Synlett 2007(18): 2907-2911  
DOI: 10.1055/s-2007-991084
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Straightforward Synthesis of Alkenyl Nonaflates from Carbonyl Compounds Using Nonafluorobutane-1-sulfonyl Fluoride in Combination with Phosphazene Bases

Michael A. K. Vogela,b, Christian B. W. Starkb, Ilya M. Lyapkalo*c
a Institute of Chemical & Engineering Sciences Ltd., 1 Pesek Road, Jurong Island, 627833 Singapore, Singapore
b Freie Universität Berlin, Institut für Chemie, Organische Chemie, Takustr. 3, 14195 Berlin, Germany
c Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n. 2, 16610 Prague 6, Czech Republic
Fax: +420(2)20183578; e-Mail: ilya.lyapkalo@uochb.cas.cz;
Further Information

Publication History

Received 8 August 2007
Publication Date:
12 October 2007 (online)

Abstract

An α-deprotonation of carbonyl compounds with phos­phazene bases in the presence of the internal quenching reagent, nonafluorobutane-1-sulfonyl fluoride furnishes the corresponding alkenyl nonaflates. The new general method provides high yields of alkenyl nonaflates from aldehydes and cyclic ketones. However, it is not applicable to acyclic ketones whose nonaflate derivatives undergo fast E2 elimination to give alkynes. Successful synthesis of nonaflates from aldehydes requires carefully controlled reaction conditions to avoid the subsequent elimination to alkynes. A kinetic control enables high regioselectivities in favor of least substituted nonaflate regioisomers derived from cyclic ketones and modest Z-selectivities of alkenyl nonaflates derived from aldehydes. A new efficient protocol for highly selective removal of perfluorosulfolane admixture from technical nonafluorobutane-1-sulfonyl fluoride by basic hydrolysis is described.

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Trialkylamines are not basic enough to promote the nonaflation whereas DBU gives low conversions due to the side reaction with NfF. The results will be reported in a subsequent full account.

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While THF is more convenient and environmentally benign solvent, DMF is found to be advantageous for the Pd-catalyzed cross-couplings of alkenyl nonaflates.2g,5b,8 Hence, should one choose to carry out a subsequent coupling reaction without isolation of the nonaflate 4, DMF is a preferable solvent for the one-pot nonaflation-coupling sequence.

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General Procedure: A one-necked round-bottomed reaction flask equipped with a three-way tap and a teflon-coated magnetic stirring bar was heated with a heat-gun under vacuum for a few minutes and then cooled under an atmosphere of dry argon. A solvent (1 mL), a carbonyl compound 3 (1.00 mmol) and NfF (1.15 mmol) were successively added via syringe into the reaction flask. The mixture was cooled to 0 °C under vigorous stirring before P-base (1.15 mmol) was added dropwise. The three-way tap was quickly replaced with a glass stopper, and the reaction mixture was stirred at r.t. unless stated otherwise for α-methylcycloalkanones and aldehydes 3j,k (see Table [1] ). After the carbonyl compound 3 had been fully consumed (1H NMR control), the resulting mixture was quenched with H2O (5 mL) and extracted with pentane (4 × 25 mL). The combined organic phase was washed with H2O (20 mL) and dried (MgSO4). After the volatiles were removed carefully under reduced pressure on a rotary evaporator (÷100 mbar for 4a; ≤20 °C water-bath temperature for all the compounds), the residue was subjected to flash chromatography [silica gel, pentane for 4a-j, hexane-EtOAc (1:1) for 4k] to give pure enol nonaflates 4 as colorless or yellowish liquids.

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Kinetically controlled nonaflation of α-methylcyclo-alkanones 3f,g and aldehydes 3j,k was carried out according to the above procedure except that the temperature was kept at -30 °C in the case of 3f,j,k, and at -20 °C in the case of 3g. For the conversion of aldehydes 3j,k, 1.08 equivalents of P1-base was used.

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A general synthesis of alkynes or allenes from acyclic ketones and NfF depending on the base employed and the structural features of the ketones will be described by us elsewhere: Vogel, M. A. K.; Stark, C. B. W.; Lyapkalo, I. M.; manuscript in preparation.

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Spectroscopic Data: 1H NMR (400.23 MHz) and 13C NMR (100.65 MHz) data in CDCl3 (δ in ppm from internal SiMe4) of the selected products 4 are given below.
4b: 1H NMR (400.23 MHz, CDCl3): δ = 0.99 (d, 3 J = 6.4 Hz, 3 H, Me), 1.39-1.49 (1 H), 1.68-1.87 (3 H), 2.20-2.34 (2 H), 2.35-2.45 (1 H) (all m, 3 × CH2, CHMe), 5.73 (m, 1 H, CH=). 13C NMR (100.65 MHz, CDCl3): δ = 20.6 (Me), 27.3 (CHMe), 27.4, 30.6, 32.0 (all CH2), 118.0 (CH=C), 149.3 (CH=C). 4e: 1H NMR (400.23 MHz, C6D6): δ = 2.99 (s, 2 H, CH2), 6.17 (s, 1 H, CH=), 6.86-6.89 (1 H), 6.94-7.08 (all m, 3 H, CHAr). 13C NMR (100.65 MHz, C6D6): δ = 37.5 (CH2), 119.8 (CH=C), 122.4, 123.9, 126.3, 127.3 (all CHAr), 137.7, 140.3 (CAr), 153.7 (CH=C). 4h: 1H NMR (400.23 MHz, CDCl3): δ = 1.13 (t, 3 J = 7.2 Hz, 3 H, Me), 2.30-2.36 (m, 2 H, CH2), 2.56 (q, 3 J = 7.2 Hz, 2 H, NCH 2Me), 2.58 (t, 3 J = 5.8 Hz, 2 H, NCH 2CH2), 3.14 (m, 2 H, NCH2C=), 5.85 (m, 1 H, CH=C). 13C NMR (100.65 MHz, CDCl3): δ = 12.3 (Me), 24.3 (CH2), 48.5, 51.4, 52.6 (all NCH2), 116.6 (CH=C), 146.2 (CH=C). (Z)-4k: 1H NMR (400.23 MHz, CDCl3): δ = 1.70 (m, 2 H, CH2CH 2CH2), 2.14 (s, 3 H, MeCO), 2.22 (q, 3 J = 7.6 Hz, 2 H, CH 2CH=), 2.46 (t, 3 J = 7.3 Hz, 2 H, COCH2), 5.23 (td, 3 J = 5.6, 7.6 Hz, 1 H, CH=CHONf), 6.61 (br d, 3 J = 5.6 Hz, 1 H, CH=CHONf). 13C NMR (100.65 MHz, CDCl3): δ = 22.4, 23.6, 42.6 (all CH2), 29.9 (Me), 119.4 (CH=CHONf), 136.2 (CH=CHONf), 208.0 (C=O). (E)-4k: 1H NMR (400.23 MHz, CDCl3, non-overlapping signals only): δ = 2.08 (q, 3 J = 7.7 Hz, 2 H, CH 2CH=), 5.74 (dt, 3 J = 7.7, 11.8 Hz, 1 H, CH=CHONf), 6.56 (br d, 3 J = 11.8 Hz, 1 H, CH=CHONf). 13C NMR (100.65 MHz, CDCl3): δ = 22.6, 26.0, 42.3 (all CH2), 30.0 (Me), 121.7 (CH=CHONf), 136.8 (CH=CHONf), 207.9 (C=O).

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Although we did not aim at recovering phosphazene bases from side products, phosphazenium fluorides, the bases could be recovered via crystallization of their salts followed by treatment with a sufficiently strong inorganic base.13,14 We are currently working on the procedure employing catalytic quantities of the phosphazene bases in combination with heterogeneous strong inorganic base NaH or KH.