Conversion of Propargylic Alcohols to β‐Oxo Esters Catalyzed by Novel Ruthenium‐Phosphoramidite Complexes

Abstract

A series of half-sandwich phosphoramidite complexes of ruthenium were synthesized and employed as catalysts in the atom-economical formation of b-oxo esters from carboxylic acids and propargylic alcohols. Reaction of the phosphoramidites (R)-BINOL-PNR 2 (R = Me, 1a; i-Pr, 1b; benzyl, 1c) and (rac)-6,6'-dibromo-BINOL-PNMe 2 (1d) with the di- propargylic alcohols and carboxylic acids. Standard conditions involve cyclohexane solvent, propargylic alcohol (1.0 equiv.), carboxylic acid (1.0 equiv.), ruthenium catalyst (1.5 mol%), and 90 8C for 5-18 h. Isolated yields of the b-oxo esters range from 87 to 16% and show broad substrate generality. The reaction proceeds without racemization if a chiral propargylic alcohol is employed. The method is practical as no additives are required and the exclusion of oxygen and moisture is not needed. Complex 7c turned out to be the most effective catalyst (5 h reaction time), showing that the ligand structure has a profound impact on the catalytic performance. The crystal structure of 7a was determined, confirming an octahedral coordination geometry about the ruthenium center.

Atom Economic Ruthenium‐Catalyzed Synthesis of Bulky β‐Oxo Esters

“…[27] So far, just with complex[ RuCl 2 (pcymene){(R)}-BINOL-N,N-dibenzyl-phosphoramidite}] (14)r eported by Bauer et al acceptable yields in the conversion of 1,1-diphenylprop-2-yn-1-ol (1i)t o benzoic acid 2-oxo-1,1-diphenylpropyl ester (3i)w ere obtained. [28] All other systems failed in this conversion as they could only detect trace amounts of the desired product. [27,46] By applying catalyst 6g we could now isolate7 4% of product 3i in 4hat 80 8 8C, whereas with complex 14 just 68% after 5hat 90 8 8Cw ere achieved.…”

“…This factc an be explained by af acilitated activation of the electron-rich C Ct riple bondb yc oordination of the propargylic alcohol to the electrophilic ruthenium atom. However, the low yields obtained with electron-rich substrates suggest that not only the formation of the b-oxo esters is accelerated, but also that undesireds ider eactions take place.F or this reason the crude reactionm ixturesw ere analyzed by GC-MS.T hereby, olefinic side productsr esulting from the cleavageo ft he C Cb ond [27,28,47] or a,b-unsaturated vinyl aldehydesa rising from aM eyer-Schuster-type rearrangement [46,48] of the propargylic alcohol were observed. Bothr eactionp athways have already been reported to occur in the ruthenium-catalyzed addition of carboxylic acids to propargylic alcohols.…”

“…[27][28][29] Results and Discussion Synthesis 2 ] with basic phosphinel igands (6a,R= n-Bu; 6b,R= pMeO-C 6 H 4 ; 6c,R= p-Me-C 6 H 4 ; 6d,R= Ph) were prepared starting from Ru 3 (CO) 12 (4)b yasingle step conversion with the respective phosphine 5 and benzoic acid (2a)a nalogouslyt oaprocedure described by Bianchi [35] (Scheme 4).…”

“…[4,16,26] Ther esulting enol ester D undergoesa ni ntramolecular transesterification to the alkenyl derivative E,which after keto-enol tautomerizationand protonation releases the b-oxo ester andr egenerates the catalytically active ruthenium species (Scheme 3). [27][28][29] Thef irst catalytic system which was able to generate b-oxo estersw as described by Mitsudo andW atanabe. [30] They employed am ixture composed of bis(h 5 -cyclooctadienyl)ruthenium, P(n-Bu) 3 [11,[27][28][29]31,32] In addition, Cadierno and co-workers have shown that ruthenium(II) complexes containingh ydrosoluble phosphine ligands enable the formation of b-oxo estersi na queous medium.…”

“…[27][28][29] Thef irst catalytic system which was able to generate b-oxo estersw as described by Mitsudo andW atanabe. [30] They employed am ixture composed of bis(h 5 -cyclooctadienyl)ruthenium, P(n-Bu) 3 [11,[27][28][29]31,32] In addition, Cadierno and co-workers have shown that ruthenium(II) complexes containingh ydrosoluble phosphine ligands enable the formation of b-oxo estersi na queous medium. [27] Recently,w ec ould show for the first time that mononuclear ruthenium compoundso ft he type [Ru(CO) 2 (PPh 3 ) 2 (O 2 CR) 2 ]( R= CH 2 OCH 3 , i-Pr, t-Bu, 2-cyclo-C 4 H 3 O, Ph) are efficientc atalysts for the addition of carboxylic acids to propargylic alcohols,e ven when challengings ubstrates were applied.…”