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.
Tetrahydropyran and dihydropyran derivates are very important frameworks in organic chemistry as this structures form the core unit of many natural substances; they also are important building blocks with widesperad applications in organic synthesis.
There are lots of methodology to access 2,3-dihydropyran derivates, such as for example hetero-Diels-Alder reactions, but there aren’t protocols for the synthesis of 1 (figure below); the presence of a C=C bond conjugated to an enol increases the possybility of further structure modifications.
Very recently Jorgensen and co-workers have reported that α,β-unsutered aldehydes 2 underwent a tandem Michela/Morita-Baylis-Hillman reaction with Nazarov reagent 3, with prolinol derivates as catalyst, to afford cycloexanone derivates with high stereoselectivity.
However, the Nazarov reagent 4 in presence of prolinol as catalyst didn’t undergo the tandem Micheal/MBH reaction, but underwent a formal [3+3] cycloaddition, which after oxidation, furnished a chiral pyranone in good yield and ee.
The optimized procedure was tyhen extended to formal [3+3] cycloaddition reactions between varius unsatured aldehydes and Nazarov reagents.
Gong e co-workers have also proposed a mechanism for the cycloaddition.
The unsutered aldehydes 5 first condensed with chiral catalyst to afford imminium salt 6. Enantioselective Micheal addition of Nazarov reagents 7 afforded intermediates 8 which can be isomerized to 9 that occur from an intramolecular oxo-addition to form intermediates 10. Then hydrolysis generates the product 11 and the catalyst.
Asymmetric Epoxidation of Olefin with Hydrogen Peroxide-Catalyst by an Aspartate-Containing Tripeptide
ACIE, 2008, 47, 3677 - 3679
The development of new methods for the asymmetric preparation of epoxide is an important goal in organic chemistry. There are a lot of methods for the synthesis of epoxide, which often involves the use of chiral metal complexes or the use of organocatalyst such as chiral ketones.
Miller and coworkers have demonstred that highly enantioselective organocatalyst can result from the combination of short oligopeptides with catalytically active functional groups. In one of the recent publications, Miller et al. presented the first enantioselective peptide-catalyst for the epoxidation of olefines by using an hydrogen peroxide as oxidant in combination with carbodiimide as activators.
Epoxidation catalyst is effected by the carboxylic acid function of L-aspartate and the incorporation of this catalytically active residue into tripeptide 1 show below provides the chiral enviroment necessary for the asymmetric epoxidation.
1
The sequence L-Pro-D-Val induces a turn that is stabilized by intramolecular hydrogen bond.
The epoxidation of 2 gives che corrispective epoxide with a very low ee (10%) while with 3 the ee is always upper than 90% also with different reaction condition. The substrate 3 infact is able to make a hidrogen bond with the catalyst; they demonstred in this way the importance of the hydrogen bond for the enantioselectivity of the reaction, Also the distance between the hydrogen-bonding moiety and the double bond to be epoxidiezed plays an important role in the reaction.
In this way the method is limited to olefin substrates with a pendant carbamate group that is important for hydrogen bonding to the peptide catalyst.
The construction of C - N bonds is a very important goal in organic chemistry. Here I report a JACS paper about the development of a catalytic amination of homoenolates by combining α,β-unsatured aldehydes with diazenes in the presence of N-Heterocyclic carbens.
Below I report the general reactioon.
The reaction mechanism is showed below.
First we have the addition of an NHC to unsatured aldehyde, to afford the tetrahedral intermediate A.
Upon rearrangement, the diene homoenolate B is generated which undergoes addition to diazene C and subsequently generates ketone D after tautomerization. This activated carbonyl species facilities catalyst turnover by intramolecular acylation to produce pyrazolidinone.
Andrei V. Malkov, Marek Figlus, and Pavel Kocovský,
J. Org. Chem. 2008, 73, 3985–3995
The development of free enviroment methodology is an important goal in organic synthetic chemistry. Here I report a very pretty JOC paper about the synthesis and use of polymer supported organocatalyst for the asymmetric reduction of ketimines with trichlorosilane.
There are several methods for the reduction of ketimines, and the development of metal-free organocatalyst is a novel synthetic plylosophy with the ambition to replace the traditional transition metal catalysis.
Several groups have developed, with very good result in terms of yield and ee, a series of organocatalyst derived from α-amino acids to promote asymmetric reduction of prochiral imines. Malkov et al. have initially developed new amino acid derived formamide-type catalysts show below (A); in order to make easier the separation of the catalyst and the product, they have introduced a fluorous tag to the catalyst which simplified the separation to an ordinary filtration through a pad of fluorous silica gel that retained the catayst (B)
As the next step toward developing a green methodology for the reduction of imines with Cl3SiH, they resolved to anchor the catalyst to a polymer by employing the ether link. They developed several catalysts (C - F) anchored to different kind of resin (Merrifield, Wang TentaGel etc): generally yield and ee are always very good.
The general synthesis of the catalyst is reported below:
Immobilization of the catalyst to the solid support was effected by alkylation of the phenolic hydroxyl with polymeric benzyl chloride using the modified Williamson method or by Mitsunobu Conditions (wiyh polymeric benzyl alcohol).
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