Synthesis of Novel Quaternary Amino Acids Using Molybdenum-Catalyzed Asymmetric Allylic Alkylation

Abstract

The Mo-catalyzed asymmetric allylic alkylation using azlactones provides extraordinary levels of selectivity. Thus, a wide range of cinnamyl-type substrates react with 2-methyl and 2-benzyl azlactones to give only the product resulting from attack at the more substituted carbon. Using other alkyl substituents such as 2-methylthioethyl, isobutyl, allyl, and isopropyl provides products that still retain excellent regioselectivity but small quantities of the linear product are also observed. In all cases, excellent diastereo- and enantioselectivity of the branched alkylated product are observed. This new asymmetric reaction provides ready access to unusual quarternary amino acids, important building blocks for biological applications. The reactions complements the Pd AAA wherein the cinnamyl substrate leads to only the product of attack at the primary terminus of the allyl moiety.

Palladium‐Catalyzed DYKAT of Butadiene Monoepoxide: Enantioselective Total Synthesis of (+)‐DMDP, (−)‐Bulgecinine, and (+)‐Broussonetine G

“…Allylic alkylation is known to be catalyzed by a variety of transition-metal complexes, including iron, [3] cobalt, [4] nickel, [5] molybdenum, [6] ruthenium, [7] rhodium, [8] palladium, [2] iridium, [9] tungsten, [10] and platinum. [11] Palladium has thus far proven to be the most versatile metal catalyst for AAA transformations.…”

Synthesis of enantiomerically pure cis- and trans-cyclopentane analogues of phenylalanine

“…9 A recent example of this last synthetic pathway was reported by Trost, who described the synthesis of a precursor of cis-1-amino-2-phenylcyclopentanecarboxylic acid through a RCM reaction on an a,a-dialkenyl N-acylglycinate, although free amino acid was not reported. 10 Other methodologies, such as palladium-mediated cyclisation, 11 enantioselective alkylidene carbene C-H insertion reactions 12 or synthesis of the cyclopentane ring through sequential aldol reactions 13 and intramolecular aldol condensation 14 have also been used. On the other hand, the introduction of the amino and acid functions on the cyclopentane skeleton was carried out in a traditional way by Bücherer-Bergs or Strecker reactions on the corresponding cyclopentanones.…”

Recent approaches towards the asymmetric synthesis of α,α-disubstituted α-amino acids

“…The palladium-catalysed allylic alkylation of azlactones was successfully utilised in the total synthesis of sphingofungin F. 25 The regioselectivity of the reaction could be generally altered to result in b-branched products by exchange of palladium for molybdenum (Scheme 9). 26 The direct palladium-catalysed allylic alkylation of aacetamido-b-ketoesters 29 to result in a,a-disubstituted a-amino acid esters was demonstrated by Kuwano and Ito (Scheme 10). Using (R)-BINAP as the ligand, they obtained a-alkylated products in good yields and enantiomeric excess.…”