Photocycloaddition Product Research Articles

A symmetry-driven approach toward the total synthesis of dodecahedrane

Herein, we describe our progress toward the total synthesis of dodecahedrane, a complex and highly symmetrical hydrocarbon that bears twelve fused rings arranged in a cage-like architecture. Central to our approach is a late-stage [2+2+2+2+2] polyene cyclization cascade, which is expected to construct five new bonds and ten new rings in a single transformation. Toward this end, we describe efforts to synthesize key monomeric fragments, along with successful dimerization studies using a pinacol coupling approach. Subsequent studies include an attempted olefin metathesis rearrangement cascade in addition to a successful intramolecular photochemical [2+2] reaction. Although attempts to elaborate the photocycloaddition product were unsuccessful, our studies provide access to complex dimeric scaffolds and are expected to help guide our future total synthesis studies.

Molecular engineering of an inverse hexacopper(II) coordination complex with a photoactive metallacyclophane centroligand as prototype of a magnetic photoswitch

A primary goal of molecular spintronics is detecting the response of the spins from a single magnetic molecule to an external stimulus and, eventually, being able to implement logic quantum memory capabilities for information data storage and processing applications in quantum computation. Having this in mind, a novel hexanuclear oxamatocopper(II) complex of formula {[Cu2(naba)2][Cu(pmdien)]4}(ClO4)4·8H2O (2) [naba = N,N'-1,5-naphthalenebis(oxamate) and pmdien = N,N,N’,N”,N”-pentamethyldiethylenetriamine] has been prepared by the reaction of stoichiometric amounts of (nBu4N)4[Cu2(naba)2] · 4H2O (1) (nBu4N+ = tetra-n-butylammonium cation) and [Cu(pmdien)](ClO4)2 (1:4 molar ratio) in water. 2 exhibits a ladder-like “dimer-of-trinuclears” structure featuring a photoactive dicopper(II) naphthalenophane core acting as inverse coordination centre (centroligand) towards four peripheral [Cu(pmdien)]2+ groups through the outer amidate/carboxylate oxygen atoms of the oxamato fragments. 2 undergoes a unique magnetic photoswitching ON/OFF behaviour upon UV light irradiation because of an intramolecular (“pseudo-bimolecular”) photocycloaddition of the two facing naphthalene spacers through the more reactive carbon atoms at the 1,4 and 1’,4’ positions of the benzene rings to afford the putative [4 + 4] cycloaddition product c-2. Hence, the two oxamato-bridged S = 1/2 CuII3 linear units antiferromagnetically coupled within the CuII6 precursor (2, ON state) become magnetically uncoupled in the corresponding [4 + 4] photocycloaddition product (c-2, OFF state) [jeff = –2.13 (2) and 0 cm−1 (c-2); H = – jeffSA.SB with SA = SB = 1/2]. This new example of inverse coordination complex constitutes thus a potential candidate to molecular magnetic photoswitch in the “bottom-up” approach to nanometer-scale spintronic and quantum computing devices.

Intramolecular [2 + 2] Photocycloaddition of Altrenogest: Confirmation of Product Structure, Theoretical Mechanistic Insight, and Bioactivity Assessment.

While studying the environmental fate of potent endocrine-active steroid hormones, we observed the formation of an intramolecular [2 + 2] photocycloaddition product (2) with a novel hexacyclic ring system following the photolysis of altrenogest (1). The structure and absolute configuration were established by X-ray diffraction analysis. Theoretical computations identified a barrierless two-step cyclization mechanism for the formation of 2 upon photoexcitation. 2 exhibited progesterone, estrogen, androgen, and pregnane X receptor activity, albeit generally with reduced potency relative to 1.

Dicopper(II) metallacyclophanes with photoswitchable oligoacene spacers: a joint experimental and computational study on molecular magnetic photoswitches

Dinuclear copper(II) complexes of the metallacyclophane-type, (nBu4N)4[Cu2(2,6-anba)2] (1) and (nBu4N)4[Cu2(1,5-naba)2]·4H2O (2) with photoactive 2,6-anthracene-(2,6-anba) and 1,5-naphthalenebis(oxamate) (1,5-naba) bridging ligands, are reported. They undergo a thermally reversible, solid-state photomagnetic (ON/OFF) switching between the moderately strong antiferromagnetically coupled dicopper(II) species and the corresponding magnetically uncoupled [4+4] photocycloaddition product. Density functional calculations give further insights on the intramolecular (“pseudo-bimolecular”) photocycloaddition reaction of the two facing 2,6-anthracene or 1,5-naphthalene spacers in this novel family of dicopper(II) oligoacenophanes. The unique ability of oligoacenes as photoswitchable antiferromagnetic wires between two CuII ions separated by relatively long intermetallic distances could be the basis for the development of new kinds of molecular spintronic devices, referred to as molecular magnetic switches.

A Zn(II) coordination polymer and its photocycloaddition product: syntheses, structures, selective luminescence sensing of iron(III) ions and selective absorption of dyes.

One coordination polymer [Zn2(L)2(bpe)2(H2O)2] (1) (L = 4,4'-((1,2-phenylenebis(methylene))bis(oxy))dibenzoic acid; bpe = (E)-1,2-di(pyridin-4-yl)ethene) was prepared and structurally determined. Compound 1 has a chain structure in which its pair of bpe ligands is arranged in a head-to-tail manner with their C=C bonds being close enough for a [2 + 2] cycloaddition reaction. Upon exposure to UV light, compound 1 undergoes a single-crystal-to-single-crystal (SCSC) [2 + 2] photodimerization to generate one 2D coordination polymer [Zn(L)(rctt-tpcb)0.5(H2O)] (1a) (rctt (regio cis, trans, trans)-tpcb = tetrakis(4-pyridyl)cyclobutane). The tpcb ligands in the crystals of 1a show an intriguing in situ thermal isomerisation. The nanospheres of 1 can be obtained by recrystallization in DMSO/alcohol. The nanospheres of 1a can also be readily produced from the corresponding nanospheres of 1 by the photocyclodimerization method. Compared with those of 1a, the nanospheres of 1 display highly selective sensing of Fe(3+) ions over mixed metal ions through fluorescence quenching. Moreover, the nanospheres of 1a can rapidly adsorb CR (congo red), MB (methylene blue) or RhB (rhodamine B) over MO (methyl orange) from aqueous solutions. This work offers a new photoinduced post-synthetic method for the synthesis of multifunctional MOFs, which show luminescence sensing of Fe(3+) ions and dye adsorption properties.

Photoswitching of the antiferromagnetic coupling in an oxamato-based dicopper(ii) anthracenophane

Thermally reversible photomagnetic (ON/OFF) switching behavior has been observed in a dinuclear oxamatocopper(II) anthracenophane upon UV light irradiation and heating; the two Cu(II) ions (S(Cu) = 1/2) that are antiferromagnetically coupled in the dicopper(II) metallacyclic precursor (ON state) become uncoupled in the corresponding [4+4] photocycloaddition product (OFF state), as substantiated from both experimental and theoretical studies.

2+2]-Photocycloaddition Reactions of Tetronic Acid Esters and Amides

Tetronic acid esters and amides, which are readily available from the corresponding tetronic acids, serve as useful starting materials in an intra- or intermolecular [2+2]-photocycloaddition reaction. Typical reaction conditions are irradiation at λ = 254 nm in diethyl ether or an alcohol as the solvent. The bi-, tri- or tetracyclic products so obtained can be further utilized by ring opening either of the lactone or the cyclobutane ring. Lactone ring opening led to the use of a tetramide photocycloaddition product as a conformationally restricted β-proline analogue and to an application of a tetronate photocycloaddition product in the total synthesis of punctaporonin C.

Unexpected Solid-State Photochemistry of an α-Thiophenyl-α‘-Thiophenyl-S,S-dioxo-Substituted Ketone

Samples of 2,4-dimethyl-2-(thiophen-3-yl)-4-(thiophen-3-yl-S,S-dioxo)pentan-3-one 2 were obtained by controlled MCPBA oxidation of 2,4-dimethyl-2,4-di(thiophen-3-yl)pentan-3-one 1. Rather than the expected photodecarbonylation, UV--vis irradiation of 2 led to the intramolecular 2 + 2 photocycloaddition product 5 in quantitative yields (by GC and NMR) both in solution and in crystalline solid state. Detailed X-ray powder diffraction analyses revealed that the solid-state reaction of sulfone 2 occurs with a loss of long-range order despite retaining some birefringence under polarized microscopy.

Conformationally Constrained β-Amino Acid Derivatives by Intramolecular [2 + 2]-Photocycloaddition of a Tetronic Acid Amide and Subsequent Lactone Ring Opening

[reaction: see text] The N-Boc-protected N-3-alkenyltetronic acid amides 9 and 12 were prepared from tetronic acid bromide (7) and the corresponding amines 6 and 10 by nucleophilic substitution and subsequent acylation in 71% and 39% overall yield. They underwent an intramolecular [2 + 2]-photocycloaddition upon direct irradiation (lambda = 254 nm) to yield diastereoselectively the strained lactones 15 (76%) and 16 (91%) with a 2-azabicyclo[3.2.0]heptane core. In attempts to defunctionalize the 1-hydroxymethyl substituent of the 2-azabicyclo[3.2.0]heptane skeleton, lactone 15 was converted into mesylate 18 (74% overall yield). Intermolecular substitution reactions on this mesylate, however, proceeded sluggishly or failed completely. Lactone 15 could be opened reductively (Dibal-H) or by substitution with benzylamine to the N-Boc-protected 2-azabicyclo[3.2.0]heptanes 21 (71%) and 22 (81%). Conformationally constrained beta-amino acid derivatives were obtained by quantitative N-Boc deprotection of photocycloaddition product 15, followed by N-functionalization and subsequent lactone ring opening. The N-functionalization was conducted by acylation (to 24-26), alkylation (to 27), tosylation (to 28), and isocyanate addition (to 30). The reactions proceeded in yields of 70-84%. Lactone ring opening reactions were conducted with amines to establish the suitability of this process for library synthesis. As an example, the tripeptide 38 was obtained from photocycloaddition product 15 in an overall yield of 51%.

The Paternò-Büchi Reaction of α-Alkyl-Substituted Enecarbamates and Benzaldehyde

The α-substituted enecarbamates and enamides 5a-d, 5f and 6 were prepared in two steps from the corresponding ketone, N-benzylamine and an appropriate acylating agent (Boc2O, Ac2O). The [2+2] photocycloaddition reactions of benzaldehyde to the alkenes 5a-d which bear a primary or secondary alkyl substituent proceeded smoothly and gave the 3-aminooxetanes 8a-d in moderate to good yields (46-71 %). The α-phenyl-substituted enecarbamate 5f did not produce a photocycloaddition product presumably due to rapid energy transfer (triplet sensitization) from the photoexcited aldehyde. For less obvious reasons the tert-butyl-substituted enamide 6 did not react in the Paternò-Büchi reaction either. The 3-alkyl-3-aminooxetanes 8 were obtained as a mixture of cis- and trans-diastereoisomers. An increase in the steric bulk of the alkyl substituent R shifted the diastereomeric ratio (cis-8/trans-8) in the direction of the thermodynamically more stable cis-product (29:71 for R = CH3 up to 57:43 for R = cyclohexyl). The separated oxetane diastereoisomers cis-8a and trans-8a (R = CH3) underwent a smooth ring opening/cyclization reaction upon treatment with trifluoroacetic acid. Oxetane trans-8a yielded the oxazolidinones 9 and trans-10 (92 %), oxetane cis-8a gave exclusively the oxazolidinone cis-10 (54 %).

The photo-Arbuzov rearrangement of dimethyl 9-anthrylmethyl phosphite and the photodimerization of the corresponding phosphonate

Upon irradiation, 9-anthrylmethyl phosphite (2) undergoes the photo-Arbuzov rearrangement to give the corresponding phosphonate 3. Prolonged irradiation led to the clean formation of the centrosymmetric, head to tail, [4 + 4] photocycloaddition product 4 as indicated by X-ray crystallographic analysis. The same photodimer results on irradiation of phosphonate 3 itself in solution or in the solid phase. Phosphite 2 does not undergo photodimerization to 6. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:155–160, 1998

Photoinstability of some tyrphostin drugs: chemical consequences of crystallinity.

The purpose of this work was to study the photostability of the antiproliferative tyrphostin drug compounds RG 13022(I) and RG 14620(II) as a part of preformulation program. The compounds were exposed to cool white fluorescent light in solution as well as in the solid state and analyzed by HPLC. The degradation products were isolated chromatographically and their structures determined by spectroscopic methods. X-ray crystallographic analyses of the above compounds and their solid state degradation products were carried out to understand the mechanism of photodegradation. The compounds were found to undergo efficient photochemical transformations in solution as well as in the solid state. The degradation in the solution was due to the photoisomerization into their E-isomers (III and IV). The solid state photodegradation products were [2 + 2]-cycloaddition products (V and VI). The stereochemistry of the photocycloaddition products was indicative of the crystal packing of their monomeric precursors. The photocycloaddition product of RG 13022 possesses the head-to-tail linkage as expected from the head-to-tail packing of RG 13022 molecules in the crystal. The photocycloaddition product of RG 14620, however, was found to involve head-to-head linkage in agreement with the head-to-head crystal packing of RG 14620. Drug compounds containing open chain olefinic double bonds could be sensitive to mild condition of light in the solid state if the distance between the two double bonds in the crystal approaches 4.2 degrees A and they have suitable UV absorption characteristics. Attractive interactions between chlorine atoms have significant influence in controlling the crystal packing of chlorinated aromatic compounds.

The direct observation of a psoralen-thymine UVA induced solid-state cycloaddition reaction product by single-crystal x-ray diffractometry.

Single-crystal x-ray diffraction methods have been used to directly observe and simultaneously determine the molecular structure of the UVA induced cis-syn photocycloaddition product in a partially photolyzed single crystal of a psoralen(pyrone ring side)-DNA(thymine) interaction model compound, 1'-(8-oxypsoralen)-8'(thym-1"yl)3',6'-dioxaoctane.

Studies directed towards the synthesis of taxane diterpenes: A remarkable rearrangement

Acid-catalyzed fragmentation of the intramolecular dioxolenone photocycloaddition product 9 leads not to 10, the desired taxane skeleton, but instead to the remarkable rearrangement product 11.

Synthetic studies of carbohydrate derivatives by photochemical reactions. Part 16. Synthesis of DL-apiose derivatives by photochemical cycloaddition of 1,3-dihydroxypropan-2-one derivatives with ethenediol or ethenol derivatives

Irradiation of a benzene solution of 1,3-diacetoxypropan-2-one (5) and 1,3-dioxol-2-one (6) with a high-pressure mercury lamp gave a photocycloaddition product, (7-acetoxymethyl-3-oxo-2,4,6-trioxabicyclo[3.2.0]heptan-7-yl)-methyl acetate (7)(55% yield). Similar photocycloadditions of (5) with (Z)-vinylene diacetate (23), with (Z)-2-(benzyloxy)vinyl acetate (25), with 2,3-dihydro-1,4-dioxin (27), with vinyl acetate (28), with isopropenyl acetate (29), with ethoxyethene (30), and with 1,1-diethoxyethene (43) afforded cis-4,4-bis(acetoxymethyl)oxetan-2,3-diyl diacetate (31)(46% yield) and the trans-isomer (32)(49% yield); 2,2-bis(acetoxymethyl)-4-(benzyloxy)-oxetan-3-yl acetate (33)(composed of the two isomers; 11% and 26% yields) and 4,4-bis-(acetoxymethyl)-3-(benzyloxy)oxetan-2-yl acetate (38)(composed of the two isomers; 11% and 9% yields); (8-acetoxymethyl-2,5,7-trioxabicyclo[4.2.0]oct-8-yl)methyl acetate (34)(25% yield); 2,2-bis(acetoxymethyl)oxetan-3-yl acetate (35)(28% yield) and 4,4-bis(acetoxymethyl)oxetan-2-yl acetate (39)(15% yield); 2,2-bis(acetoxymethyl)-3-methyloxetan-3-yl acetate (36)(55% yield); (2-acetoxymethyl-3-ethoxyoxetan-2-yl)methyl acetate (37)(53% yield); and (2-acetoxymethyl-3,3-diethoxyoxetan-2-yl)methyl acetate (44)(48% yield) and ethyl 4-acetoxy-3-acetoxymethyl-3-hydroxybutyrate (45)(19% yield), respectively. The reaction of (5) with (43) was also induced thermally to give ethyl 4-acetoxy-3-(acetoxymethyl)coronate (46)(24% yield) in addition to (45)(20% yield). Photocycloaddition of diethyl mesoxalate (21) with (6) gave diethyl 3-oxo-2,4,6-trioxabicyclo[3.2.0]heptane-7,7-dicarboxylate (22)(23% yield). On the other hand, the reactions of 1,3-dimethoxy-(8) and 1,3-bis(benzyloxy)-propan-2-one (13) respectively with (6) afforded none of the expected photocycloadducts, but several products due to the intramolecular hydrogen abstraction from (8) and (13). The reaction of 2,2-dimethyl-1,3-dioxan-5-one (2) with (6) was also accompanied by predominant decomposition of (20).

Carbonyl n–π* absorption enhancement in β-phenylketones: the molecular geometry of the 6-benzyl-2,6-dimethylcyclohexa-2,4-dienone Diels–Alder dimer and its photocage product

The molecular structures of the 6-benzyl-2,6-dimethylcyclohexa-2,4-dienone Diels–Alder dimer and its intramolecular photocycloaddition product have been determined by crystallographic methods. The enhancement of then n–π* absorption in the u.v. spectrum of the photoproduct is discussed in terms of geometrically facilitated orbital interactions between the carbonyl group and its β-phenyl substituent.

The Molecular Structure of 1-Phenoxy-1,2,2a,8b-tetrahydrocyclobuta[α]naphthalene-8b-carbonitrile

Abstract The molecular structure of the sole photocycloaddition product of α-naphthonitrile with phenyl vinyl ether, C19H15ON was determined by means of X-ray diffraction. The crystals are monoclinic, space group P21/c, unit-cell dimensions are a=11.563(2), b=9.826(1), c=14.324(2) Å, β=113.46(1)°, Z=4. The structure was solved by the direct method, the final R value being 0,042 for 2022 non-zero reflections. The molecule has an endo-configuration, and the cyclobutane ring is puckered.

Crystal and molecular structure of the photocycloaddition product between (�)-piperitone and methylcyclobutene

The structure of the reduced photocycloaddition product between (±)-piperitone and methylcyclobutene, (3b), an important synthetic intermediate, was determined by direct methods from Ni-filtered CuKα diffractometer data. The crystals of the photoadduct, (3b), are tetragonal, space groupI41/a, witha = 22.909(4),c = 10.957(3) A, andd calcd = 1.027 g cm−3 forZ = 16 (C15H26O,M = 222.37). The structure was refined toR = 0.079. Bond distances and angles are normal.

Photochemical Reactions of Some Thioparabanates

Abstract 1,3-Disubstituted thioparabanates (I) were reduced with ethanol under the action of light to yield 2-mercaptoimidazolidine-4,5-diones (II) with or without 2-(1-hydroxyethyl)-2-mercapto-imidazolidine-4,5-dione (III). It seems that these reactions may be initiated by the n–π* transition of the lone pair in the 2-thiocarbonyl group. When dimethylthioparabanate (Ic) was irradiated with a high-pressure mercury arc in a chloroform solution of amylene, a photocycloaddition product, a trimethylene sulfide (IVa), was obtained.

Photocycloaddition of 2-acetylnaphthalene to methyl cinnamate. A 2 + 4 electron photocycloaddition

Irradiation of 2-acetylnaphthalene with methyl cinnamate yields a novel 2+4 electron photocycloaddition product.