Pd-Catalyzed Directed ortho-C–H Alkenylation of Phenylalanine Derivatives

Abstract

A practical Pd-catalyzed ortho-olefination of enantioenriched N-(SO2Py)-protected aryl-alanine and norephedrine derivatives with electron-deficient alkenes has been developed using N-fluoro-2,4,6-trimethylpyridinium triflate as the terminal oxidant. The reaction occurs efficiently with excellent monosubstitution selectivity and without loss of enantiopurity. This cross-coupling proved to be broad in scope, tolerating a variety of steric and electronic changes to both coupling partners. Removal of the directing group under mild conditions provides access to optically active tetrahydroisoquinoline-3-carboxylic acid derivatives (Tics) with good diastereocontrol and with very small erosion of enantiomeric purity.

Ruthenium‐Catalyzed Sulfoalkenylation of Acetanilides and Dual‐Use of the Catalyst Directing Group

“…[45] Some scattered examples for transition metal catalyzed alkenylations of arenes with sulfonyl substituted olefins have been reported, normally in the context of exploring the scope of novel CÀ H-activation conditions. [28,[46][47][48][49] We know, however, of only very few systematic investigations into this type of olefins. In two cases dehydrogenative couplings with vinylsulfonyl fluoride, using Pd- [50] or Rh-catalysis, [51] were investigated.…”

Pd‐Catalyzed Oxidative Sulfoalkenylation of Acetanilides and Traceless Removal of the Catalyst Directing Group

“…[26] Although some examples for directed and non-directed dehydrogenative arene-alkene couplings with vinylsulfones, vinylsulfonates and occasionally vinylsulfonamides [27] and vinylsulfonyl fluoride [28] have been reported, acetamides have surprisingly never been used as catalyst directing groups (Scheme 3). [27][28][29][30][31][32][33][34][35][36][37][38][39] Herein we disclose our results on the Pd-catalyzed oxidative coupling of acetanilides and vinyl sulfonyl compounds and the suitability of the coupling products for traceless CDG removal via the sequence.…”

“…Although some examples for directed and non‐directed dehydrogenative arene‐alkene couplings with vinylsulfones, vinylsulfonates and occasionally vinylsulfonamides [27] and vinylsulfonyl fluoride [28] have been reported, acetamides have surprisingly never been used as catalyst directing groups (Scheme 3). [27–39] …”

Metal‐Catalyzed C(sp2)−H Functionalization Processes of Phenylalanine‐ and Tyrosine‐Containing Peptides

“…Driven by the successful use of sulfonylpyridine motif as efficient DG, [26a] Carretero and co‐workers reported the olefination of a variety of Phe compounds housing the N ‐methyl‐ N ‐sulfonylpyridine ( N ‐MeSO 2 Py) as optimal DG [26b] . In the presence of N ‐fluoro‐2,4,6‐trimethylpyridinium triflate [F + ] as oxidant a wide range of activated olefins could be site‐selectively incorporated into the Phe or even Tyr framework (Scheme 7).…”