Exclusive Formation of α-Methyleneoxetanes in Ketene-Alkene Cycloadditions. Evidence for Intervention of Both an α-Methyleneoxetane and the Subsequent 1,4-Zwitterion

Article abstract of DOI:10.1021/ja030191g

This paper describes a new mechanistic feature for the Staudinger ketene-alkene cycloaddition reactions to give cyclobutanones. Low-temperature NMR (¹³C, ¹⁹F, and ¹H) monitoring of a reaction between bis(trifluoromethyl)ketene (1) and ethyl vinyl ether (2) has shown that the Staudinger reaction proceeds to form initially and exclusively an α-methyleneoxetane (3) by [2 + 2]_c=o cycloaddition across the ketene C=O bond. The initial intermediate 3 undergoes ring cleavage to produce a 1,4-zwitterion (4), which is converted to the final [2 + 2] _c=c-type product, cyclobutanone (5). The key intermediate 3 has been isolated in its pure form and was found to be converted to the final products 5 on warming, via the 1,4-zwitterion 4. The α-methyleneoxetane 3 is so reactive that it reacts with methanol rapidly even at -80 °C via solvolysis to afford an adduct 7. The ion 4 derived from the pure isolated oxetane 3 was intercepted with acetone by a 1,4-dipolar cycloaddition to give a 1,3-dioxane 8. An open-chain α,β-enone (6) has been also obtained from 3. We conclude that the (1 + 2) reaction proceeds in a new three-step mechanism; formation of an α-methyleneoxetane 3, a [2 + 2]-type cycloadduct across the C=O bond of ketene, followed by ring cleavage to give the zwitterion 4 and by recombination to form the final product, cyclobutanone 5. The zwitterion 4 is not equilibrating with reactants 1 and 2 but comes from the α-methyleneoxetane 3. Exclusive formation of another oxetane 12 has been observed in a reaction between diphenylketene (9) and methyl isopropenyl ether (11). The selectivity of initial formation of cyclobutanone or oxetane has been generalized with aid of frontier-orbital theory and ab initio calculations.

Full text of DOI:10.1021/ja030191g

Published on Web 10/31/2003
Exclusive Formation of r-Methyleneoxetanes in
Ketene-Alkene Cycloadditions. Evidence for Intervention of
Both an r-Methyleneoxetane and the Subsequent
1,4-Zwitterion
Takahisa Machiguchi,*,† Junko Okamoto,† Junpei Takachi,† Toshio Hasegawa,†
Shinichi Yamabe,*,‡ and Tsutomu Minato§
Contribution from the Department of Chemistry, Faculty of Science, Saitama UniVersity,
Shimo-Ohkubo, Sakura-ku, Saitama 338-8570, Japan; Department of Chemistry, Nara UniVersity
of Education, Takabatake-cho, Nara 630-8528, Japan; and Institute for Natural Science,
Nara UniVersity, Misasagi-cho, Nara 631-8502, Japan
Received March 25, 2003; E-mail: machiguc@chem.saitama-u.ac.jp
Abstract: This paper describes a new mechanistic feature for the Staudinger ketene-alkene cycloaddition
reactions to give cyclobutanones. Low-temperature NMR (13C, 19F, and 1H) monitoring of a reaction between
bis(trifluoromethyl)ketene (1) and ethyl vinyl ether (2) has shown that the Staudinger reaction proceeds to
form initially and exclusively an R-methyleneoxetane (3) by [2 + 2]CdO cycloaddition across the ketene
CdO bond. The initial intermediate 3 undergoes ring cleavage to produce a 1,4-zwitterion (4), which is
converted to the final [2 + 2]CdC-type product, cyclobutanone (5). The key intermediate 3 has been isolated
in its pure form and was found to be converted to the final products 5 on warming, via the 1,4-zwitterion
4. The R-methyleneoxetane 3 is so reactive that it reacts with methanol rapidly even at -80 °C via solvolysis
to afford an adduct 7. The ion 4 derived from the pure isolated oxetane 3 was intercepted with acetone by
a 1,4-dipolar cycloaddition to give a 1,3-dioxane 8. An open-chain R,â-enone (6) has been also obtained
from 3. We conclude that the (1 + 2) reaction proceeds in a new three-step mechanism; formation of an
R-methyleneoxetane 3, a [2 + 2]-type cycloadduct across the CdO bond of ketene, followed by ring cleavage
to give the zwitterion 4 and by recombination to form the final product, cyclobutanone 5. The zwitterion 4
is not equilibrating with reactants 1 and 2 but comes from the R-methyleneoxetane 3. Exclusive formation
of another oxetane 12 has been observed in a reaction between diphenylketene (9) and methyl isopropenyl
ether (11). The selectivity of initial formation of cyclobutanone or oxetane has been generalized with aid of
frontier-orbital theory and ab initio calculations.
We report herein a new mechanistic feature of ketene-alkene
(2π system) cycloadditions including an exclusive formation
of an R-methyleneoxetane. Some ketenes react with activated
alkenes (e.g., alkyl enol ether here) across the ketene CdO bond
to form initially a [2 + 2]CdO cycloadduct. The R-methylene-
oxetane is isomerized via a zwitterion to the [2 + 2]CdC product,
cyclobutanone.
The pioneering studies on ketene1 and its cycloaddition by
Staudinger in the early years of the 20th century have been
followed by a large number of experiments.2 They showed the
preference for ketenes to react with alkenes across the CdC
rather than the CdO bond. There have been many arguments
on the mechanism of whether ketene-alkene reactions proceed
in two steps2a via zwitterions in analogy to that of ketene-
imine cycloadditions.3
We have recently shown that diphenylketene CdO bond
reacts with s-cis 1,3-dienes (4π system) to yield cyclobutanones
eventually.4,5 Dimerization of ketenes is usually faster than
cycloaddition to simple unactivated alkenes.6 However, activated
alkenes (very nucleophilic alkenes such as enol ethers) react
stereospecifically with ketenes much more readily than simple
alkenes.7 It is of great interest to examine whether a ketene
undergoes such a [2 + 2] cycloaddition across its CdO group
with activated alkenes.
Precedent for addition to the CdO bond of ketene exists.8,9
However, those reactions are quite rare and have been regarded
as exceptions or side reactions in ketene-alkene reactions.2 They
(4) Machiguchi. T.; Hasegawa, T.; Ishiwata, A.; Terashima, S.; Yamabe, S.;
Minato, T. J. Am. Chem. Soc. 1999, 121, 4771-4786.
(5) Yamabe, S.; Dai, T.; Minato, T.; Machiguchi. T.; Hasegawa, T. J. Am.
Chem. Soc. 1996, 118, 6518-6519.
(6) Huisgen, R.; Otto, P. J. Am. Chem. Soc. 1968, 90, 5342-5343.
(7) Huisgen, R.; Feiler, L. A.; Otto, P. Chem. Ber. 1969, 102, 3405-3427.
(8) The first report of oxetane products: (a) England, D. C.; Krespan, C. G. J.
Am. Chem. Soc. 1965, 87, 4019-4020. (b) England, D. C.; Krespan, C. G.
J. Org. Chem. 1970, 35, 3312-3322.
(9) (a) DoMinh, T.; Strautz, O. P. J. Am. Chem. Soc. 1970, 92, 1766-1768.
(b) Raynolds, P. W.; DeLoach, J. A. J. Am. Chem. Soc. 1984, 106, 4566-
4570.
† Saitama University.
‡ Nara University of Education.
§ Nara University.
(1) Staudinger, H. Chem. Ber. 1905, 38, 1735-1739.
(2) For exellent reviews, see: (a) Tidwell, T. T. Ketenes; Wiley: New York,
NY, 1995. (b) Hyatt, J.; Raynolds, R. W. Org. React. 1994, 45, 159-646.
(3) Zhou, C.; Birney, D. M. J. Am. Chem. Soc. 2002, 124, 5231-5241.
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J. AM. CHEM. SOC. 2003, 125, 14446-14448
10.1021/ja030191g CCC: $25.00 © 2003 American Chemical Society

R-Methyleneoxetanes in Ketene−Alkene Cycloadditions
A R T I C L E S
Scheme 1. New Mechanistic Scheme Obtained in a Ketene-Alkene Reactiona
a Experiments were carried out in CH2Cl2 (1.0 mol/L).
Scheme 2. MeOH and Acetone Quench Reactionsa
Scheme 3. Two Concerted [2 + 2] Cycloadditions (i and ii) and a
Subsequent Isomerization (iii)a
a Conditions: (i) pure isolated 3 + MeOH, -80 °C, 4 h, 98%; (ii) pure
isolated 3 + acetone, -30 °C, overnight, 92%.
appear not to be concerned with the continuing conversion to
cyclobutanones.8 We have become aware that a ketene [bis-
(trifluoromethyl)ketene8a (1)] reacts initially with an activated
alkene [ethyl vinyl ether (2)] across its CdO bond to form
exclusiVely a [2 + 2]CdO cycloadduct, R-methyleneoxetane (3)
at -80 °C. The R-methyleneoxetane intermediate 3 undergoes
ring cleavage to generate a zwitterion (4) at -20 °C. The
oxetane 3 is isomerized via the ion 4 to a [2 + 2]CdC product,
cyclobutanone (5) in 92% along with an open-chain product
R,â-enone10 (6) in 8% yield. To provide experimental evidence
to the reaction mechanism, we elected to examine the reaction
of 1 (an isolable and weight-measurable ketene) with alkene 2
spectroscopically (19F and 1H NMR). Careful low-temperature
experiments were conducted to monitor the time course of the
reaction.
Schemes 1 and 2 summarize the present experimental results.
Choosing experimental conditions precisely, we have observed
by NMR spectroscopy an exclusive formation of meta-stable
oxetane intermediate 3 at -80 °C. We have succeeded in the
low-temperature isolation of 3 (colorless prisms, mp -43 °C).11
The oxetane 3 is so reactive toward the protic solvent methanol
that an adduct 7 is formed rapidly even at -80 °C (solvolysis).
The color of the solution changed dramatically [colorless (-80
°C) f slight blue (-30 °C) f deep blue (-20 °C) f colorless]
depending on temperatures.12
a Conditions: (i) CH2Cl2, 25 °C, 4 h, 98%; (ii) CH2Cl2, -25 °C, 2 days,
90% (isolated yield). 12, mp 56 °C; (iii) CH2Cl2, 25 °C, 6 h, 97%.
These prominent color changes strongly suggest that the 1,4-
zwitterion 4 is formed after the initial formation of oxetane 3.
We have also succeeded in trapping the intermediate 4 which
was generated from pure isolated 3 with acetone to give a 1,4-
dipolar cycloadduct 8 [bp 50 °C (0.7 mmHg)]. The addition
path obtained by B3LYP/6-31G* SCRF calculations13 is shown
in Figure 1 (Supporting Information). The ion 4 is polar enough
to react with acetone solvent. The result indicates the interven-
tion of the zwitterion 4 after formation of the oxetane 3 in the
reaction scheme. As crucial evidence, the (1 + 2) reaction in
acetone solvent gives also 3 (not 8) exclusively at -80 °C and
the generation of acetone-quench adduct 8 was observed only
above -30 °C (see Supporting Information). Intervention of
the zwitterion 4 prior to the formation of 3 is ruled out entirely
at -80 °C.
As usual, diphenylketene 9 (another isolable and weight-
measurable ketene) reacts with 2 to give a cyclobutanone 10
(Scheme 3, step i).14 However, 9 reacts with methyl isopropenyl
ether (11), resulting in an R-methyleneoxetane 12 (colorless
prisms, mp 56 °C) exclusively and concertedly (Scheme 3, step
ii). As the next step, a zwitterion derived from 12 is unstable,
because the acetone quench adduct has not been obtained. The
cyclobutanone ring closure is prohibited by the two geminal
substituents in 12. The oxetane was isomerized to R,â-enone
(13) exclusively at room temperature (Scheme 3, step iii).
For 1 + 2, the transition-state (TS) geometry of the concerted
addition path to the cyclobutanone 5 was not found out, and
(10) The facile isomerizations, 3 f 6 and 12 f 13, are related both to the high
acidity of methylene protons [δH ) 3.4-3.7 similar to δH ) 3.36 of CH2-
(COOMe)2] and to the basicity of the exocyclic vinyl carbons in 3 and 12.
Study of the isomerization pathways is now in progress.
(11) Selected spectroscopic data for the reported compounds, 3 and 12: IR νmax
(CH2Cl2) cm-1; NMR (CD2Cl2, Me4Si or C6F6) [1H (δH), 13C (δC), and 19
F
(δF)]. 3 (-70 °C): νmax(CdC) 1703; δH 3.42 (ddqq), 3.70 (ddqq), 5.94
(dd); δC 38.85 (t, JCH ) 145.0 Hz, C-3), 92.04 (sept, 2JCF ) 35.6 Hz, C-5),
107.95 (d, JCH ) 183.1 Hz, C-2); δF -57.91 (qt), -57.18 (qt). 12 (-30
°C): νmax(CdC) 1680; δH 3.15 (d, J ) 16.5 Hz), 3.60 (d, J ) 16.5 Hz); δC
37.91 (t, JCH ) 143.0 Hz, C-3), 107.12 (s/qqt, C-2), 111.18 (s, C-5).
(12) Deep blue color of the entropy-favored 4 appeared as in Scheme 1. We
cooled the solution to -80 °C. If a (4 h 3) equilibrium is assumed, the
enthalpy-favored 3 should be recovered according to the thermal Le
Chatelier law. But, the color did not decay at -80 °C at all (at least 1
month). The equilibrium does not hold for the present reaction.
(13) GAUSSIAN 94 (revision C.4) was used for DFT calculations.
(14) The kinetic data of diphenylketene-vinyl ethers cycloadditions indicate
large negative entropy change (∆S‡ ) -40 eu) similar to those of a Diels-
Alder reaction. (a) Huisgen, R.; Feiler, L. A.; Otto, P. Tetrahedron Lett.
1968, 4485-4490. (b) Huisgen, R.; Feiler, L. A.; Otto, P. Chem. Ber. 1969,
102, 3444-3459.
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A R T I C L E S
Machiguchi et al.
Scheme 4. Selectivity in Ketene-Activated Alkene Cycloadditionsa
R1 of the ketene contains heteroatoms or is bulky, a steric
neighboring interaction interferes with the cyclobutanone ring
closure (“neighboring-group resistance” in Scheme 4). The
second channel gives the oxetane. Thus, the selective formation
of either cyclobutanone or oxetane is a general aspect of ketene-
alkene cycloadditions, which is consistent with the present
results. Zwitterions are not in equilibrium with the reactants,
ketene and alkene. They remain after oxetane formation to
become more stable species such as cyclobutanones and
quenched products. Carbon and oxygen are host atoms in
ketene-alkene reactions and are hard.16 Zwitterions with
incomplete covalent bonds are not formed initially, and cyclo-
additions precede.
a R1 T R2 means a steric repulsion.
that to the oxetane 3 was obtained (Figure 2 in Supporting
Information). The zwitterionic intermediate 4 does not form from
association of reactants 1 and 2 but does from the oxetane 3
(Figure 3 in Supporting Information). Thus, calculations agree
with the new mechanism in Scheme 1. For 9 + 2, two
cycloaddition paths coexist, and the cyclobutanone-formation
channel has a lower activation energy than that leading to the
oxetane. For 9 + 11, only the TS of the oxetane-formation path
was found. Those results of concerted cycloadditions of (9 +
2) and (9 + 11) are entirely consistent with the experimental
evidence of Scheme 3, steps i and ii.
Acknowledgment. This work was supported by the Nishida
Memorial Foundation for Fundamental Chemical Research. The
authors gratefully thank Professor Emeritus Rolf Huisgen,
Universita¨t Mu¨nchen, for his helpful suggestions.
Supporting Information Available: Selected NMR spectra
for the reported compounds and three figures of computed
reaction paths of (4 + acetone), four [2 + 2] cycloadditions,
and the 3 formation along with their Cartesian coordinates and
a concluding schematic figure (Scheme 4A). This material is
available free of charge via the Internet at http://pubs.acs.org.
Ketene-alkene reactions are illustrated concisely in Scheme
4. Basically, there are two concerted cycloadditions. The first
channel leading to cyclobutanones is more favorable through
the (HOMO f lumo) back charge-transfer (CT) interaction
(“FMO control” in Scheme 4).15 However, when the substituent
JA030191G
(15) Yamabe, S.; Minato, T.; Osamura, Y. J. Chem. Soc., Chem. Commun. 1993,
450-452.
(16) Pearson, R. G. J. Chem. Educ. 1968, 45, 581-590 and 643-648.
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