Synthetically amenable amide derivatives of tosylated-amino acids as organocatalysts for enantioselective allylation of aldehydes: computational rationale for enantioselectivity

Abstract

A phenylalanine derived chiral amide is developed that serves as an effective organocatalyst for the reaction of allyltrichlorosilane with aryl, hetero-aryl and α,β-unsaturated aldehydes to afford the desired homoallylic alcohols in good yield (up to 90%) and high enantioselectivity (up to 99%). The experimental results and DFT calculations suggest that para substituted aromatic aldehydes as substrate show higher ee in the product than their ortho/meta counterparts. The (1)H and (13)C NMR spectra study corroborated the calculated results. The chiral organocatalyst can be easily synthesized from optically pure phenylalanine in two simple steps with 90% overall yield.

Synthesis of Tripeptide Derivatives with Three Stereogenic Centers and Chiral Recognition Probed by Tetraaza Macrocyclic Chiral Solvating Agents Derived from d-Phenylalanine and (1S,2S)-(+)-1,2-Diaminocyclohexane via 1H NMR Spectroscopy

“…N -Boc- d / l -Phg 7 , d / l -PheOBn 9 , and N -Ts-D/ l -Ala 13 were initially prepared, respectively. 22 Dipeptide derivatives ( N -Boc-Phg-PheOBn) 10 were then derived from 7 and 9 . 13 Finally, enantiomers G1–1–G4–2 of tripeptide derivatives ( N -Ts-Ala-Phg-PheOBn) were obtained by an amidation reaction of 11 and 13 in 34–78% yields (Scheme 2).…”

Oxazoline derivatives tagged with tosylated amino acids as recyclable organocatalysts for enantioselective allylation of aldehydes

“…organocatalysts 1-5 with varied chirality (Scheme 1). 15,17 We also synthesized catalyst (S,S)-6 (Scheme 2) by replacing the tosyl part of the catalyst (S,S)-4 with Boc to ascertain the role of the tosyl group in the allylation reaction.…”

“…However, there are nagging issues, such as the extremely low reaction temperatures, moderate yield and ee, and nonrecyclability of these catalysts, which need to be addressed. Bearing in mind the value of oxazolines, overall stability of the catalyst and our previous experience with tosylated amino acids 15 as organocatalysts in the enantioselective allylation reaction of aldehydes, herein we have synthesized a series of oxazoline-based organocatalysts, 16,17 (S,S)-1 to (S,S,R)-5, featuring sulfonamide groups with varying steric features and two to three chiral centers. Chiral centers in organocatalysts featuring congurations with different permutations and combinations were prepared for their possible role in inuencing the product enantioselectivity.…”

Enantioselective Allylation of Thiophene‐2‐carbaldehyde: Formal Total Synthesis of Duloxetine

“…As typical examples we may mention reactions catalyzed by bipyridine N-oxides (10 mol%, 83% ee) [12] and N,N'-dioxides with a chiral terpene scaffold (10 mol%, 75% ee), [13] C 2 -symmetrical bisimidazole N,N'-dioxides (10 mol%, 76% ee), [14] and C 2 -symmetrical biscarboline N,N'-dioxides (1 mol%, 97 and 98% ee). [15] Worthy of mention is also a protocol for the addition of allyltrichlorosilane using catalysis by an amino acid (15 mol%, 82% ee) [16] or by a phosphine oxide (2 mol%, 70% ee). [17] During the last couple of years we have shown that axially chiral bipyridine N,N'-dioxides with a bis(tetrahydroisoquinoline) scaffold such as 1 and 2 ( Figure 2) are highly catalytically active substances for the enantioselective allylation of aldehydes with allyltrichlorosilane providing the corresponding homoallyl alcohols with high asymmetric inductions of up to 99% ee.…”