Studies on Elimination Pathways of β-Halovinyl Ketones Leading to Allenyl and Propargyl Ketones and Furans under the Action of Mild Bases

Abstract

The elimination pathway of stereochemically defined β-halovinyl ketones has been investigated using a mild base, NEt(3), leading to the formation of allenyl ketones and propargyl ketones. A preferential α-vinyl enolization of (E)-β-chlorovinyl ketones has been observed where a nonplanar s-cis conformation is proposed as a dominant conformation as opposed to a planar s-cis conformation of (Z)-β-chlorovinyl ketones. Other eliminative pathways, such as concerted syn- and anti-E2 as well as γ-deprotonation, are excluded on the basis of the deuterium isotope studies. The synthetic utility of the elimination reaction of β-chlorovinyl ketones was further demonstrated for a one-pot synthesis of 2,5-disubstituted furans in the presence of 1 mol % CuCl.

Ambivalent Reactivity Modes of β‐Chlorovinyl Ketones: Electrophilic Lithium [3]Cumulenolates from Soft Vinyl Enolization Strategy

“…These results were very comparable to the rates of a-vinyl enolization of (Z)-1 a and (E)-1 a in the absence of a stoichiometric amount of LiClO 4 , [12] thus suggesting little effect of the LiClO 4 (100) PhCH 3 0 9 [c] LiClO 4 (100) CH 2 Cl 2 0 10 LiClO 4 (20) CH 2 Cl 2 5 11 [d] LiClO 4 (100) CH 2 Cl 2 n.r. First, under the optimized reaction conditions, the reaction of (Z)-1 a showed the formation of 3 a in less than 5 % conversion along with 20 % of the elimination products 4 a and 5 a, whereas the reaction of (E)-1 a led to the exclusive formation of 3 a in greater than 95 %.…”

“…In contrast, the reactivity behavior of [n]cumulene derivatives, compounds with three or more consecutive double bonds, has not been fully explored because of the difficulty associated with their preparation other than tetrasubstituted [3]cumulene derivatives. [11] Recently, we reported a facile a-vinyl enolization pathway of (E)-b-chlorovinyl ketones in which transient oxy-substituted [3]cumulene derivatives [i.e., cumulenol(ate)s] were postulated as nucleophilic species, reacting either with a protic source [12] or aldehydes [13] (Scheme 2). [11] Recently, we reported a facile a-vinyl enolization pathway of (E)-b-chlorovinyl ketones in which transient oxy-substituted [3]cumulene derivatives [i.e., cumulenol(ate)s] were postulated as nucleophilic species, reacting either with a protic source [12] or aldehydes [13] (Scheme 2).…”

“…First, under the optimized reaction conditions, the reaction of (Z)-1 a showed the formation of 3 a in less than 5 % conversion along with 20 % of the elimination products 4 a and 5 a, whereas the reaction of (E)-1 a led to the exclusive formation of 3 a in greater than 95 %. [12] Next, the formation of 3 a from 4 a and 5 a was examined. 12 [e] lithium salts for the NEt 3 -promoted a-vinyl enolization.…”

A Soft Vinyl Enolization Approach to α‐Acylvinyl Anions: Direct Aldol/Aldol Condensation Reactions of (E)‐β‐Chlorovinyl Ketones

“…During our investigation of the elimination pathway of b-halovinyl ketones, [10] we observed a facile a-vinyl enolization of (E)-b-chlorovinyl ketones by the action of a weak base, NEt 3 . The non-planar conformational preference of (E)-b-chlorovinyl ketones, as opposed to the planar conformational preference of (Z)-b-chlorovinyl ketones, was believed to result in better orbital overlap between the p C-O bonding orbital and the s * aÀ CÀH anti-bonding orbital, thus allowing for a mild a-vinyl enolization of (E)-b-chlorovinyl ketones (Scheme 2).…”

“…[19] As for the Ti(OiPr) 4 -catalyzed aldol condensation reaction, whereas no reaction was observed using (Z)-b-chlorovinyl ketones, we found that a facile aldol condensation reaction between 5 a and 6 a (in a 2:1 mixture) readily occurred in the absence of NEt 3 when a catalytic amount of Ti(OiPr) 4 was used (Scheme 6). Several observations regarding the Ti(OiPr) 4 -catalyzed aldol condensation are noteworthy: 1) no aldol condensation product B was observed using g,g-disubstituted allenyl ketones (a possible aldol pathway of Ti-cumulenolate); 2) the formation of a,g-deuteriumexchanged product 8 [10] was observed from allenyl and alkynyl ketones under Ti(OiPr) 4 /CD 3 OD conditions (a possible isomerization of alkynyl ketones to allenyl ketones); 3) a catalytic amount of Ti(OiPr) 4 readily induced the dehydration of aldol product 3 c. Although our previous study established that the conformation of (E)-b-chlorovinyl ketones changes in the presence of hard and soft Lewis acids, [10] it appears that Ti(OiPr) 4 does not strongly interact with the carbonyl group of (E)-b-chlorovinyl ketones to cause the conformational change, this is possibly due to the less Lewis basic nature of the carbonyl group, as well as the less Lewis acidic nature of Ti(OiPr) 4 relative to TMSOTf. Instead, the more Lewis basic carbonyl groups of allenyl and propargyl ketones preferentially interact with Ti(OiPr) 4 and acidify the a-hydrogen for deprotonation by a proximal alkoxide.…”