Patent FR-2844791-A1 (FR)
Title: Preparation of diastereoselective olefins by Homer-Wadsworth-Emmons reaction in which phosphonate is reacted with carbonyl compound in presence of base and with addition of tris-(polyoxaalkyl)-amine sequestrant
Inventor: TOUCHARD FRANCOIS
IPC: C07C67/343
Filed: 2002-09-23
Abstract: A diastereoselective preparation of olefins by a low temperature reaction between a phosphonate and a carbonyl compound in a base and solvent, with addition of a suitable amount of a tris(polyoxaalkyl)amine sequestrant to increase the diastereoselectivity.  Preparation of diastereoselctive olefins(C) by a Horner-Wadsworth-Emmons reaction, consisting of a low temperature reaction of a phosphonate(A) with a carbonyl derivative(B) in the presence of a base in an appropriate solvent. Y  =  -COOR, -CN, -C(O)R, -SR, -S(O)R, -S(O)2R, -C(O)NRR'. -N=CRR' or -P(O)OROR';  R6, R7  =  1 - 24C aliphatic, 4 - 24C cycloaliphatic or aliphatic attached to a cyclic substituent, optionally substituted by heteroatoms in the aliphatic and/or cyclic part;  R10, R, R'  =  H, 1 - 24C aliphatic, 4 - 24C cycloaliphatic(optionally substituted by heteroatoms) or aliphatic with a cycloaliphatic substituent;  R8  =  R, halogen, -OR, -NRR';  R9  =  1 - 24C aliphatic, 4 - 24C cycloaliphatic or aliphatic with a cyclic substituent, on condition that P9 is prioritised relative to R10 according to Cahn, Ingold and Prelog rules. (R6, R7, R and R' together may form a ring , optionally with heteroatoms). A sequestrant agent is also added, consisting of a tris(polyoxaalkyl)amine of formula (I) : N-(CHR1-CHR2-O-(CHR3-CHR4-O)n-R5)3 in which  n  =  0 - 10;  R2, R2, R3, R4  =  H or 1 - 4C alkyl;  R5  =  H, 12C max alkyl or cycloalkyl, phenyl or a radical -CmH2m-OMEGA or CmH2m + 1OMEGA;  m  =  1 - 12;  OMEGA  =  phenyl. More preferably, the compound (I) is one in which :- R1, R2, R3, R4 = H or Me ; n = 0 - 3 ; and R5 = H, or 1 - 4C alkyl ; and especially a compound in which R1 = R2 = R3 = R4 = H ; n = 1 ; and R5 = Me. The amount of sequestrant is 0.05 - 10 equivalents per equivalent of phosphonate, aldehyde and base, all present in solution in the solvent. The preferred phosphonate (A) is one in which Y = COOMe, R6 and R7 = -CH2CF3 and R8 = H. The carbonyl derivative is preferably an aldehyde(R10 = H) and R9 is an aliphatic radical (n-C7H15 or cyclohexyl) ; alternatively R9 is 1 - 6C alkoxy or halogen-substituted aromatic, more preferably phenyl. The base is chosen from  (1)  (a) amides MNR''R'''(M = Li, Na, or K) , R'' and R''' being alkyl or alkylsilane;  (2)  (b) alcoholates MOR''(M = Li, Na or K);  (3)  (c) hydrides MH;  (4)  (d) carbonates M2CO3 (M = alkali or alkaline earth metal);  (5)  (e) LiOH, NaOH, KOH, CsOH, Mg(OH)2, or Ba(OH)2;  (6)  or (f) organic bases such as 1,8-diazabicyclo(5.4.0)undec-7-ene, 1,1,3,3-tetramethyl-guanidine or 1,4-diazabicyclo(2.2.2)octane. More preferably the base is the K salt of hexamethyldisilazane(KHMDS) or tertiobutylate(tBuOK). A polar solvent is used, preferably an etherated compound from tetrahydrofuran(THF) or methyl-tertbutyl ether(MTBE).The amount of solvent is 0.1 - 20 ml per mmol of phosphonate. The reaction temperature is maintained at 0degreesC or less, more preferably -20degreesC and especially -50degreesC or less.