Mannich Type Reactions of Trifluoroethyl Thioesters

Ξ August 29th, 2008 | → 0 Comments | ∇ Mannich Reaction, thioesters |

 

Organocatalytic Mannich Type Reactions of Trifluoroethyl Thioesters

Naoto Utsumi, Shinji Kitagaki, and Carlos F. Barbas, III

Org. Lett. 10 (16), 3405–3408


 

Mannich and Mannich-type reactions are very potent protocols which provide expedient access to amimno acids, amino alcohols, sugars and other importants structures in organic chemistry.

The Barbas’ gruop have devoted a great effort in the development of enantioselective Mannich and Mannich type reactions.Recently Barbas has proposed a new approach to direct organocatalytic esthers based reactions that utilizes electroning tuning of  thioesthers to provide esthers donor reactivity; here they report the application of this strategy to direct asymmetric Mannich-type reaction that utilizes thoesthers donors.

In this report Barbas has evaluated thioesthers as nuceophiles in Mannich-type reactions.

 

They initially studied the reaction of thioesthers 1 with N-Boc-imine of benzaldehyde catalyzed by DBU.

 

 

Carring out the reaction in toluene or in hexane, they obtain 2 in quantitative yield and 8:1 dr. Either the yield and the syn-anti rapport are influenced by the solvent of the reaction. They then studied a great number of reaction conditions in order to investigated the selectivity of the reaction and they found that diastereoselevtivity is low under solvent conditions wherein the product was soluble.

They also found that syn selectivity was driven by product solubility and that the syn and anti isomers could interconvert under the reaction conditions wherein the syn product was less soluble then the anti product.

They also investigated the potential of an enantioselective version ot the reaction; they adopted phase-transfer conditions with in situ N-Boc-imine generation from an aminoacid sulfone. Using a Cinchona alkaloid-based catalyst, good yield were obtained with modets enanthio / diastereoselectivity.

 

 

3,3-Disubstituted Oxindoles by Organocatalytic Mannich Reaction

Ξ July 28th, 2008 | → 0 Comments | ∇ Mannich Reaction |

 Org. Lett.  ASAP, July 19, 2008

Quaternary 3,3-disubstituted oxindoles have become important taraget in organic chemistry as this structural frameworks form the core unit of many natural molecules. Morover, the construction of chiral quaternary centres represents one of the most challenging subjects in asymmetric synthesis. Ying-Chun Chen et al. report the highly stereoselective Mannich reaction of 3-substituted oxindoles and N-Boc imines catalyzed by enviromentally benign organocatalyst.

It could be investigated that nucleophilic oxindoles and electrophilic N-Boc imines should be concertedly activated by thiourea-tertiary amine compounds, which have recently demonstred great success as bifunctional Brønsted acid Brønsted base catalysts for an array of 1,2- and 1,4- addition reactions.

Based on these considerations, bifunctional thiourea-tertiary amines A - D with diversely structured scaffolds were screened in the Mannich reaction of 3-benzyloxindole and N-Boc-benzaldimine.

 


 

The starting materials were smoothly consumed after 10 h, and the diastereomers 4a and 5a could be well separated. Catalyst D possessing a chiral 1,2- diphenylethylene-diamine (DPEN) skeleton demonstrated to be the superior one in regard to both diastereo and enantioselectivity.

With the optimal reaction conditions in hand, they then examined a variety of oxindoles and imines to establish the general utility of this novel asymmetric transformation. Generally, with oxindoles and imines various substituted, the yield and de was very good.

Moreover, to determine the absolute configuration of the asymmetric Mannich products, single crystals suitable for X-ray crystallographic analysis were fortunately obtained from enantiopure  E (below) that bears a sulfur atom.

 

 

On the basis of X-ray analysis, the structure contains a (C2S,C16S) configuration.