Stereoselectivity Sonogashira reaction

Schreiber s early efforts in this area were focused on libraries of compounds having structural features reminiscent of rigid, complex, stereochemically rich natural products. In a key early example, solid-phase split-pool synthesis was used to generate a combinatorial library of over two million complex, polycyclic compounds derived from shikimic acid [17]. A stereoselective tandem acylation-nitrone cycloaddition was used to generate 18 tetracyclic scaffolds, to which 30 alkynes were coupled using a Sonogashira reaction, 62 amines were coupled via y -lactone aminolysis, and 62 carboxylic acids were coupled by alcohol esterification (Fig. 9.1-3(c)). In addition, a portion of the solid supports were left unreacted at each of the last three steps to generate a skip codon that further increased the diversity of the library. 

A Stereoselective Synthesis volume of the Science of Synthesis series has reviewed the alkylation and allylation of carbonyl and imino groups, as well as the enantio-selective addition of metal alkynylides to imino and carbonyl compounds. Recent advances in Favorskii rearrangement, Sonogashira reactions, and catalytic enantio-selective allylic substitutions with carbon nucleophiles have been highlighted. 

A highly efficient synthesis of l-alkylidene-l,3-dihydrobenzo[f]furans from t>-hydroxymethyl iodoarenes and propargyl alcohols uses a bimetallic Pd/Cu-catalyzed Sonogashira coupling/cyclization reaction (Equation 132) <1999SL456>. Pd/l,4-bis(diphenylphosphino)butane (DPPB)-catalyzed reaction of t>-allylphenols under a CO atmosphere leads to carbonylative cyclization to form benzannulated lactones <2006ASC1855>. A similar carbonylative cyclization leads to the stereoselective formation of 3-alkenyl phthalides <2006T4563>. 

M. Bararjanian, S. Balalaie, F. Rominger, B. Movassagh, H. R. Bijanzadeh, J. Org. Chem. 2010, 75, 2806-2812. Six-component reactions for the stereoselective synthesis of 3-aryli-dene-2-oxindoles via sequential one-pot Ugi/Heck carbocycUzation/Sonogashira/nucleophilic addition. 

Studies reporting substituent effects on the palladium- and copper-catalysed Sonogashira coupling reaction between an aryl iodide and an alkyne the 5 2 allylic substitution reactions between benzyl amine and racemic allyl carbonates substituted with a j -X-Ph- group on C(l) in the presence of a Rh(15,15, 2/ ,2/ -tangphos)(COD)Bp4 catalyst the stereoselective 5 2 reactions between a-substituted linear 0-ketoesters and meta- and /Jura-substituted cinnamyl carbonates generating vicinal quaternary and tertiary stereocenters in the presence of an Ir-V-arylphosphoramidite catalyst, TBD, and LiOBu-t identity vinyl halide reactions the S N... 

Similar to the Sonogashira and related sp-sp couplings, there are no regio-or stereoselectivity complications in the Castro-Stephens coupling. Reaction conditions are quite vigorous, however, and where vinyl halides with defined geometry are used, the potential for olefin scrambling must be considered because there are rare cases where olefin isomerisation has been observed. ... 

Both ( )- and (Z)-55b can be used for cross-coupling reactions such as methoxycarbonylation, the Heck reaction, Sonogashira coupling, and Stille coupling, and the corresponding (3-fluoro-a,p-unsaturated ester 57,8-fluoro-a,(3,y,8-unsaturated ketone 58, 2-fluoro-l-alkynylalkene 59, and 4-fluoro-1,3-alkadiene 60 were successfully obtained stereoselectively [89] (Scheme 27). 

---