The catalytic conversion of chemical feedstocks into products of medicinal and agricultural value is a key theme across modern synthetic chemistry. As 1,3-dienes are readily available from industrial cracking processes, there is great interest in the development of sustainable methods for the functionalization of these simple molecules. Although initial developments in this field have required precious-transition-metal catalysts, there has been a push toward the use of inexpensive, nontoxic, and more abundant copper catalysts to promote functionalization. This Perspective covers the many developments in the area of copper-catalyzed functionalization of 1,3-dienes, in particular hydrofunctionalization, borofunctionalization, and difunctionalization (e.g., diamination).
A cooperative Cu/Pd-catalyzed asymmetric three-component reaction of styrenes, B 2 (pin) 2 , and allyl carbonates was reported. This reaction, in the presence of chiral CuOAc/SOP and achiral Pd(dppf)Cl 2 catalysts, occurs smoothly with high enantioselectivities (up to 97% ee) . The allylboration products, which contain alkene (or diene) unite and alkylboron group, are easily functionalized. The utility of this protocol was demonstrated through the synthesis of an antipsychotic drug, (−)-preclamol.M ultifunctional and enantioenriched organoboranes are useful building blocks in the synthesis of natural products and bioactive compounds. 1 Transition metal-catalyzed asymmetric carboboration reaction is an efficient and straightforward approach to access chiral multisubstituted alkyl-or alkenylboranes. 2 For instance, Ito and co-workers developed a successful copper-catalyzed borylative cyclization to prepare optically pure β-aryl or silylated cyclopropylboronates. 3 The related asymmetric carboboration of allenes, alkynes and 1,3-enynes are also applied in the synthesis of chiral di-, tri-, and tetra-substituted alkenylboron esters by Hoveyda 1c,4 and Lin. 5 However, up to date, enantioselective carboboration of alkenes for the construction of enantioenriched and multifunctional alkylborons are less developed. Sporadic examples were reported and limited to Cu-catalyzed borylative aldol carboboration 6 and Pd-catalyzed 1,1-arylboration. 7 Very recently, Semba, Nakao 8 and Brown 9 independently reported a remarkable three-component carboboration of alkenes with bis(pinacolato)diboron (B 2 (pin) 2 ) and aryl or vinyl halides by a Cu/Pd cooperative catalysis. We envisioned using this combination catalysis 10 as a platform to develop enantioselective carboboration of simple alkenes. The proposed procedure involves two cooperative catalytic cycles (Scheme 1), a Cu-catalyzed enantioselective generation of β-borylalkylcopper 11 and a Pd-catalyzed cross-coupling transformation of this enantioenriched reagent. 1a,12 We believe that the stereospecific transmetalation of alkylcopper with XPd(L)R′ in the proposed mechanism, and the compatibility of the chiral L*Cu(I)-complex with the achiral Pd(0)-or Pd(II)-complex would be the key issues. In our previous work, 13 a stereospecific copper− tin transfer was observed in Cu(I)-catalyzed enantioselective alkene stannylboration when using chiral sulfoxide-(P-aryl)-phosphine (SOP) ligand. In this work, we found that P-alkyl sulfoxide-phosphine ligands 14 can effectively promote the aforementioned Cu−Pd transmetalation and realize a highly enantioselective allylboration of alkenes.To test the feasibility, the three-component reaction of styrene (1a), B 2 (pin) 2 , and allylic electrophiles was performed in the presence of (SOP)CuCl catalyst precursor and Pd(dppf)Cl 2 cocatalyst. After screening a series of allyl substrates with different leaving groups (e.g., halides, esters and carbonates), t-butyl allyl carbonate 2a was confirmed as the best electrophile in terms of the re...
Previously, we have shown that p-cyanophenylalanine (PheCN) and tryptophan (Trp) constitute an efficient fluorescence resonance energy transfer (FRET) pair that has several advantages over commonly used dye pairs. Here, we aim to examine the general applicability of this FRET pair in protein folding–unfolding studies by applying it to the urea-induced unfolding transitions of two small proteins, the villin headpiece subdomain (HP35) and the lysin motif (LysM) domain. Depending on whether PheCN is exposed to solvent, we are able to extract either qualitative information about the folding pathway, as demonstrated by HP35, which has been suggested to unfold in a stepwise manner, or quantitative thermodynamic and structural information, as demonstrated by LysM, which has been shown to be an ideal two-state folder. Our results show that the unfolding transition of HP35 reported by FRET occurs at a denaturant concentration lower than that measured by circular dichroism (CD) and that the loop linking helix 2 and helix 3 remains compact in the denatured state, which are consistent with the notion that HP35 unfolds in discrete steps and that its unfolded state contains residual structures. On the other hand, our FRET results on the LysM domain allow us to develop a model for extracting structural and thermodynamic parameters about its unfolding, and we find that our results are in agreement with those obtained by other methods. Given the fact that PheCN is a non-natural amino acid and, thus, amenable to incorporation into peptides and proteins via existing peptide synthesis and protein expression methods, we believe that the FRET method demonstrated here is widely applicable to protein conformational studies, especially to the study of relatively small proteins.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.