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

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.

Key words

chemoselectivity - nonafluorobutane-1-sulfonyl fluoride - ketones - regioselectivity - alkenyl nonaflates

References and Notes

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• For Heck reaction, see:
• 2a Webel M. Reissig H.-U. Synlett  1997,  1141 
• 2b Bräse S. Synlett  1999,  1654 
• 2c Lyapkalo IM. Webel M. Reissig H.-U. Eur. J. Org. Chem.  2001,  4189 
• 2d Lyapkalo IM. Webel M. Reissig H.-U. Eur. J. Org. Chem.  2002,  3646 
• 2e Högermeier J. Reissig H.-U. Brüdgam I. Hartl H. Adv. Synth. Catal.  2004,  346:  1868 
• 2f Lyapkalo IM. Högermeier J. Reissig H.-U. Tetrahedron  2004,  60:  7721 
• 2g Vogel MAK. Stark CBW. Lyapkalo IM. Adv. Synth. Catal.  2007,  349:  1019 
• 3 For Negishi reaction, see: Bellina F. Ciucci D. Rossi R. Vergamini P. Tetrahedron  1999,  55:  2103 
• For Stille reaction, see:
• 4a Wada A. Ieki Y. Ito M. Synlett  2002,  1061 
• 4b Wada A. Ieki Y. Nakamura S. Ito M. Synthesis  2005,  1581 
• For Suzuki reaction, see:
• 5a Högermeier J. Reissig H.-U. Synlett  2006,  2759 
• 5b Högermeier J. Reissig H.-U. Chem. Eur. J.  2007,  13:  2410 
• For Sonagashira reaction, see ref. 4 and:
• 6a Suffert J. Eggers A. Scheuplein SW. Brückner R. Tetrahedron Lett.  1993,  34:  4177 
• 6b Okauchi T. Yano T. Fukamachi T. Ichikawa J. Minami T. Tetrahedron Lett.  1999,  40:  5337 
• 6c Lyapkalo IM. Vogel MAK. Angew. Chem. Int. Ed.  2006,  45:  4019 ; Angew. Chem. 2006, 118, 4124
• 7a Zimmer R. Webel M. Reissig H.-U. J. Prakt. Chem.  1998,  340:  274 ; and references cited therein
• 7b Lyapkalo IM. Webel M. Reissig H.-U. Eur. J. Org. Chem.  2002,  1015 
• 7c Aulenta F. Reissig H.-U. Synlett  2006,  2993 
• 8 Lyapkalo IM. Webel M. Reissig H.-U. Synlett  2001,  1293 
• 9 Subramanian LR. Bentz H. Hanack M. Synthesis  1973,  293 
• 10 Bürger H. Heyder F. Pawelke G. Niederprüm H. J. Fluorine Chem.  1979,  13:  25l 
• 11a Lithium amide bases readily react with NfF even at low temperature to give the anticipated nonafluorobutane-1-sulfonamides: Lyapkalo IM. Reissig H.-U. Schäfer A. Wagner A. Helv. Chim. Acta  2002,  85:  4206 
• 11b

  For this reason, only the stepwise procedure is possible. See refs. 5b and 8.

• 13 It has the highest basicity (pK _a = 28.35 in MeCN) among commercially available P₁-bases: Schwesinger R. Willaredt J. Schlemper H. Keller M. Schmitt D. Fritz H. Chem. Ber.  1994,  127:  2435 
• 14a

  Commercially available as a 2 M solution in THF (pK _a = 33.49 in MeCN).

• 14b According to the primary classification given by Schwesinger, the subscript designates the number of P-atoms in the molecule. For the synthesis and properties of P₂- or higher-order phosphazene bases, see: Schwesinger R. Schlemper H. Hasenfratz C. Willaredt J. Dambacher T. Breuer T. Ottaway C. Fletschinger M. Boele J. Fritz H. Putzas D. Rotter HW. Bordwell FG. Satish AV. Ji GZ. Peters EM. Peters K. von Schnering HG. Walz L. Liebigs Ann.  1996,  7:  1055 ; and references cited therein
• 15 This mode of reactivity termed as internal quenching was originally described by Corey and Gross for highly regio- and stereoselective synthesis of silyl enolates by deprotonation of carbonyl compounds with lithium dialkylamide bases in the presence of trialkylsilyl chlorides. See: Corey EJ. Gross AW. Tetrahedron Lett.  1984,  25:  495 
• 22 Subramanian LR. Hanack M. Chem. Ber.  1972,  105:  1465 
• 23 Rottländer M. Knochel P. J. Org. Chem.  1998,  63:  203 
• Nonaflate anion can easily be precipitated from aqueous solutions in form of a stable, non-hygroscopic potassium salt which is described as an efficient flame retardant additive in transparent polycarbonate compositions. See:
• 24a Singh RK, and Lin Y.-G. inventors; U.S. Patent Appl., US  2005009968. 
• 24b Singh RK, Rosenquist NR, and Fischer JM. inventors; U.S. Patent Appl., US  6462111. 

12

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.

16

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.

17

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.

18

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.

19

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.

20

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, CH_Ar). ¹³C NMR (100.65 MHz, C₆D₆): δ = 37.5 (CH₂), 119.8 (CH=C), 122.4, 123.9, 126.3, 127.3 (all CH_Ar), 137.7, 140.3 (C_Ar), 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).

21

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.