Stereoselective Access to Hydroxy Oxetanes and Tetrahydrooxepines through Isomerization of Oxiranyl Ethers

Mordini, Alessandro; Bindi, Simona; Capperucci, Antonella; Nistri, Daniele; Reginato, Gianna; Valacchi, Michela

doi:10.1021/jo0005924

Cited by 31 publications

(8 citation statements)

References 30 publications

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“…Terminal epoxy α-substituted ethers 183, upon treatment with LiCKOR or LiDAKOR at −50 °C, afforded 184 (Table 16). 241 When Y was a phenyl ring or an alkyne, 2-phenyl-or 2-alkynyloxetanes were the major products, demonstrating preferred formation of the four-membered ring over the isomeric THF. The relative stereochemistry of the oxetane products at C2/C3 was determined by consideration of the stereochemistry of epoxy ether substrates and selectivity for the anti configuration of Y and hydroxymethyl substituents (Table 16, entries 1−4).…”

Section: Cyclization Through C−c Bond Formationmentioning

confidence: 99%

Oxetanes: Recent Advances in Synthesis, Reactivity, and Medicinal Chemistry

et al. 2016

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The four-membered oxetane ring has been increasingly exploited for its contrasting behaviors: its influence on physicochemical properties as a stable motif in medicinal chemistry and its propensity to undergo ring-opening reactions as a synthetic intermediate. These applications have driven numerous studies into the synthesis of new oxetane derivatives. This review takes an overview of the literature for the synthesis of oxetane derivatives, concentrating on advances in the last five years up to the end of 2015. These methods are clustered by strategies for preparation of the ring and further derivatization of preformed oxetane-containing building blocks. Examples of the use of oxetanes in medicinal chemistry are reported, including a collation of oxetane derivatives appearing in recent patents for medicinal chemistry applications. Finally, examples of oxetane derivatives in ring-opening and ring-expansion reactions are described.

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Section: Cyclization Through C−c Bond Formationmentioning

confidence: 99%

Oxetanes: Recent Advances in Synthesis, Reactivity, and Medicinal Chemistry

et al. 2016

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“…Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187,252,253]. With allyl ethers mixtures of aand c-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields c-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29).…”

Section: A-nitrogen Carbanionsmentioning

confidence: 99%

The Alkylation of Carbanions

Dörwald

2004

Side Reactions in Organic Synthesis

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The deprotonation of organic compounds by strong, non-nucleophilic bases followed by C-alkylation with a suitable electrophile has become one of the most predictable and straightforward methods for formation of C-C bonds. The popularity of this chemistry is also a consequence of the often-seen close resemblance of feasible structural modifications by a deprotonation/alkylation strategy to an unsophisticated retrosynthetic analysis of a given target compound. Other reactions, which involve, for instance, substantial rearrangement of the carbon framework (e.g. Cope rearrangement, fragmentations, ring contractions or enlargements) are usually more difficult to take into account during retrosynthetic analysis.LDA and related, sterically hindered, lithium dialkylamides, first investigated by Levine [1], have completely replaced the more nucleophilic sodium amide, which had been the base of choice for many years [2]. Because the reactivity of an organometallic compound depends to a large extent on its state of aggregation (i.e. on the solvent and on additives) and on the metal, transmetalation of the lithiated intermediates and the choice of different solvents and additives emerged as powerful strategies for fine-tuning the reactivity of these valuable nucleophiles.In this chapter the alkylation of carbanions with simple carbon electrophiles will be discussed, with special emphasis on the structure-reactivity relationship of the carbanion and on side reactions. In this context the term "carbanion" refers to an intermediate prepared by in-situ deprotonation of an organic compound, followed by optional cation exchange (transmetalation), which tends to be alkylated at carbon by soft electrophiles such as MeI or PhCHO. This type of reactivity is characteristic of enolates with an ionic M-O bond or for organometallic compounds with a strongly polarized or ionic M-C bond, M typically being an alkali metal, Mg, Cu, or Zn. Carbanions can, alternatively, also be prepared by halogen-metal exchange [3-8], sulfoxide-or sulfone-metal exchange [9-13], or by transmetalation of stannanes. The most suitable reagents for performing such metalating exchange reactions are organometallic compounds with a metal-bound secondary or tertiary alkyl group, such as tBuLi, sBuLi, iPr 2 Zn [14, 15], or iPrMgHal [6]. These reagents are thermodynamically less stable than organometallic compounds with primary alkyl 5 146 Scheme 5.1. Approximate relative rates of proton transfer in water at thermoneutrality (DpK a = 0) [35, 39, 51]. 147 Scheme 5.2. The effect of fluorine on the acidity of organic compounds [24, 62-65]. 148 Scheme 5.3. Dependence of the reactivity of carbanions on their basicity [68, 72-74]. Regioselectivity of Deprotonations and AlkylationsThe organic chemist is occasionally confronted with the problem that a compound has several differrent X-H groups of similar pK a . If only one of these is to be alkylated, one option would be to perform a regioselective deprotonation. This can sometimes be achieved by exploiting small differences be...

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“…However, the corresponding allyl glycidyl ether gives only the oxepane as a result of 7-endo ring closure. 78 Paternò-Büchi reactions of N-acetylisatin 59 with styrene derivatives provide high yielding access to spirocyclic oxetanes with high regioselectivity (Scheme 27). 79 Bach has published detailed accounts of his group's earlier work in this area.…”

Section: Three-membered Ringsmentioning

confidence: 99%