Enantioselective Palladium‐Catalyzed Addition of 1,3‐Dicarbonyl Compounds to an Allene Derivative

Abstract

Enhancing atom economy of the metal-catalyzed asymmetric allylic alkylation (AAA) shifts from the usual nucleophilic displacement of a leaving group to an addition of a pronucleophile to a double bond. Using 1-alkoxyallenes as proelectrophiles, the palladium-catalyzed AAA proceeds with 1,3-dicarbonyl compounds as pronucleophiles with excellent regioselectivity and enantiomeric excess under optimized conditions. The pH of the medium proved crucial for reactivity/selectivity. By using the more acidic Meldrum's acids, the reactions required a co-catalytic amount of Brønsted acid, such as trifluoroacetic acid. Single regioisomeric products of 82-99 % ee were obtained. On the other hand, the less acidic 1,3-diketones failed to react under such conditions. The fact that a less acidic acid like benzoic acid sufficed, suggested the need for general base catalysis as well. Thus, a mixture of triethylamine and benzoic acid proved optimal (ee's 93-99). Employment of the (R,R)-phenyl Trost ligand gave a product with S configuration. A model to rationalize the results has been developed.

Metal catalyzed allylic alkylation: its development in the Trost laboratories

“…The alkoxy group directs the regioselectivity to give the chiral branched product. 49 There is no direct evidence that this proceeds by either mechanism A or B of Fig. 2.…”

“…78 The use of the atom economical version involving generation of the π-allyl species via protonation of an allene also gave excellent results (eq 78). 49,79 Interestingly, with 3,3-disubstituted allylating agents, the regioselectivity can be controlled to direct C-C bond formation to the disubstituted terminus of the π-allyl unit (eq 79). 80 This regioselectivity derives from attack of the nucleophile at the more electrophilic terminus of the allyl unit combined with using the naphtho linker which favors the olefin – Pd(0) coordination in the initial alkylated product to the one possessing the least substituted olefin because of its lower LUMO energy allowing increased back-bonding from the low valent metal.…”

Metal‐Catalyzed Enantioselective Allylation in Asymmetric Synthesis

“…[229] Initiated by the hydropalladation of 1,2-propadienyl benzyl ether 229, the formed p-allyl intermedidate would react with substituted Meldrums acid ester 230 as the pronucleophile to afford disubstituted Meldrums acid 231 in 61-90 % yields with 82-99 % ee. [230] The related reaction of a-alkylated azalactone 99 afforded the corresponding branched product 232 with fairly high diastereoselectivity (d.r. 13:1 to 20:1) and 85-94 % ee (Scheme 74).…”

Transition metals in organic synthesis: Highlights for the year 2005

“…(121)) [777]. Silver catalyzed selective Markovikov hydroalkylations of phenylethene using activated methylene compounds [778].…”