Nickel-Mediated Cycloaddition

The regiochemistry of nickel mediated cycloadditions of substituted norbomadienes has been investigated in detail. The regioselectivity, exo/endo selectivity and site selectivity seem to depend strongly on the substituents on both diene and dienophile. Tetracya-noethene, for example, reacted with 2-acetyloxymethyl substituted norbomadiene on the distal side331. 

The nickel-mediated [4 -i- 4] cycloaddition strategy has also provided a concise and stereocontroUed route into the sequiterpene lactone (+)-asteiiscanolide (128). The basic features of this approach are outlined in Scheme 17. The critical [4 + 4] cycloaddition st occurred under standard conditions to give the key intermediate in 67% yield. Clearly, the intramolecular version of the nickel-catalyzed diene cy-clodimerization has been established as a powerful and highly-selective protocol for the synthesis of cyclooctane ring systems and should find extensive qjplication to natural product synthesis. 

Zero-valent, nickel-mediated intramolecular enyne metathesis is also an effective method for the synthesis of functionalized ring structures. Oxidative cycloaddition of enynes having an electron-withdrawing group on the alkenyl group generates nickelacyclopentene intermediates that... 

Table 7.9 Nickel-mediated cycloadditions of o-xylylene with dienophiles."... 

Nickel-Assisted Room Temperature Generation and Diels-Alder Chemistry 283 Table 7.10 Nickel-mediated cycloadditions of substituted dIbromides with dienophiles. ... 

The direct synthesis of fully aromatic [5]-, [6]-, and [7]helicenes was achieved by the nickel-mediated intramolecular [2-1-2 + 2] cycloaddition of cw,c -dienetriynes at room temperature (Scheme 10.3) [6]. 

Vinyl Fischer carbenes can be used as three-carbon components in Ni(0)-mediated and Rh(l)-catalyzed [3 + 2 + 21-reactions with alkynes (Schemes 48 and 49)142 and with allenes (Schemes 50 and 51).143 All three of the proposed mechanisms for the [3 + 2 + 2]-cycloadditions involve an initial carbene transfer from chromium to nickel or rhodium (Schemes 49, 52, and 53). As is seen from the products of the two [3 + 2 + 2]-reactions with 1,1-dimethylallene, although the nickel and rhodium carbenes 147G and 147K appear similar, the initial insertion of the allene occurs with opposite regioselectivity. 

Scheme 1.64). The Ag(I)-mediated cyclization afforded dipole 306 for 1,3-dipolar cycloaddition with methyl vinyl ketone to yield adducts 307 and the C(2) epimer as a 1 1 mixture (48%). Hydrogenolytic N—O cleavage and simultaneous intramolecular reductive amination of the pendant ketone of the former dipolarophile afforded a mixture of alcohol 308 and the C(6) epimer. Oxidation to a single ketone was followed by carbonyl removal by conversion to the dithiolane and desulfurization with Raney nickel to afford the target compound 305 (299). By this methodology, a seven-membered nitrone (309) was prepared for a dipolar cycloaddition reaction with Al-methyl maleimide or styrene (301). 

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. ... 

Lewis acid catalyzed versions of [4 4- 2] cycloadditions are restricted to functionalized dieno-philes. Nonfunetionalized alkenes and alkynes cannot be activated with Lewis acids and in thermal [4 + 2] cycloadditions these suhstrates usually show low reactivity. It has been reported that intcrmolecular cycloaddition of unactivated alkynes to dienes can be accelerated with low-va-lent titanium, iron or rhodium catalysts via metal-mediated - -complex formation and subsequent reductive elimination39 44. Usually, however, low product selectivities are observed due to side reactions, such as aromatization, isomerization or oligomerization. More effective are nickel-catalyzed intramolecular [4 4- 2]-dienyne cycloadditions which were developed for the synthesis of polycycles containing 1.4-cyclohexadienes45. Thus, treatment of dienyne 1, derived from sorbic acid, with 10mol% of Ni(cod)2 and 30 mol % of tris(o-biphenyl) phosphite in tetrahydrofuran at room temperature affords bicyclic 1,4-dienes 2, via intramolecular [4 + 2] cycloaddition, with excellent yield and moderate to complete diastereocontrol by substituents attached to the substrate. The reaction is sensitive towards variation in the catalyst and the ligand. 

Tetracarbonylnickel and other nickel(O) compounds, as well as palladium complexes, catalyze the [2 + 2 + 1] cycloaddition of allylic systems with alkenes or alkynes and carbon monoxide to form cyclopentanones or cyclopentenones. This reaction type resembles stoichiometric zirconium- and cobalt-mediated [2 + 2 + 1] cycloadditions (vide supra), mechanistically, however, it proceeds via transition metal 7r-allyl complexes. 

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