The alkylation of silyl enol ethers with SN1-unreactive iodides in the presence of silver trifluoroacetate

0040-4039B2 $3 00 + I Pcrgamon Pacts Ltd The Alkylation of Silyl Enol Ethers with S, 1 -Unreactive Iodides in the Presence of Silver Trifluoroacetate Charles W. .Jefford, Adam W. Slecleski, Patrick Lelnndais, and John Boukouvalas Depstment of Orgnn~c Chenurtry, Unwersay of Geneva 1211 Geneva 4. Swtzerland The alkylation of carbonyl compounds at the CL position is an important reaction for forming the carbon- carbon bond 1 In prmclple, alkylatlon can be carried out by treating a carhonyl compound with a strong base, such as lithium ditsopropylarmde. and then allowing the resultmg enolate to react with an alkyl halide or to- qylate 2 Unfortunately, ttus apparently simple proce~ 1s drfficult to achieve in practice. Unwanted side-react- ions, such as O-alkylatron, bls-alkylntlon and nldol condensation usually occur X4 Furthermore, unsym- metrical ketones are hable to be alkylated ,lt both rhe c1 and CI’ positions. 5 In contrast to the alkali metal eno- lates, which require preparation irt alto, sly1 enol ethers are better behaved They are stable reagents and on catalysis with Lewis acids undergo exclusive mono-C-alkylatlon 4*6 However, the reJctlon only works well for those alkyl hahdes which are able to form stable carbocations 7-o Typ~nlly, f-butyl, benzyl, ally1 and a-slkoxyalkyl halides are effective, 6,to,11 whereas n-butyl iodide and slmllnr primary n-alkyl halides fail to react.12 Until now th1.s limitation has been clrcurnvented by actlvatmg one of the reactIon partners. lS1$ For example, tl-butyl bromide (1) may be converted into n-butyl phenyl sulfide (2) which on chlonnation fur- mshea the requlslte alkylatmg agent, u-pheny!thlo-Ii-butyl chloride (3). Treatment of 3 with stlyl enol ether 4, followed by reductive desulfurization of the alkylated product 5, affords the desired rz-pentyl ketone 6 m four steps I5 Y’ 0 N NaSPh v F’ n-C&gBr - c n-CqHgSPh n-C,H,CHSPh 1 2 3 /jXIMQ TICL, SPh 3 + CHz=C, FA n-C,H,CHCH2COR Ray NI n-&H,,COR 4 R 5 6 CF,CO,Ag - I \ + RX Me,80 0 -a 0 0 H 7 8 In the hght of previous expcrlence, it occurred to us that this cucultous procedure could be avoided by the Gmple expedient of adding an external actlvatmg agent We have demonstrated that silver trlfluoroacetate enables both SNl-reactive and SNl-unreactive alkyl halides to react with 2-tnmethylsiloxyfuran (7) to give the 4-substituted butenohdes (8) 16,17 We now report that ordmary enol ethers, which are expected to be less nu~lrophll~c than 7, are equally susccptiblr to all\ylunon *when silver tnfluoroacetlte is used 1855 856 Table, Alkylation of some Silyl En01 Ethers in the Presence of Silver Trifluoroacetate Entry Ether AIkyl iodtde Temp. OC Product=) Yieldb) (%) -70 d 25 0 a Bu-n 10 2 9 rr-BuI 25 10 3 9 Mel 0 25 a Me 4 9 EtO,CCH,I S!Meg%-t 5 n-BuI 13 &o S1Me3 6 I n-&11 14 I 0” SiMEl, I n-Eli1 16 8 16 Me1 9 Ph 19 n-BuI 2.5 11 (Z-J? CH,C02Et 12 25 10 -70 --f 25 G? &I-n 17 0 0 a Me -70 --f 25 PhCO-Pentyl-n 20 56 52 83 50 43 54 49 78 27 “‘Alkylated products were characterized by comparison with authentic samples (IH-NMI? spectral and glc data) b)Yields were determined by quantitative glc analysis using an internal standard. 1857 First of all, the alkylatmn ok l~iuunethylsiloxy)-cyclohexene (9) was explored. By using equimolecular quantltles of 9, n-butyl Iodide and sliver mfluoroacetate, the desired butylated product 10 was ob&lned in yields of 52-56s dependmg on the temperature (Table, enmes 1, 2) I8 Attempts to Improve the yield by in- creasing the amounts of n-butyl iodide or silver trifluoroacetate were unsuccessful. Further examination of the product mixture revealed that there was some hydrolysl$ tD cyclohexanone, l7 but slgmficantly, no polymer- tzatlonlg or side-reactions were observed even when the expenment was carrted out at room temperature.20 The nature of the alkyl halide appears to be crucial. Both n-butyl brormde or I$opropyl iodide were tnert towards 9 Pnm;lry alkyl ~od~des however were conslrtently reactive The best yield was shown by methyl Iodide (entry 3), while ethyl todoacetate was Just as efficient as n-butyl todide (entnes 2, 4) Employment of the bulkier I-(dtmethyl-r-butylsiloxy)cyclohexene (131Z1 resulted 111 a somewhat poorer yield of n-butylated product 10 (entry 5) 22 Even the potentldlly more reactive cychc silyl ketene acetal 1423 underwent n-butylation to about the same extent 2s 9 (entries 1, 6) Lastly, I-(mmethylbtloxy)cyclopentene (16) and ol-(trunethylslloxy)styrene (19) were studied. The be- havlor of I6 towards butylatlon and methylntion was comparable to that of the analogous compound 9; similar yields of 17 and IS were obtamrd (entnes 2, 3 and 7, 8). The acychc ether 19 gave a poor yield of butylated product (20) (entry 9) In conclu~ton, it 1~ seen that silver trtfluoroacetate, unlike conventtonal Lewis acids such as tttaruum chloride and zmc bromide, complexes with dnd activates the alkyl iodide wtthout overly damaging the acid- sensmve enol ether The resulting complex behaves essentially as a ‘soft’ elecuophlhc alkyl cation which then undergoes nucleophllic displacement by the enol ether Subsequent desllylatlon hberates the carbonyl funct- ion.24 Although yields are generally moderate, the present method offers certam synthetic advantages. It IS short, mild, easy to execute and does not require an excess of any of the reagents. Acknowledgments We are indebted to the Swiss Natlonai Scuwce Foundutmn (grant No 20-27’966 89) for support of this work We thank Mr Potrlrk M~rti for preparing compound 13 References and Notes 1 Stork, G Pure Appl Chem 1975, 43, S53, Came, D. in Curbott-Carbon Bond Formutlon (Ed. R L. Augustme), Marcel Dekker, New York, NY, 1979, Vol. 1, p. 85, Evans, D A in Asymmetric Synthesis (Ed J.D Morrison), Academic Press, Orlando, FL, 1984, Vol. 3 (Part B), p l-1 10. 2. d’Angelo, J Terruhedron 1976, 32, 2979, Durst, T in Comprehensive Carbumon Chemistry (Eds. E. Buncel and T. Durst), Elsevier, Amsterdam, 1984, Vol. 5B, pp, 239-291 3 Carruthers, W Some Modern Merhods rif Orgunr~ Synthesis, 3rd edmon, Cambridge University Press, 1986, pp. 12-26. 4 Flemmg. I Chuma 1980.34, 265. 5. Vat-lous additives have been used to suppress undesired a-proton exchange and thus improve the effi- ciency of enolate alkylation. Tardella, P.A Ten?ri?edro,l Lerr 1969, 1117, Rathke, M.W., Lmdert, A Syllth Cnmmun 1978, 8, 9: Haynes, R K , Lambert, D E , Schober, P A , Turner, S.G, Aust, J. Chem. 1987,40. 1211. Morlta, Y ; Suzuki, M., M., Noyon, R J Org Chem 1989,54, 1785 6. Reetz, M.T. Angew Chem Int Ed 1982,21,96, Brownbridge, P. Synthens 1983, 1, 8.5. 7. Weber, W P. S&cnrl ReagcntsjLr Organ? Symhesrs, Sprmger-Verlag, Berlm, 1983, pp 206-208 858 x. 9 10 11 12 13. 14. 15. 16 17 18 19. Allyhc and benzylic sulfides readily alkylate ~11~1 enol ethers and srlyl ketene acetals in the presence of stlver trillate Takeda, K : Torn, K , Ogura, H Tetrahedron Lctt , 1990,31, 265. For the Pd(0) catalyzed allylatton of silyl en01 ethers, see. Baba, T.; Nakano, K , Nishiyama, S.; Tsqa, S , Maw, M. J Chem Sot , Chem Cammun. 1990, 34X Reetz, M T : Miiller-Starke, H. Li&ys Ann Chem 1983, 1726: Hosomi, A ; Sakata, Y., Sakurai, H. C’hcm Left. 1983,405; Emus, G A : EIon, Y -S. J Am Chem Sor- 1985, 107,434l. Reetz, M T., Chatniostfidrs, I . Hdbnet, F., Helmbach, H 0~s Synth 1984,152, 95, Paterson, I Tcffah@dron Let; 1979, 1519; Takagaki, H , Yasuda, N , Acaoka, M , Takei, H B&[ C&m. Sot Jpn 1979.52, 1241, Wheeler, TN J Org Chem 1984,30,706 For methods mvolvmg activation of the silyl enol ether by conversion to a more reactive enolate, see: Stork, G.; Hudrltk, P.F. J Ant Client Snc 1968, 00, 4464, Bmkley, E S , Hr.dthcock, C.H. J 0~ Chem 1975, 40, 2156, KuwaJm~a, I.. N&amura, t : Shunizu, M J An1 C’hrf?r Sot 1982, 104, 1025; Noyon, R., Ntshtda, I., Sakata, J J Am. rhprn SOL 1983, 105, 1598, Kuw:1jlma, I. Nakamura, E Ace Chum Res 1985, IS, 181 Rzetz, M T , Htittenham, S : Wall. P , Lowe, U I‘errahedTnn I,rrt 1979. 4971 Paterson, I., Fleming, I Terruhdron Letr 1979, 2179; Flcnnng, 1. Rrtl/ Sue Chim Fr 1981, 11-7; Paterson, I Tiwzhc>dr on 1988, 44, 4207 Jefford, C W.; Sledeski, A W , Boukouvalns, J Tetrahedron Lert 1987, 28, 949, J. Chum Sot , Chem. Commun. 1988, 364, Jefford. C’.W., Sledeski, A W., Rower, J -C, Boukouvalas, J, Trwuhedron L&t. 1990, 31, 5741; Jefford, C.W , Huang, P -2, Ross&, 3 -C 1 Sledeski A W., Boukouvalas, J Synlert 1990,745. Jefford, C W.; Sledeski, A W , Boukouvalas, J. He/v Chim Acre 1989, 72, 1362 General procedure The sly1 enol ether (2 mmol) dnd alkyl halide (2 1 mmol) are successively added to a suspension of AgOCOCF3 (2 1 mmol) in dry CH2Cl2 (2 ml) with stirring under argon at -70 to 25O C (see Table). The reaction is usually complete after 10 mm at 25O C Finally, the mtxture 1s filtered over c&e. Exposure of srlyl enol ethers to conventtonal Lewis acid\ (e. g TtClq) gtves polymeric materials even at subzero temperatures. Ghan, T H: Paterson, I., Pmsonnault, J T@trahedr-nn Left 1977, 4183: see also note 10 in ref 11 Quantitative analyw of the product mixture by glc revealed that the cornbmed yield of 10, cyclohexa- none and 9 1s 100% Clark, R D , C’ntch. KG. J 01x Ciwnr 197Y, 44, 23X For the effect of smcon substituents on the phenylthiomethylatton of s11yl dienol ethers, see. Flemmg, I.; Lee, T.V Tcvruhedrnn Lett 1981. 705. Rubottom, G M : Gruber. J M Marrero, R : luve, Ir ~ H U ~ Kun, C W I 0’~ C&w 1118% 48,4P40 An analogous mechamsm was proposed for the alkylation of 2-~llnethylslloxyfurari (see ref. 17) (Received in Germany 21 November 1991)