Asymmetric Aldol Reaction of Chloral Catalyzed by Diarylprolinol

Abstract

The asymmetric cross‐aldol reaction of chloral hydrate with aldehyde pronucleophiles catalyzed by a trifluoromethyl‐substituted diarylprolinol was accomplished to afford γ‐trichloro‐β‐hydroxy aldehydes in good yields with excellent enantioselectivities. The resulting aldehyde products were converted into chiral α‐azido, α‐(4‐methyl)phenoxy, and α‐fluoro esters without a loss in the diastereo‐ or enantioselectivities.

Diaryl Prolinols in Stereoselective Catalysis and Synthesis: An Update

“…The examples described so far showed how many efforts have been directed over the years towards the creation of increasingly functionalized aldol products, intermediates transformed into several other useful chiral scaffolds. Recently, Hayashi and co‐workers developed an asymmetric aldol reaction between chloral hydrate and several aldehydes with the aim to incorporate the β‐trichlorohydroxyl moiety into aldol products (Scheme ) …”

“…Recently, Hayashi and co-workers developed an asymmetric aldol reaction between chloral hydrate and several aldehydes with the aim to incorporate the β-trichlorohydroxyl moiety into aldol products (Scheme 13). [24] α-Hydroxy, α-amino, α-fluoro, α-azido acids are some useful products obtained through easy manipulation of this unit. Only one example of aldol reaction of chloral with aliphatic aldehydes has been previously reported that exploited a proline-based amide organocatalyst, achieving modest to good diastereo-and enantioselectivity.…”

Asymmetric Aldol Reaction of Dichloroacetaldehyde Catalyzed by Diarylprolinol

“…(1)],5 while a chiral α‐fluoro ester was obtained using the aldol reaction of chloral as a key step [Eq. (2)] 6…”

Diarylprolinol‐Mediated Asymmetric Direct Cross‐Aldol Reaction of α,β‐Unsaturated Aldehyde as an Electrophilic Aldehyde

“…[5] Our group is interested in the asymmetric direct cross-aldol reaction promoted by the use of organocatalyst, and has found that the diarylprolinol-bearing 3,5-bis(trifluoromethyl)phenyl as the aryl moiety 1 [6] is an excellent aldol catalyst (Figure 1). It can catalyze the aldol reaction of acetaldehyde as an ucleophile, [7] and also catalyzet he aldol reactiono fe thyl glyoxylate, [8] chloral, [9] chloroacetaldehyde, [10] dichloroacetaldehdye, [11] and alkynyl aldehyde [12] as electrophilic aldehydes. [13] On the other hand, allyl alcohol is an important building block in organic synthesis, and one of the synthetic methods…”

“…a-Methyl substituent does not disturbt he reaction to provide the product with excellent enantioselectivity (entry 7). Not only methyls ubstituent, but also phenyl and furyl substituents are suitable and the reaction of these 4-substituted 4-oxopent-2-enal derivatives afforded the aldol products also with excellent enantioselectivity (entries 8,9). As the solubility of 2e is not good, dilute THF condition was employed (entry 9).…”