Intramolecular allenes

Allene, intramolecular, alkylative Zn-R 429h,429i,431a... 

When the stereogenic center is a chiral allene, intramolecular 12 + 2 photocycloaddition produces optically active adducts [117]. A recent reinvestigation of the photoreactivity of optically active allenic enones (156) has shown that the adducts 157a and 158a are obtained with 100% asymmetric induction [146] (Scheme 24). 

For nonactivated allenes intramolecular versions look quite promising as 258 [106] and 259 [107] indicate, but again one has to be aware of catalyst-dependent variations. 

Yasukouchi, T. and Kanematsu, K. (1989) The total synthesis of ( )-cis-trikentrm Bvia allene intramolecular cycloaddition. Tetrahedron Lett., 30, 6559-6562. 

The intermediate 190 of the intramolecular aminopalladation of an allenic bond with jV-tosylcarbamate undergoes insertion of allylic chloride. Subsequent elimination of PdCl2 occurs to afford the 1,4-diene system 191. The regeneration of Pd(II) species makes the reaction catalytic without using a reoxidant[190]. 

The catalytic oxidative carbonylation of allene with PdCb and CuCh in MeOH affords methyl a-methoxymethacrylate (559)[499]. The intramolecular oxidative aminocarbonylation of the 6-aminoallene 560 affords the unsaturated J-amino ester 561. The reaction has been applied to the enantioselective synthesis of pumiliotoxin (562)[500]. A similar intramolecular oxycarbonyla-tion of 6-hydroxyallenes affords 2-(2-tetrahydrofuranyl)acrylates[501]. 

When allene derivatives are treated with aryl halides in the presence of Pd(0), the aryl group is introduced to the central carbon by insertion of one of the allenic bonds to form the 7r-allylpalladium intermediate 271, which is attacked further by amine to give the allylic amine 272. A good ligand for the reaction is dppe[182]. Intramolecular reaction of the 7-aminoallene 273 affords the pyrrolidine derivative 274[183]. 

Allenes also react with aryl and alkenyl halides, or triflates, and the 7r-allyl-palladium intermediates are trapped with carbon nucleophiles. The formation of 283 with malonate is an example[186]. The steroid skeleton 287 has been constructed by two-step reactions of allene with the enol trillate 284, followed by trapping with 2-methyl-l,3-cyclopentanedione (285) to give 286[187]. The inter- and intramolecular reactions of dimethyl 2,3-butenylmalonate (288) with iodobenzene afford the 3-cyclopentenedicarboxylate 289 as a main product) 188]. 

The reaction of nitrones with allenes produced three main products an azepine, a pyrrolidinone and an isoxazolidine (Scheme 155) (79JOC4213). The intramolecular cycloaddition of nitrones (529) produced different products depending on the length of n (Scheme 156) (78H(10)257). 

Analogous to the allylsilane cyclizations, alkynylsilanes can also be used to synthesize 1,2-fused bicyclic compounds. The intramolecular addition of 4-[5-(trimethylsilyl)-3-pentynyl]-2-cyclo-hexenone proceeded smoothly in the presence of various Lewis acids, yielding functionalized cw-fused octahydro-5/f-inden-5-ones containing the synthetically useful terminal allene unit45. 

Those processes that can be described as intramolecular coupling belong to the same type of reaction as discussed thus far in this chapter. Intramolecular N-, O-, S-, and C-coupling reactions are known. The older literature on such ring closure reactions is particularly extensive. We will discuss only a few representative examples published in the last two decades. The older literature was reviewed briefly by Wulfman (1978, p. 277) and, in more detail, by Saunders and Allen (1985, Chap. 8). 

The classical literature on modifications of cinnoline syntheses was reviewed by Leonard (1945) and more recently by Wulfman (1978, p. 277) and by Saunders and Allen (1985, p. 467). The question of why cinnolines without a substituent in the 4-position were not obtained by the intramolecular C-coupling of 2-aminostyrene has, so far as we know, still not been answered. 

Table 10-6. Intramolecular cyclization of compounds with the general structure 10.41 (after Saunders and Allen, 1985).

Kanematsu K. Molecular Design and Syntheses of Biologically Active Compounds Via Intramolecular Allene Cycloaddition Reaction Strategy Rev. Heteroat. Chem. 1993 9 231-259... 

Secondary amines can be added to certain nonactivated alkenes if palladium(II) complexes are used as catalysts The complexation lowers the electron density of the double bond, facilitating nucleophilic attack. Markovnikov orientation is observed and the addition is anti An intramolecular addition to an alkyne unit in the presence of a palladium compound, generated a tetrahydropyridine, and a related addition to an allene is known.Amines add to allenes in the presence of a catalytic amount of CuBr " or palladium compounds.Molybdenum complexes have also been used in the addition of aniline to alkenes. Reduction of nitro compounds in the presence of rhodium catalysts, in the presence of alkenes, CO and H2, leads to an amine unit adding to the alkene moiety. An intramolecular addition of an amine unit to an alkene to form a pyrrolidine was reported using a lanthanide reagent. 

When colorless crystals of rac-s-trans-3,8-di-tert-butyl-l,5,6,10-tetraphenyl-deca-3,4,6,7-tetraene-l,9-diyne (123) were heated at 140 °C for 2 h, the ben-zodicylobutadiene derivative (126) was produced as green crystals. As shown in the sequence (Scheme 20), 123 is first isomerized to its s-ds-isomer (124), and intramolecular thermal reaction of the two allene moieties through a [2+2] conrotatory cyclization gives the intermediate 125, which upon further thermal reaction between acetylene moieties gives the final product 126 [19,22].This is another example of the crystal-to-crystal reaction. 

Eairley DJ, DR Boyd, ND Sharma, CCR Allen, P Morgan, MJ Larkin (2002) Aerobic metabolism of 4-hydroxybenzoic acid in Archaea via an unusual pathway involving an intramolecular migration (NIH shift). Appl Environ Microbiol 68 6246-6255. 

Proton-coupled intramolecular electron transfer has been investigated for the quinonoid compounds linked to the ferrocene moiety by a 7r-conjugated spacer, 72 (171) and 75 (172). The complex 72 undergoes 2e oxidation in methanol to afford 74, which consists of an unusual allene and a quinonoid structure, with the loss of two hydrogen atoms from 72 (Scheme 2). The addition of CF3SO3H to an acetonitrile solution of 74 results in two intense bands around 450 nm, characteristic of a semi-quinone radical, and a weak broad band at lOOOnm in the electronic... 

The mechanism of [3 + 2] reductive cycloadditions clearly is more complex than other aldehyde/alkyne couplings since additional bonds are formed in the process. The catalytic reductive [3 + 2] cycloaddition process likely proceeds via the intermediacy of metallacycle 29, followed by enolate protonation to afford vinyl nickel species 30, alkenyl addition to the aldehyde to afford nickel alkoxide 31, and reduction of the Ni(II) alkoxide 31 back to the catalytically active Ni(0) species by Et3B (Scheme 23). In an intramolecular case, metallacycle 29 was isolated, fully characterized, and illustrated to undergo [3 + 2] reductive cycloaddition upon exposure to methanol [45]. Related pathways have recently been described involving cobalt-catalyzed reductive cyclo additions of enones and allenes [46], suggesting that this novel mechanism may be general for a variety of metals and substrate combinations. 

This Pd(0)/formic acid system was effective for the cyclization of substituted 5-allene-l-ynes to give diene 140 (Eq. 25) through initial insertion into the internal 7r-bond of the allene followed by insertion into the alkyne [79]. All of the examples provided were geminally substituted within the backbone to facilitate cyclization. Intramolecular allene-alkyne reductive couplings to generate six-membered rings were not achieved. 

Alcaide, Aknendros and coworkers developed a combination of a 3,3-sigmatropic rearrangement of the methanesulfonate of an a-allenic alcohol to give a 1,3-bu-tadiene which is intercepted by a dienophile present in the molecule to undergo an intramolecular Diels-Alder reaction [83]. Thus, on treatment of 4-236 with CH3S02C1, the methanesulfonate was first formed as intermediate, and at higher temperature this underwent a transposition to give 4-237 (Scheme 4.51). This then led directly to the cycloadduct 4-238 via an exo transition state. 

As shown in the preceding examples, although intramolecular Pd-catalyzed poly-cyclization is a well-established procedure, some few examples exist of polycycliza-tions where the first step is an intermolecular process. In this respect, the Pd°-cata-lyzed domino reaction of allenes in the presences of iodobenzene reported by Tanaka and coworkers [40] is an intriguing transformation. As an example the Pd-catalyzed reaction of 6/1-60 in the presence of iodobenzene led to 6/1-61 in 49% yield, allowing the formation of three rings in one sequence (Scheme 6/1.14). 

Me3SiPdSnBu3 is formed primarily from 6/1-237, which then adds to the allene moiety in 6/1-236 to give a a- or Jt-allyl palladium complex. This undergoes an intramolecular carbonyl allyl addition to afford the cis-cycloalkariols 6/1-238 (Scheme 6/1.61). 

An intramolecular Pd-catalyzed ring closure of an allylic halide, acetate or carbonate containing an allene moiety as 6/1-256, followed by a Suzuki reaction, was used by Zhang and coworkers for the synthesis of five-membered carbo- and heterocycles 6/1-257 and 6/1-258 (Scheme 6/1.67) [125]. 

Fig. 4 Ground-state and excited-state energies of the TICT complexes thioflavin T (a) and 9-(dicyanovinyl)-julolidine (DCVJ) (b) as a function of the intramolecular rotation angle (data from Stsiapura et al. [13] and Allen et al. [14]). In both cases, energy levels were determined by quantum mechanical simulations. For thioflavin T, the energy difference between Si and S0 corresponds to approximately 400 nm in the planar state and 470 nm in the twisted state. In the case of DCVJ, the energy differences correspond to 310 and 960 nm, respectively. The DCVJ energy levels reflect a rotation around the vinyl double bond...

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