Enantioselective γ‐Addition of Pyrazole and Imidazole Heterocycles to Allenoates Catalyzed by Chiral Phosphine

Abstract

Chiral phosphines were found to catalyze the enantioselective asymmetric g-addition of heteroaromatic compounds to allenoates in good yields with high enantiomeric ratios and regioselectivity in the presence of (S)-BINOL. Both pyrazole and imidazole could be employed in this process.The synthetic value of these g-addition products was demonstrated by the preparation of biologically relevant molecules and structural scaffolds.R emarkably,t he synthetic utility of this strategy was demonstrated through at wo-step synthesis of aJ anus kinase (JAK) inhibitor. Angewandte ChemieCommunications

Platinum and Gold Catalysis: à la Carte Hydroamination of Terminal Activated Allenes with Azoles

“…Alkoxyallenes 1C and 1H, phenylthioallene 1D, and N-indolylallenes 1E and 1K, as well as different azoles, such as benzotriazole or 1,2,4-triazole, gave, under the optimized conditions and with good to excellent yields, a family of adducts 6 showing the attractive 1,3-bisazole motif, a recurring scaffold in medicinal chemistry 9 and in ligand design for metallic complexes, metal organic and covalent organic frameworks. 10 Metal complexes of Zn 20 and Ag 21 using 6Haa and 6Hcc were readily synthesized, 22 which highlights the synthetic utility of these 1,3-bisazoles incorporating an extra functionality and added complexity, not easy to achieve through conventional procedures, in the field of organometallic chemistry.…”

“…The combination of Pt(II)−Au(I) or Pt(II)− Au(III) in a dual catalysis strategy favored the formation of the distal addition products 2 (see compounds 2La, 2Lc, 2Ld, and 2Ma-c in the Supporting Information), but the double addition was not possible even under harsher conditions with these substrates. 22 When a deactivated allenoic ester 1N was used, 23 isomers 4, from the metal-catalyzed conjugated addition of the azole to the central carbon, were obtained as the only isomers with Au(I)− Pt(II) bimetallic strategy under more forcing conditions (see compounds 4Na, 4Na′, and 4Nc in the Supporting Information). When Au(I)−Pt(IV) was used, double addition to the central carbon was also found in the presence of pyrazole to give adduct 7Naa.…”

“…When Au(I)−Pt(IV) was used, double addition to the central carbon was also found in the presence of pyrazole to give adduct 7Naa. 22 Single catalyst reactions of activated allenes under harsher conditions (excess of azole, longer times, higher temperatures) led to mixtures of isomers 2 and 3 and uncompleted conversions toward 6, highlighting the need for the bimetallic catalysis to provide 1,3-bisazoles efficiently and pointing to compounds 2 and 3 as possible intermediates in the double nucleophilic addition to form 6. 22 Interestingly, 3Aa generated 2Aa in every experiment performed (even in the absence of azole), whereas the reverse process was not observed.…”

Phosphine‐Catalyzed [3+2] Cycloaddition and Vinylation of Indole‐Derived α,α‐Dicyanoolefins with γ‐Substituted Allenoates

“…occurs at the β-position of allenoate. [17] As shown in Scheme 3, direct N-functionalization proceeded in the presence of phosphine as catalyst. Low to moderate yields were observed probably because of further [3 + 2] cycloaddition of the generated vinylation products.…”

Asymmetric Reactions Catalyzed by Chiral Tertiary Phosphines

“…Very recently, Guo's group developed an asymmetric γ‐addition of heteroaromatic compounds to allenoates to provide γ‐heteroaryl‐butenoates. [ 100 ] Chiral phosphine ( S )‐ 107 and ( S )‐BINOL were found to catalyze this reaction efficiently, and both pyrazoles and imidazoles could be suitable in this process. γ‐heteroaryl‐butenoates 301 were accessed in good yields with high enantiomeric ratios and regioselectivity (Scheme 82).…”