Thio-Claisen Rearrangement Used in Preparing Anti-β-Functionalized γ,δ-Unsaturated Amino Acids: Scope and Limitations

Abstract

Multifunctionalized amino acids, especially amino acids with unsaturation, are important, demanding building blocks in peptide chemistry. Here we present a summary of our most recent study using the thio-Claisen rearrangement for the synthesis of anti-β-functionalized γ,δ-unsaturated amino acids. Investigations on scope, limitations, chemoselectivities and stereoselectivities regarding an FeBr(3)-catalyzed allylation strategy and a thio-enolate dianion formation strategy for asymmetric thio-Claisen rearrangement are documented. An explanation of the chirality crossover observed between the Eschenmoser-Claisen rearrangement and the thio-Claisen rearrangement is proposed. Novel optically active N(α)-protected amino acids with biologically interesting functional groups were prepared for the first time.

Developing the Scope of O→C Aryl Migrations: Exploring Amide Substrates as Potential Precursors for Asymmetric Reactions

“…generated from 4, n = 1 or 2, Scheme 1) have not been studied as precursors in the Truce-Smiles rearrangement, and because such compounds can be rendered enantiomerically pure, through auxiliary formation, aided by the associated restricted C-N bond rotation, [9][10][11] it was speculated that the scope of such OǞC aryl migrations could be further developed and extended, first to achiral amide substrates to determine their potential, followed by further advances to exploit them as precursors for new asymmetric reactions based on this rearrangement. generated from 4, n = 1 or 2, Scheme 1) have not been studied as precursors in the Truce-Smiles rearrangement, and because such compounds can be rendered enantiomerically pure, through auxiliary formation, aided by the associated restricted C-N bond rotation, [9][10][11] it was speculated that the scope of such OǞC aryl migrations could be further developed and extended, first to achiral amide substrates to determine their potential, followed by further advances to exploit them as precursors for new asymmetric reactions based on this rearrangement.…”

Synthesis of γ,δ-unsaturated amino acids by Claisen rearrangement - last 25 years

“…Encouraged by previous positive results involving the highly asymmetric Eschenmoser-Claisen rearrangement 35 and the thio-Claisen rearrangement 36,37 Hruby et al summarized their studies in a paper from 2012. 38 In this approach, the authors also presented a combined method of applying Friedel-Crafts alkylation and the use of a three commercially available C2-symmetric chiral auxiliary 88a-c (Scheme 18, Table 14). Scheme 18.…”

“…Asymmetric thio-Claisen rearrangement with C2-symmetric chiral auxiliaries. 38 They noticed that the size of R group on the chiral auxiliary increased the diastereoselectivity. It was also observed that the carbonyl group in the allylic bromides resulted in the formation of the only one compound in the reaction, which confirmed their earlier findings based on the model 84b of the transition state (Figure 9).…”

Combined Occupancy of Gadolinium at the Lattice Sites of β‐Ca3(PO4)2 and t‐ZrO2 Crystal Structures

“…β‐Tricalcium phosphate [β‐Ca 3 (PO 4 ) 2 , β‐TCP], hydroxyapatite [Ca 10 (PO 4 ) 6 (OH) 2 , HAP], zirconia [ZrO 2 ] and alumina [Al 2 O 3 ] are the most common bioceramics employed in biomedical applications . A wide range of elements have been used as dopants in β‐Ca 3 (PO 4 ) 2 , HAP and ZrO 2 for dual purposes namely as stabilizers to preserve the appropriate polymorph and divulging additional features to these ceramics . In this context, Gd 3+ has been used as a stabilizer to achieve the desired β‐Ca 3 (PO 4 ) 2 beyond 1200 °C, which usually undergoes β‐ → α‐Ca 3 (PO 4 ) 2 transformation at ≈ 1180 °C , .…”