Suarez modification

The Suarez modification of the Hofmann-Loffler-Freytag reaction was review by... 

In conclusion, the Hofmann-Loffler-Freytag reaction tends to give moderate and sometimes poor yields for the preparation pyrrolidines under the classic conditions. Nonetheless, the utility of this reaction to functionalize molecules via the aminyl radical mechanism plays an unique role in the tool box for the organic chemist, enabling transformations not easily achievable using other means. Furthermore, milder conditions and better yields can be achieved by taking advantages of the newer developments such as the Suarez modification. 

E. Suarez and co-workers prepared chiral 7-oxa-2-azabicyclo[3.2.1]octane and 8-oxa-6-azabicyclo[3.2.1]octane ring systems derived from carbohydrates via an intramolecular hydrogen abstraction reaction promoted by A/-centered radicals. The A/-centered radicals were obtained under mild conditions (Suarez modification) from phenyl and benzyl amidophosphates and alkyl and benzyl carbamate derivatives of aminoalditols by treatment with PIDA/I2 or PhlO/l2. The initial A/-radical undergoes a 1,5-hydrogen abstraction to form an alkyl radical, which is oxidized to the corresponding stabilized carbocation (oxocarbenium ion) under the reaction conditions. The overall transformation may be considered as an intramolecular N-glycosidation reaction. 

The third modification of the Hunsdiecker reaction is the so-called Sudrez modification,21 where the steroidal acids were treated with hypervalent iodine reagent in CCI4 to prepare steroidal chloride. The Sudrez modification also works for bromination using iodobenzene diacetate, bromine, and CH2Br2 as the solvent under irradiation as exemplified by transformations 14—>15.22 Unlike many variations described before, the Suarez modification tolerates a variety of functional groups. 

Scheme 13. Suarez modification of the Hofmann-Ldffler-Freytag reaction...

During the final stages of the asymmetric total synthesis of antimitotic agents (+)- and (-)-spirotryprostatin B, the C8-C9 double bond had to be installed, and at the same time the carboxylic acid moiety removed from C8. R.M. Williams et al. found that the Kochi- and Suarez modified Hunsdiecker reaction using LTA or PIDA failed and eventually the Barton modification proved to be the only way to achieve this goal. After the introduction of the bromine substituent at C8, the C8-C9 double bond was formed by exposing the compound to sodium methoxide in methanol. This step not only accomplished the expected elimination but also epimerized the C12 position to afford the desired natural product as a 2 1 mixture of diastereomers at C12. The two diastereomers were easily separated by column chromatography. 

Ramirez-Tortosa C, Lopez-Pedrosa JM, Suarez A, Ros E, Mataix J, Gil A. Olive oil and fish oil-enriched diets modify plasma lipids and susceptibility of LDL to oxidative modification in free-living male patients with peripheral vascular disease the Spanish Nutrition Study. Br J Nutr 1999 82 31-39. 

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