C O M M U N I C A T I O N S
with KMnO4 in aqueous acetone to provide, after extractive workup,
cyclobutyl mesylate in 81% overall yield. Heating cyclobutyl
mesylate with KOt-Bu in DMSO at 65 °C10 provided a distillate
of pure cyclobutene (60%).
The synthesis of the (R)-R,â-enone 6 started with readily
available (R)-4-tert-butyldimethylsilyloxy-2-cyclopentenone11 (Scheme
2) in three steps: (1) conjugate addition under steric control of the
2:1 dimethylphenylsilyllithium:CuCN reagent, (2) desilylation, and
(3) dehydration.
These studies are being continued to gain further information
on the absolute configuration and biosynthesis of 1. 1H NMR studies
on the thermal stability of the methyl ester of 1 in deuterated
chlorobenzene have revealed a half-life of only ca. 1 h at 140 °C.
From this result, it is clear despite the uniqueness of the anammoxic
lipid it may not have left a signature in geological sediments.
With regard to the question of the biosynthesis of 1, the
perspectives of synthetic chemistry may prove helpful. Although
the original synthesis of (()-13 and the new synthesis outlined
herein have relied heavily on photochemical reactions, it is doubtful
that photochemical processes are involved in the biosynthesis of 1
since the environment of C. B. anammoxidans is dark and anaerobic.
If the biosynthesis were to occur by a cascade-type polycyclization,
it would have to be novel in terms of the chemistry used because
of the unfavorable energetics and the paucity of the known chemical
reactions of this type. One possible candidate as substrate for such
a cascade polycyclization pathway would be the allenic C20 fatty
acid 9,10,12,16,18,19-docosahexaenoic acid.12 In any case, unravel-
ing the biosynthetic mechanism is fully as challenging as the
chemical synthesis.
Figure 1. ORTEP representation of the X-ray structure of 8.
Scheme 2
analysis (see Figure 1). The application of the octant rule to ketone
9, [R]23D +407 (c ) 0.35, CHCl3), allows unambiguous assignment
of the absolute configuration shown, which is that expected from
the known absolute configuration of R,â-enone 6 that led to the
exo-silyl photoadduct 7.
Finally, it should be noted that the highly selective photoreac-
tion 5 + 6 f 7 represents a useful and general solution to the
long-standing problem of creating an enantioselective version of
[2 + 2]-photocycloaddition. The use of the bulky silyl group in 6
was essential to success; TBSO was ineffective.
Racemic 9 was readily prepared by photoaddition of 2-cyclopen-
tenone to the achiral tricyclic olefin 5. The (+)- and (-)-enanti-
omers of 9 were obtained from this racemic mixture by HPLC sep-
aration on a CHIRALPAK AD column (Chiral Technologies, Inc.).8
The (+)-ketone 9 was converted to the exo aldehyde 10 by the
following sequence: (1) R-diazoketone formation by the Regitz
method (as above for 2 f 3), (2) photoinduced Wolff ring
contraction in methanol to form the pentacyclic ladderane methyl
esters (exo + endo), (3) i-Bu2AlH reduction-Swern oxidation
sequence3 to a mixture of the corresponding exo-endo aldehyde
mixture, and (4) equilibration of the mixture to the exo aldehyde
10 (as a 28:1 exo-endo mixture) using a 0.06 M solution in Et3N
at 23 °C for 6 days (80% yield for isomerization; 43% overall).
The chiral exo aldehyde 10 was then transformed into the chiral
acid 1 by a combination Wittig reaction-diimide reduction process
as previously described for (()-pentacycloanammoxic acid.3 Es-
terification of 3 afforded the chiral methyl ester 11. Both chiral 1
and 11 made from the (+)-ketone 9 were dextrorotatory. We are
currently awaiting a reference sample of naturally produced
pentacycloanammoxic acid to establish its absolute configuration.
The synthesis outlined in Scheme 1 was greatly facilitated by
the development of a convenient and practical process for preparing
cyclobutene on a molar scale in laboratory glassware. The starting
material was cyclopropyl carbinol, a compound that has been
prepared industrially by the sequence 1,3-butadiene monoepoxide
f 2,3-dihydrofuran f cyclopropanecarboxaldehyde (∆, Al2O3) f
cyclopropyl carbinol (NaBH4).9 Cyclopropyl carbinol was converted
to the corresponding mesylate (CH3SO2Cl, Et3N, CH2Cl2, -20 to
0 °C, 97-99% yield). Treatment of the mesylate with 0.06 equiv
of BF3‚Et2O in CH2Cl2 at 22 °C for 12 h gave in quantitative yield
a mixture of cyclobutyl mesylate and but-3-enyl mesylate (ratio
ca. 11:1). The latter was removed from the mixture by oxidation
Supporting Information Available: Experimental procedures and
characterization data for the process shown in Schemes 1 and 2 (PDF).
X-ray crystallographic date for 8 (CIF). This material is available free
References
(1) Damste´, J. S. S.; Strous, M.; Rijpstra, W. I. C.; Hopmans, E. C.;
Geenevasen, J. A. J.; van Duin, A. C. T.; van Niftrik, L. A.; Jetten, M. S.
M. Nature 2002, 419, 708-712.
(2) DeLong, E. F. Nature 2002, 419, 676-677.
(3) Mascitti, V.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 15664-15665.
(4) (a) Santos, J. C.; Fuentealba, P. Chem. Phys. Lett. 2003, 377, 449-454.
(b) Castan˜o, O.; Notario, R.; Abboud, J.-L. M.; Gomperts, R.; Palmeiro,
R.; Frutos, L.-M. J. Org. Chem. 1999, 64, 9015-9018. (c) Curtiss, L. A.;
Raghavachari, K.; Redfern, P. C.; Pople, J. A. J. Chem. Phys. 1997, 106,
1063-1079.
(5) Personal communication from Dr. Jaap Damste´.
(6) For a small-scale preparation of the 1,5-diene corresponding to 5, see:
Avram, M.; Dinulescu, I. G.; Marica, E.; Mateescu, G.; Sliam, E.;
Nenitzescu, C. D. Chem. Ber. 1964, 97, 382-389. A search of the literature
revealed no reliable alternative route for the synthesis of 5.
(7) For method, see: Yamashito, M.; Kato, Y.; Suemitsu, R. Chem. Lett. 1980,
847-848.
(8) The separation was conducted with a preparative CHIRALPAK AD
column using 99.5:0.5 hexanes:i-PrOH at 23 °C with a flow rate of 5
mL/min and UV detection at 306 nm. The retention time for (+)-9 was
46 min, 52 s and that for the enantiomer was 66 min, 17 s.
(9) Liang, S.; Price, T. W. U.S. Patent 5,633,410, May 27, 1997 to Eastman
Chemical Co.
(10) See: Salau¨n, J.; Fadel, A. Organic Syntheses; Wiley & Sons: New York,
1990; Collect. Vol. VII, pp 117-120.
(11) (a) Basra, S. K.; Drew, M. G. B.; Mann, J.; Kane, P. D. J. Chem. Soc.,
Perkin Trans. 1 2000, 3592-3598. (b) Harre, M.; Raddatz, P.; Walenta,
R.; Winterfeldt, E. Angew. Chem., Int. Ed. 1982, 21, 480-492. (c)
Paquette, L. A.; Earle, M. J.; Smith, G. F. Organic Syntheses; Wiley &
Sons: New York, 1998; Collect. Vol. IX, pp 132-138.
(12) A reductive polycyclization of this allenic substrate to 1 (with addition
of 2 H) would be thermodynamically favorable.
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