Halo-amides, cyclization

Kang and co-workers prepared the (3-halo amide arrangement required for oxazoline formation from allylic alcohols via a two-step process. For example, treatment of the allylic alcohol 122 with trichloroacetonitrile and base followed by activation of the double bond with iodine monochloride, provides 123. Hydrolysis of 123 gave 124 from which cyclization provided the oxazoline 18a used for paclitaxel synthesis (Scheme 8.36). 

All other cross-couplings involving terminal alkynes and halo amides have involved ring closure on nitrogen. Thus, o-halobenzamides react with simple terminal alkynes in the presence of a Pd/Cu catalyst to afford either (Z)-3-aryl(alkyl)idene isoindolin-l-ones or the corresponding 2-(l-alkynyl)benza-mides, which are readily cyclized by NaOEt/EtOH or Pd(OAc)2 catalyst to give isoindolin-l-ones (Eq. 11) [35,36]. When acetylenic aryl carbinols are employed as the alkynes, 3-(acylmethyl)isoindolin-l-ones are obtained instead (Eq.l2) [37]. 

Cyclization of a-Halo- and a-Sulfonyloxy- l-amino Esters and Amides... 

Muratake et al. reported the intramolecular a-arylation of ketones [55,56]. Thus, polycyclic compounds are readily obtained from aromatic keto-bromides and keto-triflates (Eq. 16). Bromo-amides can give the corresponding cycliza-tion products (Eq. 17) [52]. Related intramolecular vinylation reactions to give aliphatic polycyclic compounds have also been reported (Eq. 18) [57,581. The intramolecular cyclization of aromatic halo-ketones under carbon monoxide, which proceeds by mechanism C, gives the corresponding a-acylated products (Eq.l9) [321. 

During their study on 6-exo-trig radical cyclizations of axially chiral a-halo-ortho-alkenyl anihdes, Curran and coworkers [40] prepared the tricyclic amide 93/94 in moderate yield (49-51%) and excellent chirality transfer (98-99%) via a 6-exo-trig/5-exo-trig sequence (Scheme 5.20). The reaction was proposed to be initiated by an attack at the carbon-bromide bond with BujSnH, providing a-amidyl radical 97 (Scheme 5.21). 

A useful synthetic modification has been developed for the synthesis of anhydrous oxazolines. Conventional methods of cyclization of halo-substituted amides (359) generally lead to products with a high percentage of water, which is difficult to remove. The use of sodium hydride in JV-methylpyrrolidin-2-one allows the distillation of the anhydrous product direct from the reaction mixture. 

Crawford et al. (2003) have studied intramolecular cyclization reactions of 5-halo- and 5-nitro-substituted fiiranylamides under microwave heating. The rearranged dihydroquinone in 36% yield was produced from 2-alkoxy-5-bromofuran derivative, which was a product from the rearrangement of the intermediate oxabi-cycle. The 5-halo substituted ftiroyl amide was converted into the polyfunctional oxabicycle in 82% yield at a much faster rate than the unsubstituted furanyl sys-... 

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