Cyclopropyldiphenylsulfonium Tetrafluoroborate1

[33462-81-6]  · C15H15BF4S  · Cyclopropyldiphenylsulfonium Tetrafluoroborate  · (MW 314.15)

(versatile C3 building block; reagent for the spiroannulation of carbonyl compounds)

Physical Data: mp 136-138 °C.

Solubility: used as a suspension in THF, DME, DMSO, MeCN.

Form Supplied in: white solid; commercially available.

Preparative Methods: see eq 1.2


Cyclopropyldiphenylsulfonium tetrafluoroborate is primarily used for the generation of the corresponding ylide which is synthetically useful. The ylide can be used in a variety of transformations including synthesis of cyclobutanones, g-butyrolactones, cyclopentanones, and spiropentanes.

Generation of Diphenylsulfonium Cyclopropylide.

The ylide can be formed by deprotonation of the sulfonium salt under reversible or irreversible conditions. Treatment with dimsylsodium in DME at -40 °C irreversibly generates the ylide.3 Low temperatures are required in order to avoid decomposition of the ylide to cyclopropyl phenyl sulfide and benzyne. Generation of the ylide under reversible conditions with powdered Potassium Hydroxide in DMSO at room temperature2b minimizes thermal decomposition because the equilibrium between the sulfonium salt and ylide favors the salt.

Formation of Spiropentanes and Oxaspiropentanes.

Conjugate addition of diphenylsulfonium cyclopropylide to a,b-unsaturated esters and ketones affords spiropentanes (eq 2).4

Analogous to other sulfur ylides (see Dimethylsulfonium Methylide), diphenylsulfonium cyclopropylide reacts with saturated aldehydes and ketones to provide epoxide-type products known as oxaspiropentanes (eq 3).5 The reaction is general in scope and works well even for readily enolizable ketones, though exceptions are known.5,6 The good stereoselectivity in reactions with cyclic ketone partners, such as cyclohexanone, results from attack of the ylide from the less hindered equatorial direction. When epimerization of a diastereomeric mixture of ketones occurs under the reaction conditions, formation of one oxaspiropentane can result. This results because epimerization a to the ketone occurs faster than addition of the ylide to the ketone, and because one of the epimers reacts at a faster rate than the other.1e Isolated alkenes, esters, alcohols, ethers, and epoxides are some of the functional groups that can be tolerated under the reaction conditions. The ylide is chemoselective for saturated ketones over conjugated enones.1e

The chemical versatility of these highly reactive oxaspiropentanes makes them useful building blocks. For example, such highly strained epoxides are very labile towards acid catalyzed rearrangements. This reactivity can be exploited to produce cyclobutanones (eq 3) or vinylcyclopropanol products (see below). In cases where the oxaspiropentanes possess substituents capable of stabilizing a carbonium ion, rearrangement to the cyclobutanone usually occurs under the reaction conditions.5 In other cases the cyclobutanone can be obtained directly by acidic work-up of the ylide reaction. In general, the major diastereomer arises from inversion of configuration at the migration terminus, which is consistent with a concerted mechanism.1e,7 If the cyclobutanone of opposite configuration is desired, an alternate procedure can be adopted. Opening of the oxaspiropentane with phenylselenide anion gives the hydroxyselenide, which is directly subjected to oxidation with m-Chloroperbenzoic Acid. Under the reaction conditions, ionization of the selenoxide occurs, leading to rearrangement. The overall process involves two inversions, leading to the stereoreversed cyclobutanone.8 Such stereoreversed cyclobutanones can be more efficiently prepared from the starting ketones using the alternative reagent 1-lithiocyclopropyl phenyl sulfide.9 The ring strained spirocyclobutanones are useful for further structural elaborations.10 Treatment with basic Hydrogen Peroxide affords g-butyrolactones (via ring expansion with migration of the more substituted carbon),11 and fused cyclopentenones by treatment of such g-butyrolactones with acid (eq 4).12 Direct transformation of vinylcyclobutanones to fused cyclopentenones can be effected by treatment with acid.13 Cyclic enol esters can be formed via a-formylation and acid promoted fragmentation.14 Synthetic elaboration of cyclobutanones via alkylation and subsequent cleavage to release ring strain results in the selective transformation of the original carbonyl group into a variety of substitution patterns. These include geminal dialkylation and reductive alkylation of the carbonyl group.15-17

Transformation of Oxaspiropentanes to Vinylcyclopropanol Derivatives.

Treatment of oxaspiropentanes with strong base affords vinylcyclopropanols via a cis,syn elimination (eq 5). The regiochemistry of ring opening is dependent on the nature of the base, solvent, and factors determining whether the reaction is under thermodynamic or kinetic control.18 If the oxaspiropentane does not possess a suitably placed hydrogen for base abstraction, treatment with sodium phenylselenide in a nonprotic solvent at rt can afford the b-hydroxy selenide which eliminates to the vinylcyclopropanol in situ (eq 6).19 Thus the mechanism has switched from a cis,syn to a trans,anti elimination. Solvent plays an important role in this reaction; switching the solvent to ethanol affords the hydroxy selenide, an intermediate in the formation of stereoreversed cyclobutanones (see above). Attempts to effect a selenoxide elimination (oxidation of the selenide) often affords the cyclobutanone product.8

Vinylcyclopropanol silyl ethers are obtained by quenching the alkoxide formed under strong base conditions with Chlorotrimethylsilane. This composite functional group can undergo thermal rearrangements to cyclopentane trimethylsilyl enol ethers.5,20 This rearrangement is accelerated by the presence of the siloxy group. The enol silyl ether produced can be further alkylated to provide substituted cyclopentanones. This sequence results in the regiospecific annulation of a cyclopentanone ring to a carbonyl group. In addition, vinylcyclopropanol silyl ethers can undergo ring expansion to cyclobutanones upon treatment with electrophiles.17b,17c,21 Use of vinylcyclopropanol silyl ethers as cyclization terminators can result in good yields of six- to eight-membered rings (eq 7).22 The cyclopropyl ring mediates the delocalization of the lone pair on the oxygen into the alkene, enhancing the alkene nucleophilicity, and the reaction is terminated effectively by rearrangement to the cyclobutanone.

Homologs of Cyclopropyldiphenylsulfonium Tetrafluoroborate.

2-Methylcyclopropyldiphenylsulfonium tetrafluoroborate has also been prepared and is formed as a mixture of trans (major) and cis isomers (eq 8). The stereochemical integrity of the ylide derived from this mixture of sulfonium salts is variable, depending on the conditions under which it is generated. The reactivity profile of the ylide is the same as the parent, but the presence of an additional chiral center often leads to a mixture of stereoisomers.23

1. (a) Salaün, J. R. Y. Top. Curr. Chem. 1988, 144, 1. (b) Reissig, H.-U. In The Chemistry of the Cyclopropyl Group, Rappoport, Z., Ed; Wiley: Chichester, 1987; Part I, pp 404-410. (c) Trost, B. M. ACR 1974, 7, 85. (d) Trost, B. M. PAC 1975, 43, 563. (e) Trost, B. M. Top. Curr. Chem. 1986, 133, 3.
2. (a) Trost, B. M.; Bogdanowicz, M. J. JACS 1971, 93, 3773. (b) Trost, B. M.; Bogdanowicz, M. J. JACS 1973, 95, 5298. (c) Badet, B.; Julia, M. TL 1979, 1101. (d) Bogdanowicz, M. J.; Trost, B. M. OS 1974, 54, 27.
3. Corey, E. J.; Chaykovsky, M. JACS 1965, 87, 1345.
4. Trost, B. M.; Bogdanowicz, M. J. JACS 1973, 95, 5307.
5. Trost, B. M.; Bogdanowicz, M. J. JACS 1973, 95, 5311.
6. Trost, B. M.; Bogdanowicz, M. J. TL 1972, 887.
7. Trost, B. M.; Rigby, J. H. JOC 1976, 41, 3217.
8. Trost, B. M.; Scudder, P. H. JACS 1977, 99, 7601.
9. (a) Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Rigby, J. H.; Bogdanowicz, M. J. JACS 1977, 99, 3080. (b) Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Bogdanowicz, M. J. JACS 1977, 99, 3088.
10. For reviews, see Conia, J. M.; Salaün, J. R. ACR 1972, 5, 33 and Top. Curr. Chem. 1986, 133, 85.
11. Trost, B. M.; Bogdanowicz, M. J. JACS 1973, 95, 5321.
12. (a) Baldwin, J. E.; Beckwith, P. L. M. CC 1983, 279. (b) Paquette, L. A.; Wyvratt, M. J.; Schallner, O.; Muthard, J. L.; Begley, W. J.; Blankenship, R. M.; Balogh, D. JOC 1979, 44, 3616.
13. Matz, J. R.; Cohen, T. TL 1981, 22, 2459.
14. Trost, B. M.; Hiroi, K.; Holy, N. JACS 1975, 97, 5873.
15. Trost, B. M.; Bogdanowicz, M. J.; Frazee, W. J.; Salzmann, T. N. JACS 1978, 100, 5512.
16. (a) Trost, B. M.; Bogdanowicz, M. J.; Kern, J. JACS 1975, 97, 2218. (b) Trost, B. M.; Preckel. M.; Leichter, L. M. JACS 1975, 97, 2224.
17. For application of these methods in total syntheses, see (a) Trost, B. M.; Latimer, L. H. JOC 1978, 43, 1031. (b) Trost, B. M.; Mao, M. K.-T.; Balkovec, J. M.; Buhlmayer, P. JACS 1986, 108, 4965. (c) Trost, B. M.; Balkovec, J. M.; Mao, M. K.-T. JACS 1986, 108, 4974.
18. Trost, B. M.; Kurozumi, S. TL 1974, 22, 1929.
19. Trost, B. M.; Nishimura, Y.; Yamamoto, K.; McElvain, S. S. JACS 1979, 101, 1328.
20. Trost, B. M.; Bogdanowicz, M. J. JACS 1973, 95, 289.
21. Trost, B. M.; Brandi, A. JACS 1984, 106, 5041.
22. Trost, B. M.; Lee, D. C. JACS 1988, 110, 6556.
23. Trost, B. M.; Bogdanowicz, M. J. JACS 1973, 95, 5321.

Donna L. Romero

The Upjohn Company, Kalamazoo, MI, USA

William H. Pearson & P. Sivaramakrishnan Ramamoorthy

The University of Michigan, Ann Arbor, MI, USA

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