Dataset Information

Arynes and Cyclic Alkynes as Synthetic Building Blocks for Stereodefined Quaternary Centers.

ABSTRACT: We report a facile method to synthesize stereodefined quaternary centers from reactions of arynes and related strained intermediates using ?-ketoester-derived substrates. The conversion of ?-ketoesters to chiral enamines is followed by reaction with in situ generated strained arynes or cyclic alkynes. Hydrolytic workup provides the arylated or alkenylated products in enantiomeric excesses as high as 96%. We also describe the one-pot conversion of a ?-ketoester substrate to the corresponding enantioenriched ?-arylated product. Computations show how chirality is transferred from the N-bound chiral auxiliary to the final products. These are the first theoretical studies of aryne trapping by chiral nucleophiles to set new stereocenters. Our approach provides a solution to the challenging problem of stereoselective ?-ketoester arylation/alkenylation, with formation of a quaternary center.

SUBMITTER: Picazo E

PROVIDER: S-EPMC6467087 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Arynes and Cyclic Alkynes as Synthetic Building Blocks for Stereodefined Quaternary Centers.

Picazo Elias E Anthony Sarah M SM Giroud Maude M Simon Adam A Miller Margeaux A MA Houk K N KN Garg Neil K NK

Journal of the American Chemical Society 20180524 24

We report a facile method to synthesize stereodefined quaternary centers from reactions of arynes and related strained intermediates using β-ketoester-derived substrates. The conversion of β-ketoesters to chiral enamines is followed by reaction with in situ generated strained arynes or cyclic alkynes. Hydrolytic workup provides the arylated or alkenylated products in enantiomeric excesses as high as 96%. We also describe the one-pot conversion of a β-ketoester substrate to the corresponding enan ...[more]

PMID: 29716194

Similar Datasets

Project description:The development of methods for replication of synthetic information oligomers will underpin the use of directed evolution to search new chemical space. Template-directed replication of triazole oligomers has been achieved using a covalent primer in conjunction with non-covalent binding of complementary building blocks. A phenol primer equipped with an alkyne was first attached to a benzoic recognition unit on a mixed sequence template via selective covalent ester base-pair formation. The remaining phenol recognition units on the template were then used for non-covalent binding of phosphine oxide oligomers equipped with an azide. The efficiency of the templated CuAAC reaction between the primer and phosphine oxide building blocks was investigated as a function of the number of H-bonds formed with the template. Increasing the strength of the non-covalent interaction between the template and the azide lead to a significant acceleration of the templated reaction. For shorter phosphine oxide oligomers intermolecular reactions compete with the templated process, but quantitative templated primer elongation was achieved with a phosphine oxide 3-mer building block that was able to form three H-bonds with the template. NMR spectroscopy and molecular models suggest that the template can fold, but addition of the phosphine oxide 3-mer leads to a complex with three H-bonds between phosphine oxide and phenol groups, aligning the azide and alkyne groups in a favourable geometry for the CuAAC reaction. In the product duplex, 1H and 31P NMR data confirm the presence of the three H-bonded base-pairs, demonstrating that the covalent and non-covalent base-pairs are geometrically compatible. A complete replication cycle was carried out starting from the oligotriazole template by covalent attachment of the primer, followed by template-directed elongation, and hydrolysis of the the ester base-pair in the resulting duplex to regenerate the template and liberate the copy strand. We have previously demonstrated sequence-selective oligomer replication using covalent base-pairing, but the trimer building block approach described here is suitable for replication of sequence information using non-covalent binding of the monomer building blocks to a template.

Dataset Information

Arynes and Cyclic Alkynes as Synthetic Building Blocks for Stereodefined Quaternary Centers.

Publications

Arynes and Cyclic Alkynes as Synthetic Building Blocks for Stereodefined Quaternary Centers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets