Thermal Overman rearrangement

The Overman rearrangement, a thermal [3,3]-sigmatropic rearrangement of allylic trichloroacetimidates, is an attractive procedure for the preparation of ally] amines from allyl alcohols (Eq. (4)) [7]. 

The transition metai cataiyzed Overman rearrangement allows the reaction to take place at or around room temperature, so thermally sensitive substrates can be used. In the laboratory of M. Mehmandoust, this approach was applied for the synthesis of enantiomerically pure ( )- 3,y-unsaturated a-amino acids, which are potent enzyme inhibitors. ° The trichloroimidate substrates were derived from optically pure monoprotected diallylalcohols and were exposed to 10 mol% of Pd " -salt. The rearrangements took place rapidly at room temperature with complete transfer of chirality. 

Related to the Overman esterification is the Overman rearrangement. The latter allows the conversion of readily available allylic alcohols into allylic amines by a two-step synthesis involving the rearrangement of an allylic trichloroacetimidate to an allylic trichloroacetamide with clean 1,3-transposition of the alkenyl moiety. Although this rearrangement can be thermally driven, addition of palladium salts lower the needed temperature. Chiral ligands such as proline-based diamines would lead to enantioenriched material. ... 

The Overman rearrangement converts allylic trichloroacetimidates into trichlo-roacetamides in presence of o-xylene under microwave irradiation (Gajdosikova et al., 2008). The reaction time was shorter as compared to the conventional thermal rearrangement. 

Overman, L. E. Zipp, G. G. Allylic transposition of alcohol and amine functionality by thermal or Pd(II)-catalyzed rearrangements of allylic N-benzoylbenzimidates. J. Org. Chem. 1997, 62, 2288-2291. 

L. E. Overman, Thermal and mercuric ion catalyzed [3,3]-sigmatropic rearrangement of allylic trichloroacetimidates. 1,3-Transposition of alcohol and amine functions,. /. Am. Chem. Soc., 96 (1974) 597-599. 

Overman, L.E. and Zipp, G.G. 1997. AUyhc transposition of alcohol and amine functionality by thermal or palladium (ll)-catalyzed rearrangements of aUylic A-benzoylbenzimidates. Journal of Organic Chemistry, 62 2288-91. 

In a finding of greater practical significance. Overman and coworicers showed that the reactions could be carried out with catalytic amounts of the palladium(II) complex, and that the catalytic effect was broadly applicable to acyclic 1,5-dienes as well7 In a typical example (equation 32), 2-methyl-3-phe-nyl-l,5-hexadiene rearranges in 1 h at room temperature in 87% yield in the presence of 0.06 equiv. of bis(benzonitrile)palladium dichloride, in contrast to the thermal rearrangement which has t n = 13 h at 177 °C. The cat yst thus provides an estimated rate acceleration of about 10 °. The product is a 93 7 mixture of ( )- and (Z)-isomers, corresponding to the equilibrium ratio. Palladium acetate and tetra-kis(triphenylphosphine) were ineffective as catalysts. One serious limitation is that the catalyzed reaction occurs only with those 1,5-dienes which possess an alkyl or aryl substituent at C-2 or C-5 (but not both). 

Since its discovery in 1912 [1], the Claisen rearrangement, namely thermal [3,3]-sigmatropic rearrangement of an allyl vinyl ether, has received great attention as one of the most powerful methods for stereoselective carbon-carbon bond formation. Metal catalysis has been introduced to significantly accelerate the Claisen rearrangement even at room temperature. A hterature survey on metal catalysis of Claisen rearrangements is available in excellent reviews by Lutz, Overman, Frauenrath and Hiersemann [2]. 

Discovered in 1966/ " the Pd(II)-promoted" and Pd(II)-catalyzed " Cope rearrangement has become an important tool in synthetic endeavors. Catalysis of the Cope rearrangement by palladium salts such as PdCl2 provides rate enhancements as high as 10 while also offering higher levels of stereoselectivity than their thermal counterparts.In one of the early examples described by Overman, a predominant contributor in this area, 72 was smoothly converted to 73 in the presence of PdCl2(PhCN)2 at room temperature." ... 

A soln. of mercuric trifiuoroacetate in tetrahydrofuran added dropwise at 0° under N2 during 15 min. to a soln. of geranyl trichloroacetimidate in the same solvent, allowed to warm to room temp, during 1 hr., then pyridine added to complex free mercuric ions product. Y 79%. F. e., also thermal rearrangement in refluxing xylene at 138-9°, s. L. E. Overman, Am. Soc. 96, 597 (1974). 

Overman s discovery of the rearrangement of trichloroacetimidates [16, 39, 40] ushered in a powerful new method for the synthesis of alkaloids. A clever implementation of this transformation was reported in Danishefsky s synthesis of the antitumor agent pancratistatin (86, Scheme 16.9) [70]. Thermal rearrangement of imidate 84 led to amide 85, hence installing the key amine to become part of the lactam in the natural product and setting the stage for a subsequent diastereoselective dihydroxylation. 

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