Norrish-Yang Cyclization Research Articles

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes.

α-Aminoacetophenones are identified as promising building blocks for the synthesis of highly substituted dioxolanes. The presented strategy is founded on the build and release of molecular strain and achieves a formal transposition of a methyl group. During light irradiation, 3-phenylazetidinols are forged as reaction intermediates, which readily undergo ring opening upon the addition of electron-deficient ketones or boronic acids. Key to the successful development of this two-step process is the identification of a benzhydryl-protecting group, which orchestrates the photochemical Norrish-Yang cyclization and facilitates the subsequent ring opening.

Enantioselective Synthesis of (+)-Providencin and Its Unexpected Regioisomer via a Biomimetic Norrish-Yang Cyclization from (-)-Bipinnatin E.

A biomimetic semisynthesis of the diterpenoid (+)-providencin (2) and the unexpected novel C14 regioisomer 3 was achieved by photoirradiation of the proposed biosynthetic cembranoid precursor (-)-bipinnatin E (1). The absolute configuration assignments of 1 and 2 by correlation were established by X-ray analysis. A combination of NOESY data and photochemical reaction results revealed that both C2 and C14 positions of the macrocycle (-)-1 are suitable for hydrogen abstraction, thus affording an explanation to the mixture of cyclobutane photoproduct isomers obtained by a Norrish-Yang cyclization. These results also support the proposed biosynthetic hypothesis describing the genuine photochemical transformation of (-)-1 into (+)-2, without refuting that both regioisomer products 2/3 might be artifacts of isolation.

Chiral Lewis Acid-Catalyzed Norrish Type II Cyclization to Synthesize α-Oxazolidinones via Enantioselective Protonation

Chiral Lewis Acid-Catalyzed Norrish Type II Cyclization to Synthesize α-Oxazolidinones via Enantioselective Protonation

Total Synthesis of (+)-Cyclobutastellettolide B.

A convenient enantioselective total synthesis of (+)-cyclobutastellettolide B via a strategy that involves a diastereoselective Johnson-Claisen rearrangement, a regioselective cyclopropoxytrimethylsilane ring-opening reaction, and a Norrish-Yang cyclization is described. The results of computational and experimental studies indicate that the regio- and stereoselectivity of the Norrish-Yang reaction are controlled by the C-H bond dissociation energy and restricted rotation of the C13-C14 bond.

Norrish type II reactions of acyl azolium salts

The photochemical reactivity of acyl azolium salts derived from aliphatic carboxylic acids has been investigated. These species, which serve as models for intermediates generated in N-heterocyclic carbene (NHC) organocatalysis, undergo Norrish type II elimination reactions under irradiation with UVA light in analogy to structurally related aromatic ketones. Moreover, efficient Norrish-Yang cyclization was observed from an adamantyl-substituted derivative. These results further demonstrate the ability of NHCs to influence the absorption properties and photochemical reactivity of carbonyl groups during a catalytic cycle.

Sequential Norrish-Yang Cyclization and C-C Cleavage/Cross-Coupling of a [4.1.0] Fused Saturated Azacycle.

Methods that functionalize the periphery of azacylic scaffolds have garnered increasing interest in recent years. Herein, we investigate the selectivity of a solid-state Norrish-Yang cyclization (NYC) and subsequent C-C cleavage/cross-coupling reaction of a strained cyclopropane-fused azacyclic system. Surprisingly, the NYC primarily furnished a single lactam constitutional and diastereo-isomer. The regioselectivity of the C-C cleavage of the α-hydroxy-β-lactam moiety could be varied by altering the ligand set used in the coupling chemistry. Experimental and computational observations are discussed.

Regulation of an Ambient‐Light‐Induced Photocyclization Pathway (Norrish–Yang Versus 6π) by Substituent Choice

A series of donor/acceptor chromophores 1d-3d containing two types of photoresponsive motifs, namely an electron-deficient BF2-chelated ketone fused with an electron-rich thiophene have been synthesized and their photochromic performance are investigated. The results reveal that simple variation of R substituents on the diaryl moiety allows one to control the intramolecular photocyclization mechanism with high photochemical selectivity, e.g., under ambient light, methyl-substituted 1d and 2d undergo 6π photocyclization, whereas ethyl-substituted 3d exclusively undergoes Norrish-Yang photocyclization. Single-crystal X-ray analysis of Norrish-Yang cyclization products reveals the formation of four pairs of conformational enantiomers differing in the dihedral angle between benzothiophene and the BF2 core. The UV-vis absorption spectra of 1d-3d cover a broad visible light region (380-572 nm), while theoretical calculations reveal that absorption in this region is dominated by the charge transfer (CT) transition from the thiophene-centered HOMO to the LUMO of the electron-deficient π-conjugated BF2-chelated unit. The spatial separation of the HOMO and LUMO of these dyes promotestriplet state generation and self-photosensitizes intramolecular photocyclization in the visible light region. Three-dimensional time-resolved and steady-state emission spectra of 3d show that the Norrish-Yang photocyclization takes place within milliseconds with excellent conversion efficiency (96%).

A new approach towards the synthesis of bielschowskysin: Synthesis and photochemistry of an advanced macrocyclic enedione intermediate

A novel approach towards bielschowskysin is reported based on an attempted stepwise cyclobutane formation. Synthesis of the key strained framework, containing the tricyclic ring system and all requisite carbons has been developed. While photochemical studies did not result in a late-stage Norrish–Yang cyclization, the observed isomerization could provide important insights into the synthesis of other furanocembranoids.

Photo-mediated [1, 3]-Carbonyl shift of β-Ketocarbonyls

An organic amine mediated photolytic [1,3]-benzoyl migration of β-benzoyl carbonyl compounds was reported. This migration was achieved by Norrish-Yang cyclization and retro-aldol reaction under black light (365 nm) or visible light irradiation. This photolytic protocol provides an alternative approach to the synthesis of 1,5-dicarbonyl compounds. By chiral primary amine catalysis, a kinetic resolution was also developed to afford enantioenriched 1,5-dicarbonyls.

The tetraalkylammonium-accelerated Norrish-Yang photocyclization of 2-substituted acetophenones

The tetrabutylammonium-accelerated Norrish-Yang cyclization of 2-ethoxycarbonylmethyloxy- and 2-cyanomethyloxyacetophenones afforded trans-dihydrobenzofuranols in good stereoselectivities through cation-π interactions between the ammonium and the carbonyl and cyano groups. Furthermore, a new type of organocatalyst possessing both conformation-controlling and triplet-sensitizing units was developed, and was found to be effective in accelerating the Norrish-Yang photocyclization of 2-cyanomethyloxyacetophenone.

Biosynthesis of Providencin: Understanding Photochemical Cyclobutane Formation with Density Functional Theory

The unique structure of furanocembranoid natural product providencin has stimulated biosynthetic hypotheses, especially concerning the formation of its cyclobutanol ring. One such hypothesis involves a photochemically induced Norrish-Yang cyclization in bipinnatin E. We have used computations to assess the feasibility and the stereochemical outcome of this proposed biosynthetic transformation. Density functional theory calculations reveal that the proposed Norrish-Yang cyclization in bipinnatin E is possible and that the stereoselectivity of this step is consistent with that of the natural product.

2-(Hydroxyimino)aldehydes: Photo- and Physicochemical Properties of a Versatile Functional Group for Monomer Design.

In the context of our research on stimuli-responsive polymers bearing the 2-(hydroxyimino)aldehyde (HIA) group, we have explored the photochemical behavior and physicochemical properties of a number of HIAs. Interpretation of the experimental data is supported by quantum mechanical calculations. HIAs are expected to undergo photoisomerization, chelate metal ions, yield hydrogen-bonded dimers or oligomers, exhibit relatively low pKa s, and form >C=NO. radicals through OH hydrogen abstraction or oxidation of the oximate ion. Besides the well-established E/Z oxime photoisomerism, we observed a Norrish-Yang cyclization resulting in cyclobutanol oximes, to our knowledge not previously described in the literature. The acidity, bond dissociation enthalpies, and electrochemical properties of the HIAs are compared with literature data of simple oximes. The results are discussed in relation to the many potential applications for HIAs, with emphasis on the synthesis of novel HIA-containing responsive polymers.

Evolution of a Strategy for the Enantioselective Total Synthesis of (+)-Psiguadial B.

(+)-Psiguadial B is a diformyl phloroglucinol meroterpenoid that exhibits antiproliferative activity against the HepG2 human hepatoma cancer cell line. This full account details the evolution of a strategy that culminated in the first enantioselective total synthesis of (+)-psiguadial B. A key feature of the synthesis is the construction of the trans-cyclobutane motif by a Wolff rearrangement with in situ catalytic, asymmetric trapping of the ketene. An investigation of the substrate scope of this method to prepare enantioenriched 8-aminoquinolinamides is disclosed. Three routes toward (+)-psiguadial B were evaluated that featured the following key steps: (1) an ortho-quinone methide hetero-Diels-Alder cycloaddition to prepare the chroman framework, (2) a Prins cyclization to form the bridging bicyclo[4.3.1]decane system, and (3) a modified Norrish-Yang cyclization to generate the chroman. Ultimately, the successful strategy employed a ring-closing metathesis to form the seven-membered ring and an intramolecular O-arylation reaction to complete the polycyclic framework of the natural product.

Total Synthesis of Zaragozic Acid C: Implementation of Photochemical C(sp3)-H Acylation.

Zaragozic acid C (1) was isolated as a potent squalene synthase inhibitor. The 2,8-dioxabicyclo[3.2.1]octane core of 1 is decorated with the three hydroxycarbonyl (C3,4,5), two hydroxy (C4,7), one acyloxy (C6), and one alkyl (C1) groups. Installation of the contiguous C4- and C5-fully substituted carbons presents a formidable synthetic challenge. Our approach to address this problem used a two-step photochemical C(sp3)-H acylation. Persilylated d-gluconolactone 4 was derivatized into 3 with the 1,2-diketone moiety at the C5-tetrasubstituted center. Norrish-Yang cyclization of 3 under violet LED irradiation followed by oxidative opening of the resultant α-hydroxycyclobutanone regio- and stereoselectively transformed the electron-rich tertiary C(sp3)-H bond at C4 into a C(sp3)-C bond to produce densely functionalized 2. A subsequent series of judicious functional group transformations gave rise to 1.

Tetraalkylammonium-Templated Stereoselective Norrish–Yang Cyclization

Tetrabutylammonium salts serve as templates for the Norrish-Yang cyclization of 2-benzyloxy-acylbenzenes to give trans-dihydrobenzofuranols in high stereoselectivities. The dual cation-π interactions between an ammonium with a benzene ring and a carbonyl group play a key role in changing the conformation of the substrate, which was supported by ab initio calculations.

Approach for expanding triterpenoid complexity via divergent Norrish-Yang photocyclization.

Triterpenoids comprise a very diverse family of polycyclic molecules that is well-known to possess a myriad of medicinal properties. Therefore, triterpenoids constitute an attractive target for medicinal chemistry and diversity-oriented synthesis. Photochemical transformations provide a promising tool for the rapid, green, and inexpensive generation of skeletal diversity in the construction of natural product-like libraries. With this in mind, we have developed a diversity-oriented strategy, whereby the parent triterpenoids bryonolic acid and lanosterol are converted to the pseudosymmetrical polyketones by sequential allylic oxidation and oxidative cleavage of the bridging double bond at the B/C ring fusion. The resultant polyketones were hypothesized to undergo divergent Norrish-Yang cyclization to produce unique 6/4/8-fused triterpenoid analogues. The subtle differences between parent triterpenoids led to dramatically different spatial arrangements of reactive functionalities. This finding was rationalized through conformational analysis to explain unanticipated photoinduced pinacolization, as well as the regio- and stereochemical outcome of the desired Norrish-Yang cyclization.

ChemInform Abstract: Synthesis of Benzopyrrolizidinones by Norrish—Yang Cyclization of 3‐(Acylmethyl)‐2‐alkylisoindol‐1‐ones.

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Synthesis of Benzopyrrolizidinones by Norrish-Yang Cyclization of 3-(Acylmethyl)-2-alkylisoindol-1-ones

An efficient synthesis of 2-hydroxy-1,2,3,9b-tetrahydropyrrolo[2,1-a]isoindol-5-ones has been achieved by the Norrish-Yang cyclization of 3-(acylmethyl)-2-alkylisoindol-1-ones in benzene in moderate to high yields.

Reactions of Glycosan-Annelated Oxolactams

Starting with 4-imido-mannosan and 2-imido-galactosan derivatives Norrish-Yang cyclization led to saccharide-annelated azepanediones and azocanediones. Following N-protection these lactams could be opened to give higher branched-chain carbohydrate components of the 4-amino-3-dehydro type. In some cases concomitant rearrangement reactions were observed to give α,β-unsaturated hydroxy lactams as well as saccharides linked to substituted furans.

Rapid access to azepine-fused oxetanols from alkoxy-substituted maleimides.

[reaction: see text] UV irradiation of alkoxy-substituted N-alkenylmaleimides induces a sequence involving a [5 + 2] cycloaddition followed by a Norrish-Yang cyclization. The resulting highly strained alkylidene oxetanol-fused azepines are formed in good yield and with high diastereoselectivities