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Synlett 2018; 29(06): 683-688
DOI: 10.1055/s-0036-1591536
DOI: 10.1055/s-0036-1591536
synpacts
Electrophilic Metal Homoenolates and Their Application in the Synthesis of Cyclopropylamines
We thank NSERC (DG, CRC and USRA programs), the Canada Foundation for Innovation (Project Number 35261), the Ontario Research Fund and the University of Toronto for financial support of this work. L.R.M. thanks the province of Ontario for a graduate scholarship (OGS).Further Information
Publication History
Received: 20 December 2017
Accepted: 08 January 2018
Publication Date:
19 February 2018 (online)
Abstract
Since their discovery, metal homoenolates have been widely explored as carbon-based nucleophiles for the β-functionalization of carbonyl derivatives. Only recently has it been reported that metal homoenolates can react as carbonyl electrophiles. In this context, we have recently discovered that cyclopropylamines can be prepared from cyclopropanols via zinc homoenolate intermediates. This Synpacts article will present an overview of the reactivity of homoenolates and our strategy to employ these intermediates for the synthesis of cyclopropylamines. Key mechanistic observations and their influence on reaction optimization will also be discussed.
1 Introduction
2 Homoenolates as Nucleophiles—Selected Reactivity
3 Homoenolates as Electrophilic Reagents
4 Conclusion
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For early reviews on metal homoenolates, see:
For selected reviews on ring-opening reactions of cyclopropanols:
For examples of non-cyclopropanol-derived homoenolates and homoenolate equivalents e.g., lithium:
Palladium:
Boron:
For select recent examples, see: β-Arylation:
β-Benzylation:
β-Alkynylation:
β-Amination:
β-Trifluoromethylation:
β-Sulfonylation:
β-Cyanation:
Nucleophilic substitution reactions at cyclopropanol derivatives usually give ring-opened products: