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Cycloaddition and cycloisomerization based on the interaction between an allene and other π ─ components has enabled us to build a variety of useful cyclic frameworks. This account describes our recent research on the Rh ─ catalyzed cycloaddition and cycloisomerization of allene─ alkyne derivatives. Figure 2. Comparison of the strain energies of cycloalkanes. Scheme 1. Classi cation of the Rh ─ catalyzed cycloaddition and cycloisomerization of allene─ alkynes. ( 80 ) J. Synth. Org. Chem., Jpn. 1108 C─ H activation of benzylallene─ internal alkynes, which furnished the hexahydrophenanthrene skeleton (eq. 2, R ≠H). 14b Our research on the Rh ─ catalyzed cycloaddition and cycloisomerization of allene─ alkynes involving C─ C or C─ H activation has been further expanded to a novel [2+2+2] cycloaddition by taking advantage of the unique properties of allenes. Indeed, quite recently, we reported that intramolecular [2+2 +2] cycloaddition of allene─ ene─ ynes proceeded stereospeci cally as well as stereoselectively to afford tri─ and tetracyclic derivatives containing a cyclopropane ring (eq. 3). 16 Furthermore, we have developed a regioselective and partially intermolecular [2+2+2] cycloaddition of allene─ alkynes with alkynes to provide polysubstituted benzene derivatives (eq. 4). 17 This account is a full overview of these studies. 2. Rh ─ Catalyzed Intramolecular Cycloaddition and Cycloisomerization of Allenylcycloalkane─ Alkynes via C sp3─ C sp3 and C sp3─ H Bond Activation 2.1 Intramolcular [6+2] Cycloaddition of Allenylcyclobutane─ Alkynes Highly strained cyclopropane rings have often been utilized as useful and powerful acyclic C 3 building block equivalents for transition─ metal─ catalyzed ring─ forming reactions. 5 We have recently taken advantage of the release of the high strain energy of the allenylcyclopropane─ alkynes 1 (n=1) to produce bicyclo[5.4.0] compounds 2 (n=1, Scheme 2). 15a These results have been described in our previous review. 1n The smooth cleavage of the unfunctionalized cyclopropane ring activated by the adjacent allenyl moiety prompted us to examine the Rh ─ catalyzed intramolecular [6+2] cycloaddition reaction between alkyne and the one carbon homologated allenylcyclobutane (1, n=2) leading to the formation of the bicyclo[6.4.0]dodecatriene frameworks 3 (n=2, Scheme 2). 12 Our initial evaluation was carried out as follows; a solution of the N ─ tosyl derivative 1a 18 was heated at 80 °C in 1,2─ dichloroethane (DCE, 0.025 M) in the presence of [RhCl(CO) 2] 2 19 (10 mol%) for 0.2 h to afford the desired 3a in 40% yield and the monocyclic compound 4a in 52% yield (Table 1, entry 1). Compound 3a became the major product (80%) when 1a was exposed to [RhCl(CO)dppp] 2 19 in toluene (entry 2). [RhCl(dppp) 2] 20 afforded the best result (84%) (entry 3). Finally, the highest yield (87%) of 3a was attained when the reaction was performed in 0.1 M dioxane solution in the presence of 5 mol% [RhCl(dppp) 2] for 0.2 h (entry 4). The formation of 3a and 4a could be interpreted by the mechanism shown in Scheme 3. The initial coordination of 1a with Rh I would occur with three components; the allenic distal double bond, the triple bond, and a proximal carbon─ carbon single bond of the strained cyclobutane ring to form the intermediate A, which should immediately collapse to the rhodabicyclo[4.3.0]nonadiene skeleton B. 8a,21 The cyclobutane ring in B is cleaved, by β ─ carbon elimination, 7,8b which releases the ring strain to generate the nine─ membered rhodacycle C, the reductive elimination of rhodium from which would result in the formation of 3a. On the other hand, the β ─ hydride elimination from B instead produces the intermediate D, which should give 4a through the reductive elimination step. If the starting material 1a possesses a substituent at the allenic position a (Scheme 3), the intermediate B can no longer undergo β ─ hydride elimination. As a matter of fact, the methyl derivative 1b was exposed to the optimized conditions (entry 4 in Table 1) to produce 3b in 98% yield (Table 2, entry 1). The butyl, benzyloxymethyl, and ethoxycarbonyl substrates 3c,d,e were also obtained as the sole products (entries 2─ 4). The oxygen analogues such as 1f and 1g were transformed to the corresponding adducts of 3f and 3g in respective yield of 82% and 86% (entries 5 and 6). The carbon homologues 3h─ m could be obtained in moderate to high yields (entries 7─ 12). For those substrates without a substituent at the allenic position a (1f, 1h, and 1j), the formation of the side products 4 was observed (entries 5, 7, and 9). This cycloaddition protocol was applicable to an internal alkyne derivative, a substrate with a one─ atom shorter linker, and a methyl─ substituted allene derivative to furnish 3n (91%), Scheme 2. Rh ─ Catalyzed cycloaddition of allenylcyclopropane─ alkynes and allenylcyclobutane─ alkynes. Table 1. Cycloaddition reaction of allenylcyclobutane─ alkyne 1a in the presence of various Rh catalysts. a Scheme 3. Plausible mechanism for the formation of 3 and 4. Vol.74 No.11 2016 ( 81 ) 1109 5 (92%), and 6 (81%), respectively (Figure 3). The azocine─ fused bicyclic products 8 could also be obtained in high yields. 22 The use of [RhCl(CO)dppp] 2 in toluene at 80 °C was suitable in this case to provide the desired 8a in 90% yield. Several other azetidine derivatives 7 23 were exposed to the optimized conditions to afford 8b─ i in good yields as shown in Table 3. The substrates 7a,d,e,g,h without a substituent at the allenic position (R =H, entries 1, 4, 5, 7, 8) produced small amounts of 9 (detected by 1 H NMR analysis of the crude product). This cycloaddition reaction was found to be applicable to other substrates including an allenyloxacyclobutane 24 derivative to afford 10a,b, 11, and 12 in high yields (Figure 4). 2.2 Intramolcular [7+2] Cycloaddition and Cyclopropanation of Allenylcyclopentane─ Alkynes Since the strain energies of the normal─ sized cycloalkanes, namely cyclopentane and cyclohexane, had been considered too low (6.3 kcal/mol and ~0 kcal/mol, respectively, Figure 2), 11 utilization of these rings as acyclic C 5─ or C 6─ building block equivalents had never been reported. Encouraged by the successful development of the C sp3─ C sp3 bond activation of the simplest unactivated cyclobutane described above, 12 we moved on to investigate the application of this methodology to the analogous cyclopentane derivatives. Treatment of 13a with 10 mol% [RhCl(CO) 2] 2, which was effective for ring─ opening of allenylcyclopropane, 15a in re uxing xylene for 0.2 h produced the desired bicyclo[7.4.0]tridecatriene 14a in 30% yield. The novel spiro[2.4]heptane derivative 15a was isolated as well in 38% yield (Table 4, entry 1). RhCl(dppp) 2 was the most suitable catalyst for ring─ opening of allenylcyclobutane, 12 and exposure of 13a to 10 mol% RhCl(dppp) 2 resulted in increased production of 14a, formed in 39% yield along with 15a in 52% yield (entry 2). However, in this case RhCl(PPh 3) 3 was found to be the most effective catalyst. Indeed, 13a could be treated with 10 mol% RhCl(PPh 3) 3 in xylene for 0.2 h to produce 14a in a signi cantly improved yield (73%) (entry 3). Milder conditions (heating at 80 °C in toluene for 0.5 h) gave 14a in 72% yield (entry 4). Substrates 13b─ f having a gem ─ disubstituent effect 25 were exposed to the best conditions (entry 4 in Table 4) to afford 14b─ f in 53─ 85% yields (Table 5, entries 1─ 5). The reactions of the carbon─ and nitrogen─ tethered analogue such as 13g,h gave the corresponding adducts of 14g and 14h in respective yield of 53% and 60% (entries 6 and 7). The reactions of phosphonate derivative 13i and substrates 13j─ m having various substituents proceeded well to produce 14i─ m in 62─ 75% yields (entries 8─ 12). Allenylcyclopentane 13n having a butyl group gave 14n in 47% yield (entry 13), while benzyloxymethyl derivaTable 4. Rh ─ Catalyzed cycloaddition of allenylcyclopentane─ alkyne 13a. Table 2. [RhCl(dppp) 2]─ Catalyzed [6+2] cycloaddition of allenylcyclobutane─ alkynes 1. Figure 3. Various products from Rh ─ catalyzed [6+2] cycloaddition. Table 3. [RhCl(CO)dppp] 2─ Catalyzed hetero─ [6+2] cycloaddition of allenylazacyclobutane─ alkynes 7. Figure 4. Various products from Rh ─ catalyzed hetero─[6+2] cycloaddition. ( 82 ) J. Synth. Org. Chem., Jpn. 1110 tive such as 13o required more harsh condition to give 14o in 40% yield (entry 14). The novel spiro[2.4]heptane derivative 15a was consistently detected (Table 4). In particular, 15a was obtained as the major product (52%) when 13a was treated with RhCl(dppp) 2 (Table 4, entry 2). To increase the chemical yield of 15a, we reinvestigated this reaction and found that a lower reaction temperature (heated at re ux in toluene) is suf cient to obtain 15a ef ciently (81%) (Table 6, entry 1). Several other substrates 13 were examined to ascertain reaction generality as summarized in Table 6, with the spiro compounds 15 formed in good yields in all cases. Formation of 14 is tentatively rationalized on the basis of the previously proposed mechanism for ring cleavage of the allenylcyclobutane. 12 Initial coordination of 13 with Rh I would form the intermediate E, which should collapse to the intermediate F via the oxidative ring─ closing reaction (Scheme 4). This intermediate F could activate the inert C─ C bond in the cyclopentane with low strain energy (6.3 kcal/ mol, Figure 2), 11 which result in β ─ C elimination 3d─ h to form the 10─ membered rhodacycle G. Subsequent reductive elimination of rhodium from G would give the nal product 14. The intermediacy of F is strongly supported by the following experimental result. Upon exposure to the standard conditions, substrate 16 afforded the monocyclic product 17 in 86% yield (Scheme 5). Formation of 17 could be well rationalized in terms of β ─ hydride elimination 26 of I. During our ongoing program, Oonishi and Sato 27 have reported a similar cyclopropanation of

Rh<sup>I</sup>-Catalyzed Cycloaddition between Allenyl π-Bonds and C-C Triple Bonds