Cycloadditions vinylogous reactivity

An example of the vinylogous reactivity is the reaction of 52 with cyclopentadiene (Tab. 14.9) [77]. Rhodium(II) acetate-catalyzed decomposition of 52 in dichloro-methane, yields a 2 1 mixture of the bicyclic system 53 derived from the [3-1-4] cycloaddition, and the bicyclo[2.2.1]heptene 54 resulting from electrophihc attack at the vinylic position followed by ring closure. When Rh2(TFA)4 is used as the catalyst, bicy-clo[2.2.1]heptene 54 becomes the dominant product, while the reactivity of the vinyl terminus is suppressed using a hydrocarbon solvent as observed in the Rh2(OOct)4-cat-alyzed reaction in pentane, which affords a 50 1 ratio of products favoring the [3-1-4] cycloadduct 53. 

Several enamines also participate in these cycloaddition reactions. For example, the addition of methyl lithium to benzaldehyde 5 and the sequential introduction of the vinylogous amide and magnesium bromide results in the cycloaddition elimination product chromene 63 (method G, Fig. 4.33).27 The introduction of methyl magnesium bromide to a solution of the benzaldehyde 5 and two equivalents of the morpholine enamine produces the cycloadduct 64 in 70% yield with better than 50 1 diastereoselectivity (method F). Less reactive enamides, such as that used by Ohwada in Fig. 4.4, however, fail to participate in these conditions. 

Attempts to liberate l-methyl-l-aza-2,3-cyclohexadiene (329) from 3-bromo-l-methyl-l,2,5,6-tetrahydropyridine (326) by KOtBu in the presence of [18]crown-6 and furan or styrene did not lead to products that could have been ascribed to the intermediacy of 329 (Scheme 6.70) [156], Even if there is no doubt as to the allene nature of 329 on the basis of the calculations on the isopyridine 179 and 3d2-lH-quinoline (257), it is conceivable that the zwitterion 329-Za is only a few kcal mol-1 less stable than 329. This relationship could foster the reactivity of 329 towards the tert-butoxide ion to an extent that cycloadditions to activated alkenes would be too slow to compete. On the other hand, the ultimate product of the trapping of 329 by KOtBu could have been an N,0-acetal or a vinylogous N,0-acetal, which might not have survived the workup (see, for example, the sensitivity of the N,0-acetal 262 [14], Scheme 6.57). 

A third mechanistically distinct [3 -1- 2] cycloaddition between vinyl ethers and vinyl-carbenoids was discovered and reported in 2001 [26]. This reaction is remarkable because when Rh2(S-DOSP)4 is used as the catalyst, the cis-cyclopentenes 142 are formed in up to 99% enantiomeric excess. The reaction occurs between vinylcarbenoids unsubstituted or alkyl-substituted at the vinyl terminus and vinyl ethers substituted with an aryl or vinyl group. Some illustrative examples are shown in Tab. 14.12. The reaction is considered to be a concerted process, which would be consistent with the highly stereoselective nature of the reaction [26]. Contrary to the [3-1-2] cycloaddition derived by means of vinylogous carbenoid reactivity, this latest [3 -1- 2] cycloaddition is not influenced by solvent effects. Due to steric demands on the carbenoid, the [3-1-2] cycloaddi-tion only occurs with cis-vinyl ethers. 

The substrate 424 for the aza-[3+3] annulation was then prepared in 82% yield over two operations from 436 (Scheme 12.109). Treatment of vinylogous urethane 424 with the more reactive piperidinium triiluoroacetate salt provided aza-tricycle 425 stereoselectively as a single isomer with anti relative stereochemistry in 51% yield. Implementing our one-pot protocol involving in situ hydrogenation of the cycloadduct 425, after the formal cycloaddition, gave 437 in 43% yield over two steps. In this case, Pd(OH)2/C was chosen as the catalyst due to its lower tendency, relative to... 

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