Synthesis of Tyrosine‐Derived Tetrahydroisoquinolines by Lewis Acid Catalyzed Cyclization of N‐(Phenylsulfonyl)alkyloxazolidinones

Abstract

Keywords: Amino acids / Bromine / Protecting groups / Debromination / Oxazolidinones / Regioselectivity N-Boc-protected tyrosine esters 5a,b were converted into tetrahydroisoquinolines 13 and 14 in four steps by reduction and ring closure to oxazolidinones 9 and 10, addition of benzenesulfinic acid and aldehydes to sulfones 11 and 12 and subsequent Lewis acid catalyzed cyclization. In the case of m-tyrosine derivative 5a, selective protection with bromine prevented the formation of undesired regioisomers. Debromination of target compounds 13 was readily achieved under

One‐Pot α‐Amidosulfone‐Mediated Variation of the Pictet–Spengler Tetrahydroisoquinoline Synthesis, Suitable for Amide‐Type Substrates

“…Under these conditions, we obtained tetrahydroquinoline derivatives 3a – 3o , which were isolated directly in one step, normally in good to excellent yields (Scheme , Table 1). 13 Comparisons of this result with literature precedent involving a oxazolidin‐2‐one substrate bearing a 3,4‐methylenedioxyphenyl pendant side chain show that, although apparently trivial, the replacement of benzenesulfinic acid by toluenesulfinic acid increases the reactivity for all steps of the process (see the mechanistic discussion for a more detailed explanation). This new THQ synthesis can be performed under mild conditions of temperature and acidity and, as shown in Table 1, its scope covers both aliphatic (Table 1, Entries 1 and 2) and aromatic aldehydes (Table 1, Entries 3–15).…”

“…Although these species have found many synthetic applications,10 there is very little precedence for their use in the synthesis of heterocycles. Indeed, the only type of substrates previously examined for a transformation related to the one described here were relatively highly reactive cyclic carbamates derived from the oxazolidin‐2‐one system 11. These reactions required a two‐step protocol involving the isolation of the α‐amidosulfone intermediate in the presence of magnesium sulfate as a dehydrating agent and its subsequent cyclization in the presence of the strong Lewis acid TiCl 4 12…”

Synthesis and characterization of peptidomimetics containing oxazolidin-2-one and oxazolidine scaffolds

“…Several studies have exploited β-amino alcohols cyclization, especially for the synthesis of oxazolidinones. [25][26][27][28] In the first part of this article, we describe an application of this method to the synthesis of conformational constrained dipeptide mimetic from derivatives containing serine fragment. Thus, the cyclization was performed directly on the dipeptide resulting from peptide coupling with different amino acids: Val, Leu, Phe and aminocaproic acid.…”

A Synthetic Route to Highly Substituted 1,2,3,4‐Tetrahydroisoquinolines via Yb(OTf)3‐Catalyzed Diastereoselective Ring Opening of Bridged Oxazolidines: Asymmetric Synthesis of 2‐Azapodophyllotoxin

“…Keywords: 2-azapodophyllotoxin · Garner aldehyde · natural products · tetrahydroisoquinoline · total synthesis chler-Napieralski cyclization/reduction sequence of b-arylethylamines that undergo ring closure after condensation with aldehydes to produce only 1,3-syn isomers as the major product. These methods inevitably require electron-donating groups at the phenyl ring for successful cyclization, [14] and are therefore not applicable to electron-deficient aryl systems. Reported approaches for the synthesis of 1,3-anti THIQs involve nucleophilic addition to 3,4-dihydroisoquinoline (DHIQ) precursor as iminium intermediates at very low temperatures; however, these methods achieved a high level of diastereoselectivity via 1,3-asymmetric induction only when a bulky C-3 substituents was pre-installed on the DHIQ precursors.…”