Palladium-Catalyzed One-Pot Conversion of Aldehydes and Ketones into 4-Substituted Homopropargyl Alcohols and 5-En-3-yn-1-ols

Abstract

Sequential treatment of 2,3-dichloropropene with magnesium and n-BuLi generated the equivalent of 1,3-dilithiopropyne, which adds regiospecifically to aldehydes and ketones to produce homopropargyl alcohols. The lithium acetylide intermediate formed in this protocol can be further reacted with aromatic and vinyl halides, under palladium catalysis, to produce 4-substituted homopropargyl alcohols and 5-en-3-yn-1-ols, respectively, in one-pot with good overall yields.

Synthesis and Antibacterial Activity of Aromatic Homopropargyl Alcohols

“…Homopropargyl alcohols 11, 12, 13 and 18 were prepared from dichloropropene, 9, according to Scheme 3 as in [5]. Derivatives 14 and 15 were prepared from alcohol 12, by reaction with NaH and acetylation respectively.…”

“…The aim of this work is to report herein the preparation of several homopropargyl alcohols, using procedures depicted in Scheme 2 [4] and Scheme 3 [5], and the determination of its antibacterial activity against both Gram (+) and Gram (−) bacteria.…”

1-Nitro-4-(1-propyn-1-yl)benzene

“…3). The 1,3-dilithipropyne, 3, was prepared from 2,3-dichloropropene by sequential treatment with magnesium and n-BuLi as previously reported (Umañ a & Cabezas, 2017;Cabezas et al, 2018). After ether-water partition, the crude reaction was purified by column chromatography (ether:hexane, 30:70), to obtain the title compound, 1, in 72% yield.…”

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

“…We have previously observed this type of reduction in this reaction system. 32 Scheme 1 Methods for preparation of dianion 14, and its application to the synthesis of 1, 3 To determine the best reaction conditions for performing this transformation in a one-pot process, we studied different alkoxide trapping reagents and different bases. As described above, when ethyl chloroformate was used as a trapping reagent, and KOH/EtOH as the base for the elimination step, no enyne 31 was obtained ( Table 2, entry 1).…”

“…We have previously observed this type of behavior with TMEDA. 32 On the other hand, it has been re-ported that the palladium-catalyzed cross-coupling reaction between lithium acetylides and aromatic halides, in the presence of catalytic amounts of the palladium complex (without CuI), produces only very low yields of the desired alkynylation products. 28 Thus, the desired reaction is difficult to achieve, probably because the highly nucleophilic alkynyllithiums act as catalyst poisons by displacing the ligands (i.e., PPh 3 , Cl) from the palladium complex, forming lithium palladates 50 that do not exhibit catalytic activity (Scheme 5).…”