Synthesis of 2-indanones via [4 + 1] annulation reactions of (trialkylsilyl)arylketenes

Article abstract of DOI:10.1021/ol026014m

(Matrix presented) (Trialkylsilyl)arylketenes combine with (trimethylsilyl)diazomethane in a new [4 + 1] annulation process leading to 2-indanone derivatives. The (trialkylsilyl)arylketene annulation substrates are available via the photochemical Wolff rearrangement of α-silyl-α-diazo ketones, which are themselves prepared by silylation of the corresponding diazo ketones. The mechanism of the annulation reaction is proposed to involve the formation of a 2,3-bis(silyl)cyclopropanone, which is in equilibrium with an oxyallylic cation. Electrocyclic closure of this intermediate forms the new cyclopentenone ring.

Full text of DOI:10.1021/ol026014m

ORGANIC
LETTERS
2002
Vol. 4, No. 15
2465-2468
Synthesis of 2-Indanones via [4 + 1]
Annulation Reactions of
(Trialkylsilyl)arylketenes
Audra M. Dalton, Yongjun Zhang, Christopher P. Davie, and Rick L. Danheiser*
Department of Chemistry, Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139
danheisr@mit.edu
Received April 15, 2002
ABSTRACT
(Trialkylsilyl)arylketenes combine with (trimethylsilyl)diazomethane in a new [4 + 1] annulation process leading to 2-indanone derivatives. The
(trialkylsilyl)arylketene annulation substrates are available via the photochemical Wolff rearrangement of r-silyl-r-diazo ketones, which are
themselves prepared by silylation of the corresponding diazo ketones. The mechanism of the annulation reaction is proposed to involve the
formation of a 2,3-bis(silyl)cyclopropanone, which is in equilibrium with an oxyallylic cation. Electrocyclic closure of this intermediate forms
the new cyclopentenone ring.
In this Letter we describe a new [4 + 1] annulation strategy
for the synthesis of 2-indanones based on the reaction of
(trialkylsilyl)arylketenes (“TAS-arylketenes”) with (trimeth-
ylsilyl)diazomethane. The exceptional stability of silylketenes
has been known for over 35 years,1 and the utility of this
remarkable class of ketenes in organic synthesis is now well
established.2 Prior research in our laboratory has focused on
the synthesis and chemistry of TAS-Vinylketenes. Silyl
substituents suppress the tendency of vinylketenes to undergo
dimerization and [2 + 2] cycloaddition, allowing them to
express their underlying reactivity as electron-rich conjugated
dienes in Diels-Alder and hetero Diels-Alder reactions
leading to cyclohexenones, phenols, and oxygen and nitrogen
heterocycles.3-5 Recently, we have reported the application
of TAS-vinylketenes as four-carbon components in a new,
stereoselective [4 + 1] annulation strategy for the synthesis
of substituted cyclopentenones.6 As outlined in eq 1, nu-
cleophilic species bearing appropriate leaving groups (“car-
benoid reagents”) add to TAS-vinylketenes to generate
dienolate species that cyclize to form new five-membered
rings.7 The goal of the present study was to investigate the
feasibility of extending this annulation strategy to TAS-
arylketenes, i.e., systems in which the vinyl group is
embedded within the framework of an aromatic ring.8
(1) Shchukovskaya, L. L.; Pal’chik, R. I.; Lazarev, A. N. Dokl. Akad.
Nauk SSSR 1965, 164, 357.
The TAS-arylketenes required for this study were prepared
via the photochemical Wolff rearrangement of R-silyl-R-
diazo aryl ketones 2a-g (Scheme 1),9,10 which are them-
selves readily available by silylation of the corresponding
diazo ketones.11 Diazo derivatives of aryl ketones are easily
prepared by addition of diazomethane to the appropriate acid
chloride or, alternatively, via the application of our detri-
fluoroacetylative diazo transfer process12 to the corresponding
(2) Reviews: (a) Tidwell, T. T. Ketenes; Wiley: New York, 1995. (b)
Schaumann, E.; Scheiblich, S. In Methoden der Organischen Chemie
(Houben Weyl); Kropf, E., Schaumann, E., Eds.; Thieme: Stuttgart,
Germany, 1993; Vol. E15, parts 2 and 3. (c) Loebach, J. L.; Danheiser, R.
L. In Encyclopedia of Reagents for Organic Synthesis; Paquette, L. A.,
Ed.; Wiley: New York, 1995; p 5266. (d) Pommier, A.; Kocienski, P.;
Pons, J.-M. J. Chem. Soc., Perkin Trans. 1 1998, 2105.
(3) Danheiser, R. L.; Sard, H. J. Org. Chem. 1980, 45, 4810.
(4) Loebach, J. L.; Bennett, D. M.; Danheiser, R. L. J. Org. Chem. 1998,
63, 8380.
10.1021/ol026014m CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/22/2002

Scheme 1
Table 1. [4 + 1] Indanone Annulation
methyl ketones.13 As expected, TAS-arylketenes 3a-g are
remarkably robust ketenes, stable at 25 °C and at mildly
elevated temperatures, and amenable to purification using
conventional silica gel chromatography.
The feasibility of the 2-indanone [4 + 1] annulation
strategy was initially examined using phenyl(triisopropylsi-
lyl)ketene (3a). Treatment of 3a with 1.1 equiv of TMS-
diazomethane14 in a mixture of dichloromethane and hexane
at room temperature produced the desired 1,3-bis(silyl)-
indanone in nearly quantitative yield. Purification of this
compound could not be achieved without partial loss of the
trimethylsilyl group, and consequently, the crude product was
converted to the mono(silyl)indanone 4 by brief stirring at
room temperature in the presence of silica gel. In this fashion,
the desired indanone was obtained in 86% yield as a white
solid, mp 81-82 °C. 2-Indanone itself can be accessed
directly by employing phenyl(triethylsilyl)ketene for the
reaction, in which case both the TMS and TES groups can
(5) Bennett, D. M.; Okamoto, I.; Danheiser, R. L. Org. Lett. 1999, 1,
641.
(6) Loebach, J. L.; Bennett, D. M.; Danheiser, R. L. J. Am. Chem. Soc.
1998, 120, 9690.
(7) For related transformations, see: (a) Colomvakos, J. D.; Egle, I.;
Ma, J.; Pole, D. L.; Tidwell, T. T.; Warkentin, J. J. Org. Chem. 1996, 61,
9522. (b) Huang, W.; Tidwell, T. T. Synthesis 2000, 457.
(8) Scattered reports have appeared previously in which indanone
derivatives were observed in the reaction of diazo compounds with
diarylketenes. See: (a) Kende, A. S. Chem. Ind. (London) 1956, 1053. (b)
Yates, P.; Abrams, G. D.; Betts, M. J.; Goldstein, S. Can. J. Chem. 1971,
49, 2850. (c) Frey, J.; Rappoport, Z. J. Am. Chem. Soc. 1995, 117, 1161.
(d) Le´ost, F.; Doutheau, A. Tetrahedron Lett. 1999, 40, 847.
(9) For generation of silylketenes by photo-Wolff rearrangement, see refs
4-6 and: (a) Maas, G.; Bru¨ckmann, R. J. Org. Chem. 1985, 50, 2801. (b)
Bru¨ckmann, R.; Schneider, K.; Maas, G. Tetrahedron 1989, 45, 5517.
(10) Wolff rearrangement of R-silyl-R-diazo ketones can also be effected
by heating in the presence of catalytic rhodium(II) octanoate; see: Marsden,
S. P.; Pang, W.-K. J. Chem. Soc., Chem. Commun. 1999, 1199.
(11) Silylation was achieved by using our modification4 of the method
of Maas.9a,b
(12) (a) Danheiser, R. L.; Miller, R. F.; Brisbois, R. G.; Park, S. Z. J.
Org. Chem. 1990, 55, 1959. (b) Danheiser, R. L.; Miller, R. F.; Brisbois,
R. G. Organic Syntheses; Wiley: New York, 1998; Collect. Vol. IX, p
197.
(13) The methyl ketone required for the synthesis of 1f was prepared
via Stille coupling of 3-(i-Pr)-C6H4OTf with H2CdC(OEt)SnBu3.
(14) (a) Seyferth, D.; Dow, A. W.; Menzel, H.; Flood, T. C. J. Am. Chem.
Soc. 1968, 90, 1080. (b) Shioiri, T.; Aoyama, T.; Mori, S. Organic Syntheses;
Wiley: New York, 1993; Collect. Vol. VIII, pp 612-615.
a Isolated yields of products purified by column chromatography.
b Desilylation (of the Me3Si group) was achieved by stirring the crude
product in CH2Cl2 over silica gel at rt for 1 h. c Cleavage of both the Me3Si
and Et3Si groups from the crude annulation product was accomplished by
exposure to 1 N HCl in THF at rt for 4 h. d Treatment of the annulation
product with 3 equiv of K2CO3 in MeOH at room temperature for 3 min
effected desilylation. e Cleavage of the Me3Si group from the annulation
product occurred during the column chromatography on silica gel. f Exposure
of the annulation product to 1 N HCl in THF (rt, 3.5 h) effected desilylation.
g Overall yield for two steps from 2g (photo-Wolff rearrangement and [4
+ 1] annulation). h In this case, the annulation was carried out in the
presence of 0.5 equiv of i-Pr2EtN.
be conveniently cleaved by exposure of the crude annulation
product to dilute HCl in aqueous THF.
[4 + 1] Annulation with substituted arylketenes proceeds
smoothly in a similar fashion (Table 1), except for the case
of the 4-carbomethoxy derivative (entry 7), for which
successful reaction requires the addition of 0.5 equiv of i-Pr2-
EtN (vide infra). As indicated in the Table, the optimal
2466
Org. Lett., Vol. 4, No. 15, 2002

Scheme 2
protocol for cleavage of the Me3Si group varies from case
17, which would likely be in equilibrium with the oxyallyl
cation 16. Evidence in support of cyclopropanone intermedi-
ates of type 17 in the [4 + 1] annulation pathway includes
the isolation of cyclobutanone 13 in the reaction of 3a with
CH2N2 (eq 2). In this case, interception of the intermediate
cyclopropanone by diazomethane may compete with ring
opening and 4π electrocyclic closure.
Also consistent with this mechanism are the findings of
Zaitseva and co-workers, who have shown that simple
silylketenes react with diazomethane and TMS-diazomethane
to form mono- and bis(silyl)cyclopropanones.17 Finally, it
is noteworthy that 2-indanones and related hydrindenone
derivatives are produced in the oxidation of phenyl-
substituted allenes with peracid,18 processes that may well
involve the intermediacy of oxyallylic cations of type 16
generated via the ring opening of allene oxides.
to case and is achieved either by treatment with silica gel or
under mild basic (K2CO3, MeOH, rt, several min) or acidic
(1 N HCl, THF) conditions. Surprisingly, application of the
[4 + 1] strategy to arylketenes bearing meta-alkyl substit-
uents leads to mixtures of isomeric indanones (entries 5 and
6). In these cases, the regiochemical outcome of the reaction
appears to result from an intrinsic preference for cyclization
adjacent to the alkyl substituent that is opposed by steric
repulsion from this group.
As illustrated in eq 2, attempts to employ the more reactive
reagent diazomethane in place of Me3SiCHN2 for the [4 +
1] annulation were not fruitful. Addition of diazomethane
to ketene 3a proceeds rapidly at only -78 °C but affords
the desired indanone accompanied by the cyclobutanone
byproduct 13, which is isolated in 29% yield.
As noted earlier, successful [4 + 1] annulation with the
carbomethoxy-substituted ketene 3g requires the presence
(15) Pentadienyl cation electrocyclic ring closures are involved in the
mechanism of the Nazarov cyclization. For reviews, see: (a) Habermas,
K. L.; Denmark, S. E. In Organic Reactions; Paquette, L. A., Ed.; Wiley:
New York, 1994; Vol. 45, pp 1-158. (b) Denmark, S. E. In ComprehensiVe
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991;
Vol. 5, p 751.
(16) Alternatively, cyclization of intermediate 15 could produce the five-
membered ring product 18 directly, although the planar structure of the
dienolate system may not allow it to achieve an arrangement in which the
π electrons are suitably situated for direct backside displacement of the
leaving group.
(17) (a) Zaitseva, G. S.; Bogdanova, G. S.; Baukov, Yu. I.; Lutsenko, I.
F. J. Organomet. Chem. 1976, 121, C21. (b) Zaitseva, G. S.; Bogdanova,
G. S.; Baukov, Yu. I.; Lutsenko, I. F. J. Gen. Chem. USSR (Engl. Transl.)
1978, 48, 111. (c) Fedorenko, E. N.; Zaitseva, G. S.; Baukov, Yu. I.;
Lutsenko, I. F. J. Gen. Chem. USSR (Engl. Transl.) 1986, 56, 2150. (d)
Zaitseva, G. S.; Lutsenko, I. F.; Kisin, A. V.; Baukov, Yu. I.; Lorberth, J.
J. Organomet. Chem. 1988, 345, 253.
Scheme 2 outlines several alternative pathways to account
for the mechanistic course of the [4 + 1] annulation. As
discussed previously,6 addition of TMS-diazomethane to the
silylketene should be highly stereoselective due to the
shielding effect of the bulky trialkylsilyl group and should
result in the formation of the (Z)-enolate 15. Cyclization may
then proceed via ionization to form the oxidopentadienylic-
type cation 16, which should undergo stereospecific conro-
tatory electrocyclic closure to 18.15,16 Alternatively, cycliza-
tion of 15 may occur to form the 2,3-bis(silyl)cyclopropanone
(18) (a) Oku, A.; Shimada, K.; Mashio, F. Bull. Chem. Soc. Jpn. 1973,
46, 275. (b) Greibrokk, T.; Skattebol, L. Acta Chem. Scand. 1973, 27, 1421.
Org. Lett., Vol. 4, No. 15, 2002
2467

of a basic additive such as i-Pr2EtN. In the absence of base,
the major product of the reaction is the tricyclic enone 2019
(eq 3), which is obtained in 27% overall yield beginning
with R-silyl-R-diazo ketone 2g when excess TMS-diaz-
omethane is employed for the annulation. In this case, we
believe that the intermediate of type 18 is intercepted by
TMS-diazomethane in a 1,3-dipolar cycloaddition20 that, due
to the activating effect of the CO2Me group, is competitive
with the isomerization of 18 to the indanone 19. Addition
of i-Pr2EtN serves to promote the isomerization step and
delivers 12 in good yield without the formation of the
tricyclic byproduct (Table 1, entry 7).
mechanism involving the intermediacy of 2,3-bis(silyl)-
cyclopropanones, which are in equilibrium with aryl-
substituted oxyallylic cations of type 16. Electrocyclic closure
produces hydrindenone derivatives of type 18, which upon
isomerization furnish the 2-indanones. Further studies on the
application of TAS-arylketenes and related silylketenes in
organic synthesis are underway in our laboratory and will
be reported in due course.
Acknowledgment. We thank the National Institutes of
Health (GM 28273), Pharmacia, and Merck Research
Laboratories for generous financial support. Y.Z. was sup-
ported by a PoTing Ip fellowship, and C.P.D was supported
in part by a John A. Lyons fellowship.
Supporting Information Available: Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL026014M
(19) Stereochemistry of 20 assigned as shown on the basis of NOE
experiments and analysis of proton NMR coupling constant data; see
Supporting Information for details.
(20) Regitz, M.; Heydt, H. In 1,3-Dipolar Cycloaddition Chemistry;
Padwa, A., Ed.; Wiley: New York, 1984; Vol. 1, p 394.
In summary, TAS-arylketenes combine with TMS-diaz-
omethane in a new [4 + 1] annulation strategy leading to
2-indanones. Evidence has been obtained in support of a
2468
Org. Lett., Vol. 4, No. 15, 2002