One-Pot Conversion of Aldehydes and Ketones into 1-Substituted and 1,4-Disubstituted 1,3-Enynes

Abstract

Sequential treatment of 2,3-dichloropropene with magnesium and n-BuLi generates the operational equivalent of 1,3-dilithiopropyne, which upon treatment with aldehydes or ketones, produces the corresponding alkoxy lithium acetylide intermediates. Reaction of this alkoxide with tosyl chloride, and t-BuLi produces 1-substituted, or 1,1-disubstituted 1,3-enynes in a one-pot reaction. When this lithium acetylide intermediates, obtained by this procedure, were used to perform palladium-catalyzed cross-coupling reactions, followed by addition of thionyl chloride and pyridine, 1,4-disubstituted or 1,1,4-trisubstituted 1,3-enynes were obtained in a one-pot protocol.

Intermolecular Hydroaminoalkylation of Propadiene

“…As a starting point, the reaction between N ‐methylaniline ( 1 a ) and propadiene ( 2 , synthesized according to a literature procedure [13, 14] and used as a solution in toluene, c= 0.4 molL −1 ) was chosen as the benchmark reaction and a catalyst screening was performed (Scheme 2, reaction conditions: 140 °C, 30 min, 10 mol % catalyst, scale: 0.1 mmol, control by GC analysis) [15] . Due to propadiene's boiling point of −34 °C, the reactions were performed in sealed ampoules ( V= 5 mL).…”

“…[13] The formation of I is presumably based on the generation of an allylic cation intermediate from the initially formed allylamine product (II,R 1 = Ph, R 2 = H) caused by the presence of the Lewis acidic titaniumc atalyst. [13] As as tarting point, the reactionb etween N-methylaniline (1a)a nd propadiene (2,s ynthesized according to al iterature procedure [13,14] and used as as olution in toluene, c = 0.4…”

Regiospecific Palladium-Catalyzed Cross-Coupling Reactions Using the Operational Equivalent of 1,3-Dilithiopropyne

“…35 We later used this methodology to convert aldehydes and ketones into 1,4-disubstituted 1,3-enynes in a 'one-pot' reaction. 37 Having a TMEDA-free method for the preparation of dianion 6, in our hands, we were prompted to attempt its direct palladium-catalyzed cross-coupling reaction with aromatic iodides. Initial reactions of 6 (0.90 mmol) with o-iodoanisol 11 (0.80 mmol) in the presence of catalytic amounts of Pd(PPh 3 ) 4 (7 mol%) and CuI (5-10 mol%) gave the desired coupling product 12, in variable yields from 0 to 30% ( Table 1, entry 1).…”

Crystal structures and biological activity of 1,1,4-triphenyl-substituted 1,3-enyne compounds

“…The acetylide intermediate, 8, obtained from this reaction, was coupled with the corresponding substituted iodobenzene (9, 10 or 11) under palladium(0) catalysis in the presence of CuI. The tertiary alkoxy intermediates thus obtained were reacted with thionyl chloride in the presence of pyridine to afford the corresponding 1,3-enynes 1, 2 and 3 in 71, 60 and 68% overall yields, respectively, according to a literature procedure (Cabezas et al, 2018) (Fig. 1).…”