Conformational analysis in the reversible intramolecular [2+2] photocycloaddition of diphenylbicyclo[4.2.0]oct-3-ene-2,5-diones

An irradiation of diphenylbicyclo[4.2.0]oct-3-ene-2,5-diones bearing variously substituted Me groups resulted in the reversible intramolecular [2+2] cycloaddition between the excited enedione CC double bond and the facing endo-phenyl ring to exclusively give pentacyclotetradeca-10,12-diene-2,7-diones. The equilibrated product ratios were much dependent on the substitution pattern of the Me-groups as well as the irradiated wavelength. The regiochemistry of these photoadditions was elucidated on the basis of the restricted conformation of the starting enediones.     

On the regioselectivity of the intramolecular [2 + 2]-photocycloaddition of alk-3-enyl tetronates

The simple diastereoselectivity and the regioselectivity of the [2 + 2]-photocycloaddition of alk-3-enyl tetronates were studied, depending on the nature of the substituent R in the α-position. Fourteen tetronates were synthesized and their intramolecular photocycloaddition reactions performed. If R was an alkoxycarbonyl group and if the olefin, which underwent the intramolecular addition, was sterically congested, crossed photoproducts prevailed and were formed in yields between 35 and 65%. In all other cases, the straight photoproducts were obtained as the main reaction products in yields ranging from 39 to 84%. The structures of the photochemical products were thoroughly investigated by one- and two-dimensional NMR experiments. In all cases, the diastereoselectivitiy was excellent and only a single diastereoisomer was formed. A mechanistic model is proposed, which explains the regioselectivity of the [2 + 2]-photocycloaddition reaction.     

On the regioselectivity of the Ru-catalyzed intramolecular [5 + 2] cycloaddition

The influence of substituents on which cyclopropyl bond cleaves in the cycloisomerization of cyclopropylenynes catalyzed by CpRu(N&tbd1;CCH(3))(3)(+)PF(6)(-) is compared to the corresponding Rh-catalyzed reaction. With the trans cyclopropyl substrates, the bond energy of the cleaving bond appears to be an important factor. With cis cyclopropyl substrates, steric effects appear to dominate.     

Photochemical [2 + 2] cycloaddition of acetylene to chiral 2(5H)-furanones

The [2 + 2] photocycloaddition of acetylene to chiral 2(5H)-furanones was investigated. The influence on the chemical yield and facial diastereoselectivity of the substituent at the stereogenic center and also the effect of a 4-methyl group were evaluated. A mechanistic proposal based on a simple theoretical conformational analysis is presented. Using a C(2)-symmetric bis(lactone) as the substrate, a diastereomeric excess higher than 98% was found.     

Synthesis of enantiopure 3-azabicyclo[3.2.0]heptanes by diastereoselective intramolecular [2+2] photocycloaddition reactions on chiral perhydro-1,3-benzoxazines

[2+2] photocycloadditions involving chiral 3-acryloyl-2-vinylperhydro-1,3-benzoxazines derived from (-)-8-aminomenthol are highly diastereoselective reactions. The facial selectivity depends on the type of substitution at the vinyl double bond, and always leads to cis-fused bicyclic derivatives. The de is good for compounds with one substituent at the outer carbon of the double bond at C-2, but only one diastereomer is formed in cyclizations of compounds with two substituents at that position. The elimination of the menthol appendage gives enantiopure 3-azabicyclo[3.2.0]heptanes.     

Enantioselective crossed intramolecular [2+2] photocycloaddition reactions mediated by a chiral chelating Lewis acid

In intramolecular [2+2] photocycloaddition reactions, the two tethered olefins can approach each other in a straight or in a crossed fashion. Despite the fact that the latter reaction mode leads to intriguing, otherwise inaccessible bridged skeletons, there has so far not been any enantioselective variants thereof. This study concerned the crossed [2+2]-photocycloaddition of 2-(alkenyloxy)cyclohex-2-enones to bridged cyclobutanes. It was found that the reaction could be performed with high enantioselectivity (80–94% ee) under visible light conditions when employing a chiral rhodium Lewis acid as a catalyst (2 mol%).

An enantioselective crossed [2+2] photocycloaddition is presented which proceeds under visible light irradiation in the presence of a chiral Lewis acidic metal complex. Chelation of two oxygen atoms to the metal centre accounts for the observed enantioface differentiation.     

Transition state analysis on regioselectivity in [2+2] photocycloaddition reactions of substituted 2-cyclohexenone with cycloalkenecarboxylates

The experimental results of the triplet [2+2] photocycloaddition reactions of substituted 2-cyclohexenone 1 with cycloalkenylesters 2, 3, 4 have showed remarkable change in the regioselectivity of the products. The ht/hh product ratio increases with increment of the cycle-size. The FMO investigations in addition to the transition state analysis were used to rationalize such regioselectivity. The FMO method with their orbital coefficients and energies could not explain the reaction selectivity since these values of 2-4 showed tendency to form the hh adduct mainly. PM3, PM5, CIS/6-31G, and B3LYP/6-31G methods were used to locate the hh and ht transition states of the three reactions. As the potential energy barriers (TS1) on the first TS surface for the major products were lower than that for the minor products in most of the cases, the real ratio can be explained in terms of TS analysis. The recently improved PM5 and the B3LYP methods were more successful in this debate as partitioning the activation energy at the potential energy barriers into reactant deformation and the interaction (or repulsion) energies is easy and effective. The changes in the ht/hh ratio with the enlargement of the alkene ring size may be due to the increment of the repulsion energy and large changes in the deformation energy of the reactants. In the transition state structures the stabilities of the major products are thought to be due to the existence of some repulsion between the enone carbonyl and esters in the alkenylesters, and some hydrogen bonding between the reactants. The FMO and second transition state (TS2) energy on the biradical intermediates are also thought to play some role in controlling the product selectivity by lowering the closure energy of the biradicals according to the possibility of their overlapping.     

Investigating the arenyl-diene double [3 + 2] photocycloaddition reaction

The double [3 + 2] photocycloaddition reaction involving arenyl-dienes has been used to assemble seven separate [5.5.5.5] fenestrane structures that include ether and aza variants. The primary photolysis step was a meta photocycloaddition reaction, while a secondary photocycloaddition step formed the fenestrane structure. Investigations involving the insertion of an additional methylene group into the basic arenyl-diene skeleton failed to afford the desired [5.5.5.6] fenestrane structure. The presence of an oxime moiety in the aromatic photosubstrate allowed the primary photolysis step to take place; however, an attempted secondary photocycloaddition reaction involving the oxime did not provide the intended polyheterocyclic fenestrane. An alternative strategy to form various "criss-cross" double meta photocycloadducts was investigated and led to the discovery of a Paterno-Büchi cycloaddition reaction between acetone and an angular meta photocycloadduct. Other novel thermally and photochemically mediated skeletal rearrangement reactions were also recorded.     

Copper(I)-catalyzed intramolecular asymmetric [2 + 2] photocycloaddition. Synthesis of both enantiomers of cyclobutane derivatives

[reaction: see text] A simple approach for asymmetric induction in Cu(I)-catalyzed [2 + 2] photocycloaddition, where asymmetric catalysts or chiral auxiliaries were inefficient, has been developed using the concept of chirality transfer from the readily available 2, 3-di-O-cyclohexylidine-(R)-(+)-glyceraldehyde. An anion-induced cleavage of the tetrahydrofuran ring of the resulting oxa-bicyclo[3.2.0]heptanes led to a convenient access to the synthetically useful cis-1,2-disubstituted cyclobutanes in enantiomerically pure form.     

Asymmetric induction in an intramolecular [2+2] photocycloaddition within chirally modified zeolite supercages

Photoirradiation of 1-cyano-2-(5-methyl-2-oxa-4-hexenyl)naphthalene, included in NaY zeolites along with chiral inductors, such as diethyl tartrate or phenylalaninol, gives an intramolecular [2+2] photocycloadduct with a maximum 15% ee. The degree of enantioselectivity was found to depend on the Si/Al ratio, the nature of the cations in the zeolites, the structure of the chiral inductors, and the molar ratio of substrate and chiral inductors.     

Face selectivity in the [2+2] photoannelation of chiral 3(2h)-furanones with alkenes

The photocycloadditions of a series of chiral 3(2H)-furanones with alkenes show facial selectivities which parallel the steric bulk of the furanone substituents. Selectivities approaching 50:1 are observed in some instances.     

Reactions of 2(3H)-furanones

This review article presents a systematic overview of approaches and reactivity data for 2(3H)-furanones, published from 1999 until 2018.     

Enantioselective intramolecular [2+2] photocycloaddition reactions of 4-substituted coumarins catalyzed by a chiral Lewis acid

Eight coumarins, which carry a terminal alkene tethered by a CH(2)XCH(2) group to their 4-position (X = CH(2), CMe(2), O, S, NBoc, NZ, NTs, NBn), were synthesized in overall yields of 51-80?%. Starting materials for the syntheses were either commercially available 4-hydroxycoumarin or 4-formylcoumarin. The intramolecular [2+2] photocycloaddition of these coumarins gave diastereoselectively products with a tetracyclic 3,3a,4,4a-tetrahydro-1H-cyclopenta[2,3]cyclobuta[1,2-c]chromen-5(2H)-one skeleton. Direct irradiation at λ = 300?nm in dichloromethane (c = 10?mM) led to product formation in good yields for most substrates, presumably via a singlet excited state intermediate. Due to the low coumarin absorption at λ >350?nm the photocycloaddition was slow upon irradiation at λ = 366?nm. Addition of a chiral oxazaborolidine-based Lewis acid (50?mol?%) increased the reaction rate at λ = 366?nm and induced a significant enantioselectivity in the [2+2] photocycloaddition. Six out of eight coumarin substrates (X = CH(2), CMe(2), O, NBoc, NZ, NTs) gave the respective products in yields of 72-96?% and with 74-90?% enantiomeric excess (ee) upon irradiation in dichloromethane (c = 20?mM) at -75?°C. The Lewis acid presumably acts by coordination to the coumarin carbonyl oxygen atom, which leads to a bathochromic shift (redshift) of the UV absorption and which increases the singlet state lifetime. A second electrostatic interaction of the hydrogen atom at C3 with the oxygen atom of the oxazaborolidine is likely.     

Preparation of 3-azabicyclo [3.2.0] heptenones by intramolecular [2+2] cycloaddition

Pyrolysis of N-allyl enaminoesters is a general method for the stereoselective synthesis of 3-azabicyclo[3.2.0] heptenones ; the reaction involves a [2+2] intramolecular cycloaddition of an intermediate iminoketene.     

Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition of trans-vinylcyclopropane-enes

Vinylcyclopropane (VCP) has been well applied as a five-carbon component, rather than a three-carbon component, in transition-metal catalyzed cycloadditions. Here we demonstrate a Rh(I)-catalyzed [3 + 2] reaction of trans-VCP-enes, where VCP acts as a three-carbon synthon to furnish five-membered carbocycles. This novel cycloaddition is efficient in generating bicyclic cyclopentanes in good yields from simple and easily prepared substrates. When cis-VCP-ene is used as the substrate, VCP acts as a five-carbon unit to give a [5 + 2] cycloadduct. Rationalization of the [3 + 2] and [5 + 2] cycloadditions of VCP-enes has been proposed.     

Synthesis of strained tricyclic beta-lactams by intramolecular [2+2] cycloaddition reactions of 2-azetidinone-tethered enallenols: control of regioselectivity by selective alkene substitution

A convenient metal-free methodology for the preparation of structurally novel, strained tricyclic beta-lactams containing a cyclobutane ring has been developed. The first examples accounting for the intramolecular [2+2] cycloaddition reactions in beta-lactams have been achieved by the thermolysis of 2-azetidinone-tethered enallenols, which have been prepared in aqueous media by regio- and diastereoselective indium-mediated carbonyl allenylation of 4-oxoazetidine-2-carbaldehydes. Notably, the regioselectivity of the cycloaddition can be tuned in the allene component just by a subtle variation in the substitution pattern of the alkene component.     

Asymmetric total synthesis of stoechospermol using intramolecular (2+2) photocycloaddition reaction

The first asymmetric total synthesis of stoechospermol, a representative spatane diterpene having $\text{cis}$, $\text{anti}$, $\text{cis}$-tricyclo[5.3.0.0^2,6]decane ring system, was achieved. Using the intramolecular asymmetric (2+2) photocycloaddition reaction of the diastereomeric ester 11, the readily available butenolide 9 was transformed into the optically active dilactone 12a and 12b. Subsequent construction of tricyclic carbon ring system and introduction of substituents in a right stereochemistry gave rise to optically pure stoechospermol 1.