Iodination iodine-lithium exchange

Fluoro-3-iodopyridine 212 was used by Comins and Saha as the starting material in a synthesis of mappicine. The first-formed organolithium 213 rearranges to 214 and a quench gives 215. Iodine-lithium exchange allows introduction of the C-4 hydroxypropyl substituent of 216 (Scheme 104). 

Brandsma and coworkers were able to show that meta- (59a) and para-dilithiated benzene (59b) are accessible via iodine-lithium exchange, using n-butyllithium. Therefore, 1,3- and 1,4-diiodobenzene (58a and 58b) respectively were reacted with two equivalents of n-butyllithium in diethyl ether at low temperatures (Scheme 21). The polyUthiation was confirmed by trapping reactions with dimethyl disulphide. The same reactions, starting from the corresponding dibromobenzenes, had led only to monolithiated benzenes. 

Intramolecular reactions from organolithium reagents (Scheme 37) have also been reported. The organolithium reagent is produced through iodine-lithium exchange", through a carbometalation reaction or by deprotonation at a position activated by an aryl. 

Chromene[4,3-c]pyrazoles 34 are synthesized from l-(benzyloxy)-5-(2-fluorophenyl)-4-iodo-l//-pyrazole by iodine-lithium exchange using -BuLi, followed by addition of an aldehyde. Ring closure of the resulting lithium alkoxides, via an S Ar reaction, is effected using sodium hydride in THF under reflux (Scheme 11) <2001JOC4214>. 

Sequential iodine lithium exchange from the 1,5-diiodonaphthalene 63 generates either the monoiodo-monolithio species 64 or the dilithio species 65.70 Clean monolithiation is obtained by allowing the initially formed mixture of mono- and dilithiated products to equilibrate with unreacted starting material over a period of 6 h at 5 °C. No equilibration is necessary on the second lithiation, which is complete in 1 h at -78 °C. 1,8-Diiodonaphthalene 66 can similarly be converted to the dilithio compound 67.71... 

Cyclisation of iodonitrile 10559 to 107 was an early example of an anionic cyclisation. Slow transmetallation of the choronitrile 108 allowed the BuLi to attack the nitrile instead, leading to a quite different cyclisation product 109. The successful iodine-lithium exchange of primary alkyl iodide 105 to give 106 even with n-BuLi must be driven by the cyclisation itself. 

How would you make the starting material for this sequence of reactions Give a mechanism for the first reaction that explains its regio- and stereoselectivity. Your answer should include a conformational drawing of the product. What is the mechanism of the last step Attempts to carry out this last step by iodine-lithium exchange and reaction with allyl bromide fail. Why Why is the reaction sequence here successful ... 

The very fast metal-halogen exchange allows intramolecular cyclization reactions, which are known as Parham cyclizations171. The potential of Parham cyclizations as a useful stereoselective cyclization procedure has proven to be extremely interesting172. Thus, it has been recently demonstrated that iodinated IV-phenethylimides tolerate iodine-lithium exchange, giving rise to the isoquinoline nucleus 304, via a Parham-... 

In the same context, Bailey and Ovaska have described a tandem cyclization of an enynyl alkyllithium generated by low-temperature iodine-lithium exchange on iodide 269. Two sequential 5-exo cyclization reactions when warmed to room temperature afford... 

N-l-Protected 2,4,5-triiodoimidazole 243 was selectively lithiated at the 2-position via iodine-lithium exchange (Scheme 58) (2005S136>. The lithiated species was then quenched by a number of aryl aldehydes 244 to give unsymmetrical diarylmethyl alcohols 245 in high yields. The high yields of these reactions indicated that the iodine-lithium exchange of this triiodoimidazole is efficient and selective. 

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