Domino reaction of 2,3-epoxy-1-alcohols and PIFA in the presence of H 2O and the concise synthesis of (+)-tanikolide

Article abstract of DOI:10.1002/anie.200501686

(Chemical Equation Presented) Lactols are prepared by a single operation, in which 2,3-epoxy-1-alcohols are treated with phenyliodine(III) bis(trifluoroacetate) (PIFA) in the presence of H₂O. Thus, an efficient domino three- or four-step sequen

Full text of DOI:10.1002/anie.200501686

Angewandte
Chemie
Hypervalent Iodine Reagents
DOI: 10.1002/anie.200501686
Domino Reaction of 2,3-Epoxy-1-alcohols and
PIFA in the Presence of H2O and the Concise
Synthesis of (+)-Tanikolide**
Yasuyuki Kita,* Satoshi Matsuda, Eri Fujii, Mai Horai,
Kayoko Hata, and Hiromichi Fujioka
The domino reaction can perform several reactions in a single
operation and is a very powerful tool to synthesize organic
compounds. The development of new and efficient domino
[*] Prof. Dr. Y. Kita, S. Matsuda, E. Fujii, M. Horai, K. Hata,
Prof. Dr. H. Fujioka
Graduate School of Pharmaceutical Sciences
Osaka University, 1-6 Yamadaoka,
Suita, Osaka 565-0871 (Japan)
Fax: (+81)6-6879-8229
E-mail: kita@phs.osaka-u.ac.jp
[**] This work was supportedby Grants-in Aidfor Scientific Research (S)
from the Ministry of Education, Culture, Sports, Science, and
Technology (Japan). PIFA=phenyliodine(iii) bis(trifluoroacetate).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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reactions is, therefore, a very attractive subject in the field of
synthetic organic chemistry.[1] We present herein an efficient
domino reaction in which a three- or four-step sequence
occurs in a single operation. Thus, the reaction of 2,3-epoxy-1-
alcohols[2] with hypervalent iodine(iii) reagents[3] in the
presence of H2O allowed the efficient domino three- or
four-step sequence to produce lactols 3 in a single operation
(Scheme 1). The reaction was applied to the concise synthesis
of (+)-tanikolide.
Scheme 2. PIFA treatment of 1a in the presence of an oxygen-contain-
ing nucleophile.
Scheme 1. Domino reaction of 2,3-epoxy-1-alcohols with PIFA in the
presence of H2O.
The reaction of bicyclic 2,3-epoxy alco-
hol 1a with phenyliodine(iii) bis(trifluoro-
acetate) (PIFA) was examined in the pres-
ence of an oxygen-containing nucleophile,
an alcohol, or H2O (when an alcohol was
used, it was also employed as the solvent;
Scheme 3. Plausible reaction mechanism for the formation of 2 and 3.
Scheme 2). A mixture of 1a (1.0 mmol) in
ROH or H2O/CH3CN (1:4; 10 mL) was treated with PIFA
(1.0 mmol) at 08C–RT, with the reaction proceeding smoothly
for both nucleophiles. Methoxy keto aldehyde 2a was
obtained in moderate yield from the use of MeOH as the
nucleophile, and a similar product 2b was obtained from
EtOH. On the other hand, the lactol 3a (a mixture of
diastereoisomers differing at the acetal position) was
obtained from using H2O. Compound 3a was converted into
the keto lactone 4 by the Jones oxidation.
observed in the keto lactols 3a,b, possibly because access to
the ketone moieties is more hindered than to the aldehyde
moieties.
The bicyclic keto lactols were converted into the corre-
sponding lactones in two steps. Thus, the reduction of 3e,h
with diisobutylaluminum hydride (DIBAH) or the reduction
of 3i of with NaBH4 gave dihydroxy lactols 4e,h,i, which were
oxidized using Ag2CO3/celite[6] to afford the desired lactones
5e,h,i in fairly good yields (Scheme 5).
The formation of 2a,b and 3a from 1a is rationalized as
follows: first, nucleophilic attack of ROH (R = Me, Et, H) on
the oxirane ring gave the alkoxy or
ꢀ
hydroxy intermediate A, whose C
Table 1: Reaction of various 2,3-epoxy alcohols with PIFA in the presence of H2O.
C bond between the two hydroxy
groups was cleaved to give keto
aldehyde 2a,b in good yield.[4]
When H2O was used as the nucle-
ophile, a further lactol formation
occurred to afford 3a (Scheme 3).
The generality of the lactol for-
Entry
1
Substrate
Product
Yield [%]
49
1a
3a
mation was examined next by using
various types of epoxy alcohols
(Table 1). The bicyclic epoxy alco-
hols 1a,b gave bicyclic keto lactols
3a,b in fairly good yields (entries 1
and 2). The bicyclic dioxaspiro lac-
tols 3c–i were obtained in good
yields from the monocyclic trisub-
stituted epoxy alcohols 1c–i.[5] The
formation of 3c–i is rationalized as
a further lactol formation between
the hemiacetal hydroxy function
and the aldehyde (Scheme 4). No
further lactol formation was
1b
3b
66
62
2
3
1c (R1 =Me)
3c (R1 =Me)
4
5
6
7
8
1d (R1 =Et)
3d (R1 =Et)
74
72
67
72
53
1e (R1 =n-C11H23)
1 f (R1 =CH2CHMe2)
1g (R1 =CH2Ph)
1h (R1 =Ph)
3e (R1 =n-C11H23)
3 f (R1 =CH2CHMe2)
3g (R1 =CH2Ph)
3h (R1 =Ph)
1i
3i
65
9
5858
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Chemie
Scheme 4. Plausible reaction mechanism for the formation of bicyclic
lactols 3c–i.
Scheme 6. Concise asymmetric synthesis of (R)-(+)-tanikolide. a) I2,
trimethylsilyl azide, pyridine, 08C!RT (80%); b) (S)-5,5-diphenyl-2-
methyl-3,4-propan-1,3,2-oxazaborolidine, BH3Me2S, THF, 08C (93%);
c) Et3B, nBu3SnH, toluene, 08C–RT (84%); d) tBuOOH, [VO(acac)2]
(acac=acetylacetonate), benzene, 08C!RT (96%); e) DIBAH, CH2Cl2,
ꢀ15!08C; f) AgCO3/celite, benzene, reflux (57% over 2 steps).
Scheme 5. Conversion of bicyclic lactols into lactones.
With the general transformation of epoxy alcohols to
lactols and lactones now available, the application of this
method to the concise asymmetric synthesis of (+)-tanikolide
was examined next. (+)-Tanikolide is a g-lactone metabolite
of the marine cyanobacterium Lyngbya majuscula, which was
collected on Tanikeli Island, Madagascar, in 1999 and shows
antifungal activity.[7] The enone 6[8] was converted into the a-
iodo enone 7 in 80% yield by using the procedure developed
by Sha and Huang.[9] The asymmetric reduction of 7 with the
Corey reagent[10] afforded R-allyl alcohol 8 in 93% yield with
98% ee (optical purity was 98% ee, as determined by HPLC
analysis of 9 (chiralcel OD and elution with hexane/iPrOH
(99:1)). The radical reduction[11] of 8 afforded 9 in 84% yield.
The stereoselective epoxidation[12] of 9 gave the cis-epoxy
alcohol 10. The treatment of 10 with PIFA gave the lactol 11
in 72% yield. Reduction of 11 with DIBAH gave the hydroxy
lactol 12. Chemoselective oxidation of the lactol hydroxy
function with Ag2CO3/celite[6] afforded (+)-tanikolide in 57%
yield over two steps (Scheme 6). 1H NMR spectroscopic
analysis (500 MHz) of the corresponding (R)-(+)-a-methoxy-
a-(trifluoromethyl)phenylacetic acid ester of (+)-taniko-
lide[13] determined the ee value as 98%. Although several
synthetic studies of (+)-tanikolide have already been
reported,[14] our synthesis provides an alternative approach
with few steps and high optical purity.
stirred for 12 h. A saturated aqueous Na2S2O3 solution was added to a
reaction mixture, and the resulting mixture was extracted with
EtOAc. The organic layer was dried over Na2SO4 and evaporated
in vacuo. The residue was purified by column chromatography on
SiO2 using hexane/EtOAc (5:1) as the eluant to give 11 as a single
isomer (134.0 mg, 0.47 mmol, 72% yield).
11: colorless crystals; m.p. 458C; IR (KBr): n˜ = 3360 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d = 0.88 (3H, t, J = 6.6 Hz), 1.26 (20H,
m), 1.51–1.72 (6H, m), 3.27 (1H, brs), 5.17 (1H, s), 5.67 ppm (1H, s);
13C NMR (75 MHz, CDCl3): d = 14.0, 15.8, 22.6, 23.8, 29.1, 29.2, 29.3,
29.5 (2C), 29.6 (2C), 30.2, 31.8, 34.0, 83.9, 97.1, 102.2 ppm; [a]D26
=
+ 54.2 (c = 0.54, CHCl3); elemental analysis (%) for C17H23O3: C
71.79, H 11.34; found: C 71.58, H 11.09.
Received: May 17, 2005
Published online: August 11, 2005
Keywords: domino reactions · epoxy alcohols · hypervalent
.
iodine · natural products · oxygen heterocycles
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In conclusion, we have developed a novel transformation
of 2,3-epoxy-1-alcohols into lactols in a single operation. The
lactone functionality is present in a large variety of biolog-
ically active compounds and natural products. As domino
reactions can reduce the number of operations in the syn-
thesis of organic compounds, this method opens up a new
approach to obtaining optically active lactone compounds and
will be very useful in the field of synthetic organic chemistry.
Experimental Section
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iodine(iii) reagents, see: a) Y. Kita, H. Tohma, T. Yakura,
Trends Org. Chem. 1992, 113 – 128; b) Y. Kita, T. Takada, H.
General procedure for lactol formation (conversion of 10 into 11):
PIFA (281.3 mg, 0.65 mmol) was added to a stirred solution of 10
(175.6 mg, 0.65 mmol) in H2O/CH3CN (1:4 (v/v), 6.5 mL) at 08C. The
reaction mixture was allowed to warm to room temperature and then
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Communications
Tohma, Pure Appl. Chem. 1996, 68, 627 – 630; c) H. Tohma, Y.
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reagents, see: R. Criegee, H. Beucker, Ann. Chem. 1939, 541,
218 – 238.
[5] Tetrasubstituted cis-epoxy alcohol 1d afforded diketo alcohol 3d
ꢀ
in 37% yield by cleavage of the C2 C3 bond, perhaps as the
formation of the five-membered intermediate A is unfavorable
because of repulsion.
[6] M. Fetizon, M. Golfier, P. Mourgues, Tetrahedron Lett. 1972,
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[9] C.-K. Sha, S.-J. Huang, Tetrahedron Lett. 1995, 36, 6927 – 6928.
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literature and our previous study (see ref. [2]); this deduction
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the natural sample.
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[13] Use of DIBAH in place of NaBH4 increased the yield of (+)-
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