Charge‐accelerated rearrangements present interesting challenges to enantioselective catalysis, due in large part to the competing requirements for maximizing reactivity (ion‐pair separation) and stereochemical communication. Herein, we describe application of a synergistic ion‐binding strategy to catalyze the anionic oxy‐Cope rearrangement of a symmetric
- Award ID(s):
- 1844443
- NSF-PAR ID:
- 10323713
- Date Published:
- Journal Name:
- Chemical Science
- Volume:
- 13
- Issue:
- 7
- ISSN:
- 2041-6520
- Page Range / eLocation ID:
- 1951 to 1956
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract bis ‐styrenyl allyl alcohol in up to 75 : 25 e.r. Structure‐reactivity‐selectivity relationship studies, including linear free‐energy‐relationship analyses, with bifunctional urea catalysts indicate that H‐bonding and cation‐binding interactions act cooperatively to promote the chemo‐ and enantioselective [3,3]‐rearrangement. Implications for catalyst designs applicable to other transformations involving oxyanionic intermediates are discussed. -
Chemoselectivity is one of the most challenging issues facing the chemical sciences. In this study, the first highly chemoselective reactions of N -acylpyrroles via either an anionic Fries rearrangement (pyrrole dance) or a C–H functionalization of toluene to provide aryl benzyl ketones are advanced. This efficient and operationally simple approach enables the synthesis of either 2-aroylpyrroles or aryl benzyl ketones in good to excellent yields under transition metal-free conditions. The choice of base plays a crucial role in controlling the chemoselectivity. The aroylation of toluene derivatives was observed with N -acylpyrroles when subjected to KN(SiMe 3 ) 2 , while anionic Fries rearrangement products were produced with LiN(SiMe 3 ) 2 . Surprisingly, cross-over experiments indicate that the anionic Fries rearrangement is an intermolecular process. The aroylation reaction has the advantage over Weinreb amide chemistry in that it does not require preformed organometallic reagents or cryogenic temperatures.more » « less
-
more » « less
Abstract Motivation The phylogenetic signal of structural variation informs a more comprehensive understanding of evolution. As (near-)complete genome assembly becomes more commonplace, the next methodological challenge for inferring genome rearrangement trees is the identification of syntenic blocks of orthologous sequences. In this article, we studied 94 reference quality genomes of primarily Mycobacterium tuberculosis (Mtb) isolates as a benchmark to evaluate these methods. The clonal nature of Mtb evolution, the manageable genome sizes, along with substantial levels of structural variation make this an ideal benchmarking dataset.
Results We tested several methods for detecting homology and obtaining syntenic blocks and two methods for inferring phylogenies from them, then compared the resulting trees to the standard method’s tree, inferred from nucleotide substitutions. We found that, not only the choice of methods, but also their parameters can impact results, and that the tree inference method had less impact than the block determination method. Interestingly, a rearrangement tree based on blocks from the Cactus whole-genome aligner was fully compatible with the highly supported branches of the substitution-based tree, enabling the combination of the two into a high-resolution supertree. Overall, our results indicate that accurate trees can be inferred using genome rearrangements, but the choice of the methods for inferring homology requires care.
Availability and implementation Analysis scripts and code written for this study are available at https://gitlab.com/LPCDRP/rearrangement-homology.pub and https://gitlab.com/LPCDRP/syntement.
Supplementary information Supplementary data are available at Bioinformatics online.
-
more » « less
Abstract A new diastereoselective route to 2‐aminotetrahydrofurans has been developed from
N ,O ‐dialkenylhydroxylamines. These intermediates undergo a spontaneous C−C bond‐forming [3,3]‐sigmatropic rearrangement followed by a C−O bond‐forming cyclization. A copper‐catalyzedN ‐alkenylation of anN ‐Boc‐hydroxylamine with alkenyl iodides, and a base‐promoted addition of the resultingN ‐hydroxyenamines to an electron‐deficient allene, provide modular access to these novel rearrangement precursors. The scope of this de novo synthesis of simple nucleoside analogues has been explored to reveal trends in diastereoselectivity and reactivity. In addition, a base‐promoted ring‐opening and Mannich reaction has been discovered to covert 2‐aminotetrahydrofurans to cyclopentyl β‐aminoacid derivatives or cyclopentenones. -
more » « less
Abstract A new diastereoselective route to 2‐aminotetrahydrofurans has been developed from
N ,O ‐dialkenylhydroxylamines. These intermediates undergo a spontaneous C−C bond‐forming [3,3]‐sigmatropic rearrangement followed by a C−O bond‐forming cyclization. A copper‐catalyzedN ‐alkenylation of anN ‐Boc‐hydroxylamine with alkenyl iodides, and a base‐promoted addition of the resultingN ‐hydroxyenamines to an electron‐deficient allene, provide modular access to these novel rearrangement precursors. The scope of this de novo synthesis of simple nucleoside analogues has been explored to reveal trends in diastereoselectivity and reactivity. In addition, a base‐promoted ring‐opening and Mannich reaction has been discovered to covert 2‐aminotetrahydrofurans to cyclopentyl β‐aminoacid derivatives or cyclopentenones.
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d1sc06307c
