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Synlett 2022; 33(04): 307-328
DOI: 10.1055/s-0040-1719850
account

Application of Oxidative Ring Opening/Ring Closing by Reductive Amination Protocol for the Stereocontrolled Synthesis of Functionalized Azaheterocycles

Loránd Kiss∗
a   Institute of Organic Chemistry, Research Centre for Natural Sciences, 1117 Budapest, Magyar tudósok körútja 2, Hungary
,
Lamiaa Ouchakour
b   Institute of Pharmaceutical Chemistry, University of Szeged, 6720 Szeged, Eötvös u. 6, Hungary
,
Melinda Nonn∗
b   Institute of Pharmaceutical Chemistry, University of Szeged, 6720 Szeged, Eötvös u. 6, Hungary
,
Attila M. Remete
b   Institute of Pharmaceutical Chemistry, University of Szeged, 6720 Szeged, Eötvös u. 6, Hungary
› Author AffiliationsWe are grateful to the Hungarian Scientific Research Foundation (NKFIH K 119282 and FK 134586) for financial support. The financial support of the GINOP-2.3.2-15-2016-00014 project is also acknowledged. This research was supported by the EU-funded Hungarian grant EFOP-3.6.1-16-2016-00008. Emberi Eroforrások Minisztériuma (Ministry of Human Capacities, Hungary, 20391-3/2018/FEKUSTRAT) is also acknowledged.
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Abstract

The current Account gives an insight into the synthesis of some N-heterocyclic β-amino acid derivatives and various functionalized saturated azaheterocycles accessed from substituted cycloalkenes via ring C=C bond oxidative cleavage followed by ring closing across double reductive amination. The ring-cleavage protocol has been accomplished according to two common approaches: a) Os-catalyzed dihydroxylation/NaIO4 vicinal diol oxidation and b) ozonolysis. A comparative study on these methodologies has been investigated. Due to the everincreasing relevance of organofluorine chemistry in drug research as well as of the high biological potential of β-amino acid derivatives several illustrative examples to the access of various fluorine-containing piperidine or azepane β-amino acid derivatives are also presented in the current Account.

1 Introduction

2 Olefin-Bond Transformation by Oxidative Ring Cleavage

3 Synthesis of Saturated Azaheterocycles via Oxidative Ring-Opening/Ring-Closing Double Reductive Amination

3.1 Importance of Fluorine-Containing Azaheterocycles in Pharmaceutical Research

3.2 Synthesis of Azaheterocyclic Amino Acid Derivatives with a Piperidine or Azepane Framework through Oxidative Ring Opening/Reductive Amination

3.2.1 Synthesis of Piperidine β-Amino Esters

3.2.2 Synthesis of Azepane β-Amino Esters

3.2.3 Synthesis of Fluorine-Containing Piperidine γ-Amino Esters

3.3 Synthesis of Tetrahydroisoquinoline Derivatives through Oxidative Ring Opening/Reductive Amination Protocol

3.4 Synthesis of Functionalized Benzazepines through Reductive Amination

3.4.1 Synthesis of Benzo[c]azepines

3.4.2 Synthesis of Benzo[d]azepines

3.5 Synthesis of Various N-Heterocycles via Ozonolysis/Reductive Amination

3.5.1 Synthesis of Compounds with an Azepane Ring

3.5.2 Synthesis of Piperidine β-Amino Acids and Piperidine-Fused β-Lactams

3.5.3 Synthesis of γ-Lactams with a Piperidine Ring

3.5.4 Synthesis of other N-Heterocycles

4 Summary and Outlook

5 List of Abbreviations

Key words

azaheterocycles - ring opening - ring expansion - reductive amination - fluorine


Publication History

Received: 19 September 2021

Accepted after revision: 30 September 2021

Article published online:
03 November 2021

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