Stereoselective Amidoalkylation Reactions via N,O‐Acetals

Abstract

The isomerization of N,O-acetals 1 yields N-acyl-0-vinyl amino)aldehydes 3. The relative configurations of the proacetals 2 or 2-aminomethyl-l,3-butadienes 10, depending on ducts 3 have been determined by X-ray analysis and 'Hthe nature of the nitrogen substituents. In the presence of NMR experiments. The mechanism of the reaction is discustrimethylsilyl trifluoromethanesulfonate (TMSOTf) the N,O-sed. Crossover experiments indicate an intermolecular acetals 2h-u are converted stereoselectively into P-(N-acyl-course of the rearrangement. In connection with our investigations of the stereoselective rearrangements of alkyl vinyl a c e t a l~ [~~] to aldol ethers, we have also studied the reactions of 0-vinyl N,O-acetals. In this paper we report on the diastereoselective synthesis of p-(N-acy1amino)aldehydes 3 in three simple steps from easily accessible starting materials via N,O-acetals 1 and 2 (Scheme l)[331. The type of catalyst depends on the nitrogen substituents of the starting materials (Table 2).

Synthetic, Structural, and Mechanistic Aspects of an Amine Activation Process Mediated at a Zwitterionic Pd(II) Center

“…The solvents were dried over activated 3 Å molecular sieves and degassed by freeze−pump−thaw cycles prior to use. The preparation of Et 2 NC(H)CH 2 , diisopropyl(2-propenyloxymethyl)amine, (COD)PdCl 2 , Ph 2 SiP 2 , and [NBu 4 ][Ph 2 BP 2 ] was carried out following literature procedures. Amines and o -phenylpyridine were purchased from Aldrich, dried over CaH 2 , distilled or vacuum transferred, and stored over activated 3 Å molecular sieves.…”

Trimethylsilyl Trifluoromethanesulfonate

“…TMSOTf also acts as a catalyst for the analogous addition of silyl enol ethers to O, O-acetals (77) In other reactions that proceed via an acyliminium ion, O-vinyl N,O-acetals rearrange smoothly to β-(N-acylamino)aldehydes at 0 • C in CH 2 Cl 2 in the presence of TMSOTf with moderate to high diastereoselectivities (eq 78). 113 However, TMSOTf failed to promote aprotic alkyne-iminium cyclizations, which are readily enhanced by TMSCl, TMSBr, or SiCl 4 . 114 The tropane alkaloid skeleton can be accessed in one pot via domino ene-type reactions of acetone silyl enol ether, the first one of them being intermolecular, with catalytic use of TMSOTf (eq 79).…”

Brønsted Acid-Catalyzed Aza-Ferrier Reaction of N,O-Allenyl Acetals: Synthesis of β-Amino-α-methylene Aldehydes

“…Sequential C–C bond formation provides the corresponding β-amino aldehydes, which act as valuable building blocks for the synthesis of biologically active compounds such as β-amino acids and alkaloids. Initial studies on this reaction were carried out by Frauenrath et al Their group reported the Lewis acid-catalyzed reaction of N , O -alkenyl acetals to afford α-substituted-β-amino aldehydes. Our group applied this protocol to the reaction of N , O -1,3-dienyl acetals as substrates and obtained β-amino-β′,γ′-unsaturated aldehydes .…”