A Straightforward, Purification-Free Procedure for the Synthesis of Ando and Still–Gennari Type Phosphonates

Abstract

Z-Selective Still–Gennari and Ando modifications of the typically E-selective Horner–Wadsworth–Emmons reaction are highly valuable synthetic tools in organic chemistry. These procedures are based on application of bis(2,2,2-trifluoroethyl) phosphonates or diaryl phosphonates, respectively, for the olefination of carbonyl groups. In our research, we present an improved, straightforward, purification-free procedure for the synthesis of these reagents. The key step of our procedure is the reaction of phosphonic dichlorides with the appropriate sodium alkoxides, which results in 52–97% isolated yields of the desired products on a gram scale. The whole three-step process is performed in one pot. Most importantly, the product is obtained in over 95% purity after simple extraction, avoiding column chromatography and distillation. Moreover, we present the synthesis of a novel Still–Gennari type reagent, bis(1,1,1,3,3,3-hexafluoroisopropyl) phosphonates, which may exhibit improved Z-selectivity in Still–Gennari olefinations.

Key words

Horner–Wadsworth–Emmons (HWE) reaction - Still–Gennari olefination - Ando olefination - stereoselective synthesis - Wittig reaction - phosphonates - alkenes - C=C bond formation

Publikationsverlauf

Eingereicht: 01. Juli 2021

Angenommen nach Revision: 01. September 2021

Accepted Manuscript online:
01. September 2021

Artikel online veröffentlicht:
13. Oktober 2021

• References

• 1a Kobayashi K, Tanaka KIII, Kogen H. Tetrahedron Lett. 2018; 59: 568
• 1b Bisceglia J. Á, Orelli LR. Curr. Org. Chem. 2012; 16: 2206
• 1c Bisceglia J. Á, Orelli LR. Curr. Org. Chem. 2015; 19: 744
• 1d Maryanoff BE, Reitz AB. Chem. Rev. 1989; 89: 863
• 1e Horner L, Hoffmann HM. R, Wippel HG. Chem. Ber. 1958; 91: 61
• 1f Horner L, Hoffmann HM. R, Wippel HG, Klahre G. Chem. Ber. 1959; 92: 2499
• 1g Wadsworth WS, Emmons WD. J. Am. Chem. Soc. 1961; 83: 1733
• 1h Roman D, Sauer M, Beemelmanns C. Synthesis 2021; 53: 2713
• 2 Nagaoka H, Kishi Y. Tetrahedron 1981; 37: 3873
• 3a Breuer E, Bannet DM. Tetrahedron Lett. 1977; 1141
• 3b Patois C, Savignac P. Tetrahedron Lett. 1991; 32: 1317
• 4 Still WC, Gennari C. Tetrahedron Lett. 1983; 24: 4405
• 5a Ando K. Tetrahedron Lett. 1995; 36: 4105
• 5b Ando K. J. Org. Chem. 1997; 62: 1934
• 5c Ando K. J. Org. Chem. 1998; 63: 8411
• 6 Janicki I, Kiełbasiński P. Adv. Synth. Catal. 2020; 362: 2552
• 7a Motoyoshiya J, Kusaura T, Kokin K, Yokoya S, Takaguchi Y, Narita S, Aoyama H. Tetrahedron 2001; 57: 1715
• 7b Ando K. J. Org. Chem. 1999; 64: 6815
• 8a Messik F, Oberthür M. Synthesis 2013; 45: 167
• 8b Molnár K, Takács L, Kádar M, Kardos Z, Faigl F. Synthesis 2015; 47: 1085
• 8c Sano S, Matsumoto T, Toguchi M, Nakao M. Synlett 2018; 29: 1461
• 9a da Silva Prado V, Burtoloso AC. B. Synthesis 2010; 361
• 9b Yu W, Su M, Jin Z. Tetrahedron Lett. 1999; 40: 6725
• 9c Zhang TY, O’Toole JC, Dunigan JM. Tetrahedron Lett. 1998; 39: 1461
• 9d Ando K. Synlett 2001; 1272
• 9e Kojima S, Hidaka T, Ohba Y, Ohkata K. Phosphorus, Sulfur Silicon Relat. Elem. 2002; 177: 729
• 9f Fortin S, Dupont F, Deslongchamps P. J. Org. Chem. 2002; 67: 5437
• 9g Kokin K, Tsuboi S, Motoyoshiya J, Hayashi S. Synthesis 1996; 637
• 9h Midura WH, Ewas AM. M, Mikołajczyk M. Phosphorus, Sulfur Silicon Relat. Elem. 2016; 191: 535
• 9i Davis AA, Rosén JJ, Kiddle JJ. Tetrahedron Lett. 1998; 39: 6263
• 9j Janicki I, Kiełbasiński P. Synthesis 2018; 50: 4140
• 10a Touchard FP. Eur. J. Org. Chem. 2005; 1790
• 10b Touchard FP, Capelle N, Mercier M. Adv. Synth. Catal. 2005; 347: 707
• 10c Kokin K, Iitake K.-I, Takaguchi Y, Aoyama H, Hayashi S, Motoyoshiya J. Phosphorus, Sulfur Silicon Relat. Elem. 1998; 133: 21