Organocatalyzed Conjugate Addition of Carbonyl Compounds to Nitrodienes/Nitroenynes and Synthetic Applications

Abstract

The purpose of this study is to point out the synthetic utility of a new class of Michael acceptors (nitrodienes and nitroenynes). The highly enantioselective organocatalytic Michael addition of carbonyl compounds to these functionalized nitroolefins has been carried out in the presence of (S)-diphenylprolinol silyl ether to achieve some interesting building blocks in high selectivities. The adducts thus obtained can be easily converted by taking advantage of the corresponding unsaturated carbon-carbon bond. In presence of the double bond, metathesis or electrophilic activation could be carried out whereas in the presence of the triple bond electrophilic activation could be conducted. We thus focused on a gold-catalyzed cyclization of the bis-homopropargylic alcohol to afford the corresponding substituted tetrahydrofuran. Then, we also demonstrated that organic and gold catalysts were compatible in a one-pot process. Indeed, we developed a one-pot enantioselective organocatalytic Michael addition to a nitroenyne followed by a gold-catalyzed acetalization/cyclization to achieve tetrahydrofuranyl ethers in high diastereoand enantioselectivities with excellent yields.

An Aminocatalyzed Stereoselective Strategy for the Formal α‐Propargylation of Ketones

“…Among the numerous classes of alkyl moieties that can be successfully introduced in a catalytic and stereoselective fashion, propargyl chains are still somehow elusive. Among the limited number of existing protocols, representative asymmetric organocatalytic strategies have been reported by Krause, Alexakis, and co‐workers, who developed an aminocatalyzed conjugate addition of aldehydes to nitroenynes, whereas the group of Ma described the addition of ketones to the same class of Michael acceptors, using thiourea catalysis . These two protocols create a C−C bond at the α‐carbon of the starting carbonyl compound, in which the new branch installed carries both an alkynyl and a nitromethyl chain (Scheme a).…”

16O/18O Exchange of Aldehydes and Ketones caused by H218O in the Mechanistic Investigation of Organocatalyzed Michael, Mannich, and Aldol Reactions

“…(), 16 O/ 18 O=40:60]. The amount of H 2 18 O used in the experiment was not described . As the isovaleraldehyde is difficult to monitor by mass spectroscopy, we selected {(4‐benzyloxy)cyclohexyl}acetaldehyde ( 1 ) as a β,β‐disubstituted aldehyde, which is easily monitored by mass spectroscopy, for the 16 O/ 18 O exchange experiment.…”

“…On the other hand, Alexakis reported that the Michael reaction of an aldehyde with nitrodiene, catalyzed by diphenylprolinol silyl ether, in H 2 18 O afforded mixture of 16 O‐aldehyde and 18 O‐aldehyde with the ratio 1:1.5 [Eq. ()] . Tsogoeva reported that a mixture of 16 O/ 18 O products (1:1.58) were obtained in the Mannich reaction of acetone with hydrazone, catalyzed by a primary amine thiourea [Eq.…”

“…(4)]. [3] Tsogoevar eported that am ixture of 16 O/ 18 Op roducts (1:1.58) were obtainedi nt he Mannichr eaction of acetone with hydrazone, catalyzedb yaprimary amine thiourea [Eq. (5)].…”

Organocatalytic “Difficult” Michael Reaction of Ketones with Nitrodienes Utilizing a Primary Amine–Thiourea Based on Di‐tert‐butyl Aspartate

“…aldehydes and nitrodienes, [13] and Xu et al have shown the synergistic effect of an organocatalyst with a chiral thiourea for the reaction of cyclic ketones with nitrodienes. [14] However, the Michael addition of aromatic methyl ketones to nitrodienes is still a great challenge (Scheme 1).…”