Photochemical deconjugation of chiral 3-methyl-2-butenoates derived from carbohydrate-based alcohols: The influence of the sugar backbone on the facial diastereoselectivity

Article abstract of DOI:10.1021/jo001740t

The photodeconjugation of the α-(4-trimethylsilyl-3-butynyl)-substituted senecio acid esters 7 was studied. Chiral alcohols ROH (9) were employed as auxiliaries to control the facial diastereoselectivity of the protonation step. The conversion of the four sugar alcohols diacetone-D-glucofuranose, diacetone-D-allofuranose, diacetone-D-gulofuranose, and diacetone-D-fructopyranose (9a-d) to the esters 7 was achieved in four steps employing 4-iodo-1-trimethylsilylbut-1-yne (3) as the alkylating agent (27-45% yield overall). Their photodeconjugation gave the corresponding β,γ-unsaturated (R)-esters 14a-d with moderate to excellent diastereomeric excess. The best results were achieved with diacetone-D-glucofuranose and diacetone-D-fructopyranose as the auxiliary (>95% de). To achieve the synthesis of the target compound 1 which has the (S)-configuration, the deconjugation was conducted with the diacetone-L-fructopyranose (ent-9d) derived ester ent-7d. L-Fructose (20) was prepared from L-sorbose (15) in a modified procedure that allowed for the isolation of intermediates. The 2-fold inversion of configuration worked nicely, and the fructofuranose 19 was obtained in 19% yield from L-sorbose. The conversion of L-fructose to the ester ent-7d was conducted in full analogy to the synthesis of its enantiomer 7d. Deconjugation of ester ent-7d yielded the product 2d (70% yield), which was reduced to the alcohol 1 (85% yield).

Full text of DOI:10.1021/jo001740t

J . Org. Chem. 2001, 66, 3427-3434
3427
P h otoch em ica l Decon ju ga tion of Ch ir a l 3-Meth yl-2-bu ten oa tes
Der ived fr om Ca r boh yd r a te-Ba sed Alcoh ols: Th e In flu en ce of th e
Su ga r Ba ck bon e on th e F a cia l Dia ster eoselectivity
Thorsten Bach* and Frank Ho¨fer
Lehrstuhl fu¨r Organische Chemie I, Technische Universita¨t Mu¨nchen, D-85747 Garching, Germany
thorsten.bach@ch.tum.de
Received December 13, 2000
The photodeconjugation of the R-(4-trimethylsilyl-3-butynyl)-substituted senecio acid esters 7 was
studied. Chiral alcohols ROH (9) were employed as auxiliaries to control the facial diastereoselec-
tivity of the protonation step. The conversion of the four sugar alcohols diacetone-D-glucofuranose,
diacetone-D-allofuranose, diacetone-D-gulofuranose, and diacetone-D-fructopyranose (9a -d ) to the
esters 7 was achieved in four steps employing 4-iodo-1-trimethylsilylbut-1-yne (3) as the alkylating
agent (27-45% yield overall). Their photodeconjugation gave the corresponding â,γ-unsaturated
(R)-esters 14a -d with moderate to excellent diastereomeric excess. The best results were achieved
with diacetone-D-glucofuranose and diacetone-D-fructopyranose as the auxiliary (>95% de). To
achieve the synthesis of the target compound 1 which has the (S)-configuration, the deconjugation
was conducted with the diacetone-L-fructopyranose (ent-9d ) derived ester ent-7d . L-Fructose (20)
was prepared from L-sorbose (15) in a modified procedure that allowed for the isolation of
intermediates. The 2-fold inversion of configuration worked nicely, and the fructofuranose 19 was
obtained in 19% yield from L-sorbose. The conversion of L-fructose to the ester ent-7d was conducted
in full analogy to the synthesis of its enantiomer 7d . Deconjugation of ester ent-7d yielded the
product 2d (70% yield), which was reduced to the alcohol 1 (85% yield).
In tr od u ction
to these results, the less basic enolate of ethyl acetoac-
etate (5) yielded the substitution product 6 (eq 1).
In connection with the synthesis of a heterocyclic
sesquiterpene, we required a facile and straightforward
access to the enantiomerically pure homoallylic alcohol
1. A simple consideration regarding possible C-C-bond
disconnections led us to employ iodide 3 as a C4-building
block that was to be stereoselectively attached to a C5-
carbon nucleophile (Scheme 1). Reduction of an interme-
In an attempt to employ this C-C-bond formation
reaction for the synthesis of target compound 1 we looked
for possible routes to establish the stereogenic center in
the intermediate 2 starting from a substitution product
related to 6. Permuting the sequence of events outlined
in Scheme 1, one could envisage the deprotonation of a
2-substituted senecio acid ester 7 and its subsequent
stereoselective protonation as a viable pathway. The
synthesis of the latter compound starting from â-keto-
esters analogous to 6 appeared feasible. We consequently
screened the literature for known procedures that de-
scribe the stereoselective protonation2 of enolates derived
from R,â-unsaturated esters. Given our interest in photo-
chemical reactions,3 we found the work of Pete, Muzart,
and Piva particularly appealing.4 In a series of elegant
Sch em e 1
diate carboxylic acid derivative 2 was expected to yield
the desired alcohol.
The synthesis of iodide 3 was easily accomplished from
1-butyn-3-ol following a known procedure.1 Various eno-
lates generated from chiral senecio acid (3-methyl-2-
butenoic acid) derivatives 4 (X ) auxiliary), however,
failed to give the desired substitution products. Presum-
ably, an elimination of HI occurred that is facilitated by
the relatively high acidity of the alkyne at its R-position
and by the high basicity of the ester enolates. The
elimination product of iodide 3, 1-trimethylsilylbut-3-en-
1-yne, could be detected in the reaction mixture. Contrary
(2) Reviews: (a) Yanagisawa, A.; Yamamoto, H. In Comprehensive
Asymmetric Catalysis; J acobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer: Berlin 1999; Vol. III, pp 1295-1306. (b) Hu¨nig, S. In
Methoden der Organischen Chemie (Houben-Weyl) 4te Aufl.; Helmchen,
G., Hoffmann, R. W., Mulzer, J ., Schaumann, E., Eds.; Thieme,
Stuttgart 1996; Vol. E 21, pp 3851-3911. (c) Fehr, C. Angew. Chem.
1996, 108, 2726-2748; Angew. Chem., Int. Ed. Engl. 1996, 35, 2566-
2587.
(3) Reviews: (a) Bach, T. Synlett 2000, 1699-1707. (b) Bach, T.
Synthesis 1998, 683-703. (c) Bach, T. Liebigs Ann./ Recueil 1997,
1627-1634.
(1) Molander, G.; Harris, C. R. J . Am. Chem. Soc. 1996, 118, 4059-
4071.
10.1021/jo001740t CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/20/2001

3428 J . Org. Chem., Vol. 66, No. 10, 2001
Bach and Ho¨fer
experiments,5,6 they have shown that esters of the general
structure A can be photochemically deconjugated to yield
â,γ-unsaturated products. The stereoselectivity of the
reaction can be either controlled by a chiral alcohol
auxiliary R*OH attached to A (R ) R*) via the ester
bond6 or by a chiral proton source that allows for an
enantioselective protonation.5 As highly enantioselective
examples of the latter variant are limited to a few
substrates with a certain substitution pattern, we con-
sidered the auxiliary-based approach more versatile and
more promising. Indeed, the inexpensive, commercially
available chiral alcohol 1,2:5,6-di-O-isopropylidene-R-D-
glucofuranose [diacetone D-glucose, DAGOH (9a )]7 has
been successfully employed for this purpose. The syn-
thesis of the terpene alcohol (R)-(-)-lavandulol (8), for
example, was achieved via a diastereoselective photodecon-
jugation.6d
Sch em e 2
Ta ble 1. P r ep a r a tion of th e Sen ecio Acid Ester s 7a -d
yield 11a yield 12a yield 13a yield 7a
entry
R*
deriv
(%)
(%)
(%)
(%)
1
2
3
4
DAG
DAA
DAGu
DAF
a
b
c
d
quant
quant
77
46 (58)b
56 (72)b
44 (53)b
43 (64)b
77
91
89
90
88
61
73
82
96
a
b
Yield of isolated product. Yield based on recovered starting
material.
1,2-diol protective groups. In this early stage of the
investigation, a rational design appeared less promising
to us as the auxiliary-induced diastereoselectivity of
carbohydrate-derived and other alkanoates depends
strongly on the reaction conditions (vide infra). On the
basis of previous results,6c we first entertained the notion
to vary the proton source of the photodeconjugation
reaction and not the auxiliary. We discarded this idea
due to the unsatisfactory conversions we achieved in
preliminary experiments with DAGOH (9a ) as the aux-
iliary and tert-butyl alcohol as the proton source.
For the synthesis of the (S)-alcohol 1 and its immediate
precursor 2 (X ) R*O) from compound 7 an equally
effective auxiliary was required that should act as if it
was an enantiomer of diacetone D-glucose. Camphor- and
menthone-derived auxiliaries that fulfill this requirement
have been described,6a but they were prepared in multi-
step syntheses or are very expensive. We therefore
decided to study a variety of sugar-based alcohols R*OH
in order to evaluate their suitability as chiral auxiliaries8
in the photodeconjugation of compounds 7 (R ) R*). In
the following account, we would like to describe the
results of this study which finally yielded a reliable
method for the photodeconjugation of a senecio acid
derivative 7 to the corresponding (S)-ester 2 (X ) R*O)
employing a chiral alcohol readily available from L-
fructose.
Resu lts
In an empirical approach we used the alcohols 9 (9b,
DAAOH ) diacetone D-allofuranose;9 9c, DAGuOH )
diacetone D-gulofuranose;9a,10 9d , DAFOH ) diacetone
D-fructopyranose11) depicted in Scheme 2 to receive a
rough picture of the steric effects exerted by the acetonide
(4) Review: Pete, J .-P. Adv. Photochem. 1996, 21, 135-216.
(5) (a) Pete, J .-P.; Henin, F.; Mortezaei, R.; Muzart, J .; Piva, O. Pure
Appl. Chem. 1986, 58, 1257-1262. (b) Piva, O.; Mortezaei, R.; Henin,
F.; Muzart, J .; Pete, J .-P. J . Am. Chem. Soc. 1990, 112, 9263-9272.
(6) (a) Mortezaei, R.; Awandi, D.; Henin, F.; Muzart, J .; Pete, J .-P.
J . Am. Chem. Soc. 1988, 110, 4824-4826. (b) Awandi, D.; Henin, F.;
Muzart, J .; Pete, J .-P., Tetrahedron: Asymmetry 1991, 2, 1101-1104.
(c) Piva, O.; Pete, J .-P. Tetrahedron: Asymmetry 1992, 3, 759-768. (d)
Piva, O. J . Org. Chem. 1995, 60, 7879-7883. (e) Piva, O.; Caramelle,
D. Tetrahedron: Asymmetry 1995, 6, 831-832.
The reaction sequence selected for the synthesis of the
esters 7a -d followed the route earlier used by Piva in
his synthesis of (R)-(-)-lavandulol.6d To this end, the
alcohols 9 were treated with acetyl Meldrum’s acid (10)
to yield the acetoacetates 11. Subsequent alkylation with
iodide 3 as conducted previously with the achiral sub-
strate 5 (vide supra) produced the R-alkylated â-keto
esters 12. After phosphorylation with chloro diethyl
phosphate, the enol phosphates 13 were subjected to a
substitution reaction by dimethyl cuprate resulting in
enantiomerically pure senecio acid esters 7. The yields
of the individual steps are summarized in Table 1.
(7) Review on chiral pool auxiliaries: Blaser, H. U. Chem. Rev. 1992,
92, 935-952.
(8) Reviews on carbohydrate-based auxiliaries: (a) Kunz, H.; Ru¨ck,
K. Angew. Chem. 1993, 105, 355-377; Angew. Chem., Int. Ed. Engl.
1993, 32, 336-358. (b) Reissig, H.-U. Angew. Chem. 1992, 104, 295-
297; Angew. Chem., Int. Ed. Engl. 1992, 31, 288-290.
(9) (a) Morris, P. E., J r.; Kiely, D. E. J . Org. Chem. 1987, 52, 1149-
1152. (b) Baker, D. C.; Horton, D.; Tindall, C. G., J r. Carbohydr. Res.
1972, 24, 192-197.
(10) Slessor, K. N.; Tracey, A. S. Can. J . Chem. 1970, 48, 2900-
2906.
(11) Wang, J .-X.; Tu, Y.; Frohn, M.; Zhang, J .-R.; Shi, Y. J . Am.
Chem. Soc. 1997, 119, 11224-11235.

Photochemical Deconjugation of Chiral3-Methyl-2-butenoates
J . Org. Chem., Vol. 66, No. 10, 2001 3429
Sch em e 3
determine the optical purity of other mixtures containing
the alcohol ent-1 and its enantiomer 1.
In a sequence similar to the one described above the
two furanose-based esters, 7b and 7c were converted to
the deconjugated products 14b and 14c (Scheme 3, Table
2, entries 2 and 3). The diastereomeric excess (de) was
low (38% de) for the product 14b (X ) DAAO). Subse-
quent reduction of the mixture of diastereomeric products
yielded a mixture of the homoallylic alcohols 1 and ent-
1. The purified mixture of the two enantiomeric alcohols
turned out to be levorotatory, which proved the absolute
configuration of the major enantiomer to be R. The
enantiomeric excess (ee) of this sample was deduced from
its optical purity [[R]D ) -7.9 (c ) 1.0, CHCl3), 36% ee]
and it correlated well with the value expected due to the
diastereomeric excess of the corresponding ester 14b .
Similarly, the products of deconjugation and reduction
of the gulose-based ester 7c were levorotatory. The
auxiliary-induced diastereoselectivity determined from
ester 14c (X ) DAGuO) was moderate (66% de) which
translated into a moderate product enantioselectivity in
favor of alcohol ent-1 [[R]D ) -14.6 (c ) 1.0, CHCl3), 66%
ee].
Ta ble 2. Syn th esis of th e Hom oa llylic Alcoh ol en t-1 by
P h otod econ ju ga tion /Red u ction
yield 14/2a
deb
(%)
yield ent-1/ 1a eec
entry
R*
deriv
(%)
(%)
(%)
1
2
3
4
DAG
DAA
DAGu
DAF
a
b
c
d
85
73
80
70
>95d
38
88
78
80
85
>95
36
66
66
>95d
>95
a
b
Yield of isolated product. The diastereomeric excess (de) was
determined by integration of appropriate 1H NMR signals. The
detection limit for the other diastereoisomer was estimated from
previous experience to be <2.5%. c The enantiomeric excess (ee)
was determined as the optical purity from the mixture of the
d
enantiomeric alcohols 1 and ent-1. No other diastereoisomer was
observed in the 1H and 13C NMR spectra.
In view of the desired diastereoface selection, the
D-fructose-based ester 7d performed equal to the other
esters and contrary to our desire (Scheme 3, Table 2,
entry 4). Apparently, the differentiation of the diastereo-
topic faces is more effective than for esters 7b and 7c
leading to the corresponding (R)-products 14d and ent-1
with high excess. The ester 14d was obtained in >95%
de, and the reduction product ent-1 exhibited an optical
purity of >95% [[R]D ) -22.2 (c ) 1.0, CHCl3)].
Despite the moderate yields achieved in the alkylation
step, the overall yields (27-45%) for the conversion 9 f
7 were considered satisfactory and a further optimization
was not attempted.
Based on previous results6 the photochemical decon-
jugation of compound 7a was expected to give the
levorotatory (R)-alcohol ent-1 upon reduction of ester 14a
(Scheme 3, Table 2, entry 1). The reported auxiliary-
induced diastereoselectivities for related reactions are
high and we aimed at the synthesis of ent-1 as reference
material for our further studies. Indeed, the deconjuga-
tion of ester 7a proceeded smoothly and yielded the â,γ-
unsaturated product 14a with >95% de (85% yield).
Rayonet lamps RPR-2540 Å (λ ) 254 nm) were employed
as light sources, and the reaction was conducted at room
temperature in pentane as the solvent with N,N-di-
methylaminoethanol as the proton source. The crude
product was directly converted to the homoallylic alcohol
ent-1 by reduction with lithium aluminum hydride in
diethyl ether. The specific optical rotation of the alcohol
Despite the fact that this result was disappointing with
regard to the direction of the face selectivity, we consid-
ered the high auxiliary-induced diastereoselectivity ben-
eficial. Whereas the enantiomer of D-glucose is syntheti-
cally difficult to access, L-fructose can be prepared from
the commercially available, inexpensive starting material
L-sorbose. Instead of continuing the tests with D-carbo-
hydrate derivatives we decided at this point in time to
possibly shorten our synthetic effort by the preparation
of diacetone L-fructopyranose. Its conversion to the ester
ent-7d should yield the desired alcohol 1 upon photode-
conjugation and reduction. As precedence for the prepa-
ration of L-fructose, we attempted to follow a procedure
by Chen and Whistler13 according to which the transfor-
mation is conducted as a one-pot reaction or as a
sequence of two one-pot reactions. The second variant
includes the isolation of a mesylate (see compound 16 in
Scheme 4) as the reaction intermediate. The inversion
of two stereogenic centers was achieved via epoxide
formation and consecutive ring opening in an intermedi-
ate furanose. Unfortunately, we encountered problems
in the ring opening of the intermediate epoxide (see
compound 18 in Scheme 4), which did not go to comple-
tion even after heating the reaction mixture in aqueous
acetone for an extended period of time. The alternative
procedure14 we considered reported the isolation of
intermediates starting from a protected L-sorbopyranose
and appeared easier to follow. The first step of the
synthesis, however, requires a 10-fold (w/w) excess of
ent-1 was determined as [R]20 ) -27.9 (c ) 1.1, MeOH)
D
as compared to the optical rotation of (R)-(-)-lavandulol,
which was reported as [R]20 ) -10.1 (c ) 1.1, MeOH).
D
The alkyl side chain should not influence the chromophor
significantly. A literature search revealed that 2-alkyl-
substituted (R)-homoallylic alcohols are levorotatory in
CHCl3 or MeOH, and the corresponding (S)-enantiomers
are dextrorotatory.12 No exception was found. In chloro-
form, the specific optical rotation of the alcohol ent-1 was
[R]D ) -22.2 (c ) 1.0, CHCl3). Based on the known
direction of the protonation in DAGO ester derived enols
and the optical rotation data, we consider it safe to
assume that the products we obtain from the photode-
conjugation of substrate 7a bear a stereogenic center with
(R)-configuration. The reduction 14a f ent-1 should
proceed racemization-free, and we consequently assigned
an optical purity of >95% to the alcohol ent-1. The optical
rotation of this product was taken as reference to
(12) Recent examples: (a) Takano, S.; Tanaka, M.; Seo, K.; Hirama,
M.; Ogasawara, K. J . Org. Chem. 1985, 50, 931-936. (b) Bandony, R.;
Maliverney, C. Tetrahedron 1988, 44, 471-480. (c) Faure, S. S.; Piva,
O. Synlett 1998, 1414-1416.
(13) (a) Chen, C.-C.; Whistler, R. L. Carbohydr. Res. 1988, 175, 265-
271. (b) Isopropylidene formation: Morgenlie, S. Carbohydr. Res. 1982,
107, 137-141.
(14) Gizaw, Y.; BeMiller, J . N. Carbohydr. Res. 1995, 266, 81-85.

3430 J . Org. Chem., Vol. 66, No. 10, 2001
Bach and Ho¨fer
Sch em e 4
Discu ssion
Two facts render any discussion of the conformational
behavior of carbohydrates in the course of a stereoselec-
tive reaction difficult. First, the number of stereogenic
centers is comparably large, and second, multiple Lewis
acid/Lewis base interactions due to the presence of
several oxygen atoms are possible. Diacetone D-fructo-
pyranose (9d ) has been previously employed15,16 as a
chiral auxiliary in Diels-Alder reactions and the stereo-
chemical outcome of the reactions has been discussed.17
These reactions were promoted by aluminum Lewis acids
that not only coordinate to the carbonyl oxygen atom of
the acrylate dienophile but also to an oxygen atom of the
sugar by chelation. Hence, the analogy to the enols we
studied is not particularly close.
A possible discussion is further complicated by the
known fact that the face discrimination in the protona-
tion of enols depends on the proton source. Piva et al.
postulated a conformation I to account for the Si-face
protonation (priority: isopropenyl > R) of DAGO-derived
enols by N,N-dimethylaminoethanol.6d Contrary to that,
the enolate alkylation of analogous O-(E)-enolates was
suggested to occur via conformation II with the enolate
oxygen pointing toward the furanose ring due to metal
chelation.18 Although this hypothesis was questioned,19
it nicely corroborates the outcome of the facial diastereo-
selectivity in the enolate alkylation of the gulofuranose-
(DAGuO)19 and allofuranose-based (DAAO)18 esters. The
conformation III which is related to II would equally well
explain the stereochemical outcome recorded for the
photodeconjugation reaction of DAGO-based senecio acid
esters. The consensus is that it is the 5,6-isopropylidene
but not the 1,2-isopropylidene acetal which is responsible
for the face discrimination in esters of DAGOH and
DAGuOH.
Sch em e 5
CuSO4 relative to the starting material, a fact which shed
doubt on its suitability for a potentially necessary scale-
up.
Consequently, we attempted to modify the former
procedure13a by isolating intermediate products. By this
means we were able to control the reaction conditions
and to guarantee a complete conversion in each step. As
we find this protocol useful it is briefly outlined in
Scheme 4 in which all intermediates are depicted. One
key modification was the use of NaOH in dioxane for the
ring opening of epoxide 18 to the triol 19. Overall, the
reaction sequence 15 f 19 proceeded in a yield of 19%
and is amenable to scale-up.
If the oxygen atom of DAGO-derived ester enolates is
silylated20 or if R-unsubstituted DAGO enol ethers21 are
(15) (a) Ferreira, M. L. G.; Pinheiro, S.; Perrone, C. C., Costa, P. R.
R.; Ferreira, V. F. Tetrahedron: Asymmetry 1998, 9, 2671-2680. (b)
Enholm, E. J ., J iang, S. J . Org. Chem. 2000, 65, 4756-4758.
(16) Review on auxiliaries employed in cycloaddition reactions:
Ru¨ck-Braun, K.; Kunz, H. Chiral Auxiliaries in Cycloadditions, Wiley-
VCH: Weinheim 1999.
(17) Other references to the use of diacetone D-fructopyranose as
auxiliary: (a) Heathcock, C. H.; White, C. T.; Morrison, J . J .; VanDer-
veer, D. J . Org. Chem. 1981, 46, 1296-1309. (b) Kossmehl, G.;
Volkheimer, J . Liebigs Ann. 1989, 1127-1130. (c) Scherer, S., Diploma
thesis, TU Darmstadt, 1992. (d) Madsen, J .; Clausen, R. P.; Hazell, R.
G.; J acobsen, H. J .; Bols, M.; Perry, C. C. Acta Chem. Scand. 1998,
52, 1165-1170. (e) Nouguier, R.; Be´raud, V.; Vanelle, P.; Crozet, M.
P. Tetrahedon Lett. 1999, 40, 5013-5014.
(18) Kunz, H.; Mohr, J . Chem. Commun. 1988, 1315-1317.
(19) Mulzer, J .; Hiersemann, M.; Buschmann, J .; Luger, P. Liebigs
Ann. 1996, 649-654.
(20) Angiborud, P.; Chaumette, J . L.; Desmurs, J . R., Duhamel, L.;
Pee´, G.; Valnot, J . Y.; Duhamel, P. Tetrahedron: Asymmetry 1995, 6,
1919-1932.
(21) (a) Arnold, T.; Orschel, B.; Reissig, H.-U. Angew. Chem. 1992,
104, 1084-1086; Angew. Chem., Int. Ed. Engl. 1992, 31, 1033-1035.
(b) Kaluza, Z.; Furman, B.; Patel, M.; Chmielewski, M. Tetrahedron:
Asymmetry 1994, 5, 2179-2186.
Having L-fructose (20) in hand, it was converted to the
desired diacetone L-fructose ent-9d (Scheme 4), which was
taken through the seqeuence of steps already reported
for the D-enantiomer (cf. Scheme 2). The senecio acid
ester ent-7d was obtained in an overall yield of 55%
starting from the alcohol ent-9d . The final conversion to
the desired alcohol proceeded as depicted in Scheme 3
for the D-sugars. Deconjugation of the ester ent-7d gave
exclusively the â,γ-unsaturated product 2d , which was
reduced to the enantiomerically pure target compound
1. The facial diastereoselection was as desired (>95% de)
and the reduction proceeded smoothly (Scheme 5).

Photochemical Deconjugation of Chiral3-Methyl-2-butenoates
J . Org. Chem., Vol. 66, No. 10, 2001 3431
employed the mode of electrophilic attack is inverted as
compared to the enolate alkylation.
allylic alcohols. The face discrimination is opposite to the
one recorded with the well-established and frequently
used diacetone-D-glucose (DAGOH) derived enoates. Di-
acetone L-fructopyranose might consequently serve as a
useful supplement to DAGOH in photodeconjugation
reactions giving access to products that are enantiomeric
to the products obtained employing DAGOH as the
auxiliary.
Possible conformations accessible for the diacetone
L-fructopyranose-based enol 21 which is an intermediate
in the transformation ent-7d f 2d are depicted sche-
matically below. The black dots represent the cyclic
acetals which have been omitted for clarity. Rotation
around the unrestricted O-C-bonds gives rise to four
conformers. Force field calculations (MM3, Hyperchem
5.1) and molecular models reveal a clear preference of
21 vs 21′′ and of 21′ vs 21′′′. This preference is in line
with the most stable conformations acrylates of secondary
alcohols are known to adopt.22 The carbonyl oxygen atom
and the hydrogen atom are eclipsed as are the enol OH
group and the hydrogen atom at C-3 in the enol 21.
Exp er im en ta l Section
Gen er a l Meth od s. For general remarks see ref 23. Flash
chromatography24 was carried out using silica gel (Merck,
230-400 mesh) and the reported solvent mixtures of tert-butyl
methyl ether (TBME)/pentane (P) or ethyl acetate (EtOAc)/
hexanes (Hex) as eluents. Solvents used for chromatography
(Ac ) acetone, Tol ) toluene) were distilled prior to use.
Elemental analyses were carried out in the Departement of
Chemistry, University of Marburg on an Elementar vario EL
instrument. Optical rotations were measured on a Perkin-
Elmer 241MC polarimeter using sodium low-pressure light in
a standard quartz rotation cell.
(1,2:5,6-Di-O-isop r op ylid e n e -r-D-glu cofu r a n os-3-O-
yl) 3-Oxobu ta n oa te (11a ).6d Typ ica l P r oced u r e A. (1,2:5,6)-
Di-O-isopropylidene-D-glucose (9a , 15.2 g, 57.6 mmol) was
added to a stirred solution of acetyl Meldrum’s acid (13.2 g,
60.0 mmol) in toluene (100 mL). The solution was refluxed for
8 h and subsequently concentrated in vacuo. Flash chroma-
tography (TBME/P ) 20:80) yielded compound 11a as a
1
slightly yellow oil (19.8 g, 100%). H NMR: δ ) 1.31 (s, 6H),
1.40 (s, 3H), 1.52 (s, 3H), 2.28 (s, 3H), 3.47 (d, J ) 17.1 Hz,
1H), 3.55 (d, J ) 17.1 Hz, 1H), 3.97-4.11 (m, 2H), 4.15-4.25
(m, 2H), 4.57 (d, J ) 3.8 Hz, 1H), 5.27-5.33 (m, 1H), 5.87 (d,
J ) 3.8 Hz, 1H). 13C NMR: δ ) 26.4, 26.8, 26.9, 28.2, 30.5,
50.6, 60.8, 71.6, 72.0, 74.1, 75.1, 103.8, 110.1, 112.6, 167.1,
201.9. The NMR data were in agreement with the reference
data.6d
Protonation of the enol in its preferred conformation
21 from the Re-face accounts for the observed stereo-
selectivity. The 1,2-isopropylidene acetal is considered to
be responsible for the face discrimination. Possibly, the
bulky acid requires the enol to be exposed at the outer
sphere of the molecule favoring 21 over 21′′. Hydrogen
bridging to the pyranose oxygen atom is impossible for
the enol OH group. Contrary to that, hydrogen bridging
is possible to a furanose oxygen atom a fact which might
explain the enhanced population of conformation III in
the DAGO-case. Conformation III corresponds to confor-
mation 21′′ and conformation I corresponds to conforma-
tion 21′. The face discrimination observed for the photo-
deconjugation of esters 7b and 7c can be explained based
on conformations analogous to III. In line with the results
of the enolate alkylations (vide supra),18,19 the enol
protonation occurs from the same face, irrespective what
alcohol DAGOH, DAAOH, or DAGuOH is used as the
auxiliary.
(1,2:5,6-Di-O-isop r op ylid en e-r-D-a llofu r a n os-3-O-yl)
3-Oxobu ta n oa te (11b). According to typical procedure A, 6.0
g of (1,2:5,6)-di-O-isopropylidene-D-allose9 (9b, 23 mmol) yielded
7.9 g of the ester 11b (100%). Rf ) 0.26 (TBME/P ) 50:50). IR
1
(film): ν˜ ) 1750 cm-1 (s, CdO), 1721 (s, CdO). H NMR: δ )
1.28 (s, 3H), 1.29 (s, 3H), 1.36 (s, 3H), 1.47 (s, 3H), 2.25 (s,
3H), 3.44 (s, 2H), 3.83 (dd, J ) 8.6, 5.7 Hz, 1H), 4.01 (dd, J )
8.6, 6.8 Hz, 1H), 4.08 (dd, J ) 4.5, 8.5 Hz, 1H), 4.23 (dt, J )
5.7, 5.8 Hz, 1H), 4.79 (dd, J ) 5.1, 3.9 Hz, 1H), 4.84 (dd, J )
5.1, 8.6 Hz, 1H), 5.78 (d, J ) 3.9 Hz, 1H). 13C NMR: δ ) 24.8,
26.1, 26.5, 26.6, 29.7, 49.8, 65.5, 73.3, 74.9, 77.4, 77.4, 104.0,
109.8, 113.0, 166.0, 199.5. [R]20 ) +76.8 (c ) 5.3, CHCl3).
D
Anal. Calcd for C16H24O8 (344.36): C, 55.81; H, 7.02. Found:
C, 55.91; H, 6.77.
(1,2:5,6-Di-O-isop r op ylid en e-r-D-gu lofu r a n os-3-O-yl)
3-Oxobu ta n oa te (11c). According to typical procedure A, 2.0
g of (1,2:5,6)-di-O-isopropylidene-D-gulose9a (9c, 7.7 mmol)
yielded 2.03 g of the ester 11c as a colorless oil (77%). Rf )
0.49 (TBME/P ) 50:50). IR (film): ν˜ ) 1755 cm-1 (s, CdO),
1
1723 (s, CdO). H NMR: δ ) 1.35 (s, 3H), 1.37 (s, 3H), 1.43
(s, 3H), 1.55 (s, 3H), 2.29 (s, 3H), 3.52 (s, 2H), 3.55 (dd, J )
8.6, 7.2 Hz, 1H), 4.06 (dd, J ) 8.6, 6.4 Hz, 1H), 4.09 (dd, J )
8.9, 6.6 Hz, 1H), 4.55 (dt, J ) 5.8, 4.0 Hz, 1H), 4.83 (dd, J )
5.8, 4.0 Hz, 1H), 5.09 (dd, J ) 5.8, 6.6 Hz, 1H), 5.81 (d, J )
4.0 Hz, 1H). 13C NMR: δ ) 25.1, 26.6, 26.6, 26.8, 26.9, 49.6,
66.2, 72.5, 74.9, 78.5, 81.1, 105.0, 109.3, 114.6, 165.8, 182.9.
Con clu sion a n d Ou tlook
In summary, diacetone L-fructopyranose (ent-9d ) was
identified as a chiral auxiliary which can be used for the
stereoselective photodeconjugation of R-alkylated senecio
acid derivatives. A high diastereomeric excess was
achieved in the corresponding reaction of ester ent-7d to
the diastereomerically pure â,γ-unsaturated product 2d .
Reduction yielded the alcohol 1 in high optical purity. It
is projected that the reaction is applicable to other related
2-substituted senecio acids and their conversion to homo-
[R]20 ) +58.8 (c ) 0.9, CHCl3). Anal. Calcd for C16H24O8
D
(344.36): C, 55.81; H, 7.02. Found: C, 56.02; H, 6.81.
(1,2:4,5-Di-O-isop r op ylid en e-r-D-fr u ct op yr a n os-3-O-
yl) 3-Oxobu ta n oa te (11d ). According to typical procedure A,
6.5 g (1,2:4,5)-di-O-isopropylidene-D-fructose11 (9d , 25 mmol)
yielded 8.64 g of the ester 11d (96%) as a solid. Rf ) 0.26
(TBME/P ) 20:80). Mp: 63-65 °C. IR (film): ν˜ ) 1749 cm-1
1
(s, CdO); 1720 (s, CdO). H NMR: δ ) 1.36 (s, 3H), 1.38 (s,
(22) Helmchen, G.; Karge, R.; Weetman, J . In Modern Synthetic
Methods; Scheffold, R., Ed.; Springer, Berlin, 1986; Vol. 4, pp 261-
306.
(23) Bach, T.; Schro¨der, J . J . Org. Chem. 1999, 64, 1265-1273.
(24) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923-
2925.

3432 J . Org. Chem., Vol. 66, No. 10, 2001
Bach and Ho¨fer
3H), 1.48 (s, 3H), 1.54 (s, 3H), 2.29 (s, 3H), 3.53 (d, J ) 15.5
Hz, 1H), 3.59 (d, J ) 15.5 Hz, 1H), 3.94 (d, J ) 13.3 Hz, 1H),
3.97 (d, J ) 13.3 Hz, 1H), 4.07 (d, J ) 13.5 Hz, 1H), 4.13 (dd,
J ) 13.5, 2.2 Hz, 1H), 4.25 (dd, J ) 5.4, 2.2 Hz, 1H), 4.29 (dd,
J ) 7.7, 5.4 Hz, 1H), 5.14 (d, J ) 7.7 Hz, 1H). 13C NMR: δ )
26.4, 26.8, 26.9, 28.2, 30.5, 50.6, 60.8, 71.6, 72.0, 74.1, 75.1,
114.4, 114.7, 168.2, 168.3, 200.9, 201.1. Anal. Calcd for
C23H36O8Si (468.61): C, 58.95; H, 7.75. Found: C, 58.47; H,
6.47.
(1,2:4,5-Di-O-isop r op ylid en e-r-D-fr u ct op yr a n os-3-O-
yl) 2-Acetyl-6-(tr im eth ylsilyl)-5-h exyn oa te (12d ). Accord-
ing to typical procedure B, 5.0 g (14.5 mmol) of compound 11d
yielded 2.9 g of the ester 12d (43%). Mixture of diastereoiso-
mers, dr 53:47. Rf ) 0.36 (TBME/P ) 20/80). IR (KBr): ν˜ )
103.8, 110.1, 112.6, 167.1, 189.9. [R]20 ) -149.0 (c ) 0.9,
D
CHCl3). Anal. Calcd for C16H24O8 (344.36): C, 55.81; H, 7.02.
Found: C, 55.51; H, 7.20.
1
2176 cm-1 (s, CtC), 1748 (s, CdO), 1721 (s, CdO). H NMR:
δ ) 0.15 (s, 9H), 1.37 (s, 1.5H), 1.37 (s, 1.5H), 1.40 (s, 1.5H),
1.42 (s, 1.5H), 1.48 (s, 1.5H), 1.49 (s, 1.5H), 1.54 (s, 1.5H), 1.56
(s, 1.5H), 2.06-2.16 (m, 2H), 2.33 (s, 1.5H), 2.35 (s, 1.5H),
2.25-2.39 (m, 2H), 3.73-3.79 (m, 1H), 3.84 (dd, J ) 9.3, 6.0
Hz, 1H), 3.95 (dd, J ) 9.3, 5.3 Hz, 1H), 4.09-4.15 (m, 2H),
4.20-4.22 (m, 1H), 4.28 (dt, J ) 7.5, 5.3 Hz, 1H), 5.15 (d, J )
8.1 Hz, 0.5H), 5.16 (d, J ) 7.7 Hz, 0.5H). 13C NMR: δ ) 0.00,
26.0, 26.1, 26.1, 26.3, 26.5, 26.6, 26.9, 27.6, 29.0, 29.5, 57.8,
58.2, 60.5, 71.3, 71.6, 71.8, 73.6, 74.5, 74.6, 86.1, 103.3, 103.4,
105.0, 109.6, 109.7, 111.9, 112.0, 169.1, 169.2, 201.7, 202.1.
(1,2:5,6-Di-O-isop r op ylid e n e -r-D-glu cofu r a n os-3-O-
yl) 2-Acetyl-6-tr im eth ylsilyl-5-h exyn oa te (12a ). Typ ica l
P r oced u r e B. A solution of the acetoacetate 11a (4.5 g, 13
mmol) in THF (10 mL) was added to a suspension of pentane-
washed sodium hydride (60% in mineral oil, 390 mg, 15.1
mmol) in THF (20 mL) at 0 °C. After hydrogen evolution
ceased, the solution was kept at 0 °C for 2 h and 1-iodo-4-
(trimethylsilyl)-3-butyne1 (3.3 g, 13 mmol) was added rapidly
to the stirred solution. The solution was heated under reflux
for 48 h and hydrolyzed with 20 mL of a saturated NH4Cl
solution, and the layers were separated. The aqueous phase
was extracted with EtOAc (3 × 20 mL). The combined organic
layers were washed with brine, dried (MgSO4), filtered, and
concentrated in vacuo. The residue was purified by flash
chromatography (TBME/P ) 20:80) to yield compound 12a as
a slightly yellow oil (2.81 g, 46%). Mixture of diastereoisomers,
dr ) 51/49. Rf ) 0.34 (TBME/P ) 50:50). IR (film): ν˜ ) 2175
Anal. Calcd for
C23H36O8Si (468.61): C, 58.95; H, 7.74.
Found: C, 59.22; H, 7.93.
(1,2:5,6-Di-O-isop r op ylid e n e -r-D-glu cofu r a n os-3-O-
yl) 2-[1′-(Dieth ylp h osp h or yloxy)-eth ylid en e]-6-tr im eth -
ylsilyl-5-h exyn oa te (13a ). Typ ica l P r oced u r e C. Sodium
hydride (60% in mineral oil, 210 mg, 7.0 mmol, washed with
pentane) was suspended in ether (50 mL) and cooled to 0 °C.
A solution of compound 12a (2.8 g, 6.0 mmol) in ether (17 mL)
was added to this mixture dropwise via cannula. The solution
was warmed to room temperature over 30 min and cooled
again to 0 °C. Diethyl chlorophosphate (1.01 mL, 7.0 mmol)
was added dropwise, and the solution was stirred at room
temperature for 16 h. The solution was hydrolyzed with NH4-
Cl (saturated aqueous, 50 mL), and the layers were separated.
The aqueous layer was extracted with ethyl acetate (3 × 25
mL). The combined organic layers were washed with brine (25
mL), dried (MgSO4), filtered, and concentrated in vacuo. The
residue was purified by flash chromatography (EtOAc/Hex )
40/60) to yield compound 13a as a yellow oil (2.8 g, 77%). Rf )
0.15 (TBME/P ) 50:50). IR (film): ν˜ ) 2175 cm-1 (s, CtC);
1732 (s, CdO); 1652 (w, CdC). 1H NMR: δ ) 0.11 (s, 9H),
1.29 (s, 3H), 1.30 (s, 3H), 1.31-1.39 (m, 6H), 1.38 (s, 3H), 1.51
(s, 3H), 2.18 (d, J ) 1.8 Hz, 3H), 2.32-2.38 (m, 2H); 2.45-
2.53 (m, 2H); 3.99 (dd, J ) 8.5, 4.4 Hz, 1H); 4.09 (dd, J ) 8.5,
5.9 Hz, 1H); 4.13-4.25 (m, 6H), 4.62 (dd, J ) 1.8, 3.7 Hz, 1H),
5.29 (dd, J ) 1.8, 3.7 Hz, 1H), 5.89 (d, J ) 3.7 Hz, 1H). 13C
NMR: δ ) 0.0, 16.1 (d, J ) 6.9 Hz), 18.3, 19.3, 25.1, 26.3, 26.8,
27.0, 28.4, 64.6 (d, J ) 3.9 Hz), 67.5, 72.5, 76.3, 80.2, 83.2,
85.4, 105.3, 105.6, 109.4, 112.1, 117.0 (d, J ) 8.0 Hz), 152.2
(d, J ) 8.1 Hz), 164.6. 31P NMR: δ ) -6.54 (s). [R]20D ) -28.4
(c ) 0.85, CHCl3). HRMS (C27H45O11PSi): calcd 589.2234,
found 589.2229.
1
cm-1 (s, CtC); 1749 (s, CdO); 1720 (s, CdO). H NMR: δ )
0.13 (s, 9H), 1.29 (s, 3H), 1.31 (s, 3H), 1.390 (s, 1.5H), 1.394
(s, 1.5H), 1.51 (s, 3H), 2.03-2.10 (m, 2H), 2.26 (s, 1.5H), 2.28
(s, 1.5H), 2.27-2.38 (m, 2H), 3.68 (t, J ) 7.4 Hz, 0.5H), 3.74
(t, J ) 7.1 Hz, 0.5H), 3.98 (dd, J ) 8.0, 2.3 Hz, 1H), 4.09 (dd,
J ) 8.0, 4.3 Hz, 1H), 4.14-4.28 (m, 2H), 4.47 (d, J ) 3.5 Hz,
1H), 5.31 (d, J ) 2.3 Hz, 0.5H), 5.34 (d, J ) 1.5 Hz, 0.5H),
5.85 (d, J ) 3.8 Hz, 0.5H), 5.87 (d, J ) 4.0 Hz, 0.5H). 13C
NMR: δ ) 0.0, 17.7, 25.1, 26.2, 26.7, 26.8, 26.9, 29.0, 29.4,
35.3, 49.4, 57.7, 58.4, 67.5, 67.7, 72.3, 76.7, 80.0, 80.1, 83.1,
83.3, 104.8, 104.9, 105.1, 109.5, 112.4, 167.9, 168.0, 201.8,
202.3. HRMS (C22H33O8Si): calcd 453.1945, found 453.1934.
(1,2:5,6-Di-O-isop r op ylid en e-r-D-a llofu r a n os-3-O-yl) 2-
Acetyl-6-tr im eth ylsilyl-5-h exyn oa te (12b). Following typi-
cal procedure B, 7.5 g of compound 11b (22.5 mmol) was
converted to ester 12b (5.84 g, 56%). Mixture of diastereoiso-
mers, dr ) 50/50. Rf ) 0.16 (TBME/P ) 50:50). IR (film): ν˜ )
2176 cm-1 (s, CtC), 1740 (s, CdO). 1H NMR: δ ) 0.12 (s, 9H),
1.30 (s, 3H), 1.31 (s, 3H), 1.40 (s, 3H), 1.49 (s, 3H), 1.98-2.10
(m, 2H), 2.27 (s, 3H), 2.42-2.19 (m, 2H), 3.66 (t, J ) 7.5 Hz,
0.5H), 3.68 (t, J ) 7.3 Hz, 0.5H), 3.85 (dd, J ) 8.6, 5.7 Hz,
1H), 4.03-4.12 (m, 2H), 4.24 (dd, J ) 5.4, 11.4 Hz, 1H), 4.78
(dd, J ) 5.3, 8.2 Hz, 1H), 4.80-4.87 (m, 1H), 5.83 (d, J ) 4.0
Hz, 1H). 13C NMR: δ ) 0.0, 17.4, 17.5, 26.2, 26.47, 26.49, 26.50,
26.7, 26.8, 26.9, 29.0, 29.1, 57.7, 58.1, 65.8, 65.9, 73.5, 73.9,
74.86, 74.98, 77.2, 77.6, 77.9, 85.9, 86.0, 98.5, 104.2, 104.3,
109.96, 109.98, 113.0, 168.3, 168.5, 201.3, 201.6. Anal. Calcd
for C23H36O8Si (468.61): C, 61.77; H, 8.21. Found: C, 61.61;
H, 8.46.
(1,2:5,6-Di-O-isop r op ylid en e-r-D-gu lofu r a n os-3-O-yl)
2-Acetyl-6-tr im eth ylsilyl-5-h exyn oa te (12c). According to
typical procedure B, 2.0 g (5.9 mmol) of compound 11c was
converted to ester 12c in 44% yield (1.22 g). Mixture of
diastereoisomers, dr ) 53:47. Rf ) 0.16 (TBME/P ) 50:50). IR
(film): ν˜ ) 2176 cm-1 (s, CtC), 1750 (s, CdO), 1721 (s, CdO).
1H NMR: δ ) 0.13 (s, 9H), 1.32 (s, 1.5H), 1.34 (s, 1.5H), 1.36
(s, 1.5H), 1.37 (s, 1.5H), 1.43 (s, 1.5H), 1.44 (s, 1.5H), 1.55 (s,
1.5H), 1.55 (s, 1.5H), 2.01-2.11 (m, 2H), 2.28 (s, 1.5H), 2.29
(s, 1.5H), 2.20-2.45 (m, 2H), 3.55 (dd, J ) 8.7, 6.7 Hz, 0.5H),
3.56 (dd, J ) 8.7, 6.7 Hz, 0.5H), 3.71 (t, J ) 7.2 Hz, 0.5H),
3.75 (t, J ) 7.2 Hz, 0.5H), 4.03 (dd, J ) 14.3, 6.7 Hz, 0.5H),
4.06 (dd, J ) 14.3, 6.7 Hz, 0.5H), 4.09 (dd, J ) 14.3, 6.7 Hz,
0.5H), 4.10 (dd, J ) 14.3, 6.7 Hz, 0.5H), 4.49 (dd, J ) 9.2, 6.7
Hz, 0.5H), 4.57 (dt, J ) 9.2, 6.7 Hz, 0.5H), 4.83 (dd, J ) 4.0,
5.5 Hz, 1H), 5.02 (dd, J ) 5.5, 6.2 Hz, 0.5H), 5.06 (dd, J ) 5.5,
6.2 Hz, 0.5H), 5.80 (d, J ) 4.0 Hz, 0.5H), 5.81 (d, J ) 4.0 Hz,
0.5H). 13C NMR: δ ) 0.0, 17.66, 17.71, 25.1, 26.6, 26.66, 26.67,
26.94, 26.97, 57.6, 58.1, 66.2, 66.4, 72.88, 72.93, 74.90, 74.95,
78.1, 78.6, 81.0, 81.1, 86.5, 104.6, 104.9, 105.0, 109.3, 109.5,
(1,2:5,6-Di-O-isopr opyliden e-r-D-allofu r an os-3-O-yl) 2-[1′-
(Diet h ylp h osp h or yloxy)et h ylid en e]-6-t r im et h ylsilyl-5-
h exyn oa te (13b). According to typical procedure C, 5.13 g
(10.95 mmol) of compound 12b yielded phosphoenolate 13b
(6.0 g, 91%). Rf ) 0.21 (TBME/P ) 50/50). IR (film): ν˜ ) 2176
1
cm-1 (s, CtC), 1732 (s, CdO), 1645 (w, CdC). H NMR: δ )
0.13 (s, 9H), 1.30 (s, 3H),1 0.31-1.35 (m, 6H), 1.33 (s, 3H),
1.41 (s, 3H), 1.53 (s, 3H), 2.24 (d, J ) 1.7 Hz, 3H), 2.35-2.48
(m, 2H), 2.49-2.53 (m, 2H), 3.90 (dd, J ) 8.5, 6.2 Hz, 1H),
4.06 (dd, J ) 8.5, 6.8 Hz, 1H), 4.17-4.23 (m, 5H), 4.24-4.28
(m, 1H), 4.80 (dd, J ) 5.0, 8.6 Hz, 1H), 4.85 (dd, J ) 5.0, 3.9
Hz, 1H), 5.82 (d, J ) 3.9 Hz, 1H). 13C NMR: δ ) 0.0, 16.0 (d,
J ) 6.9 Hz), 18.6, 19.3, 25.1, 26.2, 26.6, 26.7, 28.3, 64.6 (d, J
) 6.6 Hz), 65.7, 72.3, 76.4, 77.7, 81.3, 85.1, 104.3, 106.1, 109.9,
113.0, 115.9 (d, J ) 8.2 Hz), 152.6 (d, J ) 7.5 Hz), 164.3. 31P
NMR: δ ) -6.82 (s). [R]20 ) +68.7 (c ) 1.0, CHCl3). Anal.
D
Calcd for C27H45O11PSi (604.71): C, 53.63; H, 7.50. Found: C,
53.36; H, 7.49.
(1,2:5,6-Di-O-isop r op ylid en e-r-D-gu lofu r a n os-3-O-yl)
2-[1′-(Die t h ylp h osp h or yloxy)e t h ylid e n e ]-6-t r im e t h yl-
silyl-5-h exyn oa te (13c). A 1.14 g (2.43 mmol) portion of
compound 12c was converted into 1.30 g (2.15 mmol) of
phosphoenolate 13c following typical procedure C (89%). Rf )
0.20 (TBME/P ) 20:80). IR (film): ν˜ ) 2176 cm-1 (s, CtC),
1734 (s, CdO), 1649 (w, CdC). 1H NMR: δ ) 0.12 (s, 9H),

Photochemical Deconjugation of Chiral3-Methyl-2-butenoates
J . Org. Chem., Vol. 66, No. 10, 2001 3433
1.31 (s, 3H), 1.31-1.36 (m, 6H), 1.36 (s, 3H), 1.43 (s, 3H), 1.56
(s, 3H), 2.21 (d, J ) 1.8 Hz, 3H), 2.26-2.54 (m, 4H), 3.60 (dd,
J ) 6.6, 8.8 Hz, 1H), 4.09 (dd, J ) 9.5, 7.0 Hz, 1H), 4.18 (dd,
J ) 6.6, 8.8 Hz, 1H), 4.20 (q, J ) 7.2 Hz, 4H), 4.62 (dt, J )
6.5, 9.5 Hz, 1H), 4.84 (dd, J ) 4.0, 5.5 Hz, 1H), 5.08 (dd, J )
5.5, 7.0 Hz, 1H), 5.81 (d, J ) 4.0 Hz, 1H). 13C NMR: δ ) 0.00,
16.0 (d, J ) 7.0 Hz), 18.4, 19.2, 25.2, 26.6, 27.0, 27.0, 28.5,
64.6 (d, J ) 6.6 Hz), 66.7, 72.4, 75.0, 78.2, 81.3, 85.5, 105.0,
105.5, 109.1, 114.2, 116.2 (d, J ) 8.2 Hz), 152.7 (d, J ) 7.5
converted into 683 mg (1.5 mmol) of compound 7c following
typical procedure D (73%). Rf ) 0.42 (TBME/P ) 50:50). IR
(film): ν˜ ) 2176 cm-1 (s, CtC), 1721 (s, CdO), 1632 (w, Cd
1
C). H NMR: δ ) 0.12 (s, 9H), 1.33 (s, 3H), 1.38 (s, 3H), 1.46
(s, 3H), 1.56 (s, 3H), 1.90 (s, 3H), 2.05 (s, 3H), 2.27 (ddd, J )
16.6, 8.8, 7.5 Hz, 1H), 2.40 (ddd, J ) 9.0, 16.6, 5.9 Hz, 1H),
2.50-2.60 (m, 2H), 3.58 (dd, J ) 8.5, 6.6 Hz, 1H), 4.10 (dd, J
) 9.4, 6.9 Hz, 1H), 4.12 (dd, J ) 8.5, 6.6 Hz, 1H), 4.63 (dt, J
) 9.4, 6.6 Hz, 1H), 4.85 (dd, J ) 5.5, 4.0 Hz, 1H), 5.11 (dd, J
) 6.9, 5.5 Hz, 1H), 5.83 (d, J ) 4.0 Hz, 1H). 13C NMR: δ )
0.0, 19.4, 22.6, 25.1, 26.6, 26.7, 26.8, 26.9, 29.1, 66.5, 72.0, 75.1,
78.4, 81.3, 84.4, 106.2, 109.2, 114.2, 123.3, 125.0, 147.4, 167.5.
Hz), 164.8. [R]20 ) +24.9 (c ) 2.2, CHCl3). Anal. Calcd for
D
C
27H45O11PSi (604.71): C, 53.63; H, 7.50. Found: C, 53.15; H,
8.68.
[R]20 ) +46.3 (c ) 1.15, CHCl3). Anal. Calcd for C24H38O7Si
D
(1,2:4,5-Di-O-isop r op ylid en e-r-D-fr u ct op yr a n os-3-O-
(466.64): C, 61.77; H, 8.21. Found: C, 61.97; H. 7.98.
yl) 2-[1′-(Dieth ylp h osp h or yloxy)eth ylid en e]-6-tr im eth -
ylsilyl-5-h exyn oa te (13d ). A 2.80 g (5.97 mmol) portion of
compound 12d was converted to 3.25 g of phosphoenolate 13d
(5.4 mmol) following typical procedure C (90%). Rf ) 0.28
(TBME/P ) 50:50). IR (KBr): ν˜ ) 2173 cm-1 (s, CtC), 1722
(s, CdO), 1655 (m, CdC). 1H NMR: δ ) 0.11 (s, 9H), 1.27-
1.32 (m, 6H), 1.31 (s, 3H), 1.39 (s, 3H), 1.46 (s, 3H), 1.51 (s,
3H), 2.23 (d, J ) 1.8 Hz, 3H), 2.36-2.57 (m, 4H), 3.87 (d, J )
9.4 Hz, 1H), 3.93 (d, J ) 9.4 Hz, 1H), 4.06-4.11 (m, 2H), 4.15-
4.28 (m, 5H), 4.31 (dd, J ) 7.8, 5.3 Hz, 1H), 5.20 (d, J ) 7.8
Hz, 1H). 13C NMR: δ ) 0.0, 16.0 (d, J ) 7.0 Hz), 18.6, 19.7,
26.2, 26.4, 26.4, 27.7, 28.2, 60.6, 64.7 (d, J ) 6.5 Hz), 69.9,
71.8, 73.7, 74.7, 85.3, 103.7, 105.9, 109.5, 111.9, 115.8 (d, J )
8.6 Hz), 153.9 (d, J ) 7.5 Hz), 164.7. 31P NMR: δ ) -7.05.
(1,2:4,5-Di-O-isop r op ylid en e-r-D-fr u ct op yr a n os-3-O-
yl) 2-(1′-Meth yleth ylid en e)-6-tr im eth ylsilyl-5-h exyn oa te
(7d ). A 3.11 g (5.13 mmol) portion of phospoenolate 13d was
converted into 1.94 g of compound 7d following typical
procedure D (4.2 mmol, 82%). Rf ) 0.65 (TBME/P ) 40:60).
IR (film) ν˜ 2176 cm-1 (s, CtC), 1721 (s, CdO), 1632 (m, Cd
1
C). H NMR: δ ) 0.12 (s, 9H), 1.23 (s, 3H), 1.29 (s, 3H), 1.36
(s, 3H), 1.44 (s, 3H), 1.79 (s, 3H), 1.95 (s, 3H), 2.31-2.40 (m,
2H), 2.57 (t, J ) 7.0 Hz, 2H), 3.85 (d, J ) 9.3 Hz, 1H), 3.97 (d,
J ) 9.3 Hz, 1H), 4.10-4.13 (m, 2H), 4.23 (ddd, J ) 5.3, 2.2,
0.9 Hz, 1H), 4.32 (dd, J ) 8.0, 5.3 Hz, 1H), 5.22 (d, J ) 8.0 Hz,
1H). 13C NMR: δ ) 0.0, 19.7, 22.9, 23.4, 26.2, 26.2, 26.8, 27.7,
29.1, 60.5, 69.7, 71.9, 73.7, 74.9, 84.6, 103.9, 106.7, 109.5, 111.8,
[R]20 ) -84.1 (c ) 1.0, CHCl3). Anal. Calcd for C27H45O11PSi
125.1, 148.0, 167.9. [R]20 ) -121.0 (c ) 1.2, CHCl3). HRMS
D
D
(604.71): C, 53.63; H 7.50. Found: C, 53.63; H, 7.51.
(C23H35O7Si): calcd 451.2152, found 451.2155.
(1,2:5,6-Di-O-isop r op ylid e n e -r-D-glu cofu r a n os-3-O-
yl) 2-(1′-Meth yleth ylid en e)-6-tr im eth ylsilyl-5-h exyn oa te
(7a ). Typ ica l P r oced u r e D. A solution of methyllithium (1.4
M in diethyl ether, 7.4 mL, 10.3 mmol) was added to a
suspension of copper(I) iodide (0.98 g, 5.15 mmol) in diethyl
ether (57 mL) at 0 °C dropwise via syringe. A solution of
phosphoenolate 13a (2.75 g, 4.6 mmol) in ether (15 mL) was
added dropwise to the cuprate solution via cannula at -78 °C
and stirred for 3 h. The reaction was quenched with a solution
of NH4Cl (saturated aqueous, 25 mL), and the layers were
separated. The aqueous layer was extracted with ether (3 ×
50 mL), and the combined organic layers were washed with
brine (100 mL). The organics were dried (MgSO4), filtered, and
concentrated in vacuo. The residue was purified by flash
chromatography (EtOAc/Hex ) 20:80) to yield conjugated ester
7a as colorless oil (1.76 g, 83%). Rf ) 0.59 (TBME/P ) 20:80).
IR (film): ν˜ ) 2174 cm-1 (s, CtC); 1721 (s, CdO); 1630 (w,
CdC). 1H NMR δ ) 0.13 (s, 9H), 1.31 (s, 3H), 1.32 (s, 3H),
1.40 (s, 3H), 1.53 (s, 3H), 1.90 (s, 3H), 2.06 (s, 3H), 2.29 (ddd,
J ) 17.0, 7.8, 8.5 Hz, 1H), 2.32 (ddd, J ) 17.0, 7.8, 7.2 Hz,
1H), 2.55 (t, J ) 7.8 Hz, 2H), 4.00 (dd, J ) 4.6, 8.5 Hz, 1H),
4.12 (dd, J ) 5.9, 8.5 Hz, 1H), 4.20 (dd, J ) 2.9, 8.6 Hz, 1H),
4.23 (pseudo dt, J ) 8.6, 5.4 Hz, 1H), 4.55 (d, J ) 3.7 Hz, 1H),
5.27 (d, J ) 2.9 Hz, 1H), 5.87 (d, J ) 3.7 Hz, 1H). 13C NMR:
δ ) 0.0, 19.5, 22.8, 23.3, 25.1, 26.2, 26.6, 26.8, 29.0, 67.7, 72.4,
76.1, 80.3, 83.5, 84.8, 105.1, 106.4, 109.4, 112.2, 125.1, 148.2,
(1,2:5,6-Di-O-isop r op ylid e n e -r-D-glu cofu r a n os-3-O-
yl) 2-Isopr open yl-6-tr im eth ylsilyl-5-h exyn oate (14a). Typi-
ca l P r oced u r e E. The R,â-unsaturated ester 7a (2.5 mmol,
1.16 g) was dissolved in pentane (250 mL) and irradiated with
a TQ150 high-pressure lamp for 8 h in the presence of 0.25
mL of N,N-dimethylaminoethanol (2.5 mmol, 223 mg). After
evaporation of the solvent and purification by flash chroma-
tography (TBME/P ) 20:80), compound 14a was obtained as
a single diastereoisomer (NMR) in 85% yield (980 mg). Rf )
0.61 (TBME/P 20/80). IR (film): ν˜ ) 3080 cm-1 (w, dC-H),
2176 (s, CtC), 1744 (s, CdO), 1647 (CdC). 1H NMR: δ ) 0.13
(s, 9H), 1.28 (s, 3H), 1.29 (s, 3H), 1.37 (s, 3H), 1.50 (s, 3H),
1.71 (s, 3H), 1.81 (dt, J ) 14.1, 6.8 Hz, 1H), 2.02 (dt, J ) 14.1,
6.8 Hz, 1H), 2.22 (t, J ) 6.8 Hz, 2H), 3.25 (t, J ) 7.8 Hz, 1H),
3.92-3.97 (m, 1H), 4.06-4.18 (m, 3H), 4.90-4.94 (m, 2H),
5.26-5.28 (m, 1H), 5.86 (d, J ) 3.5 Hz, 1H). 13C NMR δ ) 0.0,
17.5, 19.8, 25.0, 26.1, 26.6, 26.7, 26.8, 51.7, 67.5, 72.0, 75.9,
80.3, 83.3, 85.5, 105.1, 105.7, 109.2, 112.3, 114.9, 140.9, 171.5.
[R]20 ) -43.5 (c ) 1.0, CHCl3). HRMS (C23H35O7Si): calcd
D
451.2152, found 451.2143.
(1,2:5,6-Di-O-isopropylidene-r-D-allofuranos-3-O-yl)2-Iso-
p r op en yl-6-tr im eth ylsilyl-5-h exyn oa te (14b). Irradiation
of the R,â-unsaturated ester 7b (2.5 g, 5.36 mmol) for 6.5 h
according to typical procedure E produced the â,γ-unsaturated
ester 14b (1.82 g) as a 2:1 mixture of diastereoisomers in 73%
yield. Rf ) 0.31 (TBME/P ) 20:80). IR (film): ν˜ ) 3080 cm-1
167.1. [R]20 ) -46.6 (c ) 1.45, CHCl3). HRMS (C23H35O7Si):
1
D
(w, dCH2), 2176 (s, CtC), 1740 (s, CdO), 1649 (m, CdC). H
calcd 451.2152, found 451.2149.
NMR: δ ) 0.13 (s, 9H), 1.31 (s, 2.1H), 1.32 (s, 0.9H), 1.34 (s,
0.9H), 1.34 (s, 2.1H), 1.40 (s, 0.9H), 1.41 (s, 2.1H), 1.51 (s,
2.1H), 1.53 (s, 0.9H), 1.75 (s, 0.9H), 1.77 (s, 2.1H), 1.79-1.86
(m, 1H), 2.02-2.08 (m, 1H), 2.22-2.27 (m, 2H), 3.24 (t, J )
15.2 Hz, 0.7H), 3.26 (t, J ) 15.2 Hz, 0.3H), 3.85 (dd, J ) 8.6,
6.0 Hz, 0.7H), 3.89 (dd, J ) 8.6, 5.7 Hz, 0.3H), 4.05 (dd, J )
8.6, 6.8 Hz, 0.3H), 4.06 (dd, J ) 8.6, 6.8 Hz, 0.7H), 4.13 (dd, J
) 8.6, 4.5 Hz, 0.3H), 4.14 (dd, J ) 8.6, 4.5 Hz, 0.7H), 4.16-
4.29 (m, 1H), 4.77 (dd, J ) 5.2, 8.6 Hz, 1H), 4.86 (dd, J ) 4.0,
5.2 Hz, 1H), 4.92-4.95 (m, 2H), 5.81 (d, J ) 4.0 Hz, 0.7H),
5.83 (d, J ) 4.0 Hz, 0.3H). 13C NMR: δ ) 0.00, 17.5, 17.6, 19.8,
20.0, 24.9, 26.1, 26.2, 26.4, 26.5, 26.7, 26.8, 28.5, 28.6, 51.4,
51.5, 65.4, 65.6, 72.8, 72.9, 74.8, 74.9, 77.4, 77.6, 77.8, 85.2,
104.2, 106.05, 106.10, 109.8, 112.8, 114.5, 114.8, 140.9, 141.0,
(1,2:5,6-Di-O-isopr opyliden e-r-D-allofu r an os-3-O-yl) 2-(1′-
Meth yleth ylid en e)-6-tr im eth ylsilyl-5-h exyn oa te (7b). A
5.69 g (9.4 mmol) portion of phosphoenolate 13b was converted
into 2.68 g of compound 7b following typical procedure D
(61%). Rf ) 0.30 (TBME/P ) 20:80). IR (film): ν˜ ) 2174 cm-1
1
(s, CtC), 1717 (s. CdO), 1632 (w, CdC). H NMR δ ) 0.12 (s,
9H), 1.32 (s, 3H), 1.35 (s, 3H), 1.42 (s, 3H), 1.53 (s, 3H), 1.90
(s, 3H), 2.06 (s, 3H), 2.31-2.48 (m, 2H), 2.59 (t, J ) 7.6 Hz,
2H), 3.90 (dd, J ) 8.5, 6.0 Hz, 1H), 4.07 (dd, J ) 8.5, 6.8 Hz,
1H), 4.16 (dd, J ) 8.3, 4.7 Hz, 1H), 4.29 (dt, J ) 6.3, 4.7 Hz,
1H), 4.83 (dd, J ) 8.3, 5.2 Hz, 1H), 4.90 (dd, J ) 5.2, 3.8 Hz,
1H), 5.84 (d, J ) 3.8 Hz, 1H). 13C NMR: δ ) 0.0, 19.3, 22.8,
23.2, 25.0, 26.2, 26.5, 26.6, 29.1, 65.8, 72.9, 75.2, 77.7, 85.1,
104.2, 106.8, 109.9, 112.8, 125.0, 147.5, 167.5. [R]20 ) +85.3
172.1, 172.2. [R]20 ) +79.3 (c ) 1.0, CHCl3). Anal. Calcd for
D
D
(c ) 2.3, CHCl3). Anal. Calcd for C24H38O7Si (466.64): C, 61.77;
C24H38O7Si (466.64): C, 61.77; H, 8.21. Found: C, 61.61; H,
H, 8.21. Found: C, 61.48; H, 8.18.
8.46.
(1,2:5,6-Di-O-isop r op ylid en e-r-D-gu lofu r a n os-3-O-yl)
2-(1′-Meth yleth yliden e)-6-tr im eth ylsilyl-5-h exyn oate (7c).
A 1.24 g (2.05 mmol) portion of phosphoenolate 13c was
(1,2:5,6-Di-O-isop r op ylid en e-r-D-gu lofu r a n os-3-O-yl)
2-Isop r op en yl-6-tr im eth ylsilyl-5-h exyn oa te (14c). Irradia-
tion of R,â-unsaturated ester 7c (470 mg, 1.0 mmol) for 3 h

3434 J . Org. Chem., Vol. 66, No. 10, 2001
Bach and Ho¨fer
according to typical procedure E produced â,γ-unsaturated
ester 14c (316 mg) as a 5:1 mixture of diastereomers (NMR)
in 80% yield. Rf ) 0.14 (TBME/P ) 20:80). IR (film): ν˜ ) 3081
cm-1 (w, H-Cd), 2176 (s, CtC), 1744 (s, CdO), 1647 (m, Cd
20.0, 25.7, 25.9, 28.0, 38.8, 60.3, 72.1, 73.2, 73.2, 84.1, 98.2,
109.7, 111.6. [R]20 ) -32.1 (c ) 1.3, MeOH). Anal. Calcd for
D
C
13H22O8S (338.37): C, 46.14; H, 6.55. Found: C, 46.04; H,
6.23.
1,2-Isop r op ylid en e-3-m esylsor b ofu r a n ose (17). The
1
C). H NMR (major diastereomer): δ ) 0.13 (s, 9H), 1.29 (s,
3H), 1.36 (s, 3H), 1.42 (s, 3H), 1.52 (s, 3H), 1.72 (s, 3H), 1.79
(ddd, J ) 14.1, 7.0, 5.7 Hz, 1H), 2.03 (ddd, J ) 14.1, 7.0, 6.9
Hz, 1H), 2.22 (pseudo t, J ) 7.0 Hz, 1H), 2.23 (pseudo t, J )
7.0 Hz, 1H), 3.26 (dd, J ) 7.4, 8.3 Hz, 1H), 3.53 (dd, J ) 8.5,
7.0 Hz, 1H), 4.06 (dd, J ) 8.3, 6.0 Hz, 1H), 4.12 (dd, J ) 8.9,
6.6 Hz, 1H), 4.57 (dt, J ) 8.5, 6.6 Hz, 1H), 4.84 (dd, J ) 4.0,
5.4 Hz, 1H), 4.93-4.99 (m, 3H), 5.81 (d, J ) 4.0 Hz, 1H). 13C
NMR (major diastereomer): δ ) 0.0, 17.5, 19.6, 25.1, 26.4, 26.6,
26.9, 28.3, 51.5, 66.5, 72.3, 75.1, 77.8, 81.4, 85.7, 105.0, 109.0,
mesylate 16 (118.6 g, 0.35 mol) was dissolved in acetone (500
mL), and 500 mL of dilute H2SO4 (0.25% w/w) was added. A
solid formed that dissolved upon stirring for 36 h. The solution
was neutralized by adding solid NaHCO3 and filtered. The
acetone was removed under reduced pressure. Storage at 4
°C gave compound 17 as a white solid (77.8 g; 77%) that proved
to be analytically pure by NMR. Rf ) 0.16 (Ac/Tol ) 20:80).
Mp: 104.5 °C. IR (KBr): ν˜ ) 3440 cm-1 (br, O-H), 1380 (s,
1
SO2-O), 1175 (s, SO2-O). H NMR δ ) 1.32 (s, 3H), 1.41 (s,
109.3, 113.9, 115.2, 140.7, 172.0. [R]20 ) +58.1 (c ) 1.0,
3H), 3.26 (s, 3H), 3.49-3.57 (m, 2H), 4.00 (d, J ) 9.3 Hz, 1H),
4.03 (dt, J ) 6.2, 4.2 Hz, 1H), 4.06 (d, J ) 9.3 Hz, 1H), 4.36
(pseudo dt, J ) 5.5, 6.2 Hz, 1H), 4.62 (d, J ) 5.7 Hz, 1H), 4.84
(d, J ) 6.2 Hz, 1H), 5.69 (d, J ) 5.5 Hz, 1H). 13C NMR: δ )
D
CHCl3). HRMS (C23H35O7Si): calcd 451.2152, found 453.2154.
(1,2:4,5-Di-O-isop r op ylid en e-r-D-fr u ct op yr a n os-3-O-
yl) 2-Isop r op en yl-6-tr im eth ylsilyl-5-h exyn oa te (14d ). Ir-
radiation of 1.85 g (3.96 mmol) of R,â-unsaturated ester 7d
for 5 h according to typical procedure E produced â,γ-
unsaturated ester 14d as a single diastereomer (NMR) in 70%
yield (1.78 g). Rf ) 0.51 (TBME/P ) 20:80). IR (film): ν˜ ) 3075
cm-1 (w, dCH2), 2176 (s, CtC), 1732 (s, CdO), 1645 (CdC).
1H NMR: δ ) 0.12 (s, 9H), 1.33 (s, 3H), 1.39 (s, 3H), 1.46 (s,
3H), 1.51 (s, 3H), 1.75 (s, 3H), 1.78-1.85 (m, 1H), 1.99-2.11
(m, 1H), 2.22 (pseudo t, J ) 7.1 Hz, 2H), 3.28 (t, J ) 7.4 Hz,
2H), 3.79 (d, J ) 9.2 Hz, 1H), 3.94 (d, J ) 9.2 Hz, 1H), 4.07-
4.10 (m, 2H), 4.11-4.19 (m, 1H), 4.24 (dd, J ) 7.7, 5.3 Hz,
1H), 4.91 (s, 1H), 4.94 (s, 1H), 5.12 (d, J ) 7.7 Hz, 1H). 13C
NMR: δ ) 0.0, 17.6, 19.9, 26.2, 26.2, 26.3, 27.7, 28.5, 51.7,
60.5, 70.4, 71.8, 73.6, 74.7, 85.3, 103.6, 105.9, 109.5, 111.9,
26.4, 27.1, 39.1, 62.0, 71.4, 74.5, 78.7, 84.7, 107.8, 112.3. [R]20
D
) -90.5 (c ) 1.3, MeOH). Anal. Calcd for C10H18O8S (298.31):
C, 40.26; H, 6.08. Found: C, 39.95; H, 6.22.
3,4-An h yd r o-1,2-isop r op ylid e n e -r-L -t a ga t ofu r a n o-
sid e (18). The diol 17 (50 g, 0.247 mol) was dissolved in
methanol (100 mL), and aqueous NaOH (2 M, 100 mL) was
added slowly. The solution was warmed to 50 °C and kept at
this temperature for 4 h. TLC analysis showed complete
conversion. The product was isolated by extraction with CHCl3
(10 × 25 mL) after neutralization with aqueous H2SO4 (2 M)
and addition of 0.5 L of water. The combined organic layers
were washed with brine, dried (MgSO4), filtered, and concen-
trated in vacuo to give epoxide 18 as a colorless oil (28.2 g,
77%). Rf ) 0.33 (Ac/Tol ) 20:80). IR (film): ν˜ ) 3462 cm-1 (br,
114.7, 141.0, 172.7. [R]20 ) -110.0 (c ) 1.0, CHCl3). HRMS
D
1
OH), 3061 (w, epoxide CH), 1209 (s, CO). H NMR: δ ) 1.42
(C23H35O7Si): calcd 451.2152, found 453.2149.
(s, 3H), 1.45 (s, 3H), 2.30 (s, br, 1H), 3.61 (d, J ) 2.6 Hz, 1H),
3.78-3.81 (m, 3H), 3.99 (d, J ) 9.5 Hz, 1H), 4.12 (dt, J ) 5.2,
2.6 Hz, 1H), 4.26 (d, J ) 9.5 Hz, 1H). 13C NMR δ ) 25.7, 26.5,
(R)-2-(1′-Met h ylet h en yl)-6-(t r im et h ylsilyl)h exyn -1-ol
(en t-1). Typ ica l P r oced u r e F . A solution of the deconjugated
ester 14a (830 mg, 1.78 mmol) in ether (10 mL) was added to
a suspension of lithium aluminum hydride (102 mg, 2.7 mmol)
in THF (25 mL) at 0 °C dropwise via cannula. After the
mixture was stirred for 3 h, the reaction was quenched by
careful addition of water (102 µL), addition of a solution of
sodium hydroxide (15% w/w, 102 µL), and (after 5 min)
addition of more water (306 µL) MgSO4 was added. The
precipitate was filtered off and washed with ether. The
combined organic layers were concentrated and purified by
flash chromatography (EtOAc/Hex ) 20:80) to yield alcohol
ent-1 as a colorless oil (330 mg, 88%). Rf ) 0.26 (TBME/P )
20:80). IR (film): ν˜ ) 3373 cm-1 (s, OH), 3073 (w, dCH), 2174
55.2, 56.7, 61.6, 69.2, 76.9, 108.4, 111.3. [R]20 ) -33.4 (c )
D
1.1, MeOH). Anal. Calcd for C9H14O5 (202.20): C, 53.46; H,
6.98. Found: C, 53.87; H, 7.05.
1,2-O-Isop r op ylid en e-fr u ctofu r a n osid e (19). The ep-
oxide 18 (77 g, 0.38 mol) was dissolved in dioxane (500 mL),
and aqueous NaOH (9 M, 100 mL) was added. The reaction
mixture was heated at 90 °C for 24 h until TLC indicated
complete consumption of the epoxide. Upon cooling to room
temperature, the mixture was neutralized (aqueous H2SO4, 4.5
M), filtered, and concentrated in vacuo. The solid residue was
extracted with MeOH (300 mL). After evaporation of the
solvent, compound 19 was precipitated by addition of CHCl3
as a yellow semicrystalline solid (59 g, 70%). Rf ) 0.20 (Ac/
1
(s, CtC), 1646 (w, CdC). H NMR: δ ) 0.13 (s, 9H), 1.43 (t,
br, J ) 5.1 Hz, 1H), 1.51-1.62 (m, 2H), 1.68 (s, 3H), 2.14 (ddd,
J ) 17.0, 7.8, 7.8 Hz, 1H), 2.23 (ddd, J ) 17.0, 8.0, 6.0 Hz,
1H), 2.40 (ddt, J ) 8.8, 8.3, 5.6 Hz, 1H), 3.50 (dd, J ) 11.0,
3.6 Hz, 1H), 3.56 (dd, J ) 11.0, 5.7 Hz, 1H), 4.83 (dq, J ) 1.6,
0.9 Hz, 1H), 4.94-4.96 (m, 1H). 13C NMR: δ ) 0.0, 17.6, 18.9,
1
Tol ) 40:60). IR (film): ν˜ ) 3417 cm-1 (s, OH). H NMR: δ )
1.44 (s, 3H), 1.53 (s, 3H), 2.82 (s, br, 3H), 3.67 (dd, J ) 12.5,
5.2 Hz, 1H), 3.79 (dd, J ) 12.5, 3.1 Hz, 1H), 3.95 (dd, J ) 5.8,
4.3 Hz, 1H), 4.02 (ddd, J ) 5.8, 5.2, 3.1 Hz, 1H), 4.04 (d, J )
9.9 Hz, 1H), 4.18 (d, J ) 4.3 Hz, 1H), 4.31 (d, J ) 9.9 Hz, 1H).
13C NMR: δ ) 26.6, 26.7, 61.4, 69.5, 76.2, 81.3, 82.6, 109.7,
112.3. [R]D20 ) -30.6 (c ) 1.1, MeOH). HRMS (C8H13O6): calcd
205.0712, found 205.0711.
28.2, 48.7, 63.8, 84.8, 106.8, 114.1, 144.0. [R]20 ) -22.2 (c )
D
1.2, CHCl3), -27.9 (c ) 1.1, MeOH). HRMS (C11H19OSi): calcd
195.1205, found 195.1194.
1,2;4,5-Di-O-isopr opyliden e-3-m esylsor bofu r an ose (16).
L-Sorbose (150 g, 0.83 mol) was suspended in 2,2-dimethoxy-
propane (450 mL). The mixture was warmed to 70 °C, and a
solution of anhydrous SnCl2 (3.9 mmol, 750 mg) in 1,2-
dimethoxyethane (15 mL) was added dropwise via cannula.
The mixture was refluxed until a clear solution was obtained
(4-6 h). This mixture was concentrated in vacuo and dissolved
in pyridine (300 mL). The solution was cooled to 0 °C, and
methanesulfonyl chloride (100 mL, 99.7 g, 0.87 mol) was added
dropwise to the stirred solution. The black solution was stored
in a refrigerator for 14 h and at room temperature for 4 h.
Water (2 L) was added, and the resulting precipitate was
filtered and recrystallized from ethanol to yield compound 16
as colorless needles (131 g, 0.39 mol, 47%). Rf ) 0.40 (Tol/Ac
) 80:20). Mp: 123.5 °C. IR (KBr): ν˜ ) 1340 cm-1 (s, SO2-O),
1183 (s, SO2-O). 1H NMR: δ ) 1.37 (s, 3H), 1.41 (s, 3H), 1.46
(s, 3H), 1.54 (s, 3H), 3.15 (s, 3H), 3.91 (dd, J ) 13.0, 3.1 Hz,
1H), 4.00 (dd, J ) 13.0, 3.2 Hz, 1H), 4.20 (d, J ) 9.6 Hz, 1H),
4.22 (d, J ) 3.1 Hz, 1H), 4.24 (d, J ) 9.6 Hz, 1H), 4.45 (dd, J
) 3.2, 1.9 Hz, 1H), 4.87 (d, J ) 1.9 Hz, 1H). 13C NMR: δ )
L-F r u ctose (20). Compound 18 (59.0 g, 0.27 mol) was
dissolved in MeOH (200 mL) and pH ) 2 was adjusted by
dropwise addition of aqueous H2SO4 (2 M). The solution was
warmed to 40 °C for 2 h, cooled, and neutralized (2 M NaOH).
The mixture was subsequently filtered and concentrated in
vacuo. L-Fructose was obtained as a light brown oil. (33.0 g,
68%). The analytical data were in agreement with the refer-
ence data.13a L-Fructose was converted into compound ent-9d
by a known procedure.13b
Ack n ow led gm en t. This research project was sup-
ported by the Deutsche Forschungsgemeinschaft (SFB
260 and Graduiertenkolleg “Metallorganische Chemie”)
and by the Fonds der Chemischen Industrie.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra of
compounds 1, 7a ,d , 12a , 13a , 14a ,c,d , and 19. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O001740T