Iron(III)‐Catalyzed Cyclization of Alkynyl Aldehyde Acetals: Experimental and Computational Studies

Abstract

DNA and RNA analysis is of high importance for clinical diagnoses, forensic analysis, and basic studies in the biological and biomedical fields. In this paper, we report the ultrahighly sensitive homogeneous detection of DNA and microRNA by using a novel single-silver-nanoparticle counting (SSNPC) technique. The principle of SSNPC is based on the photon-burst counting of single silver nanoparticles (Ag NPs) in a highly focused laser beam (about 0.5 fL detection volume) due to Brownian motion and the strong resonance Rayleigh scattering of single Ag NPs. We first investigated the performance of the SSNPC system and then developed an ultrasensitive homogeneous detection method for DNA and microRNA based on this single-nanoparticle technique. Sandwich nucleic acid hybridization models were utilized in the assays. In the hybridization process, when two Ag-NP-oligonucleotide conjugates were mixed in a sample containing DNA (or microRNA) targets, the binding of the targets caused the Ag NPs to form dimers (or oligomers), which led to a reduction in the photon-burst counts. The SSNPC method was used to measure the change in the photon-burst counts. The relationship between the change of the photon-burst counts and the target concentration showed a good linearity. This method was used for the assay of sequence-specific DNA fragments and microRNAs. The detection limits were at about the 1 fM level, which is 2-5 orders of magnitude more sensitive than current homogeneous methods.

Substituent‐Dependent, Iron‐Mediated Tandem Cyclization of Diynes with Benzaldehyde Acetals to Form Highly Functionalized Indene Derivatives

“…O ‐Tethered diyne 1 b reacted with acetal 2 b and FeCl 3 to generate 3 h in 41 % yield (Table 2, entry 8). Unexpectedly, the reaction of C ‐tethered diyne 1 c with acetal 2 a in the presence of FeCl 3 formed the desired product 3 i (25 %) as only the minor product, while alkynyl enone 4 (60 %) was the major product (Table 2, entry 9), which suggests that one of the alkynyl moieties underwent intramolecular cyclization with 2 a 13b. These results suggest that the tethering heteroatoms may stabilize a cationic intermediate during the reaction 14.…”

“…Recently, iron catalysis has emerged as a promising, environmentally benign alternative to traditional transition‐metal catalysis due to the many advantages of utilizing iron‐catalyst precursors, such as low cost, nontoxicity, good stability, and straightforward methods of handling 10–12. Very recently, we discovered that FeCl 3 and FeCl 3 ⋅ 6H 2 O can efficiently promote the intramolecular cyclization of monoalkynyl aldehyde acetals to generate solvent‐dependent Prins‐type products13a and α,β‐unsaturated cyclic ketones,13b respectively (Scheme ). Herein, we report the FeCl 3 ‐ and FeBr 3 ‐mediated tandem cyclization of simple diynes with benzaldehyde acetals for the synthesis of highly functionalized indenes.…”

Iron(III)‐Catalyzed Cycloisomerizations of Acetal–Vinylidenecyclopropanes: An Efficient Synthetic Route to 1,2‐Disubstituted Cyclobutenes

“…In addition, FeX 3 and other Lewis acid‐promoted carbon–carbon bond‐forming cyclizations of alkenyl and allenyl acetals have been frequently reported 15. In 2009, Yu and co‐workers15d, e discovered that intramolecular alkynyl acetal derivatives could be transformed into various cyclopentanes, tetrahydropyrans, and tetrahydropyrroles in the presence of FeX 3 (Scheme B). Intrigued by the versatile interactions of Lewis acids with acetals, we envisaged that a highly strained methylenecyclopropane (MCP) carbocation might be generated from a Prins cyclization of acetal–VDCPs catalyzed by Fe III .…”

Tandem Brønsted Acid Promoted and Nazarov Carbocyclizations of Enyne Acetals to Hydroazulenones

“…[12] Strategies based on the cyclization of acyclic dienynes, mediated [13a] or catalyzed [13b] by metal carbenes, have also been reported (Scheme 1, paths d and e). [16,17] Herein we report its use in tandem with a Nazarov cyclization [7b, 18] to construct hydroazulenone skeletons 2 from enyne acetals 1 [19] (Scheme 1). [16,17] Herein we report its use in tandem with a Nazarov cyclization [7b, 18] to construct hydroazulenone skeletons 2 from enyne acetals 1 [19] (Scheme 1).…”

“…[14] As a contribution to the development of metal-free, environmentally less hazardous synthetic methods, [15] we recently described an efficient intramolecular cyclization of alkynals promoted by Brønsted acids. [16,17] Herein we report its use in tandem with a Nazarov cyclization [7b, 18] to construct hydroazulenone skeletons 2 from enyne acetals 1 [19] (Scheme 1). [20] Initially, we subjected enyne acetal 1 a (Table 1), to the optimized reaction conditions identified in our previous work (heating in DCE in the presence of excess trifluoroacetic acid).…”