Strategy for the preparation of allenes from α,β-unsaturated and saturated ketones via enol phosphates

Full text of DOI:10.1021/jo9610265

6
096
J . Org. Chem. 1996, 61, 6096-6097
Str a tegy for th e P r ep a r a tion of Allen es
fr om r,â-Un sa tu r a ted a n d Sa tu r a ted
Keton es via En ol P h osp h a tes
Sch em e 1
Kay M. Brummond,* Elizabeth A. Dingess, and
†
J oseph L. Kent
rings undergo a 1,3-phosphorus migration to afford â-keto
Department of Chemistry, West Virginia University,
Morgantown, West Virginia 26506
phosphonates upon deprotonation with lithium diisopro-
pylamide.8
In order to determine the feasibility of this method the
enol phosphate of 3-octanone (Table 1, entry A) was
readily prepared by an established procedure. The
Received J une 3, 1996
6
The versatility and synthetic utility of the allene
moiety in organic synthesis have been extensively docu-
mented in the recent literature. For instance, allenes
participate in a variety of cycloaddition and electrocyclic
reactions affording products that are not easily accessible
ketone was added to a solution of lithium diisopropyl-
amide (LDA) and THF at -78 °C and allowed to stir at
this temperature for 1 h. Then diethylchlorophosphonate
was added, and the solution was warmed to room
temperature. Warming the enol phosphate reaction
mixture to room temperature afforded a mixture of all
1
,2
by other synthetic methods.
In addition, the allene
moiety can be transformed into a variety of other
functional groups such as olefins, R,â-unsaturated car-
bonyls, and alkynes.3 Moreover, allene axial chirality has
been used to transfer asymmetry in cycloaddition reac-
tions.4 During the course of our synthetic studies di-
1
possible regio- and stereoisomers by H NMR (eq 1). The
enol phosphates were not isolated but taken on directly.
Subjection of this mixture of isomers to elimination
conditions (LDA, 2.2 equiv) at -78 °C gave a single
allene, 2,3-octadiene, in 43% yield. If the reaction
mixture was allowed to warm slowly to 0 °C during the
elimination step, 2,3-octadiene (86%) was the major
product but contamination with 2- and 3-octyne (11% and
2
rected toward the allenic Pauson-Khand reaction, we
required new, efficient protocols for the preparation of
allenes. We subsequently initiated a program which
focused on the conversion of ketones to allenes and in
this paper report on this investigation.5
9
3%, respectively, as determined by HPLC) was observed.
It is known that conversion of methyl ketones to the
However, maintaining the reaction temperature at -78
“
kinetic” enol phosphates, followed by â-elimination,
°C during the elimination step results in a higher allene
6
10
affords terminal acetylenes. We reasoned that conver-
to alkyne ratio (94.4% and 5.6%, respectively). On the
sion of a ketone to the more substituted enol phosphate
basis of this result, the E/ Z configuration and the
regiochemistry of the enol phosphate appear to have no
effect on the allene to alkyne ratio. Fortunately, the
allene can be easily separated from the isomeric alkynes
by flash chromatography. The conversion of 3-octanone
to 2,3-octadiene is a very clean reaction based upon the
HPLC trace of the crude product, so the somewhat low
yield is attributed to the volatility of 2,3-octadiene.
(Scheme 1) followed by base-induced elimination would
form an allene instead of the internal alkyne if deproto-
nation of the least substituted carbon is kinetically
preferred. Transformations of this type have been per-
formed on vinyl halides where allylic deprotonation
followed by elimination of HX affords an allene, but this
reaction is reported to suffer from competing side reac-
tions.7 Similarly, allenes have been prepared by the
elimination of enol triflates. However, this method has
5
f
structural limitations. Wiemer has demonstrated that
enol phosphates derived from five- and six-membered
*
Author to whom correspondence should be addressed: Tel: (304)
93-3435 ext 4445. FAX: (304) 293-4904. e-mail: kmb@wvnvm.wvnet.
edu†.
Current address: Davis & Elkins College, Department of Chem-
istry, 100 Campus Drive, Elkins, WV 26241.
1) Schlessinger, R. H.; Bergstrom, C. P. J . Org. Chem. 1995, 60,
6. Sigman, M. S.; Eaton, B. E. J . Org. Chem. 1994, 59, 7488. J ung,
M. E.; Zimmerman, C. N.; Lowen, G. T.; Khan, S. I. Tetrahedron Lett.
993, 34, 4453. Andemichael, Y. W.; Gu, Y. G.; Wang, K. K. J . Org.
Chem. 1992, 57, 794.
2) Kent, J . L.; Wan, H.; Brummond, K. M. Tetrahedron Lett. 1995,
6, 2407.
3) Reviews on synthesis and reactions of allenes: Schuster, H. F.;
2
(
1
1
(
3
We next examined this protocol on higher molecular
weight ketones, undecanone (entry B) and 1-phenyl-4-
octanone (entry C). Formation of the enol phosphates of
these ketones followed by LDA-induced elimination gave
a 62% yield of 5,6-undecadiene and a 73% yield of
(
Coppola, G. M. Allenes in Organic Synthesis; Wiley: New York, 1984.
Pasto, D. J . Tetrahedron 1984, 40, 2805.
(4) Gibbs, R. A.; Bartels, K.; Lee, R. W. K.; Okamura, W. H. J . Am.
Chem. Soc. 1989, 111, 3717. Okamura, W. H.; Peter, R.; Reischl, W.
J . Am. Chem. Soc. 1985, 107, 1034.
1
-phenyl-3,4-octadiene. In both examples, the HPLC
(5) For other methods of preparing allenes from ketones see: (a)
trace of the crude product showed allene accounting for
greater than 96% of the material with the remainder
being the alkyne. Alternative bases were studied for the
Satoh, T.; Itoh, N.; Watanabe, S.; Koike, H.; Matsuno, H.; Matsudo,
K.; Yamakawa, K. Tetrahedron 1995, 51, 9327. (b) Danheiser, R. L.;
Choi, Y. M.; Menichincheri, M.; Stoner, E. J .; J . Org. Chem. 1993, 58,
3
22. (c) Chan, T. H.; Mychajlowskij, W.; Ong, B. S.; Harpp, D. N. J .
Org. Chem. 1978, 43, 1526. (d) Kabalka, G. W.; Newton, R. J .;
Chandler, J . H. J . Chem. Soc., Chem. Commun. 1978, 726. (e) Posner,
G. H; Tang, P-W; Mallamo, J . P. Tetrahedron Lett. 1978, 19, 3995. (f)
Stang, P. J .; Hargrove, R. J . J . Org. Chem. 1975, 40, 657. For an
example of the elimination of an enol phosphate flanked by activating
groups, see: (g) Craig, J . C.; Moyle, M. J . Chem. Soc. 1963, 3712, 5356.
(8) Calogeropoulou, T.; Hammond, G. B.; Wiemer, D. F. J . Org.
Chem. 1987, 52, 4185.
(9) HPLC peak identity was determined by coinjection of 2- and
3-octyne with the crude product mixture. The response factor of the
RI detector to 2,3-octadiene and 2-octyne was determined to be 1.11.
(10) A control experiment was carried out where an allene was
subjected to the conditions employed for the elimination step and
isomerization of the allene to acetylene occurred at room temperature.
(
6) Negishi, E.-I.; King, A. O.; Klima, W. L. J . Org. Chem. 1980, 45,
526. Negishi, E.-I.; King, A. O.; Tour, J . M. Org. Synth. 1985, 64, 44.
7) Naso, F.; Ronzini, L. J . Chem. Soc., Perkin Trans. 1 1974, 340.
2
(
S0022-3263(96)01026-2 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 18, 1996 6097
elimination of the enol phosphate of 1-phenyl-4-octanone.
The use of n-butyllithium resulted in an identical allene
to alkyne ratio as observed with LDA, but gave a lower
yield (33%). No reaction was observed when lithium
hexamethyldisilyl azide was used as a base. Attempts
to convert 1-phenyl-2-butanone (entry D) to the allene
gave mixed results. Warming the elimination reaction
of the enol phosphate to room temperature resulted in
the conjugated alkyne as the major product (67% yield).
Whereas maintaining the reaction temperature at -78
Ta ble 1. P r ep a r a tion of Allen es fr om Keton es
°C during the elimination resulted in a mixture of allene
to alkyne (3:2 as determined by HPLC), and the allene
was isolated in 24% yield.
This method is also amenable to the preparation of
macrocyclic allenes. This is demonstrated by the conver-
sion of cyclododecanone and cyclopentadecanone to their
corresponding allenes (entries E and F) in good yields.
The allene to alkyne ratio for cyclododecanone and
cyclopentadecanone are 92:8 and 84:16, respectively, as
determined by HPLC. It is interesting to note that when
the enol triflate of cyclododecanone was treated with LDA
using the conditions described above, the product ratio
changed to afford a 7:93 mixture of allene to alkyne. The
cyclododecyne was isolated in a 95% yield (eq 2).
We have also demonstrated this method to be useful
in the preparation of allenic ketones (entry G). The
mildness of this procedure is confirmed by treatment of
the enol phosphate of 3-n-amyl-2,4-pentanedione with
LDA (3 equiv) to give the desired disubstituted allene in
3
8% yield. This new way to prepare this labile function-
ality will prove to be synthetically useful.
R,â-Unsaturated ketones can be readily converted to
allenes. The enol phosphate derived from the cuprate
addition of lithium dimethylcuprate11 to â-ionone (entry
G) gave excellent yields (81%) of the allene.
In conclusion, we have developed a new method for the
conversion of ketones to allenes by way of their enol
phosphates.12 Investigations into the use of chiral lithium
amide bases to form chiral allenes and the application
(
11) Paquette, L. A.; Pierre, F.; Cottrell, C. E. J . Am. Chem. Soc.
987, 109, 5731.
12) Sample experimental details (Table 1, entry C): 1-phenyl-4-
1
(
octanone (1.0 g, 4.9 mmol) dissolved in THF (5 mL) was added dropwise
over 10 min to a cooled (-78 °C) solution of LDA (5.9 mmol). This
solution was allowed to stir at -78 °C for an additional 1 h, and then
diethyl chlorophosphate (0.78 mL, 5.4 mmol) was added. The resulting
yellow solution was warmed slowly to 0 °C (45 min) and then cooled
to -78 °C, and freshly prepared LDA (10.3 mmol) was added. The
resulting solution was stirred for 36 h while maintaining the temper-
ature at -78 °C, during which time a precipitate formed. The mixture
was then poured onto pentane (50 mL) and ice-water (15 mL). The
aqueous layer was extracted three times with pentane, and the
combined extracts were washed with cold 1 N HCl, water, saturated
of this methodology toward natural product synthesis are
underway in our laboratories.
Ack n ow led gm en t is made to the donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, for partial support of this re-
search, the American Cancer SocietysInstitutional
Research Grant No. IN-181, and West Virginia Univer-
sity Senate Grant for Research and Scholarship. We
thank Professors R. L. Funk and K. K. Wang for helpful
discussions.
NaHCO
3 4
, water, and brine and dried over anhydrous MgSO . The
solvent was removed in vacuo to afford a yellow oil. (If this elimination
reaction is stirred at -78 °C for only 16 h, 1-phenyl-3,4-octadiene is
afforded in 63% yield and the HPLC trace of the crude product shows
a 97:3 ratio of allene to alkyne.) Purification by flash chromatography
on silica gel (eluting with pentane) furnished a 73% yield 1-phenyl-
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
1
13
cedures and copies of H NMR, C NMR, and IR spectra of
1
3
,4-octadiene and 7% combined yield of 1-phenyl-3-octyne and 1-phen-
allenes (entries A-H); H NMR spectra of enol phosphates
(entries A-H) (39 pages).
yl-4-octyne as colorless oils. The HPLC trace of the crude product shows
a 90:10 ratio of allene to alkyne. The selectivity was determined by
the HPLC method using a silica column with hexanes as the eluent.
J O9610265