Enantioselective Synthesis of γ‐Functionalized Cyclopentenones and δ‐Functionalized Cycloheptenones Utilizing a Redox‐Relay Heck Strategy

Abstract

In this report, the desymmetrization of cyclic enones under relay Heck conditions with an array of aryl boronic acids, alkenyl triflates and indole derivatives is described. This method grants facile access to diverse γ-functionalized cyclopentenones and δ-functionalized cycloheptenones. Using this approach, a formal synthesis of (S)-baclofen was completed in high yield and excellent enantioselectivity. Scheme 3. Regioselective alkylation of indole derivatives. A. Reaction conducted with 1 a (0.2 mmol) and 8 a (0.2 mmol) in DMF (2 mL). B. Reaction conducted with 1 a (0.2 mmol) and 8 b (1.0 mmol) in DMF (2 mL).

Recent Advances of Catalytic Enantioselective Heck Reactions and Reductive‐Heck Reactions

“…The reaction in the presence of Pd/chiral pyridine‐oxazoline ( L7 or L15 ) complex led to γ‐arylated or alkenylated cyclopentenones in high enantioselectivities and regioselectivities (Scheme 14). [ 22 ] Notably, although the reaction failed to extend to cyclohexenone substrate, Heck arylation of cyclohept‐4‐enone could smoothly proceed to afford 5‐substituted cyclohept‐2‐enones in excellent yields and enantioselectivities under the optimal conditions.…”

Stereoselective Remote Functionalization via Palladium‐Catalyzed Redox‐Relay Heck Methodologies

“…Investigationi nto the redox-relay oxidative Heck methodology has since progressed ontoless biaseds ystems, such as symmetricalc ycloheptenones (76)( Scheme24). [57] In this case, remote arylation proceeded in highy ield and enantioselectivity.O fn ote, longerr eactiont imes or greater equivalents of boronic acidl ed to increased levels of the diarylated product. Alkenylation was also possible with alkenyl triflates, using as tandard redox-relay Heck protocol, albeit in lower yields and more modeste nantiomeric ratios.…”

Remote Arylative Substitution of Alkenes Possessing an Acetoxy Group via β‐Acetoxy Elimination

“…One of the reasons for the difficulty in expansion of the reaction diversity is that only a limited number of strategies are available for selective product formation by effectively controlling the selectivity of the final step (termination) in the catalytic cycle. Redox-relay Mizoroki-Heck-type reaction [3][4][5] is one of the most extensively studied in this field, and three strategies have been used to terminate the reaction: 1) conversion of alcohols to carbonyl groups (Figure 1 c), [3] 2) formation of p-allyl (or benzylic) intermediates, followed by nucleophilic attack (Figure 1 d), [4] and 3) formation of a,bunsaturated systems (Figure 1 e). [5] Selectivity of all of these reactions essentially relies on the formation of thermodynamically stable products or intermediates.…”

“…Redox-relay Mizoroki-Heck-type reaction [3][4][5] is one of the most extensively studied in this field, and three strategies have been used to terminate the reaction: 1) conversion of alcohols to carbonyl groups (Figure 1 c), [3] 2) formation of p-allyl (or benzylic) intermediates, followed by nucleophilic attack (Figure 1 d), [4] and 3) formation of a,bunsaturated systems (Figure 1 e). [5] Selectivity of all of these reactions essentially relies on the formation of thermodynamically stable products or intermediates. Other types of remote functionalizations involving alkene isomerization mostly use similar termination strategies or formation of bonds at positions where metal-carbon bonds are relatively stabilized such as terminal or benzylic positions.…”