Alkynes retro

The primary and secondary products of photolysis of common diazirines are collected in Table 4. According to the table secondary reactions include not only isomerization of alkenes and hydrogen elimination to alkynes, but also a retro-Diels-Alder reaction of vibrationally excited cyclohexene, as well as obvious radical reactions in the case of excited propene. 

A rather unusual combination of a Ni-catalyzed [2+2+2] cycloaddition of oxaben-zonorbornadiene 6/4-72 with an alkyne 6/4-73 followed by a retro-electrocyclization to give an arene 6/4-75 and benzoisofuran 6/4-76 was described by Cheng and coworkers [298], Under the reaction conditions, 6/4-76 reacted with another molecule of 6/4-72 to give 6/4-77 and 6/4-78 (Scheme 6/4.18). The best yields were obtained employing phenylacetylene with 98% overall yield (58% of 6/4-78 and 40% of 6/4-77). At a lower temperature (18 °C), intermediates of type 6/4-74 could be isolated. On occasion, azabenzonorbornadienes may also be used instead of 6/4-72. 

Titanacyclobutenes, prepared readily from Tebbe reagent and alkynes, react with aldehydes and ketones to form insertion products which undergo facile retro-Diels-Alder reaction to afford substituted 1,3-dienes (equation 107)185. 

Additional examples of the Sonogashira reactions of pyridine triflates include coupling of 2-pyridyltriflate and 3-hydroxy-3-methylbut-l-yne to afford alkyne 141 [114], The carbinol adduct could be readily unmasked to give 2-ethynylpyridine via a basic-catalyzed retro-Favorsky elimination of acetone. Due to the volatility of 2-ethynylpyridine, use of a high boiling liquid such as paraffin oil for the basic hydrolysis made the distillation more convenient [115]. 

Coordination of Ni(0) to the alkyne gives a n complex, which can be written in its Ni(II) resonance form. Coordination and insertion of another alkyne forms the new C6-C7 bond and gives a nickelacyclopenta-diene. Maleimide may react with the metallacycle by coordination, insertion, and reductive elimination to give a cyclohexadiene. Alternatively, [4+2] cycloaddition to the metallacycle followed by retro [4+1] cycloaddtion to expel Ni(0) gives the same cyclohexadiene. The cyclohexadiene can undergo Diels-Alder reaction with another equivalent of maleimide to give the observed product. 

The reaction of 77 with alkynes has further been elaborated for the synthesis of substituted phthalonitriles 81. An alternative for the synthesis of these compounds is the cycloaddition reaction of 77 with enamines followed by a retro-Diels-Alder loss of N2 and elimination of the amine (Scheme 16). Generally, more forcing reaction conditions are required and lower yields are obtained in reactions with alkynes than in reactions with enamines, for example, 4-ethyl-5-methylphthalonitrile is obtained in 51% yield from 2-pentyne (xylene, 150°C, 18 days) and in 73% yield from 4-(l-ethylprop-l-en-l-yl)morpholine (CHCI3, 70°C, 7 days) <1998T1809>. The mechanism of the reaction with enamines has been studied in detail. This revealed a [1,5] sigmatropic rearrangement in the cyclohexa-2,4-dien-1-amine intermediates formed after the loss of N2 <1998T10851>. 

Reaction of an -substituted pyrrole with an alkynic dienophile provides access to a 3,4-disubstituted pyrrole through a Diels-Alder/retro-Diels-Alder cycloaddition process (73CJC1089). The 3,4-pyrroledicarboxylic ester (206) prepared in this way has been converted to the antimitotic agent Verrucarin E (207 Scheme 44). 

The reaction of oxazoles with alkynes is entirely different, leading to furans. The adducts (157) eliminate a cyanide in a retro-Diels-Alder process (equation 15). A typical example is the formation of the ester (164) from 5-ethoxy-4-methyloxazole and dimethyl acety-lenedicarboxylate (equation 16) equation (17) illustrates the production of two regioisomers in this reaction (79MI41802) a more elaborate case is the twofold addition of benzyne to 4-methyl-2,5-diphenyloxazole to give the bridged dihydroanthracene shown in equation (18) (80TL3627). 

Anhydro-4-hydroxyoxazoIium hydroxides, such as compound (231), behave as carbonyl ylides (232) in cycloaddition reactions, yielding bicyclic adducts with alkenes and carbonyl compounds (Scheme 24). The adducts produced by combination with alkynes fragment spontaneously in a retro-Diels-Alder reaction, giving furans (equation 57). The formation of a furan by the action of DMAD on the 4(5//)-oxazolone (233) shows that the latter exists in equilibrium with the mesoionic tautomer (234 equation 58) (79JOC626). 

For example, the mesoionic 1,3-dithiolones (2) combine across the 2,5-position at 90-130 °C with symmetrically substituted alkynes as dipolarophiles with formation of non-isolable primary adducts of type (85). The latter fragment in a retro Diels-Adler type... 

Acetylenic dienophiles react with oxazoles to provide furans, which arise from the retro Diels-Alder reaction with loss of RCN from the initially formed alkyne/oxazole Diels-Alder adduct. Olefinic dienophiles and oxazoles react to give pyridine derivatives resulting from a fragmentation of the initial [4 + 2] cycloadducts with subsequent aromatization. 

Since perfluoroalkyl-substituted olefins and alkynes possess low-lying frontier orbitals, [4 + 2] cycloaddition reactions to oxazoles and thiazoles without strongly electron-donating substituents are unfavorable. On the other hand, five-membered heteroaromatic compounds possessing an electron-rich diene substructure, like furans, thiophenes, and pyrroles, should be able to add perfluoroalkyl-substituted olefins as well as alkynes in a normal Diels-Alder process. A reaction sequence consisting of a Diels-Alder reaction with perfluoroalkyl-substituted alkynes as dienophile, and a subsequent retro-Diels-Alder process of the cycloadduct initially formed, represents a preparatively valuable method for regioselective introduction of perfluoroalkyl groups into five-membered heteroaromatic systems. 

Platinum-catalyzed cyclization of a 2,3-dihydrofuran to the tethered alkyne provided the fused tricyclic compound 238, as shown in Scheme 71. Acid-promoted benzannulation of 238 then produced the dihydrobenzofuran, presumably via a retro-hetero-Diels-Alder opening of the dihydropyran ring <20040L3191>. 

If D-A adduct 1 contains some 1 2 adducts as impurities, 1,4-benzoquinone is formed by a retro-Diels-Alder reaction during the pyrolytic distillations. In this case, a dark yellow solid of benzoquinone can be seen on the walls of the air condenser, and the distillate has a deeper yellow color. Contamination with a small amount of 1,4-benzoquinone apparently does not interfere with photochemical [2+2] cycloadditions of enedione 3 with alkenes and alkynes, an important application of 3. Fractional distillation of the benzoquinone-contaminated 3 as described for the second distillation of 3 can remove the benzoquinone with some loss of enedione 3. The benzoquinone deposits initially as a dark yellow solid on the walls of the distillation head and air condenser during early fractions. 

Their retro synthetic study was based around the Pauson-Khand cyclization (6), which couples an alkene, an alkyne, and a carbon monoxide source (typically dicobalt octacarbonyl) to give a cyclopentenone ring (Fig. 3.5, top). This reaction has been widely used for synthetic purposes, and some excellent reviews (7,8) have covered its principal features and the recent improvements to its experimental conditions. This reaction, in its intramolecular version, is ideal for the assembly of the l//-[2]pyrindi-none scaffold in two distinct versions, differing in the stereochemistry of the ring junction (Fig. 3.5, bottom). Hence, the readily available unsaturated amino acid derivatives 3.1a,b undergo intramolecular Pauson-Khand reaction to produce the two unsamrated scaffolds 3.2a,b. 

As an alternative, copolymerization of alkynes bearing bulky substituents with TCDTF6 (7,8-bis(trifluoromethyl)tricyclo [4.2.2.0 ]deca-3,7,9-triene) was carried out. In the course of this copolymerization, usually referred to as the Durham Route [86-89], the Feast-monomer was introduced into the polymer main chain and subsequently converted into three unsubstituted, conjugated double bonds via a thermally-induced retro-Diels Alder reaction (Scheme 3) [53]. 

Oxazoles represent the most widely recognized heteroaromatic azadiene capable of [4 + 2] cycloaddition reactions. The course of the oxazole Diels-Alder reaction and the facility with which it proceeds are dependent upon the dienophile structure (alkene, alkyne), the oxazole and dienophile substitution, and the reaction conditions. Alkene dienophiles provide pyridine products derived from fragmentation of the [4 + 2] cycloadducts which subsequently aromatize through a variety of reaction pathways to provide the substituted pyridines (Scheme 14). In comparison, alkyne dienophiles provide substituted fiirans that arise from the retro Diels-Alder reaction with loss of R CN from the initial [4 + 2] cycloadduct (Scheme 15,206 Representative applications of the [4 + 2] cycloaddition reactions of oxazoles are summarized in Table 14. Selected examples of additional five-membered heteroaromatic azadienes participatiitg in [4 + 2] cycloaddition reactions have been detailed and include the Diels-Alder reactions of thiazoles, - 1,3,4-oxadiazoles, isoxazoles, pyrroles and imidazoles. ... 

---