Cyclization unactivated olefins

Reductive Cyclization of Unactivated Olefinic Carbonyl Compounds 517... 

Several examples of intramolecular ketyl anion/unactivated olefin coupling reactions were reported by the Molander group, one of which is illustrated in equation 2884. An interesting facet of this reaction is that it is possible to further react the cyclized samarium(III) intermediate (47) with a variety of electrophiles, thereby enhancing the... 

Pandey and coworkers have reported several DCN-sensitized photocyclization of a-silylamines connected to unactivated olefins [311-314]. Thus, the silyl amines 268 (Scheme 64) were reported to proceed in a regio- and Jtereo-selective manner yielding the cyclized products 269 and 270 [311]. 

Mariano and coworkers have shown that DCN sensitized photoreaction of 268b in non-deoxygenated solutions leads to the efficient formation (75 %) of the corresponding pyrrolidone and not the azabicyclic product [315]. Earlier studies by Padwa et al. have shown that a-aminoalkyl radicals, unlike their a-amido analogs, do not add efficiently to unactivated olefins (Scheme 65) [316]. The a-silyl amines 277 connected to electron deficient olefins on the other hand, were found to undergo efficient DCN photosensitized cyclization in deaerated solutions to yield 278 and... 

Compared with unactivated olefins, activated olefins with carbonyl groups are reduc-tively cyclized with slightly lower stereoselectivity [75,79-82]. 

Stoltz et al. also reported an intramolecular reaction where C-H bond cyclization of indoles onto unactivated olefins was possible using palladium(II) and molecular oxygen as the sole stoichiometric oxidant (Scheme 41) [69]. They found the C2... 

Molander et al. studied the intramolecular coupling of unactivated olefinic ketones by a reductive ketyl-olefin radical cyclization, mediated by Sml2 in the presence of HMPA [47] (Scheme 18). 

Most of the useful iodine transfer radical reactions arise from the addition of alkyl iodides, which have been activated by one or more adjacent carbonyl or nitrile substituents, to unactivated olefins. This both labilizes the initial iodide, facilitating chain initiation, and helps ensure that the atom transfer step is exothermic. The requisite iodides are typically synthesized by deprotonation with EDA or NaH, followed by iodination with I2 or A-iodosuccinimide. Cyclization of an iodoester yields primarily lactone product, proceeding through the intermediacy of the I-transfer products as shown in Scheme 5 [19]. Reactions in which a-iodoesters cyclized with alkynes also proved efficient. Similar ketones yielded less synthetically useful mixtures of cyclopentyl and cyclohexyl (arising from 6-endo transition states) products. 

A similar approach was used for intramolecular aminofluorination of unactivated olefins mediated by the chiral hypervalent iodine(III) reagent 40 leading to the enantioselective formation of fluorinated piperidine ring derivatives (Scheme 18) [63]. Reagent 40 performs the aminofluorination of pentenamines showing total regioselective control for the 6-endo cyclization products in favour of piperidine formation in excellent enantiomeric excesses (up to 81% ee, 99% ee after recrystallization). 

Suppose you made the following observation [Schoemaker, H. E. Dijkink, J. Speckamp, W. N. Biomimetic a-acylimmonium cyclizations of unactivated olefins Tetrahedron 1978, 34,163-172. How might you develop this into an approach to the pyrrolizidine alkaloids ... 

Recently Geiger and coworkers found that the electrochemically generated CpRe(CO)3 cation catalyzes the [2+2] cycloaddition of unactivated alkenes [304]. The reaction proceeds via SET oxidation of the olefin to the corresponding radical cation, addition, cyclization, and back electron transfer (BET), which can occur either from the reduced catalyst or the alkene. 

Transition metal-mediated cycloaddition and cyclization reactions have played a vital role in the advancement and applications of modem synthetic organic chemistry. Rhodium-catalyzed cycloadditions/cyclizations have attracted significant attention because of their versatility in the transformations of activated and unactivated acetylenes, olefins, allenes, etc. These reactions are particularly valuable because of their ability to increase molecular complexity through a convergent and highly selective combination of acyclic components. In addition, these reactions allow for the preparation of molecules with chemical, biological, and medicinal importance with greater atom economy. Recent developments in rhodium-catalyzed cycloaddition and cyclization reactions are described in this section. 

As illustrated above, simple olefins and acetylenes, unactivated by electron withdrawing groups, serve well as dienophiles in the intramolecular Diels-Alder reaction. This is in contrast to the intermolecular case. Heterosub-stituted olefins can also serve as dienophiles. In addition to the two examples cited above [58, 70] the preparation and cyclization of enamides should be noted [82]. 

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