Cyclization reactions alkenyl systems

Alkenyl-lithiums, which can be prepared by metal-halogen interchange between an appropriate iodide and t-BuLi at — 78°C, undergo cyclizations on warming to room temperature before quenching with a proton source (equation 117) . This cyclization reaction has been extended for the construction of polycyclic alkanes by sequential polyolefinic cyclizations (tandem cyclizations). A propellane system could be constructed in a single step from his-intramolecular cyclization as shown in equation 118 . 

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%). 

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... 

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... 

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>. 

Copper(II) chloride was found to be the best oxidant for the system and a range of esters could be formed if ten equivalents of the corresponding alcohol was added to a THF solution. A range of substituted indoles were subjected to the reaction conditions and furnished both 6- and 7-membered annulation products, in good to excellent yields, 58-91%. 3-Alkenyl indoles were also effective substrates, under going cyclization onto the less nucleophilic C2 position in good yield albeit requiring extended reaction time (Scheme 44). 

Abstraction a to an oxygen atom. Formation of a bicyclic system starting from a free alcohol is depicted in Scheme 40 (Eq. 40.1) [136]. Malacria has recently reported the preparation of enantiomerically pure 1,2,3-triols via an unusual 1,4-hydrogen atom abstraction followed by a highly diastereoselective trapping of the resultant alkoxy substituted radical with acrylonitrile (Eq. 40.2) [19]. In this particular case, intramolecular reaction with the alkenyl group (3-cxo-trig or A-endo-ing cyclization) is not feasible therefore, reaction with an external radical trap is favored. 

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