Subscribe to RSS
DOI: 10.1055/s-0037-1611958
Formation of COOH-Ylides, and Their Reactivities and Selectivities in Wittig Reactions
This work was supported by JSPS KAKENHI Grant Number JP15H05904.Publication History
Received: 18 November 2018
Accepted: 09 December 2018
Publication Date:
08 January 2019 (online)
Abstract
Whereas two equivalents of base are typically required to prepare carboxylate (CO2 –) ylides [Ph3P+C–(H)-alk-CO2 –] (alk = alkanediyl) from carboxy (CO2H) phosphonium salts [(Ph3PCH2-alk-CO2H)+] X–, we reveal, for the first time, that carboxy ylides [Ph3P+C–(H)-alk-CO2H] can be generated with one equivalent of NaHMDS at 0 °C, and that the Wittig reaction of simple aliphatic aldehydes (1 equiv) with these carboxy ylides (1.5–2 equiv) in THF at –95 to –90 °C for one hour, then at warming temperatures to 0 °C over two hours affords (Z)-alkenoic acids. Phosphonium salts containing (CH2) n alkanediyl chains (n = 2–5) showed adequate reactivity and high Z-selectivity, whereas shorter or longer alkanediyl chains resulted in a low Z-selectivity and/or a low yield. On the basis of these results with different (CH2) n chains and that obtained with a rigid methylene group, we propose that a rapid equilibrium between Ph3PCH 2-alk-CO2 – and Ph3P+C–(H)-alk-CO2 H, through an intramolecular hydrogen exchange, accounts for the success of the Wittig reaction.
Key words
Wittig reaction - carboxy phosphonium salt - carboxy ylides - carboxylate ylides - alkenoic acidsSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611958.
- Supporting Information
-
References and Notes
- 1 Nicolaou KC, Härter MW, Gunzner JL, Nadin A. Liebigs Ann. 1997; 1283
- 2a Perlmutter P, Selajerern W, Vounatsos F. Org. Biomol. Chem. 2004; 2: 2220
- 2b Han X, Crane SN, Corey EJ. Org. Lett. 2000; 2: 3437
- 2c Nicolaou KC, Prasad CV. C, Ogilvie WW. J. Am. Chem. Soc. 1990; 112: 4988
- 2d Delorme D, Girard Y, Rokach J. J. Org. Chem. 1989; 54: 3635
- 3a Baars H, Classen MJ, Aggarwal VK. Org. Lett. 2017; 19: 6008
- 3b Prévost S, Thai K, Schützenmeister N, Coulthard G, Erb W, Aggarwal VK. Org. Lett. 2015; 17: 504
- 3c Quan LG, Cha JK. J. Am. Chem. Soc. 2002; 124: 12424
- 3d Boulton LT, Brick D, Fox ME, Jackson M, Lennon IC, McCague R, Parkin N, Rhodes D, Ruecroft G. Org. Process Res. Dev. 2002; 6: 138
- 3e Grieco PA, Reap JJ. J. Org. Chem. 1973; 38: 3413
- 4a Srinivas J, Namito Y, Matsubara R, Hayashi M. J. Org. Chem. 2017; 82: 5146
- 4b Ishigami K, Kobayashi M, Takagi M, Shin-ya K, Watanabe H. Tetrahedron 2015; 71: 8436
- 4c Critcher DJ, Connolly S, Wills M. J. Org. Chem. 1997; 62: 6638
- 4d Wang SS, Shi X.-X, Powell WS, Tieman T, Feinmark SJ, Rokach J. Tetrahedron Lett. 1995; 36: 513
- 4e Just G, Wang ZY. J. Org. Chem. 1986; 51: 4796
- 5a Ortgies S, Rieger R, Rode K, Koszinowski K, Kind J, Thiele CM, Rehbein J, Breder A. ACS Catal. 2017; 7: 7578
- 5b Hao H.-D, Trauner D. J. Am. Chem. Soc. 2017; 139: 4117
- 5c Liu Y.-T, Chen J.-Q, Li L.-P, Shao X.-Y, Xie J.-H, Zhou Q.-L. Org. Lett. 2017; 19: 3231
- 5d Paull DH, Fang C, Donald JR, Pansick AD, Martin SF. J. Am. Chem. Soc. 2012; 134: 11128
- 5e Poth D, Wollenberg KC, Vences M, Schulz S. Angew. Chem. Int. Ed. 2012; 51: 2187 ; Angew. Chem. 2012, 124, 2229
- 5f Wube AA, Hüfner A, Thomaschitz C, Blunder M, Kollroser M, Bauer R, Bucar F. Bioorg. Med. Chem. 2011; 19: 567
- 5g Seike H, Ghosh I, Kishi Y. Org. Lett. 2006; 8: 3865
- 5h Mascitti V, Corey EJ. J. Am. Chem. Soc. 2006; 128: 3118
- 6 Maryanoff BE, Reitz AB, Duhl-Emswiler BA. J. Am. Chem. Soc. 1985; 107: 217
- 7a Ling-Chung S, Sales KD, Utley JH. P. J. Chem. Soc., Chem. Commun. 1990; 662
- 7b Zhang X.-M, Bordwell FG. J. Am. Chem. Soc. 1994; 116: 968
- 7c Bordwell FG, Algrim D. J. Org. Chem. 1976; 41: 2507
- 7d Grimm DT, Bartmess JE. J. Am. Chem. Soc. 1992; 114: 1227
- 7e Fraser RR, Mansour TS, Savard S. J. Org. Chem. 1985; 50: 3232
- 7f Olmstead WN, Margolin Z, Bordwell FG. J. Org. Chem. 1980; 45: 3295
- 7g Hulla M, Chamam SM. A, Laurenczy G, Das S, Dyson PJ. Angew. Chem. Int. Ed. 2017; 56: 10559
- 7h Bordwell FG, McCallum RJ, Olmstead WN. J. Org. Chem. 1984; 49: 1424 ; and also ref. 7c
- 8a pK a Values in THF for most of compounds shown in ref. 7 are not available, except for that of HN(TMS)2, which is almost the same in THF as in DMSO.7d,e Therefore, values of other compounds in DMSO are quoted for discussion of the relative acidity.
- 8b For a collection of pK a values of compounds, see: Bordwell FG. Acc. Chem. Res. 1988; 21: 456
- 9 The 1H NMR spectrum of 3 was superimposed with that of the (E)-isomer, which was synthesized by a method described in the Supplementary Information.
- 10 Signal-to-noise ratios of the 1H and 13C NMR spectra were ~95% and ~97%, respectively.
- 11 Alkenoic acid 7 was previously synthesized by using 2c and t-BuOK (1:2); the 13C NMR spectrum provided in the Supporting Information of ref. 5a (page S97) allowed us to calculate the Z-selectivity to be 90%, by using the peak heights.
- 12 Hands AR, Mercer AJ. H. J. Chem. Soc. C 1968; 2448
- 13a Zeng X, Miao C, Wang S, Xia C, Sun W. Chem. Commun. 2013; 49: 2418
- 13b Meyers AI, Collington EW. Tetrahedron 1971; 27: 5979
- 14 Phosphonium salt 2a and NaHMDS were mixed in a ratio of 0.8:1 or 2.1:1 then quenched with D2O (10 equiv). However, the recovered material showed complicated 1H NMR spectra, which prevented calculation of the incorporation of deuterium into 2a.
- 15a Byrne PA, Gilheany DG. Chem. Soc. Rev. 2013; 42: 6670
- 15b Maryanoff BE, Reitz AB. Chem. Rev. 1989; 89: 863
- 15c Maryanoff BE, Reitz AB, Mutter MS, Inners RR, Almond HR. Jr, Whittle RR, Olofson RA. J. Am. Chem. Soc. 1986; 108: 7664
- 16 A molecular model of the (E)-5-carboxypent-3-en-1-ylphosphonium salt, the trans-olefin analogue of 22, showed easy access to E.
- 17 (4Z)-7-Phenylhept-4-enoic acid (3; Table [1], Entry 1); Typical Procedure A 1.0 M solution of NaHMDS in THF (1.0 mL, 1.0 mmol, 2 equiv) was added to an ice-cold suspension of 2a (432 mg, 1.01 mmol, 2 equiv) in THF (5 mL). The mixture was stirred at 0 °C for 1 h and then the resulting reddish-orange mixture was cooled to −95 to –90 °C in a slushy mixture of hexane and liquid N2. A solution of aldehyde 1 (67 mg, 0.50 mmol, 1 equiv) in THF (1.5 mL) was added dropwise to the mixture. After 1 h, the mixture was warmed to 0 °C over 2 h then sat. aq NH4Cl was added. The resulting mixture was extracted with Et2O (×3). The extracts were combined, dried (MgSO4), and concentrated to afford a residue that was purified by chromatography (silica gel, hexane–EtOAc) to give a colorless liquid; yield: 66 mg (63%, Z / E = 90:10); Rf = 0.13 (hexane–EtOAc, 4:1). IR (neat): 2924, 1710, 699 cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.5–3.0 (br s, 1 H), 2.24–2.44 (m, 6 H), 2.66 (t, J = 7.5 Hz, 2 H), 5.30–5.42 (m, 1 H), 5.42–5.53 (m, 1 H), 7.14–7.32 (m, 5 H). 13C-APT NMR (75 MHz, CDCl3): δ = 22.5 (–), 29.2 (–), 34.0 (–), 35.8 (–), 125.9 (+), 127.9 (+), 128.3 (+), 128.5 (+), 130.5 (+), 141.9 (–), 179.8 (–). HRMS (FAB+): m/z [M + Na]+ calcd for C13H16NaO2: 227.1048; found. 227.1045. Note that candy-like phosphonium salts, such as 2f, or longer-chain methylene salts were heated to form a viscous mass that was transferred quickly to the reaction flask. After the addition of THF and a solution of NaHMDS, the mixture was sonicated at 0 °C until the candy-like phosphonium salt that caked in the flask was sufficiently dissolved to allow smooth stirring. The mixture was stirred at 0 °C for a total of 1 h after the addition of NaHMDS, then cooled to –90 °C before addition of aldehyde 1.
For example:
For example:
For examples, see:
For examples, see:
For pK a values in DMSO of phosphonium salts (14–23), see:
For carboxylic acids (pK a= 12–13) see:
For HN(TMS)2 (pK a= 26), see:
For HN(TMS)2 in THF (pK a= 25.8), see:
For t-BuOH (pK a= 32) and ROH (R = Me, Et) (pK a= 29–30), see;
For DBU·H+ (pK a= 14), see:
Angew. Chem. 2017, 129, 10695. For PhOH (pK a= 16–18), see:
For examples, see: