New and stereospecific synthesis of allenes in a single step from propargylic alcohols

Full text of DOI:10.1021/ja960443w

4492
J. Am. Chem. Soc. 1996, 118, 4492-4493
in 62% yield after purification by chromatography on silica gel.
As anticipated, 2a fragmented under exceedingly mild condi-
tions; stirring a solution of 2a in methanol at 23 °C for 16 h
brought about the spontaneous elimination of p-toluenesulfinic
acid and dinitrogen to form the allene 3 in 79% yield. Allene
formation could also be conducted without isolation of the
intermediate 2a, by replacing the solvent benzene with methanol
after the inversion step (67% yield of 3 from 1). The elimination
reaction proceeded at a comparable rate when trifluoroethanol
was employed as solvent but was considerably slower in ethanol.
The use of a base, such as triethylamine or 1,8-diazabicyclo-
[5.4.0]undec-7-ene, had no apparent affect on the rate of the
elimination reaction, and the presence of acetic acid in the
reaction proved deleterious, with multiple products being formed
(cf. ref 7).
New and Stereospecific Synthesis of Allenes in a
Single Step from Propargylic Alcohols
Andrew G. Myers* and Bin Zheng
DiVision of Chemistry and Chemical Engineering
California Institute of Technology
Pasadena, California 91125
ReceiVed February 12, 1996
There are few reliable methods for the stereodefined con-
struction of allenes, despite their growing importance in organic
synthesis.1 As part of an earlier study, we developed a three-
step procedure for the synthesis of allenes from readily available
propargylic alcohols involving (1) mesylate formation, (2)
displacement with excess hydrazine, and (3) oxidation with an
azodicarboxylate reagent to produce a propargylic diazene
intermediate that evolves dinitrogen in a sigmatropic elimination
process (e.g., 1 f 3 below).2 Although this method did provide
a stereospecific preparation of allenes, it was lengthy, unsuc-
cessful in the preparation of the important (trimethylsilyl)-
substituted allenes,3 and proceeded in 48-81% yield. We
describe herein a new and stereospecific method for the synthesis
of allenes from propargylic alcohols that proceeds in a single
operation, is efficient, and provides access to a wide range of
stereodefined, substituted allenes, to include (trimethylsilyl)-
allenes.
The new methodology evolved from the speculation that the
sulfonamide group of arenesulfonylhydrazines would function
as the nucleophilic component in a Mitsunobu inversion reaction
(e.g., 1 f 2).4,5 In addition, results from a study of the
fragmentation of 1-(trialkylsilyl)-1-tosylhydrazines6 suggested
that a 1-alkyl-1-arenesulfonylhydrazine (e.g., 2) might fragment
under much milder conditions than suggested by prior work.7
Initial experiments were conducted with tosylhydrazine. Ad-
dition of a solution of diethyl azodicarboxylate (DEAD, 3.0
equiv) in benzene to a solution of alcohol 1 (1 equiv),
triphenylphosphine (3.0 equiv), and tosylhydrazine (2.0 equiv)
in benzene at 5-8 °C led to the formation of the crystalline
1-alkyl-1-tosylhydrazine derivative 2a (mp 115-116 °C, dec)
On the basis of these observations, we hypothesized that the
elimination reaction proceeded by a unimolecular, polar transi-
tion state. We felt that the overall process could benefit
substantially by the modification of the arenesulfonyl group so
as to accelerate the elimination reaction, potentially reducing
the entire sequence to a single operation. Hu¨nig et al. have
documented that electron-withdrawing arene substituents ac-
celerate the thermal decomposition of arenesulfonylhydrazines.8
In addition, it was anticipated that the greater acidity of electron-
withdrawing arenesulfonylhydrazine derivatives would improve
the efficiency of the Mitsunobu reaction. After a survey of
several candidates, o-nitrobenzenesulfonylhydrazine (NBSH)
was determined to be the reagent of choice for the one-step
conversion of propargylic alcohols to allenes. NBSH, a known
compound,9 is efficiently prepared from o-nitrobenzenesulfonyl
chloride and anhydrous hydrazine in tetrahydrofuran (THF) at
-15 °C. NBSH is isolated as a pale yellow, crystalline solid
(81-85% yield, mp 97-99 °C, dec, lit mp 101 °C,9 dec) that
can be stored at ambient temperature for several days but should
be refrigerated for long-term storage. When we implemented
an order of addition sequence typically employed in the
Mitsunobu inversion reaction (with carboxylic acids as nucleo-
philes)4 for the reaction of 1 with NBSH (Ph3P, 3 equiv; 1, 1
equiv; NBSH, 3 equiv; then DEAD, 3 equiv), the major product
was not the anticipated allene 3 (yield 12%), but a 1:1.4 mixture
of the diastereomeric propargylic sulfinate esters (52%). Further
experimentation revealed that NBSH was much more reactive
toward the reagent combination Ph3P‚DEAD than was tosyl-
hydrazine and apparently underwent rapid degradation to
o-nitrobenzenesulfinic acid, which then served as a nucleophile
in a Mitsunobu reaction with 1. By modifying the order of
addition, premixing Ph3P (1.5 equiv) and DEAD (1.5 equiv) in
THF at -15 °C and then adding 1 (1 equiv) and finally NBSH
(1.5 equiv), the allene 3 was obtained reproducibly in 72-77%
yield, in a single operation.
(1) Reviews: (a) Rossi, R.; Diversi, P. Synthesis 1973, 25. (b) The
Chemistry of Ketenes, Allenes, and Related Compounds; Patai, S., Ed.;
Wiley: New York, 1980. (c) The Chemistry of the Allenes; Landor, S. R.,
Ed.; Academic Press: London, 1982. (d) Coppola, G. M.; Schuster, H. F.
Allenes in Organic Synthesis; Wiley: New York, 1984. (e) Pasto, D. J.
Tetrahedron 1984, 40, 2805. For leading references into the preparation
and synthetic utility of the important (trialkylsilyl)allenes, see: (f) Danheiser,
R. L.; Tsai, Y.-M.; Fink, D. M. Org. Synth. 1988, 66, 1. (g) Danheiser, R.
L.; Stoner, E. J.; Koyama, H.; Yamashita, D. S.; Klade, C. A. J. Am. Chem.
Soc. 1989, 111, 4407.
(2) Myers, A. G.; Finney, N. S.; Kuo, E. Y. Tetrahedron Lett. 1989, 30,
5747.
(3) Unpublished results; desilylation is observed.
(4) (a) Mitsunobu, O. Synthesis 1981, 1. (b) Hughes, D. L. Org. React.
1992, 42, 335.
(5) Mitsunobu reactions with N-alkylsulfonamides as nucleophiles are
known: (a) Henry, J. R.; Marcin, L. R.; McIntosh, M. C.; Scola, P. M.;
Harris, Jr., G. D.; Weinreb, S. M. Tetrahedron Lett. 1989, 30, 5709. (b)
Fukuyama, T.; Jow, C.-K.; Cheung, M. Tetrahedron Lett. 1995, 36, 6373.
(c) Bell, K. E.; Knight, D. W.; Gravestock, M. B. Tetrahedron Lett. 1995,
36, 8681. Reference 5a discusses the fact that primary sulfonamides (ArSO2-
NH2) are incompatible with the Mitsunobu reaction.
(6) (a) Myers, A. G.; Kukkola, P. J. J. Am. Chem. Soc. 1990, 112, 8208.
Prior to this work, Corey et al. had developed a method for reductive allylic
transposition based on the air-oxidation of an allylic hydrazine: (b) Corey,
E. J.; Wess, G.; Xiang, Y. B.; Singh, A. K. J. Am. Chem. Soc. 1987, 109,
4717.
(7) 1-Allyl-1-sulfonylhydrazines have been prepared by base-promoted
alkylation, and their fragmentation has been induced by heating (60 °C) in
acetic acid: (a) Sato, T.; Homma, I. Bull. Chem. Soc. Jpn. 1971, 44, 1885.
(b) Corey, E. J.; Cane, D. E.; Libit, L. J. Am. Chem. Soc. 1971, 93, 7016.
1-Alkyl-1-sulfonylhydrazines have been prepared and fragmented in situ
by the amination of sulfonamides with chloramine in refluxing THF in the
presence of hydroxide: (c) Nickon, A.; Hill, A. S. J. Am. Chem. Soc. 1964,
86, 1152. (d) Guziec, F. S., Jr.; Wei, D. J. Org. Chem. 1992, 57, 3772.
This procedure has proven to be a general method for the
synthesis of a wide range of allenes from propargylic alcohols
(Table 1).10 Typically, the Mitsunobu inversion reaction of a
propargylic alcohol with NBSH occurs within 1-2 h at -15
°C; elimination of the resultant alkylated sulfonylhydrazine is
complete within 1-8 h at 23 °C. Thin-layer chromatographic
(8) Hu¨nig, S.; Mu¨ller, H. R.; Thier, W. Angew. Chem., Int. Ed. Engl.
1965, 4, 271.
(9) Dann, A. T.; Davies, W. J. Chem. Soc. 1929, 1050.
S0002-7863(96)00443-X CCC: $12.00 © 1996 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 118, No. 18, 1996 4493
Table 1. Synthesis of Allenes from Propargylic Alcohols
the alkylated sulfonylhydrazine (e.g., 2b), which decomposes
during elution to form the allene 3. The allenes of entries 1-12
(Table 1) were obtained using 1.2-1.6 equiv each of Ph3P,
DEAD, and NBSH. More hindered alcohols (entries 13 and
14) required 3.0 equiv of each reagent to complete the
Mitsunobu reaction.
As is evident from the examples of Table 1, the method is
tolerant of a wide variety of functional groups, to include tertiary
amines, tertiary alcohols, acetals and ketals, silyl ethers and
nitriles. It is also useful for the preparation of the important
(trialkylsilyl)allenes.1 In particular, (trimethylsilyl)- and (tert-
butyldimethylsilyl)allene11 are now easily synthesized in one
step from the corresponding C-silylated propargyl alcohol
derivatives (entries 9 and 10). The general transformation
proceeds with complete stereospecificity. For example, the
optically active propargylic alcohol of entry 1 (78 ( 2% ee)
produced the (R)-allene ([R]21 ) -184°, c ) 1.33, acetone)
D
with 77 ( 2% ee, as determined by 1H NMR analysis with the
chiral shift reagent Ag(fod)-Yb(hfc)3.2 This demonstrates that
the overall process occurs with the stereospecificity implied by
structures 1-3. Entries 11-14 further establish the stereospeci-
ficity of the process; each substrate produced the corresponding
allene without detectable contamination by the alternative
diastereomer. The syntheses of the sensitive allene-ene-ynes
of entries 7 and 8 are especially noteworthy and represent a
considerable advance over previous methodology.2
In summary, we have developed an expedient, one-step
synthesis of allenes from propargylic alcohols. The success of
the method depends critically upon the following ordering of
three reaction rates: Mitsunobu inversion (several minutes at
-15 °C) > fragmentation of the intermediate 1-alkyl-1-o-
nitrobenzenesulfonylhydrazine (1-8 h in THF at 23 °C) >
spontaneous generation of diimide from NBSH (days to weeks
at 23 °C). We have shown that the transformation proceeds
with complete stereospecificity and, given the wide availability
of optically active propargylic alcohols, should provide access
to an equally wide range of optically active allenes.
Acknowledgment. Financial support from American Cyanamid
Company is gratefully acknowledged. We express our appreciation
to Professor Erick Carreira and Mr. Vincent Tai for a gift of the
substrate of entry 6, Table 1.
Supporting Information Available: Listings of analytical data for
2a, 3, and new compounds in Table 1 (5 pages). This material is
contained in many libraries on microfiche, immediately follows this
article in the microfilm version of this journal, can be ordered from
the ACS, and can be downloaded from the Internet; see any current
masthead page for ordering information and Internet access instructions.
JA960443W
(10) A representative experimental procedure, 1-Dimethylamino-2,3-
heptadiene (entry 3, Table 1): DEAD (0.10 mL, 0.65 mmol, 1.3 equiv)
was added to a solution of Ph3P (170 mg, 0.65 mmol, 1.3 equiv) in THF (2
mL) at -15 °C. After 10 min, a solution of 1-dimethylamino-2-heptyn-
4-ol (78 mg, 0.50 mmol, 1 equiv) in THF (1.5 mL) was added to the yellow
reaction mixture, followed 10 min later by a solution of NBSH (0.14 g,
0.65 mmol, 1.3 equiv) in THF (2.0 mL). The resulting suspension was
held at -15 °C for 1 h, after which time TLC analysis indicated complete
consumption of the starting alcohol. The reaction mixture was warmed to
23 °C and allowed to stand overnight (8 h). Concentration of the reaction
mixture and purification of the residue by chromatography on silica gel
afforded the title allene as a colorless oil (57 mg, 83%).
a Racemic substrate. b Isolated yield; yield in parentheses was
obtained by gas chromatography. c The configuration of the products
was assigned on the basis of the stereochemistry of the transformation
of entry 1.
(11) (a) Danheiser, R. L.; Carini, D. J.; Fink, D. M.; Basak, A.
Tetrahedron, 1983, 39, 935. (b) Hopf, H.; Naujoks, E. Tetrahedron Lett.
1988, 29, 609.
(TLC) analysis of the reaction mixture at -15 °C reveals the
formation of a more polar, unstable intermediate, presumably