An official website of the United States government
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
Catalysis‐Enabled Concise and Stereoselective Total Synthesis of the Tricyclic Prostaglandin D 2 Metabolite Methyl Ester
Abstract A concise and stereoselective total synthesis of the clinically relevant tricyclic prostaglandin D2metabolite (tricyclic‐PGDM) methyl ester in racemic form was accomplished in eight steps from a readily available known cyclopentene‐diol derivative. The synthesis features a nickel‐catalyzed Ueno–Stork‐type dicarbofunctionalization to generate two consecutive stereocenters, a palladium‐catalyzed carbonylative spirolactonization to build the core oxaspirolactone, and aZ‐selective cross‐metathesis to introduce the (Z)‐3‐butenoate side chain, a group challenging to introduce through traditional Wittig protocols and troublesome for the two previous total syntheses. A generalZ‐selective cross‐metathesis protocol to construct (Z)‐β,γ‐unsaturated esters was also developed that has broad functional group tolerance and high stereoselectivity. Additionally, our synthesis already accumulated 75 mg of valuable material for an18O‐tricyclic‐PGDM‐based assay used in clinical settings for inflammation.
more »
« less
- Award ID(s):
- 2102022
- PAR ID:
- 10445881
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 61
- Issue:
- 5
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Although many monometallic active sites have been installed in metal–organic frameworks (MOFs) for catalytic reactions, there are no effective strategies to generate bimetallic catalysts in MOFs. Here we report the synthesis of a robust, efficient, and reusable MOF catalyst, MOF‐NiH, by adaptively generating and stabilizing dinickel active sites using the bipyridine groups in MOF‐253 with the formula of Al(OH)(2,2′‐bipyridine‐5,5′‐dicarboxylate) forZ‐selective semihydrogenation of alkynes and selective hydrogenation of C=C bonds in α,β‐unsaturated aldehydes and ketones. Spectroscopic studies established the dinickel complex (bpy⋅−)NiII(μ2‐H)2NiII(bpy⋅−) as the active catalyst. MOF‐NiH efficiently catalyzed selective hydrogenation reactions with turnover numbers of up to 192 and could be used in five cycles of hydrogenation reactions without catalyst leaching or significant decrease of catalytic activities. The present work uncovers a synthetic strategy toward solution‐inaccessible Earth‐abundant bimetallic MOF catalysts for sustainable catalysis.more » « less
-
Abstract We combine data sets from the CGM2and CASBaH surveys to model a transition point,Rcross, between circumgalactic and intergalactic media (CGM and IGM, respectively). In total, our data consist of 7244 galaxies atz< 0.5 with precisely measured spectroscopic redshifts, all having impact parameters of 0.01–20 comoving Mpc from 28 QSO sightlines with high-resolution UV spectra that cover HiLyα. Our best-fitting model is a two-component model that combines a 3D absorber–galaxy cross-correlation function with a simple Gaussian profile at inner radii to represent the CGM. By design, this model gives rise to a determination ofRcrossas a function of galaxy stellar mass, which can be interpreted as the boundary between the CGM and IGM. For galaxies with 108≤M⋆/M⊙≤ 1010.5, we find thatRcross(M⋆) ≈ 2.0 ± 0.6Rvir. Additionally, we find excellent agreement betweenRcross(M⋆) and the theoretically determined splashback radius for galaxies in this mass range. Overall, our results favor models of galaxy evolution atz< 0.5 that distributeT≈ 104K gas to distances beyond the virial radius.more » « less
-
Abstract A modular platform for facile access to 1,2,3,9‐tetrahydro‐4H‐carbazol‐4‐ones (H4‐carbazolones) and 3,4‐dihydrocyclopenta[b]indol‐1(2H)‐ones (H2‐indolones) is described. The requisite 6‐ and 5‐membered 2‐arylcycloalkane‐1,3‐dione precursors were readily obtained through a Cu‐catalyzed arylation of 1,3‐cyclohexanediones or by a ring expansion of aryl succinoin derivatives. Enolization of one carbonyl group in the diones, conversion to a leaving group, and subsequent azidation gave 2‐aryl‐3‐azidocycloalk‐2‐en‐1‐ones. This two‐step, one‐pot azidation is highly regioselective with unsymmetrically substituted 2‐arylcyclohexane‐1,3‐diones. The regioselectivity, which is important for access to single isomers of 3,3‐disubstituted carbazolones, was analyzed mechanistically and computationally. Finally, a Rh‐catalyzed nitrene/nitrenoid insertion into theorthoC−H bond of the aryl moiety gave the H4‐carbazolones and H2‐indolones. One carbazolone was elaborated to an intermediate reported in the total synthesis ofN‐decarbomethoxychanofruticosinate, (−)‐aspidospermidine, (+)‐kopsihainanine A. With 2‐phenylcycloheptane‐1,3‐dione, prepared from cyclohexanone and benzaldehyde, the azidation reaction was readily accomplished. However, the Rh‐catalyzed reaction unexpectedly led to a labile but characterizable azirine rather than the indole derivative. Computations were performed to understand the differences in reactivities of the 5‐ and 6‐membered 2‐aryl‐3‐azidocycloalk‐2‐en‐1‐ones in comparison to the 7‐membered analogue, and to support the structural assignment of the azirine.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
