(Chloromethyl)lithium:  efficient generation and capture by boronic esters and a simple preparation of diisopropyl (chloromethyl)boronate

Sadhu, Kizhakethil Mathew; Matteson, Donald S.

doi:10.1021/om00128a038

Cited by 230 publications

(117 citation statements)

References 5 publications

(7 reference statements)

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“…This key coupling step was performed on a gram scale. The highly regio-and diastereoselective hydroboration 36 of 38 afforded secondary boronate 39, which was subjected to a Matteson homologation 37 to afford, after an oxidative work-up, the alcohol intermediate 40. Because the latter is a known, advanced intermediate to paroxetine 38 , this sequence constitutes a formal synthesis of (þ)-paroxetine that can be accomplished in only seven steps from commercial t-Boc 4-piperidinone.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

2014

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Non-aromatic nitrogen-and oxygen-containing heterocycles such as piperidines and pyrans are prevalent components of natural products and pharmaceutical drugs. Although it has been a workhorse as a synthetic method for assembling unsaturated sp 2 -hybridized substrates, transition metal-catalysed cross-coupling chemistry is traditionally not a suitable approach to prepare chiral non-aromatic heterocycles. Several mechanistic issues hamper the coupling of stereogenic secondary sp 3 -hybridized carbon-metal centres. Moreover, use of unsymmetrical allylic boronates in the Suzuki Miyaura cross-coupling is further complicated by the possibility of forming two regioisomeric products. Here we address this two-pronged problem and demonstrate that chiral enantiomerically enriched heterocyclic allylic boronates can be coupled with high stereochemical retention with a wide variety of aryl and alkenyl halides to independently afford both regioisomeric 2-and 4-substituted dihydropyrans and dehydropiperidines in high selectivity. A divergent mechanism is proposed where regiochemistry is governed by the nature of the ligands on the palladium catalyst. This scalable method is applied to the efficient preparation of the neuroactive alkaloid anabasine and the antidepressant drug paroxetine.

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Section: Resultsmentioning

confidence: 99%

Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

2014

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“…Alkenylboronates can be converted into functionalized allylboronates such as 42 by way of a Matteson homologation (Equation 24) [63][64][65]. This strategy is the reverse of the addition of alkenylmetal intermediates to halomethylboronates described in Section 6.2.1.2.…”

Section: Allylboronates From Homologation Of Alkenylboronatesmentioning

confidence: 99%

Recent Advances in the Preparation of Allylboronates and Their Use in Tandem Reactions with Carbonyl Compounds

Kennedy

Hall

2005

Boronic Acids

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“…The required 2-bromo-1-butene (34) was obtained via bromoboration of 1-butyne. Insertion of a simple methylene group to form 38 was accomplished with (chloromethyl)lithium generated in situ from chloroiodomethane and butyllithium [33]. The steps from 38 to 39 are straightforward.…”

Section: Boronic Ester Intermediates In Synthesismentioning

confidence: 99%

(α‐Haloalkyl)boronic Esters in Asymmetric Synthesis

Matteson¹

2005

Boronic Acids

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The utility of (α-haloalkyl)boronic esters in asymmetric synthesis results from a unique combination of several features of their chemistry. A wide variety of products can be obtained in very high stereopurity, and the reactions are compatible with a considerable variety of functional substituents, provided that OH and NH groups are masked. Stereospecific displacement of halide from an (α-haloalkyl)boronic ester with a nucleophile yields an asymmetric boronic ester, which can either be converted stereospecifically into another product such as an alcohol or put into another cycle of reaction with (dihalomethyl)lithium to install additional stereocenters. The general synthetic utility of these boronic esters can best be understood from a detailed outline of the general processes involved.The most useful biological applications of these compounds have included the synthesis of some asymmetric insect pheromones in very high stereopurity, described in Sections 8.3.1 and 8.3.3, and the proteasome inhibitor "Velcade™" (bortezomib) developed by Millennium Pharmaceuticals and recently approved by the United States FDA as well as the European Union for treatment of relapsed and refractory multiple myeloma, Section 8.3.6. General Description of (α-Haloalkyl)boronic Ester Chemistry A Brief History of Boronic Ester ChemistryFirst, simple achiral boronic acids and esters are readily available from various sources (Chapter 1). The first synthesis from an organozinc reagent preceded general acceptance of Avogadro's hypothesis [1], and was superseded nearly a century ago by the now standard preparation from Grignard reagents [2,3]. Hydroboration has Boronic Acids. Edited by Dennis G. Hall

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(Chloromethyl)lithium: efficient generation and capture by boronic esters and a simple preparation of diisopropyl (chloromethyl)boronate

Cited by 230 publications

References 5 publications

Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

Recent Advances in the Preparation of Allylboronates and Their Use in Tandem Reactions with Carbonyl Compounds

(α‐Haloalkyl)boronic Esters in Asymmetric Synthesis

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