Ene-allenes

Nicolaou, K. C. Maligres, P. Shin, J. De Leon, E. Rideout, D. DNA-cleavage and antitumor activity of designed molecules with conjugated phosphine oxide-allene-ene-yne functionalities, J. Am. Chem. Soc. 1990,112, 7825-7826. Schmittel, M. Kiau, S. Strittmatter, M. Steric effects in enyne-aUene thermolyses switch from the Myers-Saito reaction to the —C -cyclization and DNA strand cleavage, Tetrahedron Lett. 1996, 37, 7691-7694. 

Ring annulation by radical cyclization of ene-diynes and (Z)-allene-ene-ynes in a thermal reaction to give aromatics (electrocyclization). 

Scheme 2-72. Rh-catalyzed intermolecular [4-1-2] cycloaddition of allene-ene with alkynes.

Radical reactions ofallenes are largely unknown [57]. Recently, Ma and coworkers [58] developed the first example of a radical addition/cyclization reaction of allene-enes in an alkene-to-allene manner (Scheme 5.32). The reaction of the allene 146 and polyfluoro alkyl iodide 147 with zinc powder as a cheap, readily available, efficient, and mild initiator led to 148 in moderate to good yields (53-86%), which on treatment with TBAF (tetra-n-butylammonium fluoride) gave the allene 149. 

Scheme 5.32 Radical addition/cyclization reactions of allene-enes.

L,2-propadiene, allene, CH2=C = CH2, CjH4. Colourless gas prepared by the electrolysis of potassium itaeonate, or by the action of zinc and alcohol on 1,3-dibromopropane. It is easily isomerized to propyne (methylacetyl-ene), and is produced as a mixture with this substance from some reactions. 

Note 1. The lithiation of monoalky1al 1 enes is not completely regiospecific. The ratio of a- to ylithiated allene varies from about 80 20 for methyl-allene to 93 7 for hexylallene. tert.-Butylallene, however, is metallated exclusively on the terminal carbon atom. 

A number of reaction pathways have been proposed for the Fischer indolization reaction. The mechanism proposed by Robinson and Robinson in 1918, which was extended by Allen and Wilson in 1943 and interpreted in light of modem electronic theory by Carlin and Fischer in 1948 is now generally accepted. The mechanism consists of three stages (I) hydrazone-ene-hydrazine equilibrium (II) formation of the new C-C bond via a [3,3]-sigmatropic rearrangement (III) generation of the indole nucleus by loss of... 

Treating diene-yne derivatives 50 with ferrate 40 does not lead to the expected ene-allenes, instead the [4 + 2]-cycloaddition products 51 are obtained in moderate yields (eq. 1 in Scheme 11). As metal-catalyzed Diels-Alder-reactions of unactivated aUcynes and dienophiles are assumed to proceed via metaUacyclic intermediates, this supports the mechanism for the Alder-ene-reaction discussed before. 

The allene 149 gave by reaction with maleic anhydride (entry 1) and N-phenylmaleimide (entry 2) the [2 + 2] adducts 155a, b as mixtures of two diastereoisomers [36], Nevertheless, their chemical yield was very low and competitive reactions, mostly [4 + 2] cycloadditions on a rearranged al-lylidenecyclopropane and on a primary 1 1 adduct derived from an ene reaction (see Sect. 2.1.2), prevailed. Allenes 149 and 563 cycloadded to tetracyano- and l,l-bistrifluoromethyl-2,2-dicyanoethylene (Table 45, entries 3-6) also selectively at the cyclopropyl substituted double bond in order to remove most of the ring strain [149a],... 

A nickel-chromium catalyst prepared from chromous chloride and (p-diphenylphos-phinopolystyrene)nickel dichloride mediates the ring-closure of the ene-allene 236 (R = H) to a mixture of 3.4 parts of 237 and 1 part of 238 (equation 120)121. An analogous reaction of the t-butyldimethylsilyl ether of 236 yields solely the (E)-isomer 237 (R = t-BuMeaSi). Cyclization of the ene-allene 239 affords the perhydroindane 240 in 72%... 

Finally, another interesting use of singlet oxygen in the oxidation of dienes concerns the reactivity of allenes. Besides the formation of endoperoxides by addition to dienes and hydroperoxide formation via the ene reaction, singlet oxygen reacts with electron-rich... 

A novel use of Buchwald s titanium-based Alder-ene protocol is the cycloisomerization of dienynes to allenes (Equation (47)). Somewhat surprisingly, the Diels-Alder product was observed in trace amounts only in the cycloisomerization of amine 76. 

Allenes, while arguably underused in synthesis as a whole, have become popular functionalities in cycloisomerization chemistry and provide access to a wide variety of products. Ruthenium, cobalt, platinum, palladium, rhodium, and iridium catalysts are efficient in the transition metal-catalyzed Alder-ene reactions of allenes. 

Trost et alJ2 also explored the compatibility of di-, tri-, and tetrasubstituted allenes with their intermolecular Alder-ene protocol. Multiple substituents present the opportunity for a mixture of products to arise from differing regio- and chemoselectivity. 1,1-Disubstituted allenes were coupled to methyl vinyl ketone with excellent chemo-selectivity only when one set of /3-hydrogens was activated by an cy-ester or amide (Equation (69)). If the /3-hydrogens were of similar acidity, a mixture of products was obtained, as in the coupling of allenol 103 with methyl vinyl ketone dienes 104 and 105 are produced in a 1.3 1 mixture (Equation (70)). 

Trost et al 2 briefly explored using non-enone enophiles. Simple alkenes led to the formation of complex mixtures of isomers due to the presence of an additional set of /3-hydrogens. Many other types of substrates were incompatible with reaction conditions. Vinyl ketones were, therefore, the only coupling partners shown to be effective in the ruthenium-catalyzed Alder-ene couplings of allenes and alkenes. 

PtCl2 was shown to catalyze a similar Alder-ene transformation, as in the cycloisomerization of allenyne 117 to triene 118 (Equation (76)).78 In the same study, it was noticed that tetrasubstituted allenes cyclized to bicyclic compounds, such as 120 (Scheme 23), under identical PtCl2 conditions, presumably due to A(1,3) strain in intermediate 119. 

Weinreb86 has reported the Alder-ene cyclization of enallenes under thermal conditions (Equation (85)). Varying the substitution pattern of alkene and allene groups had little effect on the yield of cyclized product. One exception was a,/ -unsaturated ester 130(Equation (86)) cycloisomerization under thermal conditions led to the formation of the Alder-ene product 131 and the unexpected hetero-Diels-Alder product 132 in a 3 1 ratio. 

Weinreb et al86 have also studied the participation of allenes in imino-ene and carbonyl-ene reactions. Gycloisomerization of imine 133 in the presence of stannic chloride gave exclusively the m-substituted cyclopentyl isomer 135 (Scheme 27). The thermal imino-ene reaction of 136 was equally effective. More highly substituted... 

Product stabilization is much more pronounced when the enediyne or ene-yne-allene starting materials are not already part of an aromatic system, since forming an aromatic system constitutes a much higher degree of stabilization than expanding an aromatic system (Fig. 24). Conjugation of the radical center provides additional stabilization to the 71-radical formed by the Myers-Saito and Schmittel cyclizations. 

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. 

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