Alkynes, cycloaddition with dienes

Fluorinated cyclobutanes and cyclobutenes are relatively easy to prepare because of the propensity of many gem-difluoroolefins to thermally cyclodimerize and cycloadd to alkenes and alkynes. Even with dienes, fluoroolefins commonly prefer to form cyclobutane rather than six-membered-ring Diels-Alder adducts. Tetrafluoroethylene, chlorotrifluoroethylene, and l,l-dichloro-2,2-difluoroethyl-ene are especially reactive in this context. Most evidence favors a stepwise diradical or, less often, a dipolar mechanism for [2+2] cycloadditions of fluoroalkenes [S5, (5], although arguments for a symmetry-allowed, concerted [2j-t-2J process persist [87], The scope, characteristic features, and mechanistic studies of fluoroolefin... 

Ditertiary phosphane complexes of nickel were found to be effective in the formation of pyrone 108 by cyclocotrimerization of alkynes with carbon dioxide. The formation of the nickelacyclopentadiene 105 from two moles of alkyne and a nickel complex is followed by CO2 insertion into a nickel-carbon bond to give the oxanickelacycloheptadienone 106, which then eliminates 108 with intramolecular C—O coupling. Another route involving [4 + 2] cycloadditions of 105 with CO2 in a Diels - Alder reaction to give 107 cannot be ruled out but is less probable because CO2 does not undergo [4 + 2] cycloaddition with dienes. Addition of another alkyne to 105 results in the formation of a benzene derivative (Scheme 38). ... 

The scope of the Diels-Alder cycloaddition in synthesis planning is extended by the fact that both terminal and internal alkynes (RC=CH, RC=CR) enter into [4 - - 2] cycloadditions with dienes in the presence of Co(0) catalysts. These cycloadditions result in cyclohexa-1,4-dienes arising from a formal Diels-Alder reaction [33, 34]. Finally, numerous synthetic equivalents for ketene to be used in [4 + 2] cycloadditions have been developed in the context of prostaglandin sjmtheses. Thus, a broad range of possibilities for achieving these cycloadditions is now available [35, 36, 37] (Scheme 6.13). 

The vinylcarbene complexes Cr(CX))5 =C(OEt)C=CXR) (X = NMe2, OEt R = alkyl, aryl) react with alkynes R OCH to form various cyclopenta[b]pyrans.30S In a two step process, addition of the alkynes NEt20Chfe u> the l-metalla-l,3-diene W(CX))s =C(OEt)CHsCHHi) results in metallatriene species that cyclise U) fwm cyclopentadiene complexes 40. Chromium Fischer type alkoxyalkenyl carbene complexes react with ketoalkynes to fcxm bicyclic lactones in a number of different processes involving 8 and 10-e cyclizations. Various dienyl carbene complexes whose parent in Crortho-substituted aromatic alcohols through a variation upon the more usual benzannulation reaction involving alkyne cycloaddition with carbene complexes. ... 

Products from the Cycloaddition Reactions of (Me3Si) R2. Si=C(OSiMe3)R with Dienes, Alkenes, and Alkynes (% Yields)... 

Af-Acyliminium ions are known to serve as electron-deficient 4n components and undergo [4+2] cycloaddition with alkenes and alkynes.15 The reaction has been utilized as a useftil method for the construction of heterocycles and acyclic amino alcohols. The reaction can be explained in terms of an inverse electron demand Diels-Alder type process that involves an electron-deficient hetero-diene with an electron-rich dienophile. Af-Acyliminium ions generated by the cation pool method were also found to undergo [4+2] cycloaddition reaction to give adduct 7 as shown in Scheme 7.16 The reaction with an aliphatic olefin seems to proceed by a concerted mechanism, whereas the reaction with styrene derivatives seems to proceed by a stepwise mechanism. In the latter case, significant amounts of polymeric products were obtained as byproducts. The formation of polymeric byproducts can be suppressed by micromixing. 

Beside [2+2+2] cycloaddition, [4+2] and [5+1] cycloadditions represent other approaches for the construction of six-membered ring systems. In parhcular, the intermolecular and intramolecular [4+2] cycloadditions of diene and alkyne have been extensively studied, and a variety of transition-metal complexes-including those of Fe, Ni and Rh-have been reported as efficient catalysts. The first enanh-oselective reaction was achieved with a chiral Rh complex, although the substrates were limited to dienynes with a substituent on the diene terminus [36]. Later, Shibata and coworkers developed an intramolecular and enanhoselective [4+2] cycloaddition using an Ir-BDPP (l,3-bis(diphenylphosphino)pentane) complex (Scheme 11.24) [37], where dienynes with an unsubstituted diene terminus were transformed into bicyclic cyclohexa-1,4-diene with up to 98% ee. 

The acidity of the methylene protons of siIacycIohexa-2,4-dienes promotes dehydrochlori-nation of (155) to give silatoluene (Scheme 245) (77JA5199). It also results from thermolysis of the allyl or methoxy derivatives (156), and readily dimerizes and adds alkynes (Scheme 246) (78JA5246, 81JA6788). The hindered l,4-di-f-butyl-l-silabenzene (157) can be prepared by the dehydrochlorination route. It readily dimerizes but through a less hindered [2+2] cycloaddition and forms Diels-AIder adducts with dienes (Scheme 247) (79AG(E)789>. 

The intramolecular 2 + 2-photo-cycloadditions of optically active allenesilanes (5) with enones and enoates produce silyl-substituted exo-methylenecyclobutanes (6) in high enantiometric excess. Photo-desilation leads to the parent unsaturated exo-methylenecyclobutanes (7) (Scheme 3).19 The cycloaddition of naphthoquinone to allyltrimethylsilane in the presence of Me2 A1C1 yields the expected 2 + 2-cycloadduct that slowly rearranges to the 2 + 3-adduct.20 hi the presence of bases, Cephalosporin triflates (8) undergo 2 + 2- and 4 + 2-cycloaddition with alkenes, alkynes, and dienes via an intermediate six-membered cyclic allene (9) (Scheme 4).21... 

TABLE 11. Product distribution (given as % of characterized product) from the cycloaddition reactions of 2-siloxysilenes with dienes, alkenes and alkynes. 

The Rh-catalysed intermolecular [4+2] cycloaddition of a diene and a terminal alkyne affords the l,4-disubstituted-l,3-cyclohexadiene 58 via 57 [18], The 1,2,6-trisubstituted-l,4-cyclohexadiene 60 is obtained by the Fe-catalysed [4+2] cycloaddition of dienes and internal alkynes. The catalyst 59 is prepared by the reaction of a 1,4-diaza-1,3-diene complex of FeCl2 59 with EtMgBr [19]. 

The cycloheptatriene complex undergoes cycloadditions with various unsaturated bonds, such as monoenes, dienes and alkynes, under mild conditions to afford interesting polycyclic compounds. In particular, the intramolecular version offers efficient methods for the construction of strained polycyclic skeletons, which are difficult to synthesize by other means [72]. 

Drawn from these examples it is apparent that controlling the chemose-lectivity in inter-intermolecular Heck-Diels-Alder reactions of two different alkenes can be tedious if the alkenes show comparable reactivities. Nevertheless, the stepwise approach was realized in several other cases. In a synthesis of a derivative of cephalostatin 1 containing a central benzene instead of the pyrazine ring, Winterfeldt et al. linked two steroidal systems by a Heck coupling and subsequently performed high pressure Diels-Alder reactions of the conjugated diene with electron-deficient alkynes [34], Another example, reported by Hayashi et al., involves a selective Heck reaction of a bromoglu-cal with ethylene or acrylic acid derivatives followed by cycloadditions with maleic anhydride or N-phenylmaleimide [35]. 

F2 Cycloadditions of Trifluoromethyl-Substitutcd Alkynes with Dienes... 

The oxidation of the reactive M R compounds through cycloaddition with organic multiple-bonded reagents, such as alkynes, dienes, and heterodynes, produces heterocychc compounds that contain M (Scheme 8). In the case of A1 C1, the initial cycloaddition products often ohgomerize to form larger heterocycles and clusters compounds. 

Dienophiles substituted with appropriate heteroatoms may offer a number of advantages such as (1) provide dienophilic equivalents of C-—C and moieties which do not undergo [4 + 2] cycloadditions to 1,3-dienes because of low (e.g. isolated alkenes, alkynes, allenes) or different reactivities (e.g. ketenes) (2) enhance or invert the regiochemistry of the Diels-Alder process (3) permit facile removal of the activating and/or regiocontrolling group after cycloaddition with or without introduction of further functionalities. The use of nitroalkenes as dienophiles demonstrates these issues most strikingly. 

Nonetheless, there are a small number of systems that do mediate such [2 -i- 2 -t- 2] cycloadditions. With allenes as the alkene , cycloaddition with both acetylene and terminal alkynes proceeds regio-selectively to give 3,5-dimethylenecyclohexenes using Ni catalysts, and mostly 3,6-dimethylenecyclo-hexenes using Ni° catalyst precursors (equation 19). Norbomadiene undergoes so-called homo-Diels-Alder cycloaddition with both alkenes and a ynes in the presence of nickel catalysts. Further elaboration of this chemistry with alkynes but not alkenes has been described using a Co/Al catalyst system (equation 20). Attempts to produce cyclohexenes via all-intramolecular [2 + 2 + 2] cycloaddition of l,13-dien-7-ynes or 1,1 l-dien-6-ynes have been unsuccessful. ... 

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