Switch in Selectivity for Formal Hydroalkylation of 1,3‐Dienes and Enynes with Simple Hydrazones

Abstract

Controlling reaction selectivity is a permanent pursuit for chemists. Regioselective catalysis, which exploits and/or overcomes innate steric and electronic bias to deliver diverse regio‐enriched products from the same starting materials, represents a powerful tool for divergent synthesis. Recently, the 1,2‐Markovnikov hydroalkylation of 1,3‐dienes with simple hydrazones was reported to generate branched allylic compounds when a nickel catalyst was used. As part of the effort, shown here is that a complete switch of Markovnikov to anti‐Markovnikov addition is obtained by changing to a ruthenium catalyst, thus providing direct and efficient access to homoallylic products exclusively. Isotopic substitution experiments indicate that no reversible hydro‐metallation across the metal‐π‐allyl system occurred under ruthenium catalysis. Moreover, this protocol is applicable to the regiospecific hydroalkylation of the distal C=C bond of 1,3‐enynes.

Regioselective Access to 3‐Ethylideneflavanones via Rhodium(I)‐Catalyzed 1,3‐Enyne Hydroacylation/Annulation Cascades

“…In the last two decades, meticulous efforts have been exerted to the regioselective reductive coupling of 1,3‐enynes with simple aldehydes enabled by an array of metallic catalytic systems (Scheme 1). [2f] For instance, Li and co‐workers very recently developed an impressive Ru(II)‐catalyzed 1,2‐anti‐Markovnikov formal hydroalkylation of 1,3‐enynes with umpolung carbonyls to deliver the linear products with remarkable regioselectivity (Scheme 1a) [4] . Several site‐selective carbonyl propargylation reactions from the aldehyde oxidation level through Ru(II) or Ir(I)‐catalyzed transfer hydrogenation were accomplished by the Krische group (Scheme 1b) [5] .…”

Catalytic Generation of Carbanions through Carbonyl Umpolung

“…This new catalysis opens new possibilities to harness the carbanions generated from readily available carbonyl compounds in the WK reaction for catalytic C−C bond‐forming reactions. The Ru catalytic system was later extended and the carbanionic species reacted with a broad range of electrophiles, including imines, [21] alkenes,[ 22 , 23 ] CO 2 , [24] dienes, [25] multi‐fluoro arenes, [26] carbonyl compounds (for C=C bond construction), [27] and in situ generated carbonyl compounds (Scheme 3 ). [28]…”

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

“…In early 2020, an anti‐Markovnikov conjugate addition of hydrazones to terminal olefins was successfully implemented, introducing a vast array of highly functionalized alkyl fragments to 1,3‐dienes ( 9.24 and 9.25 ) and 1,3‐enynes ( 9.26 to 9.28 , Scheme 9 D). [63] …”