The reaction course was monitored by TLC (cyclohexane/
become better radical traps. Thus, terminal olefins can be ethyl acetate, 1:1). At the end of the irradiation the solvent was
Eur. J. Org. Chem. 1999, 1057Ϫ1073 1063

H. Graalfs, R. Fröhlich, C. Wolff, J. Mattay
removed under reduced pressure and the residue was separated by irradiated for 44 h (procedure A). The crude mixture was separated
FULL PAPER
HPLC (cyclohexane/ethyl acetate).
by HPLC (cyclohexane/ethyl acetate, 3:1) to yield crystalline 8a (3
mg, 3%) and 7a (80 mg, 75%). Ϫ (4R,6S,7S,10R) Isomer 7a: 1H
NMR (300 MHz, CDCl3): δ ϭ 0.75 (d, J ϭ 6.9 Hz, 3 H, CH3),
0.80Ϫ0.93 (m, 1 H), 0.84 (d, J ϭ 6.7 Hz, 3 H, CH3), 0.86 (d, J ϭ
6.7 Hz, 3 H, CH3), 1.09 (t, J ϭ 12.9 Hz, 1 H, 11-Hax), 1.34Ϫ1.60
(m, 3 H), 1.61Ϫ1.78 (m, 2 H), 2.11 (ddd, J ϭ 13.0, 3.6, 2.1 Hz, 1
H, 11-Heq), 2.22 [dsept, J ϭ 7.0, 2.2 Hz, 1 H, CH(CH3)2], 2.47 (dd,
J ϭ 17.7, 5.7 Hz, 1 H, 3-Ha), 2.56 (dd, J ϭ 17.9, 9.8 Hz, 1 H, 3-
Hb), 3.83Ϫ3.97 (m, 4 H, 4Ј-H), 4.20 (ddd, J ϭ 9.5, 5.2, 3.8 Hz, 1
H, 4-H), 4.88 (d, J ϭ 3.8 Hz, 1 H, 2Ј-H). Ϫ 13C NMR (75 MHz,
CDCl3): δ ϭ 17.15 [CH3, C(CH3)2], 20.66 (CH2, C-8), 20.91 [CH3,
C(CH3)2], 22.45 (CH3, 10-CH3), 23.36 [CH, CH(CH3)2], 28.11
(CH, C-10), 29.02 (CH2, C-9), 33.16 (CH2, C-3), 43.23 (CH2, C-
11), 49.09 (CH, C-7), 64.43, 64.64 (CH2, C-4Ј, C-5Ј), 66.59 (CH,
C-4), 102.44 (CH, C-2Ј), 107.10 (C, C-6), 166.03 (C, C-2). Ϫ MS
(70 eV); m/z (%): 299 (9) [Mϩ ϩ H], 298 (3) [Mϩ], 283 (2), 255 (2),
225 (8), 183 (3), 154 (10), 139 (13), 127 (64), 112 (45), 99 (21), 73
(100), 69 (29). Ϫ (4S,6S,7S,10R) Isomer (8a, Less Polar Product):
M.p. 93°C (pentane). Ϫ IR (CH2Cl2): ν˜ ϭ 2930 cmϪ1 (m), 1742 (s,
CϭO), 1458 (w), 1372 (w), 1313 (m), 1283 (m), 1258 (m), 1196 (m),
1152 (m), 1078 (m), 1023 (m), 988 (m). Ϫ 1H NMR (300 MHz,
CDCl3): δ ϭ 0.80Ϫ1.00 (m, 1 H), 0.87 (d, J ϭ 7.2 Hz, 3 H, CH3),
0.87 (d, J ϭ 5.7 Hz, 3 H, CH3), 0.94 (d, J ϭ 6.9 Hz, 3 H, CH3),
1.16Ϫ1.66 (m, 5 H), 1.67Ϫ1.93 (m, 2 H), 2.24 [dsept, J ϭ 6.9, 2.0
Hz, 1 H, CH(CH3)2], 2.64 (dd, J ϭ 16.9, 4.8 Hz, 1 H, 3-Ha), 2.72
(dd, J ϭ 17.4, 9.8 Hz, 1 H, 3-Hb), 3.86Ϫ4.04 (m, 4 H, 4Ј-H), 4.18
(ddd, J ϭ 10.0, 5.0, 3.6 Hz, 1 H, 4-H), 4.97 (d, J ϭ 3.6 Hz, 1 H,
2Ј-H). Ϫ MS (70 eV); m/z (%): 299 (6) [Mϩ ϩ H], 255 (2), 225 (7)
[Mϩ Ϫ dioxolanyl], 183 (2), 154 (8) [menthoneϩ], 139 (11), 127
(66), 112 (37), 99 (21), 73 (100), 69 (30). Ϫ X-ray crystal structure
analysis of 8a: Empirical formula C16H26O5, M ϭ 298.37, 0.6 ϫ
(4R,6S,7S,10R)-4-(1-Hydroxy-1-methylethyl)-7-isopropyl-10-
methyl-1,5-dioxaspiro[5.5]undecan-2-one (4): A solution of 168 mg
(0.75 mmol) of 1a[38] and 20 mg (0.11 mmol) of benzophenone in
60 mL of 2-propanol was irradiated for 20 h (procedure A). The
product was purified by column chromatography (diethyl ether/
petroleum ether, 1:1) to yield 4 (60 mg, 28%) as an oil. Ϫ 1H NMR
(360 MHz, C6D6): δ ϭ 0.73 (ddt, J ϭ 12.2, 11.8, 3.8 Hz, 1 H), 0.80
(d, J ϭ 6.6 Hz, 3 H, 10-CH3), 0.94 (d, J ϭ 7.0 Hz, 3 H, CH3), 0.98
(s, 3 H, 1Ј-CH3), 1.01 (d, J ϭ 6.9 Hz, 3 H, CH3), 1.01 (t, J ϭ 12.9
Hz, 1 H, 11-Hax), 1.23 (s, 3 H, 1Ј-CH3), 1.28Ϫ1.80 (m, 6 H), 2.02
(ddd, J ϭ 13.3, 3.3, 1.8 Hz, 1 H, 11-Heq), 2.15 (dd, J ϭ 16.0, 4.9
Hz, 1 H, 3-Ha), 2.40 [dsept, J ϭ 7.0, 1.1 Hz, 1 H, CH(CH3)2], 2.51
(dd, J ϭ 16.0, 8.4 Hz, 1 H, 3-Hb), 4.29 (dd, J ϭ 8.4, 4.9 Hz, 1 H,
4-H). Ϫ 13C NMR (90 MHz, C6D6): δ ϭ 18.55 (CH3), 22.26 (CH3),
23.04 (CH2, C-8), 23.61 (CH3), 23.69 (CH3), 24.56 [CH,
CH(CH3)2], 28.31 (CH, C-10), 30.61 (CH3), 34.88 (CH2, C-9),
35.33 (CH2, C-3), 45.17 (CH2, C-11), 49.11 (CH, C-7), 78.82 (C,
C-1Ј), 79.07 (CH, C-4), 110.92 (C, C-6), 176.90 (C, C-2). Ϫ MS (70
eV); m/z (%): 284 (14) [Mϩ], 269 (17), 227 (30), 199 (19), 154 (15),
139 (31), 121 (12), 113 (62), 112 (38), 97 (47), 69 (70), 55 (50),
41 (100).
(4S,6R,7S,10R)-4-(1-Hydroxy-1-methylethyl)-7-isopropyl-10-
methyl-1,5-dioxaspiro[5.5]undecan-2-one (5): A solution of 95 mg
(0.42 mmol) of 1b[6] and 10 mg (0.05 mmol) of benzophenone in
30 mL of 2-propanol was irradiated for 20 h (procedure A). Purifi-
cation by HPLC (ethyl acetate/cyclohexane, 1:4) yielded 5 (20 mg,
1
17%) as an oil. Ϫ H NMR (300 MHz, C6D6): δ ϭ 0.74 (ddt, J ϭ
12.2, 12.2, 4.1 Hz, 1 H), 0.83 (d, J ϭ 6.9 Hz, 3 H, CH3), 0.92 (s, 3
H, 1Ј-CH3), 0.97 (d, J ϭ 6.9 Hz, 3 H, CH3), 0.98 (d, J ϭ 6.9 Hz,
3 H, CH3), 0.98 (m, 1 H, 11-Hax), 1.15 (s, 3 H, 1Ј-CH3), 1.32 (ddd,
J ϭ 12.4, 4.3, 1.7 Hz, 1 H), 1.36Ϫ1.68 (m, 4 H), 1.72 (mc, 1 H),
1.95 (ddd, J ϭ 12.9, 4.3, 1.9 Hz, 1 H, 11-Heq), 2.15 (dd, J ϭ 16.0,
4.8 Hz, 1 H, 3-Ha), 2.34 [dsept, J ϭ 6.9, 1.7 Hz, 1 H, CH(CH3)2],
2.54 (dd, J ϭ 16.0, 8.6 Hz, 1 H, 3-Hb), 4.42 (dd, J ϭ 8.6, 4.5 Hz,
1 H, 4-H). Ϫ 13C NMR (75 MHz, C6D6): δ ϭ 19.15 (CH3), 22.36
(CH3), 23.94 (CH3 and C-8), 24.88 (CH3), 24.95 [CH(CH3)2], 28.42
(C-10), 30.07 (CH3), 34.93 (C-9), 35.50 (C-3), 45.58 (C-11), 48.54
(C-7), 78.40 (C-1Ј), 79.64 (C-4), 110.14 (C-6), 175.48 (C-2).
˚
0.4 ϫ 0.2 mm, a ϭ 8.145(1), b ϭ 9.694(1), c ϭ 20.398(2) A, V ϭ
3
1610.6(3) A , ρcalcd. ϭ 1.230 g cmϪ3, µ ϭ 7.39 cmϪ1, empirical
˚
absorption correction with ψ scan data (0.975 Յ C Յ 0.999), Z ϭ
˚
4, orthorhombic, space group P212121 (no. 19), λ ϭ 1.54178 A,
T ϭ 293 K, ω/2θ scans, 1902 reflections collected (Ϫh, ϩk, Ϫl),
[(sin θ)/λ] ϭ 0.62 AϪ1, 1902 independent and 1812 observed reflec-
˚
tions [I Ն 2 σ(I)], 194 refined parameters, R ϭ 0.034, wR2 ϭ 0.100,
max. residual electron density 0.17 (Ϫ0.12) e AϪ3, Flack parameter
˚
0.0(2), hydrogen atoms calculated and riding.[17]
(4S)-4-Hydroxy-5,5-dimethyldihydrofuran-2-one (6): A solution of
168 mg (0.75 mmol) of 2a[38] and 20 mg (0.11 mmol) of benzo-
phenone in 60 mL of 2-propanol was irradiated for 20 h (procedure
A). After removal of the solvent, the residue was treated with 2 mL
of 2  HCl in 10 mL of THF. The solution was stirred at room
temperature for 4 d, and then extracted with diethyl ether. The
combined organic layers were dried (MgSO4) and concentrated in
vacuo. Purification by distillation (Kugelrohr, 100°C bath temp./
0.01 Torr) and by HPLC (ethyl acetate/cyclohexane, 7:3) yielded 6
(4RS,6R,7S,10R)-4-(1,3-Dioxolan-2-yl)-7-isopropyl-10-methyl-1,5-
dioxaspiro[5.5]undecan-2-one (9a and 10a): 120 mg (0.53 mmol) of
2a[38] was dissolved in 10 mL of 1,3-dioxolane. The solution was
irradiated for 27 h (procedure A). The crude mixture was separated
by HPLC (cyclohexane/ethyl acetate, 4:1) to yield recovered 2a (20
mg) and two adducts as oils: 10a (10 mg, 6%) and 9a (90 mg, 56%).
Ϫ (4S,6R,7S,10R) Isomer (9a): 1H NMR (300 MHz, C6D6): δ ϭ
0.62 (mc, 1 H), 0.66 (d, J ϭ 6.2 Hz, 3 H, CH3), 0.86 (d, J ϭ 6.9
Hz, 3 H, CH3), 0.94 (d, J ϭ 6.9 Hz, 3 H, CH3), 0.98 (dd, J ϭ 14.1,
12.6 Hz, 1 H, 11-Hax), 1.30Ϫ1.52 (m, 5 H), 1.80 (ddd, J ϭ 14.1,
2.9, 2.4 Hz, 1 H, 11-Heq), 2.20 [dsept, J ϭ 7.2, 1.7 Hz, 1 H,
CH(CH3)2], 2.32 (dd, J ϭ 17.6, 4.5 Hz, 1 H, 3-Ha), 2.51 (dd, J ϭ
17.6, 10.5 Hz, 1 H, 3-Hb), 3.22Ϫ3.30 (m, 4 H, 4Ј-H), 3.74 (ddd,
J ϭ 10.5, 4.3, 3.3 Hz, 1 H, 4-H), 4.64 (d, J ϭ 3.3 Hz, 1 H, 2Ј-H).
(17 mg, 17%) as an oil: [α]20 ϭ Ϫ11.5 (c ϭ 0.4, CHCl3) {ref.[15]
D
[α]20 ϭ Ϫ11 (c ϭ 1.5, CHCl3)}. Ϫ IR (neat): ν˜ ϭ 3417 cmϪ1 (s),
D
2980 (m), 2937 (m), 1760 (s, CϭO), 1388 (m), 1280 (m), 1178 (m),
1126 (m), 1072 (m), 959 (m), 941 (m). Ϫ 1H NMR (300 MHz,
CDCl3): δ ϭ 1.48 (s, 3 H, 5-CH3), 1.55 (s, 3 H, 5-CH3), 2.55 (dd,
J ϭ 18.0, 3.1 Hz, 1 H, 3-Ha), 2.95 (dd, J ϭ 18.0, 6.3 Hz, 1 H, 3-
Hb), 3.05 (s, br., 1 H, OH), 4.21 (dd, J ϭ 6.3, 3.1 Hz, 1 H, 4-H).
Ϫ
13C NMR (75 MHz, C6D6): δ ϭ 19.07 [CH3, C(CH3)2], 21.68
[CH3, C(CH3)2], 22.73 (CH2, C-8), 23.56 (CH3, 10-CH3), 25.53
[CH, CH(CH3)2], 29.33 (CH, C-10), 30.29 (CH2, C-9), 34.36 (CH2,
C-3), 42.61 (CH2, C-11), 50.81 (CH, C-7), 65.21, 65.43 (CH2, C-
4Ј,C-5Ј), 68.16 (CH, C-4), 103.48 (CH, C-2Ј), 108.71 (C, C-6),
Ϫ
13C NMR (125 MHz, CDCl3): δ ϭ 21.06 (q, CH3), 25.99 (q,
CH3), 38.27 (t, C-3), 73.56 (d, C-4), 88.15 (s, C-5), 175.53 (s, C-2).
Ϫ MS (CI); m/z (%): 131 (100) [Mϩ ϩ H], 113 (16), 71 (8).
(4RS,6S,7S,10R)-4-(1,3-Dioxolan-2-yl)-7-isopropyl-10-methyl-1,5-
166.25 (C, C-2). Ϫ (4R,6R,7S,10R) Isomer (10a, Less Polar Prod-
1
dioxaspiro[5.5]undecan-2-one (7a and 8a): 80 mg (0.36 mmol) of uct): H NMR (300 MHz, C6D6): δ ϭ 0.66 (mc, 1 H), 0.71 (d, J ϭ
1a[38] was dissolved in 10 mL of 1,3-dioxolane. The solution was
6.7 Hz, 3 H, CH3), 0.89 (d, J ϭ 7.0 Hz, 3 H, CH3), 0.91 (d, J ϭ
Eur. J. Org. Chem. 1999, 1057Ϫ1073
1064

Diastereoselective Addition of Radicals to Chiral 1,3-Dioxin-4-ones
FULL PAPER
7.0 Hz, 3 H, CH3), 1.08 (t, J ϭ 12.6 Hz, 1 H, 11-Hax), 1.25Ϫ1.52
(100), 69 (19). Ϫ C17H28O5 (312.41): calcd. C 65.36; H 9.03; found
(m, 4 H), 1.64 (mc, 1 H), 1.69 (ddd, J ϭ 12.4, 3.6, 1.9 Hz, 1 H, 11- C 65.02; H 9.21. Ϫ X-ray crystal structure analysis of 9b: Empirical
Heq), 2.22 [dsept, J ϭ 6.9, 1.7 Hz, 1 H, CH(CH3)2], 2.39 (dd, J ϭ formula C17H28O5, M ϭ 312.39, 1.0 ϫ 0.6 ϫ 0.5 mm, a ϭ 8.997(1),
3
˚
˚
17.2, 5.5 Hz, 1 H, 3-Ha), 2.47 (dd, J ϭ 17.2, 10.0 Hz, 1 H, 3-Hb), b ϭ 10.830(1), c ϭ 17.800(2) A, V ϭ 1734.4(3) A , ρcalcd. ϭ 1.196
3.14Ϫ3.30 (m, 4 H, 4Ј-H), 3.80 (ddd, J ϭ 10.0, 5.5, 3.1 Hz, 1 H,
g cmϪ3, µ ϭ 7.07 cmϪ1, empirical absorption correction with ψ
4-H), 4.62 (d, J ϭ 3.3 Hz, 1 H, 2Ј-H). Ϫ 13C NMR (75 MHz, scan data (0.947 Յ C Յ 0.999), Z ϭ 4, orthorhombic, space group
˚
C6D6): δ ϭ 18.52 [CH3, C(CH3)2], 21.68 [CH3, C(CH3)2], 22.42
P212121 (No. 19), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 2037
(CH2, C-8), 23.64 (CH3, 10-CH3), 24.95 [CH, CH(CH3)2], 29.64 reflections collected (ϩh, ϩk, Ϫl), [(sin θ)/λ] ϭ 0.62 AϪ1, 2037
(CH, C-10 and CH2, C-9), 34.15 (CH2, C-3), 48.54 (CH2, C-11), independent and 1974 observed reflections [I Ն 2σ(I)], 204 refined
51.03 (CH, C-7), 64.92, 65.22 (CH2, C-4Ј,C-5Ј), 71.52 (CH, C-4), parameters, R ϭ 0.034, wR2 ϭ 0.094, max. residual electron density
˚
103.74 (CH, C-2Ј), 108.22 (C, C-6), 165.80 (C, C-2). Ϫ MS (70 eV); 0.22 (Ϫ0.14) e AϪ3, Flack parameter 0.1(2), hydrogen atoms calcu-
˚
m/z (%): 298 (7) [Mϩ], 283 (1), 255 (1), 225 (6), 213 (16), 154 (10), lated and riding.[17]
139 (10), 127 (82), 112 (25), 99 (12), 73 (100), 69 (25).
(4R,6S,7S,10R,2ЈRS)-7-Isopropyl-10-methyl-4-oxolan-2Ј-yl-1,5-
(4R,6S,7S,10R)-4-(1,3-Dioxolan-2-yl)-7-isopropyl-4,10-dimethyl-
dioxaspiro[5.5]undecan-2-one (11a): 130 mg (0.58 mmol) of 1a[38]
1,5-dioxaspiro[5.5]undecan-2-one (7b): 100 mg (0.42 mmol) of 1b[6] was dissolved in 16 mL of THF. The solution was irradiated for 5
was dissolved in 10 mL of 1,3-dioxolane. The solution was ir-
radiated for 12 d (procedure A). Purification by HPLC (cyclohex-
ane/ethyl acetate, 4:1) gave recovered 1b (20 mg) and crystalline 7b
d (procedure A). Purification by HPLC (cyclohexane/ethyl acetate,
4:1) yielded the two crystalline adducts (2ЈR)-11a and (2ЈS)-11a
(less polar isomer 38 mg, 22% and more polar isomer 70 mg, 41%).
(30 mg, 23%): M.p. 87°C. [α]20 ϭ Ϫ44.3 (c ϭ 1.1, CHCl3). Ϫ IR The isomers were separated but the stereochemistry was not as-
D
(KBr): ν˜ ϭ 2960 cmϪ1 (m), 1747 (s, CϭO), 1458 (m), 1375 (m), signed. Ϫ 11a (Less Polar Product): M.p. 100°C (pentane). [α]20D ϭ
1319 (m), 1238 (m), 1197 (w), 1152 (m), 1112 (m), 889 (w), 570 (w). ϩ41.4 (c ϭ 0.4, CHCl3). Ϫ IR (neat): ν˜ ϭ 2953 cmϪ1 (s), 1747 (s,
1
Ϫ H NMR (300 MHz, C6D6): δ ϭ 0.65 (mc, 1 H), 0.70 (d, J ϭ
6.4 Hz, 3 H, CH3), 0.94 (d J ϭ 7.2 Hz, 3 H, CH3), 1.07 (t, J ϭ
CϭO), 1455 (m), 1316 (m), 1237 (m), 1154 (m), 1075 (m), 1007
1
(m), 972 (m). Ϫ H NMR (300 MHz, C6D6): δ ϭ 0.66 (mc, 1 H),
12.7 Hz, 1 H, 11-Hax), 1.11 (d, J ϭ 6.4 Hz, 3 H, CH3), 1.12 (s, 3 0.74 (d, J ϭ 6.4 Hz, 3 H, 10-CH3), 0.81 (t, J ϭ 12.6 Hz, 1 H, 11-
H, 4-CH3), 1.31 (ddd, J ϭ 12.9, 3.6, 1.9 Hz, 1 H, 7-H), 1.38Ϫ1.68 Hax), 0.90 [d, J ϭ 6.9 Hz, 3 H, CH(CH3)2], 0.96 [d, J ϭ 6.9 Hz, 3
(m, 4 H), 1.90 (ddd, J ϭ 13.4, 3.3, 1.9 Hz, 1 H, 11-Heq), 2.15 (d, H, CH(CH3)2], 1.28 (ddd, J ϭ 12.8, 3.9, 2.2 Hz, 1 H, 7-H),
J ϭ 17.2 Hz, 1 H, 3-Ha), 2.61 (d, J ϭ 17.2 Hz, 1 H, 3-Hb), 2.72 1.32Ϫ1.80 (m, 8 H), 1.93 (ddd, J ϭ 13.1, 3.8, 1.7 Hz, 1 H, 11-Heq),
[dsept, J ϭ 6.9, 1.9 Hz, 1 H, CH(CH3)2], 3.16 (ddd, J ϭ 7.2, 6.9,
6.9 Hz, 1 H), 3.26 (ddd, J ϭ 7.2, 6.9, 4.0 Hz, 1 H), 3.38 (ddd, J ϭ
6.9, 6.4, 4.0 Hz, 1 H), 3.46 (ddd, J ϭ 7.2, 6.9, 6.4 Hz, 1 H), 4.58
2.31 (dd, J ϭ 17.6, 10.3 Hz, 1 H, 3-Ha), 2.40 [dsept, J ϭ 6.9, 2.1
Hz, 1 H, CH(CH3)2], 2.42 (dd, J ϭ 17.6, 4.5 Hz, 1 H, 3-Hb),
3.40Ϫ3.61 (m, 3 H, 2Ј-H, 5Ј-H), 3.75 (ddd, J ϭ 10.1, 5.5, 4.6 Hz,
(s, 1 H, 2Ј-H). Ϫ 13C NMR (75 MHz, C6D6): δ ϭ 18.25 [CH3, 1 H, 4-H). Ϫ 13C NMR (75 MHz, C6D6): δ ϭ 18.31 [CH3,
CH(CH3)2], 21.62 (CH2, C-8), 22.05 [CH3, CH(CH3)2], 23.84 (CH3, C(CH3)2], 21.95 (CH2, C-8), 22.05 [CH3, C(CH3)2], 23.67 (CH3, 10-
10-CH3), 24.41 [CH, CH(CH3)2], 25.15 (CH3, 4-CH3), 29.70 (CH, CH3), 24.81 [CH, CH(CH3)2], 25.63 (CH2, C-3Ј), 27.55 (CH2, C-
C-10), 33.58, 34.42 (CH2, C-3, C-9), 47.77 (CH2, C-11), 51.44 (CH, 2Ј), 29.16 (CH, C-10), 33.14, 34.42 (CH2, C-3, C-9), 44.36 (CH2,
C-7), 65.32, 65.66 (CH2, C-4Ј, C-5Ј), 76.54 (C, C-4), 107.01 (C, C-
6 and CH, C-2Ј), 166.04 (C, C-2). Ϫ MS (70 eV); m/z (%): 312 (4)
C-11), 50.63 (CH, C-7), 68.46 (CH2, C-4Ј), 68.89 (CH, C-4), 80.42
(CH, C-2Ј), 107.07 (C, C-6), 165.74 (C, C-2). Ϫ MS (70 eV); m/z
[Mϩ], 297 (1), 269 (1), 256 (1), 239 (7), 155 (8), 154 (7), 141 (66), (%): 296 (5) [Mϩ], 255 (6), 211 (25), 155 (19), 154 (12), 143 (15),
112 (13), 73 (100), 69 (18). Ϫ C17H28O5 (312.41): calcd. C 65.36;
139 (20), 125 (100), 112 (30), 97 (48), 83 (30), 71 (47), 69 (40). Ϫ
H 9.03; found C 64.58; H 9.30.
C17H28O4 (296.4): calcd. C 68.89; H 9.52; found C 69.14; H 9.68.
Ϫ 11a (More Polar Product): M.p. 50°C. [α]20 ϭ ϩ27.6 (c ϭ 0.6,
D
(4S,6R,7S,10R)-4-(1,3-Dioxolan-2-yl)-7-isopropyl-4,10-dimethyl-
1,5-dioxaspiro[5.5]undecan-2-one (9b): 110 mg (0.46 mmol) of 2b[6]
was dissolved in 10 mL of 1,3-dioxolane. The solution was ir-
radiated for 12 d (procedure A). Purification by HPLC (cyclohex-
ane/ethyl acetate, 4:1) gave recovered 2b (50 mg) and crystalline 9b
CHCl3). Ϫ IR (CH2Cl2): ν˜ ϭ 2954 cmϪ1 (m), 1734 (s, CϭO), 1318
1
(w), 1237 (m), 1062 (m), 970 (w). Ϫ H NMR (300 MHz, C6D6):
δ ϭ 0.64 (mc, 1 H), 0.74 (d, J ϭ 6.4 Hz, 3 H, 10-CH3), 0.79 (t, J ϭ
12.6 Hz, 1 H, 11-Hax), 0.90 [d, J ϭ 7.2 Hz, 3 H, CH(CH3)2], 0.96
[d, J ϭ 6.9 Hz, 3 H, CH(CH3)2], 1.25 (ddd, J ϭ 12.9, 4.1, 2.2 Hz,
1 H, 7-H), 1.26Ϫ1.78 (m, 8 H), 1.91 (ddd, J ϭ 12.9, 3.6, 1.7 Hz, 1
H, 11-Heq), 2.13 (dd, J ϭ 17.4, 4.0 Hz, 1 H, 3-Ha), 2.40 [dsept, J ϭ
6.9, 2.2 Hz, 1 H, CH(CH3)2], 2.52 (dd, J ϭ 17.4, 11.0 Hz, 1 H, 3-
Hb), 3.46Ϫ3.56 (m, 2 H), 3.59Ϫ3.66 (m, 1 H), 3.67 (ddd, J ϭ 4.0,
4.0, 11.0 Hz, 1 H, 4-H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 18.16
[q, C(CH3)2], 21.77 (t, C-8), 21.93 [q, C(CH3)2], 23.49 (q, 10-CH3),
24.58 [d, CH(CH3)2], 25.89 (t, C-3Ј), 27.14 (t, C-2Ј), 29.13 (d, C-
10), 32.13, 34.26 (t, C-3, C-9), 44.38 (t, C-11), 50.22 (d, C-7), 68.90
(t, C-4Ј), 69.00 (d, C-4), 79.56 (d, C-2Ј), 108.19 (s, C-6), 167.46 (s,
C-2). Ϫ MS (70 eV); m/z (%): 296 (3) [Mϩ], 225 (7), 211 (17), 155
(7), 154 (10), 143 (16), 139 (21), 125 (100), 112 (37), 97 (52), 83
(36), 71 (33), 69 (48).
(60 mg, 42%): M.p. 84°C. [α]20 ϭ Ϫ16.8 (c ϭ 1.0, CHCl3). Ϫ IR
D
(KBr): ν˜ ϭ 2958 cmϪ1 (m), 1744 (s, CϭO), 1458 (m), 1369 (m),
1317 (m), 1109 (s), 1043 (m), 1003 (s), 811 (m), 550 (w). Ϫ 1H
NMR (300 MHz, C6D6): δ ϭ 0.67 (mc, 1 H), 0.70 (d, J ϭ 6.4 Hz,
3 H, CH3), 0.93 (d, J ϭ 6.9 Hz, 3 H, CH3), 1.01 (d, J ϭ 6.9 Hz, 3
H, CH3), 1.04 (dd, J ϭ 13.4, 12.4 Hz, 1 H, 11-Hax), 1.06 (s, 3 H,
4-CH3), 1.26Ϫ1.37 (m, 1 H), 1.39Ϫ1.59 (m, 4 H), 1.72 (ddd, J ϭ
13.4, 3.1, 1.9 Hz, 1 H, 11-Heq), 2.10 (d, J ϭ 17.4 Hz, 1 H, 3-Ha),
2.60 (d, J ϭ 17.2 Hz, 1 H, 3-Hb), 2.60 [dsept, J ϭ 6.9, 1.7 Hz, 1
H, CH(CH3)2], 3.15 (ddd, J ϭ 6.9, 6.9, 6.7 Hz, 1 H), 3.24 (ddd,
J ϭ 6.9, 6.7, 4.5 Hz, 1 H), 3.37 (ddd, J ϭ 6.9, 6.7, 4.1 Hz, 1 H),
3.45 (ddd, J ϭ 6.9, 6.7, 6.4 Hz, 1 H), 4.54 (s, 1 H, 2Ј-H). Ϫ 13C
NMR (75 MHz, C6D6): δ ϭ 19.02 [CH3, CH(CH3)2], 21.72 [CH3,
CH(CH3)2], 22.56 (CH2, C-8), 23.97 (CH3, 10-CH3), 24.68 [CH, (4S,6R,7S,10R,2ЈRS)-7-Isopropyl-10-methyl-4-oxolan-2Ј-yl-1,5-
CH(CH3)2], 24.82 (CH3, 4-CH3), 29.97 (CH, C-10), 33.54, 34.45 dioxaspiro[5.5]undecan-2-one (12a): 70 mg (0.31 mmol) of 2a[38] was
(CH2, C-3, C-9), 46.05 (CH2, C-11), 51.67 (CH, C-7), 65.32, 65.69 dissolved in 7 mL of THF. The solution was irradiated for 4 d
(CH2, C-4Ј, C-5Ј), 76.78 (C, C-4), 106.84 (CH, C-2Ј), 107.78 (CH, (procedure A). Purification by HPLC (cyclohexane/ethyl acetate,
C-6), 166.55 (C, C-2). Ϫ MS (70 eV); m/z (%): 312 (5) [Mϩ], 297 4:1) gave an oil (20 mg, 22%) and a solid (20 mg, 22%). The stereo-
(1), 269 (1), 239 (6), 227 (5), 155 (8), 154 (8), 141 (84), 112 (17), 73 chemistry of the isomers (2ЈR)-12a and (2ЈS)-12a was not assigned.
Eur. J. Org. Chem. 1999, 1057Ϫ1073
1065

H. Graalfs, R. Fröhlich, C. Wolff, J. Mattay
FULL PAPER
Ϫ 12a (Less Polar Product): Ϫ IR (CH2Cl2): ν˜ ϭ 2966 cmϪ1 (m),
arable. Ϫ 12b (Major Isomer): 1H NMR (300 MHz, C6D6): δ ϭ
0.66 (mc, 1 H), 0.70 (d, J ϭ 6.4 Hz, 3 H, 10-CH3), 0.89 (d, J ϭ 6.7
1734 (s, CϭO), 1182 (m). Ϫ 1H NMR (300 MHz, C6D6): δ ϭ 0.64
(mc, 1 H), 0.71 (d, J ϭ 6.7 Hz, 3 H, 10-CH3), 0.91 [d, J ϭ 6.9 Hz, Hz, 3 H, C(CH3)2], 0.95 [d, J ϭ 7.2 Hz, 3 H, C(CH3)2], 1.05 (dd,
3 H, CH(CH3)2], 0.92 [d, J ϭ 6.9 Hz, 3 H, CH(CH3)2], 1.11 (t, J ϭ J ϭ 13.6, 12.4 Hz, 1 H, 11-Hax), 1.06 (s, 3 H, 4-CH3), 1.20Ϫ1.67
14.1, 12.6 Hz, 1 H, 11-Hax), 1.28Ϫ1.55 (m, 9 H), 1.84 (ddd, J ϭ (m, 9 H), 1.77 (ddd, J ϭ 13.6, 2.8, 2.2 Hz, 1 H, 11-Heq), 2.15 (d,
14.1, 3.3, 2.2 Hz, 1 H, 11-Heq), 2.20 [dsept, J ϭ 6.9, 1.0 Hz, 1 H,
CH(CH3)2], 2.27 (dd, J ϭ 17.6, 10.5 Hz, 1 H, 3-Ha), 2.42 (dd, J ϭ
J ϭ 17.6 Hz, 1 H, 3-Ha), 2.35 [dsept, J ϭ 6.9, 1.2 Hz, 1 H,
CH(CH3)2], 2.77 (d, J ϭ 17.6 Hz, 1 H, 3-Hb), 3.38 (dd, J ϭ 7.9,
17.6, 4.3 Hz, 1 H, 3-Hb), 3.40Ϫ3.60 (m, 4 H, 4-H, 2Ј-H, 5Ј-H). Ϫ 6.9 Hz, 1 H, 2Ј-H), 3.43 (dt, J ϭ 7.9, 5.7 Hz, 1 H, 5Ј-Ha), 3.62 (dt,
1
13C NMR (75 MHz, C6D6): δ ϭ 19.16 [CH3, C(CH3)2], 21.65 [CH3, J ϭ 8.3, 6.4 Hz, 1 H, 5Ј-Hb). Ϫ 12b (Minor Isomer): Ϫ H NMR
C(CH3)2], 22.86 (CH2, C-8), 23.60 (CH3, 10-CH3), 25.39 [CH,
(300 MHz, C6D6): δ ϭ 0.66 (mc, 1 H), 0.72 (d, J ϭ 6.7 Hz, 3 H,
CH(CH3)2], 25.66 (CH2, C-3Ј), 27.61 (CH2, C-2Ј), 29.50 (CH, C- 10-CH3), 0.90 (s, 3 H, 4-CH3), 0.96 [d, J ϭ 6.9 Hz, 3 H, C(CH3)2],
10), 33.14, 34.35 (CH2, C-3, C-9), 42.61 (CH2, C-11), 50.79 (CH, 0.97 [d, J ϭ 6.9 Hz, 3 H, C(CH3)2], 1.06 (m, 1 H, 11-Hax),
C-7), 68.45 (CH2, C-4Ј), 69.43 (CH, C-4), 80.45 (CH, C-2Ј), 108.35
1.20Ϫ1.68 (m, 9 H), 1.77 (ddd, J ϭ 13.6, 2.8, 2.2 Hz, 1 H, 11-Heq),
(C, C-6), 166.17 (C, C-2). Ϫ MS (70 eV); m/z (%): 296 (4) [Mϩ], 2.18 (d, J ϭ 17.2 Hz, 1 H, 3-Ha), 2.48 [dsept, J ϭ 6.9, 1.8 Hz, 1
225 (7), 211 (28), 155 (19), 154 (7) [menthoneϩ], 143 (11), 139 (11), H, CH(CH3)2], 2.66 (d, J ϭ 17.2 Hz, 1 H, 3-Hb), 3.38Ϫ3.63 (m, 3
125 (100), 112 (22), 97 (34), 83 (20), 71 (27) [oxolanylϩ], 69 (22),
H, 2Ј-H, 5Ј-H).
55 (24), 41 (56). Ϫ 12a (More Polar Product): Ϫ IR (neat): ν˜ ϭ
General Procedure B (Alkylation of 1,3-Dioxin-4-ones): In a flame-
dried flask, 3 mL of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimi-
dinone and diisopropylamine (350 mg, 3.46 mmol) were dissolved
in 20 mL of THF under argon. The solution was cooled to Ϫ78°C,
n-butyllithium (1.9 mL, 3.0 mmol, 1.6  in hexanes) was added.
After being stirred for 20 min at this temperature, the mixture was
allowed to warm to 20°C, and stirred for additional 10 min. The
LDA solution was cooled to Ϫ78°C and 1,3-dioxin-4-one (2.10
mmol) in 2 mL of THF was added dropwise. After the yellow solu-
tion was stirred for 30 min, the bromide (2.1Ϫ11.0 mmol) was ad-
ded, and the mixture was allowed to warm slowly to room tempera-
ture. After being stirred for 14 h, the reaction was quenched with
30 mL of a saturated ammonium chloride solution, and then ex-
tracted with diethyl ether (3 ϫ 30 mL). The combined organic lay-
ers were washed with brine and dried (MgSO4). The solvent was
removed in vacuo and the resulting mixture of dioxinones was puri-
fied by column chromatography (n-pentane/diethyl ether).
1
2966 cmϪ1 (m), 1714 (s, CϭO), 1183 (m). Ϫ H NMR (300 MHz,
C6D6): δ ϭ 0.63 (mc, 1 H), 0.72 (d, J ϭ 6.4 Hz, 3 H, 10-CH3), 0.91
[d, J ϭ 6.9 Hz, 3 H, CH(CH3)2], 0.95 [(d, J ϭ 6.9 Hz, 3 H,
CH(CH3)2], 1.03 (dd, J ϭ 13.8,12.6 Hz, 1 H, 11-Hax), 1.22Ϫ1.60
(m, 9 H), 1.85 (ddd, J ϭ 13.8, 2.9, 2.2 Hz, 1 H, 11-Heq), 2.14 (dd,
J ϭ 17.4, 3.6 Hz, 1 H, 3-Ha), 2.21 [sept, J ϭ 6.9 Hz, 1 H,
CH(CH3)2], 2.58 (dd, J ϭ 17.4, 11.0 Hz, 1 H, 3-Hb), 3.37Ϫ3.51 (m,
3 H, 2Ј-H, 5Ј-H), 3.62 (mc, 1 H, 4-H). Ϫ 13C NMR (75 MHz,
C6D6): δ ϭ 18.95 [CH3, C(CH3)2], 21.68 [CH3, C(CH3)2], 22.83
(CH2, C-8), 23.54 (CH3, 10-CH3), 25.46 [CH, CH(CH3)2], 26.03
(CH2, C-3Ј), 27.07 (CH2, C-2Ј), 29.47 (CH, C-10), 32.40, 34.35
(CH2, C-3, C-9), 42.64 (CH2, C-11), 50.97 (CH, C-7), 68.56 (CH2,
C-4Ј), 69.00 (CH, C-4), 79.00 (CH, C-2Ј), 108.45 (C, C-6), 166.62
(C, C-2). Ϫ MS (70 eV); m/z (%): 296 (2) [Mϩ], 225 (5), 211 (5),
210 (7), 155 (6), 154 (15), 143 (10), 139 (27), 125 (74), 112 (44), 97
(52), 83 (49), 71 (28), 69 (58), 55 (62), 41 (100).
(4R,6S,7S,10R,2ЈRS)-7-Isopropyl-4,10-dimethyl-4-oxolan-2Ј-yl-1,5-
dioxaspiro[5.5]undecan-2-one (11b): 70 mg (0.29 mmol) of 1b[6] was
dissolved in 7 mL of THF. The solution was irradiated for 12 d
(procedure A). Purification by HPLC (cyclohexane/ethyl acetate,
3:1) gave recovered 1b (50 mg) and two adducts (2ЈR)-11b and
(2ЈS)-11b (less polar isomer 3 mg, 3% and more polar isomer 6 mg,
6%). The stereochemistry of neither isomers was assigned. Ϫ 11b
6-[3-(1,3-Dioxolan-2-yl)propyl]-2,2-dimethyl-1,3-dioxin-4-one (14a)
and 5-[2-(1,3-Dioxolan-2-yl)ethyl]-2,2,6-trimethyl-1,3-dioxin-4-one
(17a): Compounds 14a and 17a were prepared by procedure B
using 2,2,6-trimethyl-1,3-dioxin-4-one (1.73 g, 12.2 mmol) and 2-
(2-bromoethyl)-1,3-dioxolane (3.64 g, 20.1 mmol). Purification by
column chromotography (n-pentane/diethyl ether, 1:1) gave a mix-
ture of 14a and 17a. This mixture was separated by HPLC (cyclo-
hexane/ethyl acetate, 7:3) to yield 17a (91 mg, 5%) and 14a (436
mg, 15%). Ϫ 14a: IR (neat): ν˜ ϭ 2951 cmϪ1 (m), 2880 (s), 1729 (s,
CϭO), 1633 (m), 1391 (s), 1273 (m), 1205 (m), 1140 (m), 1014 (m),
902 (w). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 1.61 (s, 6 H, 2-CH3),
1.63 (mc, 4 H), 2.21 (m, 2 H, 1ЈЈ-H), 3.75Ϫ3.95 (m, 4 H, 4ЈЈ-H),
4.80 (mc, 1 H, 2Ј-H), 5.19 (t, J ϭ 0.8 Hz, 1 H, 5-H). Ϫ 13C NMR
(75 MHz, CDCl3): δ ϭ 20.12 (t, C-2ЈЈ), 25.01 (q, 2-CH3), 32.90,
33.36 (t, C-1ЈЈ, C-3ЈЈ), 64.93 (t, C-4Ј), 93.34 (d, C-5), 103.86 (d, C-
2Ј), 106.35 (s, C-2), 161.41 (s, C-6), 171.56 (s, C-4). Ϫ MS (70 eV);
m/z (%): 242 (1) [Mϩ], 184 (3), 183 (5), 156 (10), 99 (42), 86 (7), 73
(100), 69 (10). Ϫ 17a: IR (neat): ν˜ ϭ 2886 cmϪ1 (m), 1716 (s, Cϭ
O), 1645 (s), 1398 (s), 1356 (m), 1270 (m), 1236 (m), 1207 (m), 1142
1
(Less Polar Product): H NMR (300 MHz, C6D6): δ ϭ 0.66 (ddt,
J ϭ 12.2, 12.2, 3.6 Hz, 1 H), 0.72 (d, J ϭ 6.4 Hz, 3 H, 10-CH3),
0.95 [d, J ϭ 7.2 Hz, 3 H, C(CH3)2], 0.98 (s, 3 H, 4-CH3), 1.10 [mc,
1 H, therein d, J ϭ 6.9 Hz, 3 H, C(CH3)2], 1.26Ϫ1.68 (m, 9 H),
1.93 (ddd, J ϭ 13.4, 3.6, 1.7 Hz, 1 H, 11-Heq), 2.22 (d, J ϭ 17.2
Hz, 1 H, 3-Ha), 2.60 [dsept, J ϭ 7.2, 1.7 Hz, 1 H, CH(CH3)2], 2.69
(d, J ϭ 17.2 Hz, 1 H, 3-Hb), 3.45 (mc, 1 H, 2Ј-H), 3.54Ϫ3.67 (m,
2 H, 5Ј-H). Ϫ 11a (More Polar Product): 1H NMR (300 MHz,
C6D6): δ ϭ 0.66 (ddt, J ϭ 12.2, 12.2, 3.6 Hz, 1 H), 0.72 (d, J ϭ
6.4 Hz, 3 H, 10-CH3), 0.92 [d, J ϭ 7.2 Hz, 3 H, C(CH3)2], 1.04 (s,
3 H, 4-CH3), 1.05 [d, J ϭ 7.9 Hz, 3 H, C(CH3)2], 1.06 (t, J ϭ 12.2
Hz, 1 H, 11-Hax), 1.29 (ddd, J ϭ 12.9, 3.6, 1.7 Hz, 1 H), 1.37Ϫ1.74
(m, 8 H), 1.94 (ddd, J ϭ 13.4, 3.6, 1.9 Hz, 1 H, 11-Heq), 2.20 (d,
J ϭ 17.4 Hz, 1 H, 3-Ha), 2.55 [dsept, J ϭ 7.2, 1.4 Hz, 1 H,
CH(CH3)2], 2.78 (d, J ϭ 17.4 Hz, 1 H, 3-Hb), 3.34 (dd, J ϭ 8.6,
6.7 Hz, 1 H, 1Ј-H), 3.48 (dt, J ϭ 8.1, 5.5 Hz, 1 H, 4Ј-Ha), 3.64 (dt,
J ϭ 8.1, 6.7 Hz, 1 H, 4Ј-Hb).
1
(m), 1031 (m), 904 (w). Ϫ H NMR (200 MHz, CDCl3): δ ϭ 1.65
(s, 6 H, 2-CH3), 1.83 (m, 2 H, 2ЈЈ-H), 2.00 (s, 3 H, 6-CH3), 2.40
(m, 2 H, 1ЈЈ-H), 3.78Ϫ4.03 (m, 4 H, 4Ј-H), 4.87 (t, J ϭ 4.7 Hz, 1
H, 2Ј-H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 17.26 (q, 6-CH3),
19.96 (t, C-2ЈЈ), 25.14 (q, 2-CH3), 33.06 (t, C-1ЈЈ), 64.89 (t, C-4Ј),
103.97 (d, C-2Ј), 104.78, 104.83 (s, C-2, C-5), 161.96 (s, C-6), 163.26
(s, C-4). Ϫ MS (70 eV); m/z (%): 242 (5) [Mϩ], 184 (18), 167 (2),
156 (31), 141 (13), 156 (6), 111 (11), 99 (15), 97 (13), 86 (100),
73 (92).
(4S,6R,7S,10R,2ЈRS)-7-Isopropyl-4,10-dimethyl-4-oxolan-2Ј-yl-1,5-
dioxaspiro[5.5]undecan-2-one (12b): 75 mg (0.31 mmol) of 2b[6] was
dissolved in 16 mL of THF. The solution was irradiated for 12 d
(procedure A). Purification by HPLC (cyclohexane/ethyl acetate,
3:1) gave recovered 2b (50 mg) and a mixture of (2ЈR)-12b and 6-[3-(1,3-Dioxan-2-yl)propyl]-2,2-dimethyl-1,3-dioxin-4-one (14b)
(2ЈS)-12b (10 mg, 10%) as an oil. The mixture of isomers was insep-
and 5-[2-(1,3-Dioxan-2-yl)ethyl]-2,2,6-trimethyl-1,3-dioxin-4-one
1066
Eur. J. Org. Chem. 1999, 1057Ϫ1073

Diastereoselective Addition of Radicals to Chiral 1,3-Dioxin-4-ones
FULL PAPER
(17b): Compounds 14b and 17b were prepared by procedure B
4 H, 4ЈЈ-H), 4.88 (t, J ϭ 4.7 Hz, 1 H, 2ЈЈ-H). Ϫ 13C NMR (50
using 2,2,6-trimethyl-1,3-dioxin-4-one (1.21 g, 8.51 mmol) and 2- MHz, CDCl3): δ ϭ 17.43 (q, 4-CH3), 18.57 (q, CH3), 19.96 (t, C-
(2-bromoethyl)-1,3-dioxane (1.67 g, 8.56 mmol). Purification by 2Ј), 21.77 (q, CH3), 22.14 (t, C-8), 23.33 (q, CH3), 25.48 [d,
column chromatography (n-pentane/diethyl ether, 1:1) gave 17b (68
CH(CH3)2], 28.61 (d, C-10), 33.10 (t, C-1Ј), 34.21 (t, C-9), 41.13 (t,
mg, 3%) as a solid and 14b (232 mg, 11%) as an oil. Ϫ 14b: IR C-11), 49.56 (d, C-7), 64.84 (t, C-4ЈЈ), 103.89 (s, C-3), 103.95 (d, C-
(neat): ν˜ ϭ 2960 cmϪ1 (w), 2851 (w), 1730 (s, CϭO), 1633 (m),
2ЈЈ), 107.99 (s, C-6), 161.75 (s, C-4), 163.23 (s, C-2). Ϫ MS (70 eV);
1391 (m), 1273 (m), 1204 (m), 1146 (m), 1089 (w), 1012 (m), 901 m/z (%): 338 (1) [Mϩ], 185 (16), 184 (20), 166 (3), 156 (37), 154 (3),
1
(w). Ϫ H NMR (200 MHz, CDCl3): δ ϭ 1.35 (dtt, J ϭ 13.4, 2.7, 141 (12), 139 (9), 112 (15), 111(11), 86 (100), 73 (66), 69 (23).
1,2 Hz, 1 H, 5ЈЈ-Ha), 1.65 (m, 4 H), 1.68 (s, 6 H, 2-CH3), 2.11 (dtt,
(6R,7S,10R)-4-[3-(1,3-Dioxolan-2-yl)propyl]-7-isopropyl-10-methyl-
1,5-dioxaspiro[5.5]undec-3-en-2-one (16) and (6R,7S,10R)-3-[2-(1.3-
D i oxo l a n- 2- yl )e thyl ]-7- isop ro py l-4, 10 -d im et hyl-1, 5-
dioxaspiro[5.5]undec-3-en-2-one (19): Compounds 15 and 18 were
prepared by procedure B using 2b[6] (504 mg, 2.11 mmol) and 2-
(2-bromoethyl)-1,3-dioxolane (2.37 g, 13.1 mmol). Purification by
HPLC (cyclohexane/ethyl acetate, 7:3) gave 19 (50 mg, 7%) and 16
J ϭ 13.5, 12.4, 5.0 Hz, 1 H, 5ЈЈ-Hb), 2.25 (m, 2 H, 1Ј-H), 3.76 (m,
2 H, 4ЈЈ-Ha), 4.10 (m, 2 H, 4ЈЈ-Hb), 4.54 (m, 1 H, 2ЈЈ-H), 5.25 (t,
J ϭ 0.8 Hz, 1 H, 5-H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 20.20
(t, C-2Ј), 25.07 (q, 2-CH3), 25.81 (t, C-5ЈЈ), 33.43, 34.33 (t, C-1Ј,
C-3Ј), 66.87 (t, C-4ЈЈ), 93.30 (d, C-5), 101.54 (d, C-2ЈЈ), 106.26 (s,
C-2), 161.19 (s, C-6), 171.59 (s, C-4). Ϫ MS (70 eV); m/z (%): 256
(2) [Mϩ], 198 (5), 197 (6), 170 (10), 113 (29), 87 (100), 71 (18), 69
(19). Ϫ 17b: M.p. 60Ϫ62°C. Ϫ IR (KBr): ν˜ ϭ 2948 cmϪ1 (m), 1717
(s, CϭO), 1643 (m), 1408 (m), 1343 (w), 1272 (m), 1239 (m), 1206
(90 mg, 13%). Ϫ 16: M.p. 64°C. [α]20 ϭ Ϫ2.3 (c ϭ 1.0, CHCl3).
D
Ϫ IR (neat): ν˜ ϭ 2919 cmϪ1 (m), 1732 (s, CϭO), 1633 (m), 1384
1
1
(m), 1281 (m), 1137 (m), 824 (m). Ϫ H NMR (200 MHz, CDCl3):
(m), 1141 (s), 1000 (w), 894 (w). Ϫ H NMR (300 MHz, CDCl3):
δ ϭ 0.87 [d, J ϭ 6.9 Hz, 3 H, C(CH3)2], 0.89 (d, J ϭ 6.6 Hz, 3 H,
10-CH3), 0.95 [d, J ϭ 7.0 Hz, 3 H, C(CH3)2], 1.00 (m, 1 H), 1.10
(dd, J ϭ 13.7, 12.6 Hz, 1 H, 11-Hax), 1.40Ϫ1.84 (m, 9 H), 2.28 (m,
2 H), 2.34 [dsept, J ϭ 6.9, 1.6 Hz, 1 H, CH(CH3)2], 2.62 (ddd, J ϭ
13.7, 3.6, 2.0 Hz, 1 H, 11-Heq), 3.80Ϫ4.03 (m, 4 H, 4ЈЈ-H), 4.87
(mc, 1 H, 2ЈЈ-H), 5.22 (t, J ϭ 0.8 Hz, 1 H, 3-H). Ϫ 13C NMR (50
MHz, CDCl3): δ ϭ 18.26 (q, CH3), 20.22 (t, C-2Ј), 21.59 (q, CH3),
21.95 (t, C-8), 23.17 (q, CH3), 25.12 [d, CH(CH3)2], 29.70 (d, C-
10), 32.91, 33.56 (t, C-1Ј, C-3Ј), 33.96 (t, C-9), 40.59 (t, C-11), 49.36
(d, C-7), 64.96 (t, C-4ЈЈ), 93.49 (d, C-3), 103.89 (d, C-2ЈЈ), 109.46
(s, C-6), 161.61 (s, C-4), 170.81 (s, C-2). Ϫ MS (70 eV); m/z (%):
338 (5) [Mϩ], 310 (1), 295 (1), 185 (31), 184 (7), 156 (20), 154 (20),
139 (22), 136 (7), 112 (63), 111 (12), 99 (35), 73 (100), 69 (40). Ϫ
δ ϭ 1.34 (dtt, J ϭ 13.5, 2.6, 1.3 Hz, 1 H, 5ЈЈ-Hb), 1.65 (s, 6 H, 2-
CH3), 1.76 (m, 2 H), 1.99 (s, 3 H, 6-CH3), 2.07 (dtt, J ϭ 13.5, 12.4,
5.1 Hz, 1 H, 5ЈЈ-Ha), 2.37 (m, 2 H), 3.74 (m, 2 H, 4ЈЈ-Ha), 4.09 (m,
2 H, 4ЈЈ-Hb), 4.54 (t, J ϭ 5.1 Hz, 1 H, 2ЈЈ-H). Ϫ 13C NMR (50
MHz, CDCl3): δ ϭ 17.25 (q, 6-CH3), 19.97 (t, C-1Ј), 25.09 (q, 2-
CH3), 25.82 (t, C-5ЈЈ), 34.26 (C-2Ј), 66.67 (t, C-4ЈЈ), 101.79 (d, C-
2ЈЈ), 104.75, 104.90 (s, C-5, C-2), 162.10 (s, C-6), 163.23 (s, C-4).
Ϫ MS (70 eV); m/z (%): 256 (4) [Mϩ], 198 (100) [Mϩ Ϫ acetone],
180 (10), 155 (82), 140 (31), 139 (29), 100 (85), 97 (71), 87 (95).
(6S,7S,10R)-4-[3-(1,3-Dioxolan-2-yl)propyl]-7-isopropyl-10-methyl-
1,5-dioxaspiro[5.5]undec-3-en-2-one (15) and (6S,7S,10R)-3-[2-(1,3-
Dioxolan-2-yl)ethyl]-7-isopropyl-4,10-dimethyl-1,5-dioxaspiro-
[5.5]undec-3-en-2-one (18): Compounds 15 and 18 were prepared by
procedure B using 1b[6] (506 mg, 2.12 mmol) and 2-(2-bromoethyl)-
1,3-dioxolane (955 mg, 5.28 mmol). Purification by HPLC (cyclo-
hexane/ethyl acetate, 7:3) gave crystalline 18 (50 mg, 7%) and 15
19: [α]20 ϭ Ϫ44.9 (c ϭ 0.5, CHCl3). Ϫ IR (neat): ν˜ ϭ 2954 cmϪ1
D
(s), 1723 (s, CϭO), 1650 (s), 1454 (s), 1396 (s), 1310 (m), 1279 (m),
1200 (m), 1162 (m), 1092 (m), 930 (w). Ϫ 1H NMR (300 MHz,
CDCl3): δ ϭ 0.85Ϫ0.96 (m, 1 H), 0.87 [d, J ϭ 6.9 Hz, 3 H,
C(CH3)2], 0.88 (d, J ϭ 6.6 Hz, 3 H, 10-CH3), 0.93 [d, J ϭ 7.0 Hz,
3 H, C(CH3)2], 1.05 (dd, J ϭ 13.6, 12.5 Hz, 1 H, 11-Hax), 1.40Ϫ1.82
(m, 5 H), 1.84 (dt, J ϭ 7.7, 4.7 Hz, 2 H, 2Ј-H), 2.00 (s, 3 H, 4-
CH3), 2.34 (dt, J ϭ 14.1, 7.1 Hz, 1 H, 1Ј-Ha), 2.34 [dsept, J ϭ 7.0,
1.5 Hz, 1 H, CH(CH3)2], 2.47 (dt, J ϭ 14.2, 7.7 Hz, 1 H, 1Ј-Hb),
2.63 (ddd, J ϭ 13.6, 3.6, 2.0 Hz, 1 H), 3.79Ϫ4.01 (m, 4 H, 4ЈЈ-H),
4.87 (t, J ϭ 4.7 Hz, 1 H, 2ЈЈ-H). Ϫ 13C NMR (75 MHz, CDCl3):
δ ϭ 17.35 (q, 4-CH3), 18.26 (q, CH3), 20.05 (t, C-2Ј), 21.68 (q,
CH3), 21.99 (t, C-8), 23.18 (q, CH3), 24.14 [d, CH(CH3)2], 29.82
(d, C-10), 33.10 (t, C-1Ј), 34.14 (t, C-9), 40.73 (t, C-11), 49.46 (d,
C-7), 64.86, 64.90 (t, C-4ЈЈ, C-5ЈЈ), 104.05 (d, C-2ЈЈ), 104.64 (s, C-
3), 107.94 (s, C-6), 162.27 (s, C-4), 162.60 (s, C-2). Ϫ MS (70 eV);
m/z (%): 338 (1) [Mϩ], 295 (1), 185 (17), 184 (19), 166 (3), 156 (36),
154 (4), 141 (12), 139 (10), 112 (17), 111(149, 99 (11), 97 (14), 86
(100), 73 (68), 69 (31).
(100 mg, 14%) as an oil. Ϫ 15: [α]20 ϭ Ϫ20.6 (c ϭ 0.2, CHCl3).
D
Ϫ IR (neat): ν˜ ϭ 2954 cmϪ1 (m), 1732 (s, CϭO), 1633 (m), 1456
(w), 1384 (m), 1309 (w), 1228 (m), 1142 (m), 1080 (w), 805 (w). Ϫ
1H NMR (200 MHz, CDCl3): δ ϭ 0.8 (mc, 1 H), 0.88 (d, J ϭ 5.9
Hz, 3 H, 10-CH3), 0.91 [d, J ϭ 6.8 Hz, 3 H, C(CH3)2], 0.96 [d, J ϭ
6.8 Hz, 3 H, C(CH3)2], 1.00 (dd, J ϭ 13.3, 12.2 Hz, 1 H, 11-Hax),
1.46Ϫ186 (m, 9 H), 2.20 [dsept, J ϭ 7.0, 2.4 Hz, 1 H, CH(CH3)2],
2.27 (m, 2 H, 1Ј-H), 2.60 (ddd, J ϭ 13.2, 5.4, 2.0 Hz, 1 H, 11-Heq),
3.80Ϫ4.04 (m, 4 H, 4ЈЈ-H), 4.88 (mc, 1 H, 2ЈЈ-H), 5.18 (s, 1 H, 3-
H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 18.73 (q, CH3), 20.29
(t, C-2Ј), 21.69 (q, CH3), 22.58 (t, C-8), 23.32 (q, CH3), 25.88 [d,
CH(CH3)2], 28.68 (d, C-10), 33.07, 33.62 (t,C-1Ј,C-3Ј), 34.27 (t, C-
9), 41.23 (t, C-11), 49.69 (d, C-7), 64.98 (t, C-4ЈЈ), 92.79 (d, C-3),
104.03 (d, C-2ЈЈ), 109.82 (s, C-6), 161.07 (s, C-4), 171.40 (s, C-2).
Ϫ MS (70 eV); m/z (%): 338 (1) [Mϩ], 310 (2), 295 (2), 274 (9), 249
(3), 247 (3), 185 (47), 184 (12) [Mϩ Ϫ menthone], 156 (34), 154
824), 139 (38), 136 (11), 112 (69), 111 (14), 99 (47), 73 (100), 69
(35). Ϫ C19H30O5 (338.4): calcd. C 67.43; H 8.94; found C 67.54;
General Procedure C (1,3-Dioxin-4-ones from β-Oxo Esters): Con-
centrated sulfuric acid (56 µL, 1.0 mmol) was added dropwise to a
mixture of ketone (2.0 mmol), acetic anhydride (3.0 mmol) and β-
H 8.93. Ϫ 18: M.p. 92°C. [α]20 ϭ ϩ11.7 (c ϭ 0.3, CHCl3). Ϫ IR
D
(neat): ν˜ ϭ 2954 cmϪ1 (s), 2876 (s), 1723 (s, CϭO), 1644 (m), 1398 oxo ester (1.0 mmol), and the temperature was kept below Ϫ5°C
(m), 1272 (m), 1140 (m). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ during the addition. The mixture was stirred at Ϫ5 to 0°C for 3 h
0.85Ϫ1.14 (m, 2 H), 0.87 (d, J ϭ 6.2 Hz, 3 H, 10-CH3), 0.91 [d,
J ϭ 6.8 Hz, 3 H, C(CH3)2], 0.95 [d, J ϭ 7.0 Hz, 3 H, C(CH3)2],
and then kept at 0°C for 14 h. Under ice-cooling a cold (0°C) 10%
Na2SO4 solution (5 mL) was added. After being stirred for 30 min
1.40Ϫ1.80 (m, 5 H), 1.81 (ddd, J ϭ 8.3,4.8, 2.4 Hz, 1 H, 2Ј-Ha), at room temperature, the mixture was extracted with diethyl ether
1.85 (ddd, J ϭ 8.1, 4.7, 1.7 Hz, 1 H, 1Ј-Hb), 2.00 (s, 3 H, 4-CH3), (4 ϫ 5 mL). The combined organic layers were washed with water,
2.24 [dsept, J ϭ 2.5, 7.0 Hz, 1 H, CH(CH3)2], 2.31 (ddd, J ϭ 14.1,
dried (MgSO4), and the solvent was removed in vacuo. Recrystalli-
8.3, 6.7 Hz, 1 H, 1Ј-Ha), 2.46 (ddd, J ϭ 14.1, 8.3, 6.3 Hz, 1 H, 1Ј- zation or column chromatography (n-pentane/diethyl ether) gave
Hb), 2.63 (ddd, J ϭ 13.3, 3.4, 2.1 Hz, 1 H, 11-Heq), 3.81Ϫ4.02 (m,
Eur. J. Org. Chem. 1999, 1057Ϫ1073
the desired 1,3-dioxin-4-ones.
1067

H. Graalfs, R. Fröhlich, C. Wolff, J. Mattay
FULL PAPER
2,2-Dimethyl-2,3,3a,4,5,6-hexahydrobenzofuran-7-carboxylic Acid
(21): Following the general procedure C, 20[31] (500 mg, 1.94 mmol)
was treated with acetone (225 mg, 3.88 mmol). Purification by col-
ture analysis of 22b: Empirical formula C13H20O5, M ϭ 256.29, 0.6
ϫ 0.5 ϫ 0.2 mm, a ϭ 7.403(1), b ϭ 8.535(1), c ϭ 11.186(1) A, α ϭ
˚
3
˚
67.27(1), β ϭ 73.53(1), γ ϭ 77.63(1)°, V ϭ 620.75(12) A , ρcalcd.
ϭ
umn chromatography (diethyl ether/n-pentane, 1:9) gave 21 (84 mg, 1.371 g cmϪ3, µ ϭ 8.70 cmϪ1, empirical absorption correction with
22%) as a solid: M.p. 95°C. Ϫ IR (KBr): ν˜ ϭ 2979 cmϪ1 (w), 2940
ψ scan data (0.941 Յ C Յ 0.999), Z ϭ 2, triclinic, space group
˚
(m), 2872 (w), 1637 (s, CϭO), 1615 (sh, m), 1453 (w), 1404 (m), P1bar (no. 2), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 2740 reflec-
1
1325 (m), 1224 (m), 1182 (m), 1122 (m), 1046 (m), 891 (m). Ϫ H tions collected (Ϫh, ±k, ±l), [(sin θ)/λ] ϭ 0.62 AϪ1, 2534 independ-
˚
NMR (500 MHz, CDCl3): δ ϭ 1.17 (dddd, J ϭ 13.7, 12.6, 11.1, ent and 2381 observed reflections [I Ն 2σ(I)], 166 refined param-
3.0 Hz, 1 H, 4-Ha), 1.39 (t, J ϭ 0.5 Hz, 3 H, 2-CH3), 1.42 (d, J ϭ
eters, R ϭ 0.037, wR2 ϭ 0.098, max. residual electron density 0.29
0.5 Hz, 3 H, 2-CH3), 1.45 (ddq, J ϭ 13.6, 12.9, 0.7 Hz, 1 H, 3-Ha), (Ϫ0.23) e AϪ3, hydrogen atoms calculated and riding.[17]
˚
1.69 (ddddd, J ϭ 13.6, 13.6, 9.4, 9.4, 3.2 Hz, 1 H, 5-Ha), 1.82 (dd,
(6RS,8S,9S,12R)-9-Isopropyl-12-methyl-1,4,7,14-tetraoxatrispiro-
J ϭ 13.5, 4.2 Hz, 1 H, 3-Hb), 1.84 (mc, 1 H, 4-Hb), 1.95 (mc, 1 H,
[4.0.1.5.3.3]nonadecan-15-one (24 and 25): A solution of 15 (100
5-Hb), 2.37Ϫ2.42 (m, 2 H, 6-H), 2.59 (ddddddd, J ϭ 13.0, 11.1,
mg, 0.30 mmol) and 500 µL of acetone in 60 mL of cyclohexane
was irradiated for 4 d (procedure A). Purification by HPLC (cyclo-
hexane/ethyl acetate, 4:1) gave two crystalline products 25 (9 mg,
4.1, 2.0, 2.0, 2.0, 2.0 Hz, 1 H, 3a-H), 13.44 (s, 1 H, OH). Ϫ 13C
NMR (75 MHz, CDCl3): δ ϭ 21.04 (t, C-5), 26.64 (q, 2-CH3),
29.10 (t), 29.40 (d, C-3a), 29.59 (t), 30.33 (q, 2-CH3), 40.93 (t, C-3),
9%) and 24 (14 mg, 14%). Ϫ 25 (Less Polar Product): M.p. 122°C.
80.91 (s, C-2), 96.19 (s, C-7), 171.68 (s, C-7a), 175.07 (c, COOH). Ϫ
[α]20 ϭ Ϫ43.3 (c ϭ 0.2, CHCl3). Ϫ IR (CH2Cl2): ν˜ ϭ 2955 cmϪ1
D
MS (70 eV); m/z (%): 197 (5) [Mϩ ϩ H], 196 (29) [Mϩ], 181 (7),
(s), 1747 (s, CϭO), 1458 (w), 1309 (m), 1253 (m), 1222 (m), 1154
178 (17), 163 (38), 150 (12), 141 (33), 135 (12), 123 (100), 95 (13),
84 (7), 79 (7). Ϫ C11H16O3 (196.2): calcd. C 67.32; H 8.22; found
C 67.27; H 8.40.
1
(m), 1008 (m). Ϫ H NMR (200 MHz, CDCl3): δ ϭ 0.86 [d, J ϭ
7.0 Hz, 3 H, C(CH3)2], 0.87 (d, , J ϭ 6.4 Hz, 3 H, 10-CH3), 0.9
(mc, 1 H), 0.92 [d, J ϭ 6.7 Hz, 3 H, C(CH3)2], 1.26 (dd, J ϭ 12.6,
8,8-Dimethyl-1,4,7,9-tetraoxadispiro[4.0.5.3]tetradecan-10-one (22a)
and 11-Hydroxy-8,8-dimethyl-1,4,7,9-tetraoxadispiro[4.0.5.3]tetra-
13.9 Hz, 1 H, 13-Hax), 1.32 (m, 2 H), 1.44Ϫ2.05 (m, 9 H), 2.07
(ddd, J ϭ 13.9, 3.3, 1.8 Hz, 1 H, 13-Heq), 2.29 [dsept, J ϭ 7.0, 2.0
decan-10-one (23): A solution of 14a (116 mg, 0.48 mmol) and 200 Hz, 1 H, CH(CH3)2], 2.50 (d, J ϭ 16.8 Hz, 1 H, 16-Ha), 3.00 (d,
µL of acetone in 20 mL of cyclohexane was irradiated for 4 d (pro-
J ϭ 16.8 Hz, 1 H, 16-Hb), 3.92Ϫ4.09 (m, 4 H, 2-H, 3-H). Ϫ MS
cedure A). Purification by HPLC (cyclohexane/ethyl acetate, 13:7)
(70 eV); m/z (%): 338 (8) [Mϩ], 295 (3) [Mϩ Ϫ (CH3)2CϭCH2], 253
yielded 22a (13 mg, 11%) and 23 (9 mg, 7%). Ϫ 22a: IR (neat): ν˜ ϭ (3), 184 (7) [Mϩ Ϫ menthone], 167 (20), 156 (54), 139 (11), 123 (7),
2948 cmϪ1 (m, br.), 1748 (s, CϭO), 1358 (m), 1296 (m), 1157 (m), 112 (26), 99 (100), 86 (19), 69 (22). Ϫ HRMS: calcd. for C19H30O5
1
1032 (m), 960 (m). Ϫ H NMR (300 MHz, CDCl3): δ ϭ 1.60 (q,
338.2093, found 338.2091. Ϫ 24 (More Polar Product): M.p. 132°C;
J ϭ 0.7 Hz, 3 H, 8-CH3), 1.62 (q, J ϭ 0.7 Hz, 3 H, 8-CH3), 1.65 [α]20 ϭ Ϫ5.0 (c ϭ 0.4, CHCl3). Ϫ IR (CH2Cl2): ν˜ ϭ 2926 cmϪ1
D
(m, 2 H), 1.75Ϫ2.06 (m, 4 H), 2.59 (d, J ϭ 17.1 Hz, 1 H, 11-Ha), (s), 1742 (s, CϭO), 1458 (w), 1316 (m), 1252 (m), 1150 (m), 974
1
2.93 (d, J ϭ 17.2 Hz, 1 H, 11-Hb), 3.89Ϫ4.05 (m, 4 H, 2-H, 3-H). (m). Ϫ H NMR (300 MHz, CDCl3): δ ϭ 0.86 [d, J ϭ 6.9 Hz, 3
Ϫ
13C NMR (50 MHz, CDCl3): δ ϭ 16.72 (t, C-13), 28.27 (q, 8- H, C(CH3)2], 0.88 (d, J ϭ 6.4 Hz, 3 H, 12-CH3), 0.9 (mc, 1 H),
CH3), 29.65 (q, 8-CH3), 31.13 33.17 (t, C-12, C-14), 36.10 (t, C-
11), 65.37, 65.89 (t, C-3, C-2), 82.91 (s, C-6), 105.09 (s, C-8), 116.12
0.91 [d, J ϭ 7.2 Hz, 3 H, C(CH3)2], 1.29 (dd, J ϭ 13,5, 12.9 Hz, 1
H, 13-Hax), 1.25 (m, 2 H), 1.54Ϫ2.05 (m, 9 H), 2.14 (ddd, J ϭ 13.5,
(s, C-5), 168.30 (s, C-10). Ϫ MS (70 eV); m/z (%): 242 (6) [Mϩ], 3.6, 1.9 Hz, 1 H, 13-Heq), 2.47 [dsept, J ϭ 6.9, 1.9 Hz, 1 H,
184 (3), 183 (5), 167 (4), 156 (20), 140 (4), 139 (4), 113 (8), 112 (13), CH(CH3)2], 2.54 (d,, J ϭ 17.4 Hz, 1 H, 16-Ha), 2.90 (d, J ϭ 17.4
99 (100), 86 (25), 69 (12). Ϫ C12H18O5: (242.3): calcd. C 59.49; H
7.49; found C 59.47; H 7.53. Ϫ 23: IR (CH2Cl2): ν˜ ϭ 3450 cmϪ1 m/z (%): 338 (7) [Mϩ], 295 (2), 253 (2), 184 (8), 167 (18), 156 (57),
(m, br., OH), 2944 (m), 1748 (s, CϭO), 1385 (m), 1278 (m), 1109 154 (14), 140 (11), 139 (28), 112 (66), 99 (100), 69 (41). Ϫ HRMS:
Hz, 1 H, 16-Hb), 3.92Ϫ4.03 (m, 4 H, 2-H, 3-H). Ϫ MS (70 eV);
1
(s), 1050 (m), 953 (w), 869 (m). Ϫ H NMR (300 MHz, CDCl3): calcd. for C19H30O5 338.2093, found 338.2091. Ϫ X-ray crystal
δ ϭ 1.61 (q, J ϭ 0.7 Hz, 3 H, 8-CH3), 1.64 (q, J ϭ 0.7 Hz, 3 H, structure analysis of 24: Empirical formula C19H30O5, M ϭ 338.43,
˚
8-CH3), 1.65Ϫ2.18 (m, 6 H), 3.45 (s, 1 H, OH), 3.97Ϫ4.13 (m, 4 1.2 ϫ 1.2 ϫ 0.3 mm, a ϭ 9.833(1), b ϭ 8.679(1), c ϭ 10.803(1) A,
3
H, 2-H, 3-H), 4.64 (s, 1 H, 11-H). Ϫ MS (CI); m/z (%): 259 (46) β ϭ 95.00(1)°, V ϭ 918.4(2) A , ρcalcd. ϭ 1.224 g cmϪ3, µ ϭ 7.07
˚
[Mϩ ϩ H], 243 (4), 241 (5), 201 (100), 183 (31), 173 (17), 157 (8), cmϪ1, empirical absorption correction with ψ scan data (0.905 Յ
99 (26), 73 (2), 69 (3).
C Յ 0.999), Z ϭ 2, monoclinic, space group P21 (no. 4), λ ϭ
˚
1.54178 A, T ϭ 223 K, ω/2θ scans, 2113 reflections collected (±h,
2,2-Dimethyl-1,3,8,12-tetraoxadispiro[5.0.5.3]pentadecan-4-one
(22b): A solution of 14b (98 mg, 0.38 mmol) and 100 µL of acetone
in 10 mL of cyclohexane was irradiated for 2 d (procedure A).
Purification by HPLC (cyclohexane/ethyl acetate, 4:1) yielded crys-
talline 22b (17 mg, 17%): M.p. 112°C (pentane). Ϫ IR (KBr): ν˜ ϭ
ϩk, Ϫl), [(sin θ)/λ] ϭ 0.62 AϪ1, 2008 independent and 1964 ob-
˚
served reflections [I Ն 2σ(I)], 221 refined parameters, R ϭ 0.048,
Ϫ3
wR2 ϭ 0.132, max. residual electron density 0.22 (Ϫ0.22) e A
,
˚
Flack parameter Ϫ0.1(3), hydrogen atoms calculated and riding.[17]
2965 cmϪ1 (m), 2873 (m), 1743 (s, CϭO), 1438 (w), 1388 (m), 1293 (6RS,8R,9S,12R)-9-Isopropyl-12-methyl-1,4,7,14-tetraoxatri-
(m), 1227 (m), 1148 (m), 1108 (m), 1064 (m), 957 (m), 829 (m), 807 spiro[4.0.1.5.3.3]nonadecan-15-one (26 and 27): A solution of 16 (90
1
(m). Ϫ H NMR (300 MHz, CDCl3): δ ϭ 1.35 (dtt, J ϭ 13.3, 2.6,
1.7 Hz, 1 H, 10-Ha), 1.59 (q, J ϭ 0.9 Hz, 3 H, 2-CH3), 1.61 (q,
mg, 0.27 mmol) and 600 µL of acetone in 70 mL of cyclohexane
was irradiated for 4 d (procedure A). Purification by HPLC (cyclo-
J ϭ 0.8 Hz, 3 H, 2-CH3), 1.54Ϫ2.26 (m, 6 H), 2.22 (mc, 1 H), 2.51 hexane/ethyl acetate, 4:1) gave the less polar isomer (8 mg, 9%) as
(d, J ϭ 17.2 Hz, 1 H, 5-HA), 3.12 (d, J ϭ 17.1 Hz, 1 H, 5-HB), a solid, 19 mg of a not characterized oil, and the more polar isomer
3.79Ϫ4.00 (m, 4 H, 9-H, 11-H). Ϫ 13C NMR (50 MHz, CDCl3): (9 mg, 10%) as an oil. Ϫ Less Polar Isomer: M.p. 66°C. [α]20
ϭ
D
δ ϭ 17.77 (t, C-14), 25.70 (2 t, C-10, C-15), 29.30 (q, 2-CH3), 29.34 ϩ15.8 (c ϭ 0.2, CHCl3). Ϫ IR (KBr): ν˜ ϭ 2955 cmϪ1 (s), 1751 (s,
(q, 2-CH3), 31.85 (t, C-13), 35.90 (t, C-5), 60.75, 62.05 (t, C-9, C- CϭO), 1458 (w), 1348 (w), 1298 (m), 1214 (m), 1155 (m), 1114 (m),
11), 84.19 (s, C-6), 105.22 (s, C-7), 106.25 (s, C-2), 169.06 (s, C-4). 981 (m). Ϫ 1H NMR (500 MHz, CDCl3): δ ϭ 0.88 (d, J ϭ 6.0 Hz,
Ϫ MS (70 eV); m/z (%): 256 (69) [Mϩ], 198 (1), 181 (2), 170 (28),
154 (4), 139 (3), 113 (100), 100 (169, 85 (4). Ϫ X-ray crystal struc-
3 H, 12-CH3), 0.88 [d, J ϭ 7.0 Hz, 3 H, C(CH3)2], 0.91 (mc, 1 H),
0.92 [d, J ϭ 7.0 Hz, 3 H, C(CH3)2], 1.24 (t, J ϭ 12.6 Hz, 1 H, 13-
1068
Eur. J. Org. Chem. 1999, 1057Ϫ1073

Diastereoselective Addition of Radicals to Chiral 1,3-Dioxin-4-ones
FULL PAPER
Hax), 1.38 (ddd, J ϭ 1.3, 2.4, 1.1 Hz, 1 H, 12-H), 1.43 (ddd, J ϭ n-butyllithium (13.1 mL, 21.0 mmol, 1.6  in hexanes) was added
13.1, 12.2, 3.4 Hz, 1 H), 1.56Ϫ1.77 (m, 5 H), 1.78Ϫ1.89 (m, 2 H), over 15 min. The orange solution was stirred for additional 30 min
1.90Ϫ1.98 (m, 2 H), 2.09 (ddd, J ϭ 12.9, 3.4, 1.9 Hz, 1 H, 13-Heq), at 0°C, and the alkyl bromide (22.0 mmol) in 5 mL of THF was
2.16 [dsept, J ϭ 7.0, 1.2 Hz, 1 H, CH(CH3)2], 2.52 (d, J ϭ 17.0 added dropwise. The mixture was allowed to warm slowly to room
Hz, 1 H, 16-Ha), 2.94 (d, J ϭ 17.0 Hz, 1 H, 16-Hb), 3.92Ϫ4.06 (m, temperature. After being stirred for 3 h at room temperature, the
4 H, 2-H, 3-H). Ϫ 13C NMR (125 MHz, CDCl3): δ ϭ 17.03 (t, C-
18), 18.57 (q, CH3), 21.80 (q, CH3), 22.57 (t, C-10), 23.77 (q, 12-
reaction was quenched with 100 mL of a saturated ammonium
chloride solution, and the product was extracted with diethyl ether
CH3), 24.98 [d, CH(CH3)2], 29.77 (d, C-12), 30.77, 32.44 (t, C-17, (3 ϫ 100 mL). The combined organic layers were washed succes-
C-19), 34.01 (t, C-11), 36.66 (t, C-16), 46.51 (t, C-13), 51.00 (d, C- sively with water and brine, dried (MgSO4), and the solvent was
9), 64.61, 66.01 (t, C-2, C-3), 83.09 (s, C-6), 109.31 (s, C-8), 116.17 removed in vacuo. Distillation gave the desired product as an oil.
(s, C-5), 169.29 (s, C-15). Ϫ MS (70 eV); m/z (%): 338 (10) [Mϩ],
tert-Butyl 3-Oxohept-6-enoate (31a): Compound 31a was prepared
following the procedure D using 10 mmol of the acetoacetate and
allyl bromide for alkylation. The crude product was distilled (55°C/
295 (3) [Mϩ Ϫ (CH3)2CϭCH2], 184 (9) [Mϩ Ϫ menthone], 167
(23), 156 (37), 154 (9) [menthoneϩ], 139 (28), 125 (38), 112 (42),
111 (39), 99 (100), 83 (67), 71 (59), 69 (66). Ϫ HRMS: calcd. for
0.01 Torr) to give 31a (1.69 g, 85%) as an oil: Ϫ IR (neat): ν˜ ϭ
C19H30O5 338.2093, found 338.2091.
Ϫ More Polar Isomer:
2980 cmϪ1 (m), 1743 (s, CϭO), 1716 (s, CϭO), 1643 (w), 1369 (m),
1320 (m), 1254 (m), 1150 (s), 916 (w). Ϫ 1H NMR (300 MHz,
CDCl3): δ ϭ 1.47 (s, 9 H, CH3), 2.34 (m, 2 H, 5-H), 2.64 (t, J ϭ
7.4 Hz, 2 H, 4-H), 3.35 (s, 2 H, 2-H), 4.90 (t, J ϭ 0.7 Hz, 2-H,
enolic form), 4.99 (ddt, J ϭ 10.1, 1.7, 1.3 Hz, 1 H, 7-Ha), 5.04 (ddt,
J ϭ 17.2, 1.7, 1.6 Hz, 1 H, 7-Hb), 5.81 (ddt, J ϭ 17.2, 10.1, 6.5 Hz,
1 H, 6-H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 27.50 (t, C-5),
28.00 (q, CH3), 41.97 (t, C-4), 50.71 (t, C-2), 81.86 [s, C(CH3)3],
90.67 (d, C-2, enolic form), 115.40 (t, C-7), 136.72 (d, C-6), 166.32
(s, C-1), 202.17 (s, C-3). Ϫ MS (CI); m/z (%): 199 (2) [Mϩ ϩ H],
183 (1), 143 (77), 125 (2), 101 (30), 89 (11), 87 (5), 71 (100).
[α]20 ϭ Ϫ39.6 (c ϭ 0.3, CHCl3). Ϫ IR (CH2Cl2): ν˜ ϭ 2954 cmϪ1
D
(s), 1747 (s, CϭO), 1458 (w), 1311 (m), 1214 (w), 1160 (m), 1102
(w), 1050 (w), 978 (m). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ
0.83Ϫ0.95 (m, 2 H), 0.86 (d, J ϭ 6.9 Hz, 6 H, CH3), 0.9 [d, J ϭ
7.0 Hz, 3 H, CH(CH3)2], 1.20Ϫ2.02 (m, 11 H), 2.10 (ddd, J ϭ 13.4,
3.1, 2.0 Hz, 1 H, 13-Heq), 2.20 (mc, 1 H), 2.59 (d, J ϭ 17.5 Hz, 1
H, 16-Ha), 2.87 (d, J ϭ 17.5 Hz, 1 H, 16-Hb), 3.85Ϫ4.00 (m, 4 H,
2-H, 3-H). Ϫ 13C NMR (125 MHz, CDCl3): δ ϭ 17.05 (t, C-18),
18.52 (q, CH3), 21.74 (q, CH3), 22.81 (t, C-10), 23.82 (q, 12-CH3),
24.65 [d, CH(CH3)2], 30.15 (d, C-12), 31.09, 32.23 (t, C-17, C-19),
34.30 (t, C-11), 35.15 (t, C-16), 45.20 (t, C-13), 51.61 (d, C-9),
65.21, 65.85 (t, C-2, C-3), 82.37 (s, C-6), 109.33 (s, C-8), 116.18 (s,
C-5), 168.79 (s, C-16). Ϫ MS (70 eV); m/z (%): 338 (8) [Mϩ], 295
(4), 253 (5), 184 (8), 167 (34), 156 (45), 139 (18), 125 (13), 123 (20),
112 (33), 111 (22), 99 (100), 85 (28), 83 (44), 71 (39), 69 (47). Ϫ
HRMS: calcd. for C19H30O5 338.2093, found 338.2091.
(6RS,7S,10R)-4-But-3-enyl-7-isopropyl-10-methyl-1,5-dioxaspiro-
[5.5]undec-3-en-2-one (32a and 33a): Following the general pro-
cedure C, 31a (2.96 g, 14.9 mmol) was treated with (Ϫ)-menthone
(4.60 g, 29.8 mmol). The residue was purified by column chroma-
tography. Elution with diethyl ether/n-pentane (3:97) gave unre-
acted menthone. Further elution with diethyl ether/n-pentane
(10:90) gave a mixture of isomers which was separated by HPLC
(ethyl acetate/cyclohexane, 7:93) to yield 32a (0.56 g, 14%) as an
oil and 33a (166 mg, 4%) as a solid. Ϫ 32a (Less Polar Product):
[α]20D ϭ Ϫ28.0 (c ϭ 1.0, CHCl3). Ϫ IR (neat): ν˜ ϭ 2955 cmϪ1 (m),
2923 (m), 2869 (w), 1738 (s, CϭO), 1634 (m), 1383 (m), 1309 (w),
1227 (m), 1079 (w). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 0.85Ϫ1.00
(m, 1 H), 0.88 (d, J ϭ 6.1 Hz, 3 H, 10-CH3), 0.92 [d, J ϭ 6.8 Hz,
3 H, C(CH3)2], 0.97 [d, J ϭ 7.0 Hz, 3 H, C(CH3)2], 1.00 (dd, J ϭ
13.3, 12.4 Hz, 1 H, 11-Hax), 1.44Ϫ1.90 (m, 5 H), 2.21 [dsept, J ϭ
6.9, 2.4 Hz, 1 H, CH(CH3)2], 2.25Ϫ2.39 (m, 4 H, 1Ј-H, 2Ј-H), 2.60
(ddd, J ϭ 13.3, 3.5, 2.1 Hz, 1 H, 11-Heq), 5.01Ϫ5.14 (m, 2 H, 4Ј-
H), 5.18 (s, 1 H, 3-H), 5.79 (ddt, J ϭ 17.0, 10.2, 6.5 Hz, 1 H, 3Ј-
H). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 18.54 [q, C(CH3)2], 21.61
[q, C(CH3)2], 22.31 (t, C-8), 23.25 (q, 10-CH3), 25.65 [d, C(CH3)2],
28.56 (d, C-10), 29.76 (t, C-2Ј), 33.04 (t, C-1Ј), 34.08 (t, C-9), 41.11
(t, C-11), 49.46 (d, C-7), 92.82 (d, C-3), 109.75 (s, C-6), 116.10 (t,
C-4Ј), 135.97 (d, C-3Ј), 161.07 (s, C-4), 170.97 (s, C-2). Ϫ MS (70
eV); m/z (%): 278 (2) [Mϩ], 155 (10), 154 (25), 140 (5), 139 (44),
125 (22), 124 (84), 112 (100), 111 (5), 97 (18), 96 (16), 95 (16), 84
(15), 83 (21), 82 (11), 81 (10), 69 (80). Ϫ C17H26O3 (278.4): calcd.
C 73.35; H 9.41; found C 72.85; H 9.67. Ϫ 33a (More Polar Prod-
Ethyl 4-[4-(1,3-Dioxolan-2-yl)-2,2-dimethyl-6-oxo-1,3-dioxan-4-yl]-
butyrate (28): A solution of 14a (217 mg, 0.88 mmol) and 400 µL
of acetone in 40 mL of 1,3-dioxolane was irradiated for 5 d (pro-
cedure A). The crude product was separated by HPLC (cyclohex-
ane/ethyl acetate, 7:3). Bidioxolanyls 29 (29 mg) and 30 (16 mg)
eluted first. Ϫ 28 (23 mg, 8%) was isolated as an oil. Ϫ IR (neat):
ν˜ ϭ 2984 cmϪ1 (m), 2943 (m), 2892 (m), 1749 (s, CϭO), 1732 (s,
CϭO), 1633 (w), 1387 (m), 1287 (m), 1180 (m), 1101 (m), 1946 (m),
978 (m), 814 (w). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 1.24 (t, J ϭ
7.0 Hz, 3 H, CH2CH3), 1.59 (s, 3 H, 2Ј-CH3), 1.60 (s, 3 H, 2Ј-CH3),
1.61Ϫ1.82 (m, 4 H), 2.31 (m, 2 H, 2-H), 2.46 (d, J ϭ 17.2 Hz, 1
H, 5Ј-Ha), 2.74 (d, J ϭ 17.2 Hz, 1 H, 5Ј-Hb), 3.82Ϫ4.04 (m, 4 H,
4ЈЈ-H, 5ЈЈ-H), 4.12 (q, J ϭ 7.0 Hz, 2 H, CH2CH3), 4.81 (s, 1 H,
2ЈЈ-H). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 14.22 (q, CH2CH3),
18.29 (t, C-3), 28.91 (q, 2Ј-CH3), 29.55 (q, 2Ј-CH3), 32.25, 34.22 (t,
C-2, C-4), 37.51 (t, C-5Ј), 60.38 (t, CH2CH3), 65.49, 65.87 (t, C-
4ЈЈ, C-5ЈЈ), 78.53 (s, C-4Ј), 104.94 (s, C-2Ј), 105.18 (d, C-2ЈЈ), 168.16
(s, C-6Ј), 173.11 (s, C-1). Ϫ MS (CI); m/z (%): 317 (5) [Mϩ ϩ H],
299 (1) [Mϩ Ϫ OH], 287 (3), 259 (12) [Mϩ Ϫ acetone], 157 (34),
243 (4), 185 (9), 167 (5), 147 (100), 103 (11), 73 (31). Ϫ [2,2Ј]Bi(1,3-
dioxolanyl) (29): IR (KBr): ν˜ ϭ 2895 cmϪ1 (s), 1313 (m), 1111 (s),
1
1033 (m), 954 (m). Ϫ H NMR (90 MHz, CDCl3): δ ϭ 3.80Ϫ4.18
uct): M.p. 45°C. [α]20 ϭ Ϫ29.1 (c ϭ 1.0, CHCl3). Ϫ IR (neat):
D
(m, 8 H, 4-H), 4.68 (s, 2 H, 2-H). Ϫ MS (CI); m/z (%): 147 (100)
ν˜ ϭ 2954 cmϪ1 (m), 2872 (m), 1739 (s, CϭO), 1630 (m), 1449 (w),
1383 (m), 1305 (w), 1283 (m), 1219 (w), 1079 (m), 920 (m), 824
(m). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 0.90Ϫ1.10 (m, 1 H), 0.88
[d, J ϭ 6.9 Hz, 3 H, C(CH3)2], 0.89 (d, J ϭ 6.6 Hz, 3 H, 10-CH3),
0.95 [d, J ϭ 7.0 Hz, 3 H, C(CH3)2], 1.10 (dd, J ϭ 13.7, 12.5 Hz, 1
H, 11-Hax), 1.40Ϫ1.84 (m, 5 H), 2.24Ϫ2.42 [m, 5 H, 1Ј-H, 2Ј-H,
CH(CH3)2], 2.62 (ddd, J ϭ 13.7, 3.7, 2.0 Hz, 1 H, 11-Heq),
5.02Ϫ5.15 (m, 2 H, 4Ј-H), 5.21 (s, 1 H, 3-H), 5.79 (ddt, J ϭ 17.0,
10.3, 6.0 Hz, 1 H, 3Ј-H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 18.38
[Mϩ ϩ H], 75 (18), 73 (9). Ϫ [2.4Ј]Bi(1,3-dioxolanyl) (30): IR (neat):
1
ν˜ ϭ 2889 cmϪ1 (m), 1159 (m), 1087 (s), 1035 (m), 930 (m). Ϫ H
NMR (90 MHz, CDCl3): δ ϭ 3.77Ϫ4.26 (m, 7 H), 4.87Ϫ5.08 (m,
3 H). Ϫ MS (CI); m/z (%): 147 (100) [Mϩ ϩ H].
General Procedure D (γ-Alkylation of tert-Butyl Acetoacetate): In a
flame-dried flask, sodium hydride (880 mg, 22.0 mmol, 60% in min-
eral oil) was suspended in 50 mL of THF under argon and tert-
butyl acetoacetate (3.16 g, 20.0 mmol) was added dropwise by can-
nula at 0°C. The mixture was stirred for 15 min at 0°C, and then [q, C(CH3)2], 21.56 [q, C(CH3)2], 22.18 (t, C-8), 23.18 (q, 10-CH3),
Eur. J. Org. Chem. 1999, 1057Ϫ1073 1069

H. Graalfs, R. Fröhlich, C. Wolff, J. Mattay
FULL PAPER
25.29 [d, C(CH3)2], 29.80 (d, C-10), 29.80 (t, C-2Ј), 33.17 (t, C-1Ј), 2Ј), 25.28 [d, C(CH3)2], 29.79 (d, C-10), 32.82, 33.13 (t, C-1Ј, C-
34.05 (t, C-9), 40.74 (t, C-11), 49.55 (d, C-7), 93.67 (d, C-3), 109.60 3Ј), 34.07 (t, C-9), 40.75 (t, C-11), 49.54 (d, C-7), 93.53 (d, C-3),
(s, C-6), 116.17 (t, C-4Ј), 136.00 (d, C-3Ј), 161.41 (s, C-4), 170.32 109.49 (s, C-6), 115.75 (t, C-4Ј), 137.24 (d, C-3Ј), 161.49 (s, C-4),
(s, C-2). Ϫ MS (70 eV); m/z (%): 278 (3) [Mϩ], 155 (10), 154 (21),
170.95 (s, C-2). Ϫ MS (70 eV); m/z (%): 292 (2) [Mϩ], 250 (1) [Mϩ
140 (4), 139 (34), 125 (25), 124 (98), 112 (100), 111 (15), 97 (15), Ϫ CH3CHϭCH2], 155 (16), 154 (31) [menthoneϩ], 139 (57), 138
96 (17), 95 (17), 84 (9), 83 (19), 82 (14), 81 (14), 69 (84). Ϫ (81) [Mϩ Ϫ menthone], 112 (100), 97 (12), 95 (10), 84 (28), 83 (11),
C17H26O3 (278.4): calcd. C 73.35; H 9.41; found C 73.11; H 9.67.
69 (61). Ϫ C18H28O3 (292.4): calcd. C 73.93; H 9.65; found C 73.21;
H 9.75.
tert-Butyl 3-Oxooct-7-enoate (31b): Compound 31b was prepared
following the procedure D using 20 mmol of acetoacetate and 4-
bromobut-1-ene for alkylation. The crude product was distilled
through a Vigreux column (77°C/0.01 Torr) to give 31b (2.46 g,
(6S,7S,10R)-4-[4-(1,3-Dioxolan-2-yl)butyl]-7-isopropyl-10-methyl-
1,5-dioxaspiro[5.5]undec-3-en-2-one (34) and (6S,7S,10R)-4-[4-(1,3-
Dioxolan-4-yl)-butyl]-7-isopropyl-10-methyl-1,5-dioxaspiro-
58%): Ϫ IR (neat): ν˜ ϭ 2978 cmϪ1 (w), 2932 (w), 1739 (s, CϭO), [5.5]undec-3-en-2-one (35): A solution of 32a (51 mg, 0.18 mmol)
1715 (s, CϭO), 1641 (w),1368 (m), 1319 (m), 1252 (m), 1149 (s),
914 (w). Ϫ H NMR (300 MHz, CDCl3): δ ϭ 1.46 (s, 9 H, CH3), for 24 h (procedure A). Purification by HPLC (cyclohexane/ethyl
1.70 (quint, J ϭ 7.4 Hz, 2 H, 5-H), 2.07 (m, 2 H, 6-H), 2.53 (t, J ϭ acetate, 4:1) gave 35 (4 mg, 6%) as a solid and 34 (21 mg, 33%) as
and 200 µL of acetone in 20 mL of 1,3-dioxolane was irradiated
1
7.3 Hz, 2 H, 4-H), 3.33 (s, 2 H, 2-H), 4.89 (s, 2-H, enolic form),
an oil. Ϫ 34 (More Polar Product): [α]20 ϭ Ϫ20.0 (c ϭ 0.3,
D
4.98 (ddt, J ϭ 10.0, 1.9, 1.2 Hz, 1 H, 8-Ha), 5.01 (ddt, J ϭ 17.2, CHCl3). Ϫ IR (neat): ν˜ ϭ 2952 cmϪ1 (m), 2872 (m), 1732 (s, Cϭ
2.1, 1.4 Hz, 1 H, 8-Hb), 5.76 (ddt, J ϭ 16.9, 10.2, 6.7 Hz, 1 H, 7-
O), 1633 (m), 1456 (w), 1384 (m), 1309 (m), 1227 (m), 1142 (m),
1
H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 22.34 (CH2, C-5), 27.80 1080 (m), 956 (m), 805 (m). Ϫ H NMR (200 MHz, CDCl3): δ ϭ
(CH3, CH3), 32.72 (CH2, C-6), 41.85 (CH2, C-4), 50.58 (CH2, C- 0.85Ϫ0.95 (m, 1 H), 0.89 (d, J ϭ 6.3 Hz, 3 H, 10-CH3), 0.91 [d,
2), 81.68 [C, C(CH3)3], 90.41 (CH, C-2, enolic form), 115.18 (CH2,
J ϭ 6.9 Hz, 3 H, C(CH3)2], 0.96 [d, J ϭ 7.1 Hz, 3 H, C(CH3)2],
C-8), 137.62 (CH, C-7), 166.30 (C, C-1), 202.90 (C, C-3). Ϫ MS 0.99 (dd, J ϭ 12.3, 13.4 Hz, 1 H, 11-Hax), 1.38Ϫ1.86 (m, 11 H),
(CI); m/z (%): 212 (13) [Mϩ], 211 (100) [Mϩ Ϫ H], 157 (14) [Mϩ 2.19 [dsept, J ϭ 2.0, 7.0 Hz, 1 H, CH(CH3)2], 2.22 (m, 2 H), 2.60
ϩ H Ϫ (CH3)2CϭCH2], 139 (5) [Mϩ Ϫ OC(CH3)3], 113 (7).
(ddd, J ϭ 13.4, 3.4, 2.2 Hz, 1 H, 11-Heq), 3.78Ϫ4.02 (m, 4 H, 4ЈЈ-
H), 4.85 (t, J ϭ 4.5 Hz, 1 H, 2ЈЈ-H), 5.16 (t, J ϭ 0.7 Hz, 1 H, 3-
H). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 18.70 (q, CH3), 21.68
(q, CH3), 22.53 (t, C-8), 23.30 (t, C-3Ј), 23.34 (q, CH3), 25.74 [d,
CH(CH3)2], 25.83 (t, C-2Ј), 28.65 (d, C-10), 33.43, 33.72 (t, C-1Ј,
C-4Ј), 34.22 (t, C-9), 41.15 (t, C-11), 49.63 (d, C-7), 64.90 (t, C-
4ЈЈ), 92.63 (d, C-3), 104.23 (d, C-2ЈЈ), 109.76 (s, C-6), 161.18 (s, C-
4), 171.66 (s, C-2). Ϫ MS (70 eV); m/z (%): 352 (1) [Mϩ], 267 (1),
199 (16), 154 (17), 139 (20), 112 (73), 73 (100), 69 (37). Ϫ 35 (Less
Polar Product): M.p. 73°C. [α]20D ϭ Ϫ20.0 (c ϭ 0.1, CHCl3). Ϫ IR
(KBr): ν˜ ϭ 2931 cmϪ1 (m), 2866 (w), 1721 (s, CϭO), 1636 (m),
1458 (w), 1383 (m), 1310 (w), 1227 (m), 1143 (w), 1080 (m), 928
(6RS,7S,10R)-7-Isopropyl-10-methyl-4-pent-4-enyl-1,5-dioxaspiro-
[5.5]undec-3-en-2-one (32b and 33b): Following the general pro-
cedure C, 31b (2.46 mg, 11.64 mmol) and (Ϫ)-menthone (3.60 g,
23.3 mmol) were allowed to react. The residue was purified by col-
umn chromatography. Elution with diethyl ether/n-pentane (3:97)
gave unreacted menthone. Further elution with diethyl ether/n-pen-
tane (10:90) gave a mixture of isomers which was separated by
HPLC (ethyl acetate/cyclohexane, 7:93) to yield 32b (0.66 g, 19%)
as an oil and 33b (0.21 g, 6%) as a solid. Ϫ 32b (Less Polar Prod-
uct): [α]20D ϭ Ϫ27.5 (c ϭ 1.2, CHCl3). Ϫ IR (neat): ν˜ ϭ 3076 cmϪ1
(w), 2954 (m), 2870 (w), 1737 (s, CϭO), 1634 (m), 1456 (w), 1382
1
(w). Ϫ H NMR (200 MHz, CDCl3): δ ϭ 0.88 (d, J ϭ 5.9 Hz, 3
1
(m), 1308 (w), 1226 (m), 1070 (w), 927 (w), 805 (w). Ϫ H NMR
H, 10-CH3), 0.89 (m, 1 H), 0.92 [d, J ϭ 6.8 Hz, 3 H, C(CH3)2],
0.96 [d, J ϭ 7.0 Hz, 3 H, CH(CH3)2], 0.99 (dd, J ϭ 12.6, 13.2 Hz,
1 H, 11-Hax), 1.45Ϫ1.86 (m, 11 H), 2.20 [dsept, J ϭ 2.4, 7.0 Hz, 1
H, CH(CH3)2], 2.24 (m, 2 H, 1Ј-H), 2.61 (ddd, J ϭ 2.1, 3.4, 13.3
Hz, 1 H, 11 Heq), 3.43 (dd, J ϭ 9.6, 10.5 Hz, 1 H, 5ЈЈ-H), 3.92Ϫ4.03
(m, 2 H), 4.87 (s, 1 H, 2ЈЈ-Ha), 5.02 (s, 1 H, 2ЈЈ-Hb), 5.17 (s, 1 H,
3-H). Ϫ MS (CI); m/z (%): 353 (98) [MϩϩH], 309 (6), 199 (79),
155 (100), 112 (8).
(200 MHz, CDCl3): δ ϭ 0.85Ϫ1.00 (m, 1 H), 0.89 (d, J ϭ 6.1 Hz,
3 H, 10-CH3), 0.92 [d, J ϭ 6.7 Hz, 3 H, C(CH3)2], 0.96 [d, J ϭ 7.0
Hz, 3 H, C(CH3)2], 0.99 (dd, J ϭ 13.3, 12.3 Hz, 1 H, 11-Hax),
1.45Ϫ1.87 (m, 7 H), 2.05Ϫ2.28 (m, 5 H, 1Ј-H, 3Ј-H, CH(CH3)2],
2.61 (ddd, J ϭ 13.2, 3.5, 2.1 Hz, 1 H, 11-Heq), 4.98Ϫ5.10 (m, 2 H,
5Ј-H), 5.17 (t, J ϭ 0.8 Hz, 1 H, 3-H), 5.78 (ddt, J ϭ 17.0, 10.3, 6.7
Hz, 1 H, 4Ј-H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 18.66 [q,
C(CH3)2], 21.60 [q, C(CH3)2], 22.52 (t, C-8), 23.23 (q, 10-CH3),
24.98 (t, C-2Ј), 25.82 [d, C(CH3)2], 28.59 (d, C-10), 32.84, 33.03 (t,
(1R,5R,7S,8S,11R)-1-(1,3-Dioxolan-2-ylmethyl)-8-isopropyl-11-
C-1Ј, C-3Ј), 34.17 (t, C-9), 41.15 (t, C-11), 49.62 (d, C-7), 92.64 (d, methyl-6,13-dioxadispiro[4.1.5.3]pentadecan-14-one (36): A solution
C-3), 109.69 (s, C-6), 115.64 (t, C-4Ј), 137.27 (d, C-3Ј), 160.99 (s, of 32b (138 mg, 0.47 mmol) and 300 µL of acetone in 36 mL of
C-4), 171.53 (s, C-2). Ϫ MS (70 eV); m/z (%): 292 (2) [Mϩ], 250 (1) 1,3-dioxolane was irradiated for 2 d (procedure A). Purification by
[Mϩ Ϫ CH3CHϭCH2], 155 (16), 154 (32) [menthoneϩ], 139 (56), HPLC (cyclohexane/ethyl acetate, 7:3) gave 36 (24 mg, 14%) as a
138 (82) [Mϩ Ϫ menthone], 112 (100), 97 (12), 84 (30), 83 (11), 69 solid: M.p. 80°C. [α]20 ϭ ϩ13.3 (c ϭ 0.5, CHCl3). Ϫ IR (KBr):
D
(63). Ϫ 33b (More Polar Product): M.p. 53°C. [α]20D ϭ Ϫ28.5 (c ϭ ν˜ ϭ 2955 cmϪ1 (m), 1737 (s), 1457 (w), 1371 (w), 1319 (m), 1234
1.2, CHCl3). Ϫ IR (neat): ν˜ ϭ 3076 cmϪ1 (w), 2955 (m), 2871 (w), (m), 1152 (m), 1080 (w), 1023 (w), 957 (m). Ϫ 1H NMR (500 MHz,
1735 (s, CϭO), 1636 (m), 1456 (w), 1383 (m), 1307 (w), 1280 (m), CDCl3): δ ϭ 0.77 [d, J ϭ 7.0 Hz, 3 H, C(CH3)2], 0.81 (d, J ϭ 6.5
1217 (w), 1080 (w), 912 (w), 808 (w). Ϫ 1H NMR (200 MHz,
Hz, 3 H, 11-CH3), 0.84 (mc, 1 H, 10-Ha), 0.86 [d, J ϭ 7.0 Hz, 3 H,
CDCl3): δ ϭ 0.85Ϫ1.10 (m, 1 H), 0.87 [d, J ϭ 7.1 Hz, 3 H, C(CH3)2], 1.14 (dddd, J ϭ 13.5, 11.1, 11.1, 7.0 Hz, 1 H, 2-Ha), 1.16
C(CH3)2], 0.89 (d, J ϭ 6.6 Hz, 3 H, 10-CH3), 0.95 [d, J ϭ 7.1 Hz,
3 H, C(CH3)2], 1.11 (dd, J ϭ 13.7, 12.7 Hz, 1 H, 11-Hax), 1.40Ϫ1.87
(dd, J ϭ 13.5, 12.4 Hz, 1 H, 12-Hax), 1.33 (ddd, J ϭ 12.7, 5.1, 2.0
Hz, 1 H, 8-H), 1.39 (ddd, J ϭ 13.3, 11.2, 4.4 Hz, 1 H, 1Ј-Ha), 1.49
(m, 7 H), 2.02Ϫ2.31 (m, 4 H, 1Ј-H, 3Ј-H), 2.34 [dsept, J ϭ 7.1, 1.7 (mc, 1 H, 9-Ha), 1.51 (mc, 1 H, 9-Hb), 1.52 (mc, 1 H, 3-Ha), 1.67
Hz, 1 H, CH(CH3)2], 2.63 (ddd, J ϭ 13.7, 3.7, 2.0 Hz, 1 H, 11- (mc, 1 H, 11-H), 1.70 (mc, 1 H, 10-Hb), 1.73 (mc, 1 H, 3-Hb), 1.75
Heq), 5.02 (ddt, J ϭ 10.5, 2.0, 1.2 Hz, 1 H, 5Ј-Ha) 5.14 (mc, 1 H, (mc, 1 H, 4-Ha), 1.80 (ddd, J ϭ 13.2, 5.5, 2.9 Hz, 1 H, 1Ј-Hb), 1.87
5Ј-Hb), 5.21 (s, 1 H, 3-H), 5.77 (ddt, J ϭ 16.9, 10.5, 6.8 Hz, 1 H, (ddd, J ϭ 13.0, 10.5, 9.7 Hz, 1 H, 4-Hb), 1.94 (dddd, J ϭ 17.3, 9.5,
4Ј-H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 18.33 [q, C(CH3)2], 9.5, 3.9 Hz, 1 H, 2-Hb), 2.06 (ddd, J ϭ 13.5, 3.6, 2.1 Hz, 1 H, 12-
21.59 [q, C(CH3)2], 22.16 (t, C-8), 23.17 (q, 10-CH3), 25.04 (t, C-
Heq), 2.10 (dddd, J ϭ 11.4, 11.4, 8.2, 2.8 Hz, 1 H, 1-H), 2.29 [dqq,
1070
Eur. J. Org. Chem. 1999, 1057Ϫ1073

Diastereoselective Addition of Radicals to Chiral 1,3-Dioxin-4-ones
FULL PAPER
J ϭ 7.0, 7.0, 2.0 Hz, 1 H, CH(CH3)2], 2.40 (d, J ϭ 17.2 Hz, 1 H, 0.92 [d, J ϭ 7.0 Hz, 3 H, C(CH3)2], 1.00 (dd, J ϭ 13.2, 13.2 Hz, 1
15-Ha), 2.50 (d, J ϭ 17.2 Hz, 1 H, 15-Hb), 3.77 (mc, 1 H), 3.78 (mc, H, 11-Hax), 1.38Ϫ1.89 (m, 11 H), 2.20 [dsept, J ϭ 2.4, 6.9 Hz, 1
1 H), 3.86 (mc, 1 H), 3.90 (mc, 1 H), 4.84 (dd, J ϭ 4.5, 5.5 Hz, 1 H, CH(CH3)2], 2.26 (m, 2 H, 1Ј-H), 2.61 (ddd, J ϭ 2.1, 3.4, 13.3
H, 2Ј-H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 17.76 [q, C(CH3)2], Hz, 1 H, 11-Heq), 2.68 (m, 2 H, 5Ј-H), 5.18 (s, 1 H, 3-H). Ϫ MS
19.98 (t, C-3), 21.28 (t, C-9), 21.10 (q, 11-CH3), 23.64 [q, C(CH3)2], (CI); m/z (%): 415 (18) [Mϩ ϩ H], 413 (52) [Mϩ ϩ H], 411 (53)
24.38 [d, CH(CH3)2], 26.35 (t, C-2), 29.45 (d, C-11), 33.51 (t, C- [Mϩ ϩ H], 379 (3), 377 (5), 261 (2), 259 (7), 172 (16), 155 (100),
1ЈЈ), 34.13 (t, C-10), 35.05 (t, C-15), 40.23 (t, C-4), 45.32 (d, C-1), 112 (5). Ϫ 40: M.p. 108°C. Ϫ IR (KBr): ν˜ ϭ 2959 cmϪ1 (s), 2873
46.96 (t, C-12), 51.05 (d, C-8), 64.58, 64.94 (t, C-4Ј, C-5Ј), 82.68 (s, (m), 1734 (s, CϭO), 1457 (w), 1373 (w), 1324 (s), 1281 (w), 1237
1
C-5), 103.91 (d, C-2Ј), 107.88 (s, C-7), 168.09 (s, C-14). Ϫ MS (CI); (m), 1153 (m), 970 (m), 780 (w), 746 (m). Ϫ H NMR (300 MHz,
m/z (%): 367 (4) [Mϩ ϩ H], 213 (100), 195 (8), 155 (56), 73 (64). Ϫ CDCl3): δ ϭ 0.88 (mc, 1 H), 0.88 (d, J ϭ 7.0 Hz, 3 H), 0.89 (d,
HRMS: calcd. for C21H34O5 366.2406, found 366.2405.
J ϭ 6.4 Hz, 3 H), 0.94 (d, J ϭ 7.0 Hz, 3 H), 1.10Ϫ1.49 (m, 6 H),
1.52Ϫ2.17 (m, 7 H), 2.30Ϫ2.56 (m, 4 H), 2.56 (s, 2 H), 5.74 (dd,
J ϭ 4.4, 7.7 Hz, 1 H, 2Ј-H). Ϫ MS (70 eV); m/z (%): 380 (0.7)
[Mϩ], 378 (3.8) [Mϩ], 376 (4.4) [Mϩ], 293 (5), 291 (3), 225 (1), 223
(1), 209 (2), 207 (12), 205 (18), 155 (44), 154 (24) [menthoneϩ], 139
(26), 137 (11), 112 (100), 97 (15), 95 (22), 69 (55). Ϫ X-ray crystal
structure analysis of 40: Empirical formula C19H30O3Cl2, M ϭ
(6S,7S,10R,4ЈRS)-4-(4Ј-Bromo-6,6,6-trichlorohexyl)-7-isopropyl-10-
methyl-1,5-dioxaspiro[5.5]undec -3 -e n- 2- one ( 37 ) a nd
(6S,7S,10R,4ЈRS)-4-(4Ј-Bromomethyl-5,5,5-trichloropentyl)-7-
isopropyl-10-methyl-1,5-dioxaspiro[5.5]undec-3-en-2-one (38): A
solution of 32b (100 mg, 0.34 mmol) in 0.5 mL of bromotrichloro-
methane was irradiated for 4 h (procedure A). Separation by HPLC
(cyclohexane/ethyl acetate, 93:7) gave 37 (60 mg, 36%) as an oil and
377.33, 0.3 ϫ 0.2 ϫ 0.2 mm, a ϭ 11.037(5), b ϭ 10.997(4), c ϭ
3
17.043(8) A, β ϭ 98.53(4), V ϭ 2046(2) A , ρcalcd. ϭ 1.225 g cmϪ3
,
˚
˚
1
µ ϭ 29.56 cmϪ1, empirical absorption correction with ψ scan data
a mixture of 37 and 38 (7 mg, 37/38 ϭ 1:1). Ϫ 37: H NMR (300
MHz, CDCl3): δ ϭ 0.86Ϫ1.07 (m, 1 H), 0.89/0.88 (each d, J ϭ 6.4
Hz, 3 H), 0.92 (d, J ϭ 6.9 Hz, 3 H), 0.96/0.97 (each d, J ϭ 6.9 Hz,
3 H), 1.01/1.02 (each t, J ϭ 13.1 Hz, 1 H, 11-Hax), 1.47Ϫ2.03 (m,
8 H), 2.06Ϫ2.39 (m, 4 H), 2.60 (mc, 1 H, 11-Heq), 3.22 (dd, J ϭ
5.7, 5.7 Hz, 1 H, 5Ј-Ha), 3.49 (dd, J ϭ 4.8, 15.9 Hz, 1 H, 5Ј-Hb),
4.31 (mc, 1 H, 4Ј-H), 5.18 (s, 1 H, 3-H). Ϫ 13C NMR (75 MHz,
CDCl3): δ ϭ 18.60 (CH3), 21.63 (CH3), 22.24 (CH2, C-8), 23.28
(CH3), 23.63 (CH2, C-2), 25.77 [CH, CH(CH)3], 28.62 (CH, C-10),
32.79 (CH2, C-1Ј), 34.11 (CH2, C-9), 38.39/38.44 (CH2, C-3Ј), 41.20
(CH, C-11), 48.04 (CH, C-4Ј), 49.54 (CH, C-7), 62.67 (CH2, C-5Ј),
93.11 (CH, C-3), 96.88 (C, C-6Ј), 109.92 (C, C-6), 160.77 (C, C-4),
170.49 (C, C-2). Ϫ MS (CI); m/z (%): 495 (3) [Mϩ ϩ H], 494 (2)
[Mϩ ϩ H], 493 (11) [Mϩ ϩ H], 492 (3) [Mϩ ϩ H], 491 (16) [Mϩ
ϩ H], 490 (2) [Mϩ ϩ H], 489 (9) [Mϩ ϩ H], 457 (1) [Mϩ Ϫ Cl],
375 (1) [Mϩ Ϫ Cl Ϫ Br], 339 (3) [Mϩ ϩ H Ϫ menthone], 337 (5)
[Mϩ ϩ H Ϫ menthone], 335 (3) [Mϩ ϩ H Ϫ menthone], 172 (15),
155 (100) [menthone ϩ Hϩ], 112 (6), 81 (3), 69 (4). Ϫ 38 (Mixture
with 37): Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 0.89 (d, J ϭ 6.9 Hz,
3 H), 0.90Ϫ1.08 (m, 2 H), 0.92 (d, J ϭ 6.9 Hz, 3 H), 0.97 (d, J ϭ
6.9 Hz, 3 H), 1.48Ϫ2.39 (m, 12 H), 2.61 (m, 1 H), 3.60 (t, J ϭ 10.3
Hz, 1 H), 3.87 (dd, J ϭ 4.1, 10.3 Hz, 1 H), 4.14 (m, 1 H), 5.18 (s,
1 H).
(0.976 Յ C Յ 0.999), Z ϭ 4, monoclinic, space group P21 (no. 4),
˚
λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 4621 reflections collected
(ϩh, ϩk, ±l), [(sin θ)/λ] ϭ 0.62 AϪ1, 4392 independent and 2361
˚
observed reflections [I Ն 2σ(I)], 440 refined parameters, R ϭ 0.046,
Ϫ3
wR2 ϭ 0.094, max. residual electron density 0.19 (Ϫ0.23) e A
,
˚
Flack parameter Ϫ0.00(2), hydrogen atoms calculated and rid-
ing.[17]
6-[2-(Bromophenyl)ethyl]-2,2-dimethyl-1,3-dioxin-4-one (41): Fol-
lowing the general procedure D, 10 mmol of the acetoacetate and
2-bromobenzyl bromide were allowed to react. The crude product
was distilled through a Vigreux column (145Ϫ147°C/0.02 Torr) to
give tert-butyl 5-(2-bromophenyl)-3-oxopentanoate (0.71 g, 23%):
Ϫ IR (neat): ν˜ ϭ 2978 cmϪ1 (m), 1737 (s, CϭO), 1715 (s, CϭO),
1643 (w), 1566 (w), 1472 (m), 1368 (m), 1321 (m), 1160 (s), 1026
(m), 752 (m). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 1.45 (s, 9 H,
CH3), 2.87 (dd, J ϭ 8.7, 6.6 Hz, 1 H, 4-Ha), 2.88 (dd, J ϭ 8.0, 6.6
Hz, 1 H, 4-Hb), 3.03 (dd, J ϭ 8.0, 6.6 Hz, 1 H, 5-Ha), 3.04 (dd,
J ϭ 8.7, 6.6 Hz, 1 H, 5-Hb), 3.36 (s, 2 H, 2-H), 4.92 (s, 2-H, enolic
form), 7.07 (ddd, J ϭ 7.7, 6.2, 3.1 Hz, 1 H, 4Ј-H), 7.18Ϫ7.27 (m,
2 H, 5Ј-H, 6Ј-H), 7.52 (dd, J ϭ 7.7, 1.4 Hz, 1 H, 3Ј-H). Ϫ 13C
NMR (50 MHz, CDCl3): δ ϭ 27.95 (q, CH3), 29.99 (t, C-5), 42.62
(t, C-4), 50.67 (t, C-2), 82.05 (s, C(CH3)3), 124.26 (s, C-2Ј), 127.56
(6S,7S,10R)-7-Isopropyl-10-methyl-4-(6,6,6-trichlorohexyl)-15- (d, C-3Ј), 128.03 (d, C-5Ј), 130.70 (d, C-3Ј), 132.85 (d, C-6Ј), 139.95
dioxaspiro[5.5]undec-3-en-2-one (39) and (1R,5R,7S,8S,11R)-1-(2,2- (s, C-1Ј), 166.27 (s,C-1), 201.97 (s, C-3). Ϫ MS (CI); m/z (%): no
Dichloroethyl)-8-isopropyl-11-methyl-6,13-dioxadispiro[4.1.5.3]- Mϩ, 313 (2) [Mϩ Ϫ CH3], 311 (6) [Mϩ Ϫ CH3], 275 (41), 273 (95),
pentadecan-14-one (40): A solution of 37 (41 mg, 84 µmol), (36 mg, 271 (100), 255 (3), 253 (4), 235 (5), 233 (14), 229 (5), 227 (5), 193
0.12 mmol) tributyltin hydride and AIBN (4 mg, 24 µmol) in 10 (8), 191 (16), 157 (4), 155 (3), 117 (96), 91 (81), 75 (26). Ϫ Following
mL of benzene was irradiated for 5 d [procedure A, using a water- the general procedure C, tert-butyl 5-(2-bromophenyl)-3-oxopen-
cooled well with a high-pressure mercury lamp (HPK 125 W, Phi- tanoate (500 mg, 1.53 mmol) and acetone (186 mg, 3.20 mmol)
lips) as source of light]. AIBN (2 mg, 12 µmol) was added every were allowed to react. Recrystallization of the crude product from
day. The solvent was removed in vacuo and the residue was dis- diethyl ether/n-pentane gave 41 (190 mg, 38%) as a yellow solid:
solved in 10 mL of wet diethyl ether. 1,8-Diazabicyclo[5.4.0]undec- M.p. 63Ϫ64°C. Ϫ IR (KBr): ν˜ ϭ 3082 cmϪ1 (w), 1724 (s, CϭO),
7-ene (37 mg, 0.24 mmol) was added, the mixture was treated with 1634 (m), 1468 (w), 1446 (w), 1387 (m), 1375 (m), 1188 (m), 1032
1
iodine solution (0.1  in diethyl ether) until the iodine colour just (m), 1006 (m), 748 (m). Ϫ H NMR (300 MHz, CDCl3): δ ϭ 1.69
persisted, and the suspension was filtered through a short silica (s, 6 H, 2-CH3), 2.56 (m, 2 H), 2.99 (m, 2 H), 5.26 (d, J ϭ 0.7 Hz,
cloumn (diethyl ether). Purification by HPLC (cyclohexane/ethyl 1 H, 5-H), 7.10 (ddd, J ϭ 8.0, 6.9, 2.2 Hz, 1 H, 4Ј-H), 7.21 (dd,
acetate, 4:1) gave 39 (9 mg, 26%) as an oil, a mixture of not cyclized J ϭ 7.7, 2.2 Hz, 1 H, 6Ј-H), 7.26 (ddd, J ϭ 7.7, 6.8, 1.3 Hz, 1 H,
reduction products (11 mg) and crystalline 40 (2 mg, 6%). Ϫ 39: 5Ј-H), 7.55 (dd, J ϭ 7.9, 1.3 Hz, 1 H, 3Ј-H). Ϫ 13C NMR (50 MHz,
[α]20 ϭ Ϫ18.0 (c ϭ 0.1, CHCl3). Ϫ IR (neat): ν˜ ϭ 2955 cmϪ1 (s), CDCl3): δ ϭ 25.04 (q, 2-CH3), 32.40, 33.49 (t, C-1ЈЈ, C-2ЈЈ), 93.69
D
2870 (m), 1732 (s, CϭO), 1633 (m), 1455 (m), 1384 (s), 1309 (m), (d, C-5), 106.48 (s, C-2), 124.27 (s, C-2Ј), 127.69 (d, C-4Ј), 128.38
1227 (m), 1175 (m), 1143 (m), 1079 (m), 1002 (w), 780 (m), 695 (d, C-5Ј), 130.28 (d, C-3Ј), 133.05 (d, C-6Ј), 138.93 (s, C-1Ј), 161.07
1
(m). Ϫ H NMR (300 MHz, CDCl3): δ ϭ 0.89 (d, J ϭ 5.9 Hz, 3 (s, C-6), 170.41 (s, C-4). Ϫ MS (CI); m/z (%): 313 (99) [Mϩ ϩ H],
H, 10-CH3), 0.90 (m, 1 H), 0.92 [d, J ϭ 6.8 Hz, 3 H, C(CH3)2], 311 (100) [Mϩ ϩ H], 255 (11) [Mϩ ϩ H Ϫ acetone], 253 (11) [Mϩ
Eur. J. Org. Chem. 1999, 1057Ϫ1073
1071

H. Graalfs, R. Fröhlich, C. Wolff, J. Mattay
FULL PAPER
ϩ H Ϫ acetone], 233 (31), 175 (28), 173 (35), 99 (13). Ϫ
C14H15BrO3 (311.2): calcd. C 54.04; H 4.86; found C 54.19; H 4.87.
1.75Ϫ1.96 (m, 4 H), 1.92 (ddd, J ϭ 1.9, 4.2, 14.5 Hz, 1 H), 1.98
(ddd, J ϭ 4.0, 4.9, 14.5 Hz, 1 H), 2.18 (m, 1 H, 2-Ha), 2.91 (ddd,
J ϭ 2.6, 2.6, 5.2 Hz, 1 H, 1-H), 3.88 (dd, J ϭ 2.4, 6.5 Hz, 1 H, 9-
H), 3.87Ϫ4.07 (m, 4 H, 4Ј-H), 5.05 (d, J ϭ 6.7 Hz, 1 H, 2Ј-H). Ϫ
13C NMR (75 MHz, CDCl3): δ ϭ 21.74 (t), 24.63 (t), 27.83 (t),
28.39 (q, 6-CH3), 40.42 (d, C-1), 41.80 (t), 65.25, 65.30 (t, C-4Ј, C-
5Ј), 72.79 (d, C-9), 101.65 (d, C-2Ј), 108.47 (s, C-6), 173.99 (s, C-
8). Ϫ MS (CI); m/z (%): 243 (100) [Mϩ ϩ H], 225 (11), 197 (5), 73
Spiro Compound 42 and 2,2-Dimethyl-6-phenylethyl-1,3-dioxin-4-
one (43): A solution of 41 (278 mg, 0.89 mmol), tributyltin hydride
(329 mg, 1.13 mmol) and AIBN (31 mg, 0.19 mmol) in 84 mL of
benzene was irradiated for 3 d [procedure A, using a water-cooled
well with a high-pressure mercury lamp (HPK 125 W, Philips) as
source of light]. The solution was diluted with 100 mL of wet di-
ethyl ether and treated with iodine solution (0.1  in ether) until
the iodine colour just persisted. 1,8-Diazabicyclo[5.4.0]undec-7-ene
(200 mg) was added and the mixture was filtered through a short
silica column (diethyl ether). Purification by HPLC (ethyl acetate/
cyclohexane, 1:4) gave 42 (60 mg, 29%) as a solid, 43 (12 mg, 6%)
as an oil and recovered 41 (24 mg, 8%). Ϫ 42 (Less Polar Product):
M.p. 70°C. Ϫ IR (KBr): ν˜ ϭ 2996 cmϪ1 (w), 2930 (m), 1744 (s,
CϭO), 1605 (w), 1316 (m), 1293 (s), 1272 (m), 1113 (m), 948 (m),
820 (w), 761 (m). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 1.67 (q,
J ϭ 0.7 Hz, 3 H, 2-CH3), 1.70 (q, J ϭ 0.7 Hz, 3 H, 2-CH3), 2.25
(ddd, J ϭ 12.9, 7.8, 4.6 Hz, 1 H, 2Ј-Ha), 2.45 (ddd, J ϭ 12.9, 8.3,
6.8 Hz, 1 H, 2Ј-Hb), 2.86 (ddd, J ϭ 16.1, 7.8, 6.8 Hz, 1 H, 3Ј-Ha),
2.89 (s, 2 H, 5-H), 3.08 (ddd, J ϭ 16.1, 8.3, 4.6 Hz, 1 H, 3Ј-Hb),
7.21Ϫ7.36 (m, 4 H, arom. H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ
28.93 (q, 2-CH3), 29.39 (t, C-3Ј), 30.11 (q, 2-CH3), 39.35, 41.09 (t,
C-5, C-2Ј), 84.33 (s, C-6), 105.96 (s, C-2), 122.91, 125.03, 127.31,
129.00 (d, 4 arom. C), 141.94 (s, C-3Јa), 144.86 (s, C-7Јa), 167.90
(s, C-4). Ϫ MS (70 eV); m/z (%): 232 (7) [Mϩ], 217 (4), 174 (57),
157 (30), 146 (19), 133 (17), 132 (79), 131 (25), 130 (100), 129 (91),
128 (49), 127 (20), 115 (47), 104 (33), 103 (15), 91 (6), 77 (18). Ϫ
C14H16O3 (232.3): calcd. C 72.39; H 6.94; found C 73.16; H 6.72.
Ϫ 43 (More Polar Product): IR (neat): ν˜ ϭ 2922 cmϪ1 (w), 1729 (s,
CϭO), 1623 (m), 1390 (m), 1272 (m), 1203 (m), 1018 (m). Ϫ 1H
NMR (300 MHz, CDCl3): δ ϭ 1.66 (s, 6 H, 2-CH3), 2.56 (m, 2 H),
2.42 (m, 2 H), 5.22 (t, J ϭ 0.7 Hz, 1 H, 5-H), 7.17Ϫ7.33 (m, 5 H,
(6).
؊ 8-(1,3-Dioxolan-2-yl)-2,5-dimethyl-6,9-dioxabicyclo[3.2.2]-
nonan-7-one (46a): IR (neat): ν˜ ϭ 2984 cmϪ1 (m), 1754 (s, CϭO),
1460 (w), 1384 (m), 1297 (m), 1243 (m), 1174 (m), 1154 (m), 1060
(m), 960 (m). Ϫ 1H NMR (500 MHz, CDCl3): δ ϭ 1.01 (d, J ϭ
6.8 Hz, 3 H, 2-CH3), 1.50 (s, 3 H, 5-CH3), 1.58 (dddd, J ϭ 6.0,
11.5, 11.5, 14.5 Hz, 1 H, 3-Ha), 1.66 (ddddd, J ϭ 1.0, 3.6, 5.1, 5.1,
14.5 Hz, 1 H, 3-Hb), 1.96 (ddd,, J ϭ 5.2, 11.5, 15.1 Hz, 1 H, 4-Ha),
2.01 (ddd, J ϭ 3.6, 6.0, 15.1 Hz, 1 H, 4-Hb), 2.10 (dqdd, J ϭ 1.4,
5.3, 6.8, 11.5 Hz, 1 H, 2-H), 2.49 (dd, J ϭ 1.2, 1.3 Hz, 1 H, 1-H),
3.84Ϫ3.90 (m, 2 H, 4Ј-H), 3.90Ϫ4.01 (m, 2 H, 4Ј-H), 4.29 (d, J ϭ
2.8 Hz, 1 H, 8-H), 4.88 (d, J ϭ 2.8 Hz, 1 H, 2Ј-H). Ϫ MS (CI);
m/z (%): 243 (100) [Mϩ ϩ H], 73 (5). Ϫ (1R*,2R*,5S*,8S*)-8-(1,3-
Dioxolan-2-yl)-2,5-dimethyl-6,9-dioxabicyclo[3.2.2]nonan-7-one
(46b, More Polar Product): IR (neat): ν˜ ϭ 2963 cmϪ1 (m), 2930
(m), 1740 (s, CϭO), 1464 (w), 1288 (m), 1250 (w), 1191 (w), 1152
1
(m), 1060 (m), 954 (m). Ϫ H NMR (500 MHz, CDCl3): δ ϭ 1.07
(d, J ϭ 6.8 Hz, 3 H, 2-CH3), 1.19 (dddd, J ϭ 5.1, 11.2, 12.4, 14.6
Hz, 1 H, 3-Ha), 1.53 (s, 3 H, 5-CH3), 1.74 (ddddd,, J ϭ 0.7, 4.6,
4.9, 4.9, 14.6 Hz, 1 H, 3-Hb), 1.91 (m, 1 H, 2-H), 1.93 (ddd, J ϭ
4.6, 12.4, 15.1 Hz, 1 H, 4-Ha), 2.11 (ddd, J ϭ 4.6, 4.6, 15.0 Hz, 1
H, 4-Hb), 2.62 (dd, J ϭ 0.9, 1.1 Hz, 1 H, 1-H), 3.83Ϫ3.91 (m, 2 H,
4Ј-H), 3.92Ϫ4.11 (m, 2 H, 4Ј-H), 4.04 (d, J ϭ 3.1 Hz, 1 H, 8Ј-H),
4.87 (d, J ϭ 3.1 Hz, 1 H, 2Ј-H). Ϫ MS (CI); m/z (%): 243 (100)
[Mϩ ϩ H].
arom. H). Ϫ MS (70 eV); m/z (%): 232 (2) [Mϩ], 174 (100) [Mϩ
Ϫ
Acknowledgments
acetone], 156 (18), 145 (21), 128 (11), 105 (35), 104 (37), 91 (38),
77 (9), 69 (23).
Financial support of the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie is gratefully acknowledged. H.
G. thanks the Graduierten Kolleg (Universität Münster), the Land
Nordrhein-Westfalen for a predoctoral fellowship, and Mrs. H.
Pohl for experimental assistance.
2-(But-3-enyl)-2-methyl-1,3-dioxin-4-one (44): To a refluxing solu-
tion of 5-hexen-2-one (4.90 g, 49.9 mmol) in 50 mL of xylol was
added hydroxymethylene MeldrumЈs acid[39] (1.72 g, 10.0 mmol),
portionwise over 15 min. The reaction was heated under reflux for
further 20 min, cooled, and the solvent was removed under reduced
pressure. Purification by column chromatography (cyclohexane/
ethyl acetate, 3:2) gave 44 (80 mg, 5%) as a colourless oil. Ϫ 1H
NMR (300 MHz, CDCl3): δ ϭ 1.69 (s, 3 H, 2-CH3), 2.04 (m, 2 H),
2.20Ϫ2.30 (m, 2 H), 5.00 (ddt, J ϭ 10.3, 1.2 Hz, 1 H, 4Ј-Ha), 5.06
(ddt, J ϭ 17.2, 1.7 Hz, 1 H, 4Ј-Hb), 5.38 (d, J ϭ 6.0 Hz, 1 H, 5-
H), 5.81 (ddt, J ϭ 16.9, 10.3, 6.3 Hz, 1 H, 3Ј-H), 7.12 (d, J ϭ 5.96
Hz, 1 H, 6-H). Ϫ 13C NMR (75 MHz, C6D6): δ ϭ 22.27 (CH3),
27.50 (CH2, C-2Ј), 37.73 (CH2, C-1Ј), 97.68 (CH, C-5), 108.03 (C,
C-2), 115.17 (CH2, C-4Ј), 137.26 (CH, C-3Ј), 157.13 (CH, C-6),
158.98 (C, C-4). Ϫ MS (CI); m/z (%): 169 (100) [Mϩ ϩ H], 99 (52),
71 (8).
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