Intramolecular cascade

Chiral l,3-dioxin-4-ones photochemically react intermolecular with (cyclic) ethers, acetals, and secondary alcohols to give the addition products in reasonable yields. The radical addition was completely stereoselective at C-6 of the heterocycle <1999EJO1057>. The exocyclic diastereoselectivity, where relevant, was about 2 1 (Equation 30). In analogy, an intramolecular cascade reaction of a 1,3-dioxin -one derived from menthone was used to get a terpenoid or a steroid framework in optically active form <1997JA1129, 1999JA4894>. 

Hodgson and co-workers have studied the intramolecular cascade carbonyl ylide formation-cycloaddition with chiral Rh(ii) catalysts.After screening a series of chiral Rh(ii) catalysts, high enantioselectivity was achieved in the reaction of 98 by using the Rh(ii) catalyst with binaphthyl phosphate-derived chiral ligands dirhodium(ii) tetrakis[(i )-6,6 -didodecylbinaphtholphosphate] [Rh2(i -DDBNP)4] (Equation (13)). 

Intramolecular cascade cyclization of compounds 481 in the presence of catalytic amount of HgCl2 gave l,2,3,4-tetrahydro-6H-pyrido[l,2-a]pyr-azin-6-ones 483 (09TL4050). NMR investigations indicated that the reaction goes through intermediate 482, which then cyclized to 483. In the absence of catalyst, the cyclization was found to be sluggish. When instead of (2-N02-Ph)S02 derivative N-benzyloxycarbonyl derivative was used, no cyclized product was obtained. Similar reaction of compound 484 provided a mixture of tricyclic compounds 485 and 486. 

An intramolecular cascade reaction initiated by the addition of an alkenyl radical to a furan was used to synthesize an indene <1998SL1215>. As illustrated in Scheme 31, radical fragmentation in the spiro-dihydrofuran radical 52 provided the intermediate triene 53, which underwent Cope-type rearrangement to form the product. A related reaction with 1-bromocyclohexene that led to unsaturated ketone product was also developed <2003EJ01729>. 

However, oxidations based on addition of O-centered radicals to unsaturated compounds appear to be a highly desirable synthetic goal, especially when the new C—O bond could be formed under the mild conditions that are typical for radical reactions. If this radical addition would involve C = C triple bonds, the resulting reactive vinyl radical would be highly suitable for the promotion of intramolecular cascade reactions. 

Purely intramolecular cascade reactions using triple bonds as a kind of relay station are well known (Schemes 3-10, 3-16, 3-20, 3-21, 3-22, and 3-24). An inter-intramolecular variant was developed as an elegant access route to calcitriol (60) (Scheme 3-18) [170]. 

Scheme 3-29 An intra-intramolecular cascade reaction leading to heterobicycles [181bj.

B. INTER-INTRAMOLECULAR CASCADE CARBOPALLADATIONS B.i. Termination by Alkenes... 

TABLE 1. Inter—Intramolecular Cascade Heck Reaction to Form 9,10-Dibenzylidenedihydroanthracenes (for Details See Scheme 4)... 

An inter-intramolecular cascade starting with a bromoalkene and a 1,7-enyne was developed as an elegant access to calcitriol (Scheme... 

The Pd-catalyzed intramolecular cascade CTOss-coupling of l-halo-l,(< l)-dienynes [for 2-halo-l,(ft> l)-dienynes see Scheme 32] with a terminal double bond leads to 2-methylenecycloalkyIidenecycloalkenes (Sch ne 29), ° whereas halodienynes with the initiating iodoalkenyl unit incorporated in the chain between the alkynyl relay and the alkenyl terminator yield methylenebicycloalkadienes (Scheme 29). ° ... 

Intra-intramolecular cascade reactions combined with termination by an external nucleophile provide access to various kinds of ring systems. 

All-intramolecular cascade reactions provide an access to various ring systems with at least two newly formed rings. Stereoelectronic effects exerted by the metal and its ligands are remarkably high, and a vast number of accessible oligocyclic structures can be conceived. Interestingly, compared wiih a number of known examples for cascade... 

Cyclohydrocarbonylation (CHC) is the hydroformylation of a functionalized olefin followed by concomitant intramolecular nucleophillic attack to the newly formed aldehyde moiety leading to a cyclized product. As a variant, the CHC reaction also includes an intramolecular cascade process involving the hydrocarbonylation of a functional alkene, generating an acyl-metal intermediate, which undergoes an intramolecular nucleophilic attack to give the corresponding cyclic compound. CHC reactions have been developed into sophisticated cascade reactions forming bicylic and polycyclic compounds. ... 

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. 

Enantioselective intramolecular cascade Mizoroki-Heck reactions have been shown to proceed with moderate to good selectivity via the cationic manifold. There are surprisingly few enantioselective examples, given the wide array of transformations known for cr-alkylpalladium intermediates in racemic or diastereoselective reactions. All of the nongroup-selective, enantioselective, cascade, intramolecular Mizoroki-Heck reactions reported to date involve formation of one quaternary centre. A substantial advance would be to expand the range of transformations available for the a-alkylpalladium species and... 

Zwitterionic ladder stilbenes (220) with phosphonium and borate bridge were prepared by intramolecular cascade photocyclization by Fukazawa and Yamaguchi. Ghosh found intramolecular photoinduced-Wittig reaction to give 2-aryl(or 2-alkyl)benzofurans (222)." ... 

Early findings by Heck et al. [149a, 337] revealed that coupling reactions of haloalkenes 126 with aUcenes 125 in the presence of secondary amines gave allylamines (Scheme 8.30 132/133 Nu = NR2). On the basis of this observation, inter-intermolecular as well as intra-intramolecular cascade reactions (Scheme 8.34) [338], the latter ones leading to a variety of bicycles (Scheme 8.35) [339], were developed. 

A few examples of naphtho[c]chromenes arise from the intramolecular cascade hydroarylation—cycloisomerization reaction of l-(3-phenoxy-l-propynyl)-2-(l-propynyl)benzene derivatives, catalyzed by a PtCl2/PtCl4 system (13EJO260). 3-Trifluoromethylated benzo[ chromenes are readily accessible through the one-pot reaction of a,P-unsaturated trifluoromethyl ketones with 2-naphthols carried out in the presence of DBU and concentrated sulfuric acid (13SC2883). 

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