An official website of the United States government
Abstract We report herein the development of stereodivergent syntheses of enantioenriched homoallylic alcohols using chiral nonracemic α‐CH2Bpin‐substituted crotylboronate. Chiral phosphoric acid (S)‐A‐catalyzed asymmetric allyl addition with the reagent gaveZ‐anti‐homoallylic alcohols with excellent enantioselectivities andZ‐selectivities. When the enantiomeric acid catalyst (R)‐Awas utilized, the stereoselectivity was completely reversed andE‐anti‐homoallylic alcohols were obtained with highE‐selectivities and excellent enantioselectivities. By pairing the chirality of the boron reagent with the catalyst, two complementary stereoisomers of chiral homoallylic alcohols can be obtained selectively from the same boron reagent. DFT computational studies were conducted to probe the origins of the observed stereoselectivity. These reactions generate highly enantioenriched homoallylic alcohol products that are valuable for rapid construction of polyketide structural frameworks.
more »
« less
Copper‐Catalyzed Asymmetric Acylboration of 1,3‐Butadienylboronate with Acyl Fluorides
Abstract We report herein a Cu‐catalyzed regio‐, diastereo‐ and enantioselective acylboration of 1,3‐butadienylboronate with acyl fluorides. Under the developed conditions, the reactions provide (Z)‐β,γ‐unsaturated ketones bearing an α‐tertiary stereocenter with highZ‐selectivity and excellent enantioselectivities. While direct access to highly enantioenrichedE‐isomers was not successful, we showed that such molecules can be synthesized with excellentE‐selectivity and optical purities via Pd‐catalyzed alkene isomerization from the correspondingZ‐isomers. The orthogonal chemical reactivities of the functional groups embedded in the ketone products allow for diverse chemoselective transformations, which provides a valuable platform for further derivatization.
more »
« less
- Award ID(s):
- 2426500
- PAR ID:
- 10463129
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 62
- Issue:
- 43
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract We describe convenient preparations ofN,N′‐dialkyl‐1,3‐propanedialdiminium chlorides,N,N′‐dialkyl‐1,3‐propanedialdimines, and lithiumN,N′‐dialkyl‐1,3‐propanedialdiminates in which the alkyl groups are methyl, ethyl, isopropyl, ortert‐butyl. For the dialdiminium salts, the N2C3backbone is always in thetrans‐s‐transconfiguration. Three isomers are present in solution except for thetert‐butyl compound, for which only two isomers are present; increasing the steric bulk of theN‐alkyl substituents shifts the equilibrium away from the (Z,Z) isomer in favor of the (E,Z), and (E,E) isomers. For the neutral dialdimines, crystal structures show that the methyl and isopropyl compounds adopt the (E,Z) form, whereas thetert‐butyl compound is in the (E,E) form. In aprotic solvents all four dialdimines (as well as the lithium dialdiminate salts) adoptcis‐s‐cisconformations in which there presumably is either an intramolecular hydrogen bond (or a lithium cation) between the two nitrogen atoms.more » « less
-
Abstract Because internal alkenes are more challenging synthetic targets than terminal alkenes, metal‐catalyzed olefin mono‐transposition (i.e., positional isomerization) approaches have emerged to afford valuableE‐ orZ‐internal alkenes from their complementary terminal alkene feedstocks. However, the applicability of these methods has been hampered by lack of generality, commercial availability of precatalysts, and scalability. Here, we report a nickel‐catalyzed platform for the stereodivergentE/Z‐selective synthesis of internal alkenes at room temperature. Commercial reagents enable this one‐carbon transposition of terminal alkenes to valuableE‐ orZ‐internal alkenes via a Ni−H‐mediated insertion/elimination mechanism. Though the mechanistic regime is the same in both systems, the underlying pathways that lead to each of the active catalysts are distinct, with theZ‐selective catalyst forming from comproportionation of an oxidative addition complex followed by oxidative addition with substrate and theE‐selective catalyst forming from protonation of the metal by the trialkylphosphonium salt additive. In each case, ligand sterics and denticity control stereochemistry and prevent over‐isomerization.more » « less
-
Abstract A variety of 1‐aryl‐1,3‐dienes were isomerized fromEtoZisomers by photocatalysis using Ru(bpy)3[PF6]2and blue LED light. Enrichment of theZ‐isomer is thought to occur by selective triplet energy transfer from the photocatalyst to the stereoisomeric mixture. The 1,3‐diene starting materials are easily made by catalytic ene‐yne metathesis (EYM). To access 1,3‐dieneZ‐stereoisomers directly, a one pot procedure was developed. Additional 1,3‐dienes were investigated for both isomerization andZ‐enrichment. The combination of cross EYM with photocatalysis allows for the stereoconvergent synthesis ofZ‐1,3‐dienes.more » « less
-
Abstract Palladium(II)‐catalyzed C(alkenyl)−H alkenylation enabled by a transient directing group (TDG) strategy is described. The dual catalytic process takes advantage of reversible condensation between an alkenyl aldehyde substrate and an amino acid TDG to facilitate coordination of the metal catalyst and subsequent C(alkenyl)−H activation by a tailored carboxylate base. The resulting palladacycle then engages an acceptor alkene, furnishing a 1,3‐diene with high regio‐ andE/Z‐selectivity. The reaction enables the synthesis of enantioenriched atropoisomeric 2‐aryl‐substituted 1,3‐dienes, which have seldom been examined in previous literature. Catalytically relevant alkenyl palladacycles were synthesized and characterized by X‐ray crystallography, and the energy profiles of the C(alkenyl)−H activation step and the stereoinduction model were elucidated by density functional theory (DFT) calculations.more » « less
