(R = THP)

[83606-32-0]  · C9H14O3  · 1-(Tetrahydropyranyloxy)cyclopropanecarbaldehyde  · (MW 170.23) (R = TBDMS)

[90660-09-6]  · C10H20O2Si  · 1-(t-Butyldimethylsilyloxy)cyclopropanecarbaldehyde  · (MW 200.39)

(1-hydroxycyclopropanecarbaldehyde derivatives provide readily 1-donor substituted vinylcyclopropanes, which can undergo ring expansions selectively to four- to eight-membered rings)

Solubility: sol usual organic solvents (ether, THF, CH2Cl2).

Purification: by chromatography on silica gel.

Preparative Methods: acyloin condensation of succinic esters by Sodium in the presence of Chlorotrimethylsilane provides 1,2-disilyloxycyclobutene.2 One-pot bromination in CH2Cl2 at -10 °C and addition of ice-water gives the 1-hydroxycyclopropanecarboxylic acid.3 Successive esterification (MeOH, Thionyl Chloride), O-protection (3,4-Dihydro-2H-pyran, Pyridinium p-Toluenesulfonate.4 or t-Butyldimethylchlorosilane5), reduction with Lithium Aluminum Hydride, and finally oxidation with Pyridinium Dichromate,6 Pyridinium Chlorochromate,7 or Dimethyl Sulfoxide-Oxalyl Chloride8 produce the expected aldehyde in high yields (eq 1).3b,9

Other routes involve cyclopropanone cyanohydrin as intermediate,10 or ring closure of 2-chloropropionaldehyde cyanohydrin ethoxyethyl ether with Sodium Hexamethyldisilazide.11

Optically active (1S,2R)- and (1R,2S)-1-t-butyldimethylsilyloxy 2-methylcyclopropanecarbaldehydes (>95% ee) have been prepared by acyloin cyclization of (R)- and (S)-dimethyl 2-methylsuccinate obtained by enzymatic resolution.12

Handling, Storage, and Precautions: must be stored in the absence of oxygen to avoid oxidation into cyclopropanecarboxylic acid. Cleavage of the protective group leads to 2-hydroxycyclobutanone.1

Ring Expansions to 2-Vinylcyclobutanones.

Addition of Vinylmagnesium Bromide and deprotection (PPTS, EtOH)13 lead to 1-(1-hydroxycyclopropyl)allyl alcohol, which undergoes quantitative C3 -> C4 ring expansion to 2-vinylcyclobutanone upon addition of a catalytic amount of Boron Trifluoride Etherate (eq 2).3b

This rearrangement provides a new synthesis of 2-vinylcyclobutanones;3b,13,14 these versatile building blocks can undergo further ring expansions leading to five-, six-, or eight-membered ring derivatives in acid, base, thermally, or photochemically induced ring rearrangements.1b

Optically active 2-vinylcyclobutanones have been prepared by regio- and stereoselective rearrangement and used in the total synthesis of natural g-lactones (eq 3).12

2-Alkynylcyclobutanones have been also obtained from ring expansion induced by Lithium Chloride.9b

C3 -> C5 Ring Expansions to Silylated Cyclopentanone Enol Ethers.

Alkenations of the aldehyde (Wittig reaction or successive aldolization and dehydration) provide, after cleavage of the THP group4 and O-silylation,15 1-silyloxyvinylcyclopropane derivatives which undergo the thermal vinylcyclopropane-cyclopentane rearrangement16 to cyclopentanone silyl enol ethers, regioselectively, either on heating neat in a sealed tube or by flash vacuum thermolysis (FVT) (eqs 4-6).

Total syntheses of cis-jasmone and dihydrojasmone9a (important raw material as a perfume ingredient), dicranenone A17 (a new antimicrobial fatty acid containing a cyclopentanone ring), and the spirovetivane framework9c (found in sesquiterpenes of the spirovetivane and acorane class) have been performed by the thermal ring enlargement of these readily available vinylcyclopropanes.

Other recent applications of this aldehyde involve the synthesis of eicosanoid compounds18 (5-lipoxygenase inhibitors), the enantioselective total syntheses of (R)-(+)-dodecan-5-olide, and (S)-(+)- and (R)-(-)-dihydrofuran-2(3H)-ones.19

Related Reagents.

Cyclobutanone; Cyclopropanone; Cyclopropyldiphenylsulfonium Tetrafluoroborate; 1-Ethoxycyclopropanol; 1-Ethoxy-1-(trimethylsilyloxy)cyclopropane; 1-Lithio-1-methoxycyclopropane.

1. (a) Salaün, J. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987; Chapter 13, pp 809-878. (b) Salaün, J. Top. Curr. Chem. 1988, 144, 1. (c) Salaün, J. MOC in press. (d) Lee-Ruff, E. In Advances in Strain in Organic Chemistry; Halton, B., Ed.; JAI: Greenwich, CT, 1991; Vol. 1, Chapter 5. (e) Bellus, D.; Ernst, B. AG(E) 1988, 27, 197; (f) Conia, J. M.; Robson, M. J. AG(E) 1975, 14, 473.
2. Bloomfield, J. J.; Nelke, J. M. OS 1977, 57, 1.
3. (a) Heine, H. G.; Wendisch, D. LA 1976, 463. (b) Ollivier, J.; Salaün, J. TL 1984, 25, 1269.
4. Miyashita, N.; Yoshikoshi, A.; Grieco, P. A. JOC 1977, 42, 3772.
5. Corey, E. J.; Venkateswarlu, A. JACS 1972, 94, 6190.
6. Corey, E. J.; Schmidt, G. TL 1979, 399.
7. Corey, E. J.; Suggs, J. W. TL 1975, 2647.
8. Mancuso, A. J.; Huang, S. L.; Swern, D. JOC 1978, 43, 2480.
9. (a) Salaün, J.; Almirantis, Y. T 1983, 39, 2421. (b) Salaün, J.; Fadel, A.; Conia, J. M. TL 1979, 1429. (c) Barnier, J. P.; Salaün, J. TL 1984, 25, 1273.
10. Kato, K.; Takita, T.; Umezawa, H. TL 1980, 21, 4925.
11. Cochoy, R. E. Ph. D. Dissertation, Yale University, 1969.
12. Salaün, J.; Karkour, B.; Ollivier, J. T 1989, 45, 3151.
13. Barnier, J. P.; Karkour, B.; Salaün, J. CC 1985, 1270.
14. Barnier, J. P.; Ollivier, J.; Salaün, J. TL 1989, 30, 2525.
15. Visser, R. G.; Bos, H. J. T.; Brandsma, L. RTC 1980, 99, 70.
16. Neureiter, N. P. JOC 1959, 24, 2044.
17. Ollivier, J.; Salaün, J. CC 1985, 1269.
18. Arai, Y.; Shimoji, K.; Konno, M.; Konishi, Y.; Okuyama, S.; Iguchi, S.; Hayashi, M.; Miyamoto, T.; Toda, M. JMC 1983, 26, 72.
19. Nemoto, H.; Ishibashi, H.; Mori, M.; Fujita, S.; Fukumoto, K. JCS(P1) 1990, 2835; H 1990, 31, 1237.

Jacques Salaün

Université de Paris-Sud, France

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