Anionic cyclization cascade reactions

On addition of S04 to the triple bond in the lO-member cycloalkyne 24 and cyclo-aUcynone 27, a nonchain, and anionic, self-terminating radical cyclization cascade is induced. In the former reaction (equation 22) the bicyclic ketones 25 and 26 are formed, and in the latter reaction (equation 23) the a,/3-epoxy ketones 28 and 29 are formed in good yields. Because of the difficulty of oxidizing isolated triple bonds, 804 does not react as an electron-transfer reagent in these reactions but acts as a donor of atomic oxygen. 

Triazole Derivatives. Triazole derivatives are known to possess tumor necrosis factor-a (TNF-a) production inhibitor activity. The synthesis of triazole derivatives can be achieved from alkynes or diynes by a tandem cascade reaction involving 1,3-dipolar cycloaddition, anionic cyclization and sigmatropic rearrangement on reaction with sodium azide. Some of the benzoyl triazole derivatives were considered to be potent local anaesthetics and are comparable with Lidocaine. The triazoles can also be prepared from benzoyl acetylenes,triazoloquina-zoline derivatives, 2-trifluoromethyl chromones, aliphatic alkynes, 2-nitroazobenzenes, ring opening of [ 1,2,4]triazolo [5,1-c] [2,4]benzothiazepin-10 (5//)-one, alkenyl esters and dendrimers. A number of these reactions are outlined in eqs 44 8. 

The above section considered anionic cyclization of enediynes and related molecules in a one-pot process, in contrast to the known classical multi-step methods [260, 327-329]. One-step anionic cycloaromatization of enediynes is also an effective method for the synthesis of biarenes [328]. Depending on the reaction conditions and substrate structure, the process can go by two routes. For example, when a methoxide ion attacks the nitrile function of enediyne 3.691, there follows a cascade of cycloaromatization reactions by an anionic pathway, affording phenanthridinones 3.692 in 50% yield after chromatographic purification. On the other hand, reaction of enediyne 3.691 with sodium methoxide in methanol in the presence of two equivalents of tetra-butylammonium iodide at reflux leads to biaryl derivative 3.693 in 56-64% yield. Diynes 3.691 were synthesized in 40-98% yield by the Pd-catalyzed coupling reaction of 2-ethynylbenzonitrile 3.689 with 2-alkynyliodbenzenes 3.690 (Scheme 3.72) [327]. A similar procedure was applied to the cycloaromatization of a series of (Z)-l-aryl-3-decene-l,5-diynes 3.694 to produce biphenyls 3.695 in yields from 14% to 34% (Scheme 3.73) [327]. 

Rainier devised a variant of the 5-exo-dig radical cyclization of 2-alkynylisocyanides 122 wherein thiols were utilized to both initiate the radical cascade as well as act as nucleophiles in the reaction with the indolenine intermediate 123 yielding the indoles 124 . When R = TMS, elimination of the C-10 thioether can be effected in a gramine-like fashion so as to add nucleophiles (e.g., malonate anion) in the presence of Bu3P allowing for the preparation of more highly functionalized indoles. 

The use of allene as a relay switch introduces the benefits/challenges of regio- and stereo-selectivity. Our initial studies of cyclization-anion capture with allene as a relay switch generated allylic amines in excellent yield. Reactions were conducted in toluene (90 °C, 20 h) in a Schlenk tube, and employed 0.5-1 atm of allene and various amines, using alkenes/alkynes as relay species (Scheme 5.6.23)." The use of organostannanes as anion-capture agents in this cascade has yet to be explored. 

A one-pot sequential and cascade sequence involving the formation of allylic azides, from aryl/heteroaryl/vinyl halides, allene and sodium azide, by palladium catalyzed anion capture, and cyclization-anion capture, followed by 1,3-dipolar cycloaddition provided a variety of 1,2,3-triazoles in good yields <01T7729>. Reaction of a,P-acetylenic aldehydes 107 with sodium azide in dimethylsulfoxide followed by hydrolysis afforded 5-substituted-4-carbaldehyde-1,2,3-triazole derivatives 108 <01TL9117>. 

The first example of an enantioselective intramolecular cascade Mizoroki-Heck-cyanation sequence was recently reported which included the reaction of amide 104 (Scheme 12.24) [33], The cyanide source employed was potassium ferro(II)cyanide, which has been utilized for the palladium-catalysed cyanation of aryl halides. The proposed reaction pathway for the Mizoroki-Heck-cyanation involves capture of a a-alkylpalladium intermediate. Previous examples of enantioselective Mizoroki-Heck cyclization-anion capture most often involve trapping of the 7r-allylpalladium complexes in group-selective reactions. Reaction conditions were surveyed for the Mizoroki-Heck cyanation sequence. It was found that Pd(dba)2 afforded better enantioselectivities than Pd(OAc)2 with Ag3P04 as the additive. Using PMP under neutral conditions led to racemic product. To improve the enantioselectivity, several bidentate ligands were screened, and the ligand DIFLUORPHOS 54a was found to give the best enantioselectivity. 

Kovalenko and Alabugin reported that Cj-C cyclization of benzannelated enediynes with tetra-fluoropyridinyl (TFP) substituents at the terminal alkyne carbons forms indenes rather than fulvenes (Scheme 30.22). The radical/anionic Cj-Cj cyclization of enediynes represents a new type of cycloaromatization reaction—the cyclorearomatization process driven by rearomatization in the vicinity of the TS. This process is triggered via photoinduced electron transfer (PET) [35-38]. Expaimental work unambiguously established PET as the triggering event for the Cj-C cascade and the intermediacy of the second PET step in the indene-forming cascade [39]. Unlike the stable benzene product... 

CycUzation-Anion-Capture Process. Grigg et were interested in devising ring-forming processes with concomitant introduction of functionality by replacing the /3-hydride elimination step of the Heck reaction with a group or atom transfer. This led to the development of cascade cyclization-anion-capture processes. 

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