Cross-Conjugation in Synthesis

The investigation of the photochemistry of steroidal cross-conjugated dienones was initiated by both Barton and Jeger and was pursued most extensively by the latter group. Despite the frequently complex product patterns which result from prolonged dienone irradiations, some prepara-tively convenient and useful methods for the synthesis of novel systems have been worked out in this field. 

Synthesis of cross-conjugated mesomeric betaines containing l-oxo-l//-pyrazolo[l,2-tf]pyrazol-4-ium-3-olate, 1-oxo-1 //-pyrazolof 11.2,4]triazol-4-ium-3-olate, 7-oxo-7//-pyrazolo[l,2-tf][l,2,4]triazol-4-ium-5-olate, 7-oxo-7.//-pyrazolo[ 1.2-//][ 1.2.3 ]mazol-4-ium-5-olate, 3-oxo-3//-pyrazolo[l,2- ][l,2,3,5]thiatriazol-8-ium-l-olate, and 2-hydroxy-pyrazolof 1.2-//][ 1.2.5]m.izin-5-iumH-olate structures was duly covered in CHEC-II(1996) <1996CHEC-II(8)747> and... 

The literature of diene and polyene photochemistry provides many cases of synthetically useful reactions. As a result, certain arbitrary decisions have been made regarding what is covered in this chapter. For example, intramolecular [2 + 2]-photocycloaddition reactions of a, >-dienes can be formally included under the general rubric of diene photochemistry. However, we have chosen to restrict our discussion to dienes and polyenes which constitute a self-contained chromophore, viz. conjugated, cross-conjugated and 1,4-diene systems. Likewise, arene-olefin photocycloadditions will not be considered. These two broad classes of photoreactions have been applied extensively in synthesis, and have been the subject of recent reviews3,4. 

Malacria and co-workers76 were the first to report the transition metal-catalyzed intramolecular cycloisomerization of allenynes in 1996. The cobalt-mediated process was presumed to proceed via a 7r-allyl intermediate (111, Scheme 22) following C-H activation. Alkyne insertion and reductive elimination give cross-conjugated triene 112 cobalt-catalyzed olefin isomerization of the Alder-ene product is presumed to be the mechanism by which 113 is formed. While exploring the cobalt(i)-catalyzed synthesis of steroidal skeletons, Malacria and co-workers77 observed the formation of Alder-ene product 115 from cis-114 (Equation (74)) in contrast, trans-114 underwent [2 + 2 + 2]-cyclization under identical conditions to form 116 (Equation (75)). 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

Cross-conjugated trienes have attracted interest in polymer chemistry and theoretical chemistry as well as in synthetic chemistry.11 Although a palladium complex catalyzed 1,2-propadiene dimerization in the presence of water or an amine produced hydroxylated or aminated 2,3-dimethyl-2,3-butadiene,12 the method was not applied to the synthesis of cross-conjugated trienes. Another interesting feature... 

Other exploits have focused on the electronic manipulation of the PPEs via side chains (Table 4, entries 7-16) [36]. If a conjugated side chain is utilized, then the electronic properties of the resulting PPE are influenced. The synthesis of such cross-conjugated PPE-PPV derivatives involves the Pd-catalyzed coupling of a diethynylbenzene derivative with a l,4-distyryl-2,5-diiodoben-zene. The electronic properties of such PPEs are variable by changing the styryl side chain (Table 4, entries 7-12). The polymers are attractive as active layers in light-emitting diodes (LEDs) and thin-film transistors. 

Recently, Kochi et al. described a novel photochemical synthesis for a-nitration of ketones via enol silyl ethers. Despite the already well-known classical methods, this one uses the photochemical excitation of the intermolecular electron-donor-acceptor complexes between enol silyl ethers and tetranitrometh-ane. In addition to high yields of nitration products, the authors also provided new insights into the mechanism on this nitration reaction via time-resolved spectroscopy, thus providing, for instance, an explanation of the disparate behavior of a- and (3-tetralone enol silyl ethers [75], In contrast to the more reactive cross-conjugated a-isomer, the radical cation of (3-tetralone enol silyl ether is stabilized owing to extensive Tr-delocalization (Scheme 50). 

Several applications of photoreactive peptides require the presence of a radionuclide to allow specific and sensitive detection of the photo-cross-linked conjugates. In several cases, radioiodination of tyrosyl moieties and radiolabeled Bolton-Hunter reagents have been used. However, the presence of a radiolabel within the benzophenone photophore is desirable, particularly when the objective is to identify the site of photo-insertion of benzophenone. To this end some radiolabeled, benzophenone-based compounds have been developed and used in peptide synthesis, in particular tritiated Phe(4-Bz) (Scheme 24)J2161 [1-14C-carboxy]-4-benzoylbenzoic acid,1221 and 4-benzoyl-(2,3-3H2)-dihydrocinnamic acid.[154l In addition, 4-(4-hydroxybenzoyl)phenylalanine (Scheme 25) has been directly radioiodinated with Na125I and Chloramine-T)151 ... 

The preparation of azulene (Expt 6.16) provides an interesting series of rearrangements.9 The key step in the synthesis is the intramolecular insertion reaction, carried out under conditions of high dilution, of the ketocarbene (22) into the 1,2-position of the benzene ring. The unstable norcaradiene (23) which is formed then ring-opens to the bicyclic trienone (24), which isomerises to the more stable cross-conjugated trienone (25) during isolation. Dehydration of the trienone with a mixture of phosphorus pentoxide and methanesulphonic acid yields azulene. 

The masked dendralenes 36 are crystalline compounds, stable at room temperature, from which, as hoped, the hydrocarbons 37 could be released on demand in good yields by high-temperature pyrolysis. No solvent is required in these cheletropic reactions which facilitates the work-up. The dendralenes 37 obtained, up to [8]dendralene, have been completely characterized by the usual spectroscopic and analytical methods and can, although they tend to polymerize, be handled under the usual laboratory conditions (see below). The sulfolene decomposition route has recently been applied to the synthesis of many other cross-conjugated compounds, among them the hydrocarbons 39-42 (Scheme 7) [12]. 

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