Cyclizations alkenyl systems

The cascade sequence that affords bicyclic systems fails with the lithium derivatives of 2-bromo-iV,iV-diallylaniline. The methodology is useful for the synthesis of 3-substituted indolines and indoles, but the substrate undergoes only one anionic cyclization. Alkenyl vinyllithiums and alkenyl aryllithiums have also been employed in the preparation of alkylidenecyclopentanes and indanes. The intramolecular addition of vinyllithium reagents... 

The intramolecular coupling of organostannanes is applied to macrolide synthesis. In the zearalenone synthesis, no cyclization was observed between arylstannane and alkenyl iodide. However, intramolecular coupling take.s place between the alkenylstannane and aryl iodide in 706. A similar cyclization is possible by the reaction of the alkenylstannane 707 with enol triflate[579]. The coupling was applied to the preparation of the bicyclic 1,3-diene system 708[580]. 

Representatives of the pyrrolo[3,2-/][l,7]naphthyridine ring system, viz. 61, have been obtained by palladium-catalyzed cyclization of the corresponding 5-alkenyl-6-amino[l,7]naphthyridines (Scheme 19) <2002H(56)443>, although this reaction appears not to be general and its scope is as yet undefined. 

Gilchrist examined the cyclization of Af-alkenyl-2-iodoindoles with palladium [268, 269], For example, reaction of A-pentenylindole 244 under Heck conditions affords a mixture of 245 and 246 in very good yield. In the absence of TIOAc, 246 is the major product. Further exposure of 245 to Pd(OAc)2 gives 246. Reaction of l-(4-butenyl)-2-iodoindole under similar conditions affords the pyrrolo[l,2-a]indole ring system in modest yield (35%). 

Indolizidines.1 The N-chloro derivative (1) of a c -2,6-dialkylsubstituted piperidine in the presence of this redox system undergoes homolytic cyclization with the alkenyl side chain at -45° to provide two isomeric indolizidines (2 and 3). 

Reaction of alkylthiyl ladicals with alkenyl cyclopropanes (44) furnishes intermediate radicals (45) aftei addition and ring opening. Addition of a further radical acceptor leads to tricyclic [5,5, ] systems via addition followed by cyclization and elimination (Scheme 17).52... 

Bridged and spirocyclic bicycloalkenones. The conversion of silyl enol ethers to a,/J-enones by Pd(OAc)2 (8, 378) can result in cyclization to bicyclic systems when applied to silyl enol ethers of cyclohexanones bearing an alkenyl side chain a or y to the carbonyl group. Although the factors favoring cyclization are not fully defined, this cyclization offers a route to a variety of bridged and spirocyclic systems.1... 

The copper complexed aminyl radical cyclization has been used as a key step in a short total synthesis of ( )-gephyrotoxin 223AB (60). The alkenyl substituted ALchloropiperidine 59 was stereoselectively cyclized to construct the indolizidine ring system (Scheme 17) (86JOC5043). Tribu-... 

The direct alkenylation of arylamines at the ortho position has been reported in reactions of o -chloroalkenylmagnesium chloride with N-lithioarylamines.22 Use of the CuI-L-proline catalyst system in DMSO has been found to be successful in promoting reactions of aryl iodides and bromides with activated methylene compounds, such as ethyl acetoacetate and diethyl malonate.23 The same catalyst in dioxane has been used in intramolecular cyclization of ene-carbamates leading to indoles or pyrrolo[2,3-cjpyridines.24... 

When the dipolar cycloadduct 65, derived from the unsubstituted alkenyl dia-zoimide 64, was exposed to BF3 - OEt2, the resulting cyclized product 66 (90%) was identified as the all syn tetracyclic lactam 66 by X-ray crystal analysis. Thus, in contrast to the other three systems, the bridgehead proton of 66 lies syn to the hydroxyl stereocenter of the original cycloadduct. 

Similar methodology was employed to the synthesis of more complex polycyclic ring system, as shown in Scheme 32 <1997TL9069>. The initial alkenyl radical 54, formed by an intramolecular radical 13-< 4t>-dig macro-cyclization, initiated a radical cascade reaction by first reacting at the a-position of the furan ring. 

A considerable number of pyrroles 30 with alkyl, alkenyl, or aryl substituents were synthesized by spontaneous cyclization of the enyne precursors 31 (when R = H, Ph, CH2OTHP), or upon treatment of 31 with the catalytic system PdCV KCl (when = H), or alternatively, by treatment of 31 with CuCb (when R H) <03JOC7853>. Treatment of y-ketoalkynes with amines in the presence of catalytic amounts of platinum dichloride constitutes a new route to 1,2,3,5-substituted pyrroles <03AG(E)2681>. An intramolecular rhodium(lI)-catalyzed N-H insertion reaction of 5-amino-7,Y-difluoro-a-diazo-P-ketoesters has been used for the synthesis of a series of 3-fluoropyrroles <03OL745>. 

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