Alkyl bromide, chain reaction sequence

N-Alkoxylamines 88 are a class of initiators in "living" radical polymerization (Scheme 14). A new methodology for their synthesis mediated by (TMSlsSiH has been developed. The method consists of the trapping of alkyl radicals generated in situ by stable nitroxide radicals. To accomplish this simple reaction sequence, an alkyl bromide or iodide 87 was treated with (TMSlsSiH in the presence of thermally generated f-BuO radicals. The reaction is not a radical chain process and stoichiometric quantities of the radical initiator are required. This method allows the generation of a variety of carbon-centered radicals such as primary, secondary, tertiary, benzylic, allylic, and a-carbonyl, which can be trapped with various nitroxides. 

Hydroxy alkenyl and alkynyl nitriles can be subjected to a one-pot addition-alkylation sequence, leading to polysubstituted products. In the case of open-chain systems, diastereoselectivity from 2.3 1 to 6.6 1 was achieved. Cyclic systems may lead to a highly diastereoselective reaction.234,234a 234c iv-Chloroalkenylmagnesium bromides give bicyclic products (Scheme 77 ) 235>236... 

Indanones are very useful and versatile intermediates in the synthesis of metallocene catalysts. Scheme 1 has the synthetic scheme originally used for the preparation of 2-alkyl-4-aryl-substituted ansa metallocenes [9-11]. In the first part of this sequence, the biaryl unit is assembled and the missing carbon atoms are introduced as a side chain. The reaction of 2-phenylbenzyl bromide with malonic acid ethyl ester under basic conditions, followed by a decarboxylation, affords the 2-(2-phenylbenzyl)propionic acid. Chlorination and Friedel-Crafts acylation yields the 2-methyl-4-phenylindanone in 93 % yield. From here, only a few standard transformations are required to complete the synthesis, finally yielding the desired metallocene. 

The stereoselective total synthesis of ( )-lepadiformine was accomplished in the laboratory of S.M. Weinreb. The introduction of the hexyl chain in a stereoselective fashion was achieved by a Grignard reaction to an iminium salt during the last steps of the synthetic sequence. The iminium salt was generated in situ from an a-amino nitrile with boron trifluoride etherate, and the addition of hexylmagnesium bromide gave a 3 1 mixture of alkylated products favoring the desired stereoisomer. Removal of the benzyl group completed the total synthesis. 

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