[1,2] Boc migration during pyroglutamate alkylations

When a mixture of a pyroglutamate and an isocyanate in THF is treated with NaH, a ring transformation occurs leading to functionalised hydantoins. The novel reaction involves a ring‐closing ring‐opening sequence providing a new and straightforward access to an interesting class of heterocyclic compounds. Furthermore, starting from pyroglutamates allows the synthesis of highly substituted hydantoins under very mild conditions. This ring transformation in combination with ring‐closing metathesis is used in a four‐step reaction sequence for the synthesis of multi‐functionalised bicyclic hydantoin derivatives.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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“…This kind of fragmentation has been observed before. [33] Therefore, all following reactions were carried out on the ethyl ester. Scheme 3.…”

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confidence: 99%

The Pyroglutamate Hydantoin Rearrangement

et al. 2006

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“…Initially, deprotonation of the starting material can occur at the nitrogen atom, this process being favored over CH deprotonation of the acidic malonate moiety because of the kinetic conditions used. Next, the formed amide anion is proposed to undergo intramolecular addition to one of the two carboxylate groups, leading to the formation of a key 2‐alkoxyaziridine‐2‐olate intermediate 12. This strained intermediate would next undergo a fast and irreversible ring‐opening process, generating the intermediate enolate species, which is finally quenched by the addition of a proton source or an alkylating agent.…”

Section: Methodsmentioning

confidence: 99%

Base‐Promoted C→N Acyl Rearrangement: An Unconventional Approach to α‐Amino Acid Derivatives

Ugarriza¹,

Uria²,

Carrillo³

et al. 2014

Chemistry A European J

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We have discovered that N-alkyl aminomalonates undergo a fast and selective intramolecular C→N acyl rearrangement reaction in the presence of a strong base, leading to N-protected glycinates in excellent yield. Moreover, the fact that the reaction proceeds through a nucleophilic enolate intermediate has been used for implementing a tandem rearrangement/alkylation sequence that has been applied to the preparation of synthetically relevant nonproteinogenic tertiary and quaternary N-alkyl α-amino acids in a very simple and reliable way.

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“…As a result, we are able to present a comprehensive study on the solid state behavior of this synthetically useful type of compound and discuss the general influence of ring size and substitution pattern on the COOH and COOR moieties at the N α position of lactams. The respective moieties can adopt either an axial or an equatorial site, which is of crucial importance for their reactivity, e.g., in transannular cyclization reactions. ,, For steric reasons only ester groups in axial positions will allow such conversions (Figure ). Despite the axial and the equatorial conformation being connected via equilibrium in solution, the molecular structures of the title compounds deliver valuable insights into their reactive conformation and give most beneficial information on distances and interactions in and between the molecules.…”

Section: Introductionmentioning

confidence: 99%

“…The respective moieties can adopt either an axial or an equatorial site, which is of crucial importance for their reactivity, e.g., in transannular cyclization reactions. 19,41,42 For steric reasons only ester groups in axial positions will allow such conversions (Figure 3). Despite the axial and the equatorial conformation being connected via equilibrium in solution, the molecular structures of the title compounds deliver valuable insights into their reactive conformation and give most beneficial information on distances and interactions in and between the molecules.…”

Section: ■ Introductionmentioning

confidence: 99%

Does the Exception Prove the Rule? A Comparative Study of Supramolecular Synthons in a Series of Lactam Esters

Weck

Nauha

Gruber

2019

Crystal Growth & Design

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In this paper a series of simple lactam esters and carboxylic acids is studied with respect to their overall conformation and hydrogen bonding patterns. In total, eight lactams featuring Nαsubstitution have been synthesized. Additionally, the molecular structures of related lactam esters have been considered. The length of the amide bonds does not seem to be majorly influenced by different substituents unless the electron withdrawing N-Boc-protection group is introduced, resulting in a higher susceptibility towards hydrolytic ring opening. As known from other lactams, the Nα ester moiety of the title compounds can be in an axial or equatorial conformation. Smaller ester groups were found to prefer equatorial positions, while larger ones occupy axial sites. N-substitution seems to promote axial conformations of the respective Nα group, with enantholactams being the only studied exception. In addition to the two common amide packing motifs, i.e. the R 2 2 (8) amide dimer (NH•••O/NH•••O) and the C(4) amide chain, a third graph-set was found: the R 2 2 (8) NH•••O/CH•••O=C heterodimer. In general, there seems to be a tendency for medium-sized lactams as well as lactams with small esters to form R 2 2 (8) amide dimers. Larger esters and enantholactam esters lead to C(4) amide chains. In this respect the formation of R 2 2 (8) N-H•••O/C-H•••O=C heterodimers should be seen as a remarkable exception.

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[1,2] Boc migration during pyroglutamate alkylations

Cited by 21 publications

References 16 publications

The Pyroglutamate Hydantoin Rearrangement

The Pyroglutamate Hydantoin Rearrangement

Base‐Promoted C→N Acyl Rearrangement: An Unconventional Approach to α‐Amino Acid Derivatives

Does the Exception Prove the Rule? A Comparative Study of Supramolecular Synthons in a Series of Lactam Esters

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