Bromamine-T as an efficient amine source for Sharpless asymmetric aminohydroxylation of olefins

Asymmetric aminohydroxylation of various olefins was carried out using bromamine-T as nitrogen source in the presence of (DHQ)₂PHAL ligand. The new nitrogen source has been found to be effective in terms of yield and reaction time. The optical purities of the products could be obtained with up to 99% ee.     

Reversal of regioselection in the sharpless asymmetric aminohydroxylation of aryl ester substrates

[formula: see text] The asymmetric synthesis of beta-hydroxy-alpha-amino acids is reported which relies on the use of alpha,beta-unsaturated aryl ester substrates and the dihydroquinyl alkaloid ligand system (DHQ)2-AQN to control the regio- and enantioselectivity of the asymmetric aminohydroxylation (AA) process. alpha,beta-Unsaturated ester substrates of type 1 have a significant effect on the substrate-ligand recognition event which results in a reversal of regioselectivity in the AA reaction.     

First asymmetric aminohydroxylation of acrylamides

The first examples of the asymmetric aminohydroxylation of acryl amides are reported. This was accomplished with chiral acrylamides as substrates, which undergo diastereoselective oxidative transformation within the so-called ‘second catalytic cycle’ with diastereomeric excesses reaching 100:0. The reaction relies solely on the stereochemical information provided by the enantiomerically pure starting materials. A stereochemical model for the observed asymmetric induction is provided.     

Synthesis of unit-B of cryptophycin-24 via Sharpless asymmetric dihydroxylation

A synthetic pathway for the synthesis of unit-B of cryptophycin-24 has been developed using Sharpless asymmetric dihydroxylation as the key step. This study shows that direct azidation of α-hydroxy acid ester using diphenylphosphoryl azide is beneficial to asymmetric synthesis of α-amino acid without the loss of chirality during the transformation.     

The Sharpless asymmetric aminohydroxylation reaction: optimising ligand/substrate control of regioselectivity for the synthesis of 3- and 4-aminosugars

An investigation of the factors responsible for the sense and magnitude of regioselectivity in the Sharpless asymmetric aminohydroxylation (AA) has been conducted. Theoretical investigations of ligand-osmium binding geometry and experimental investigations of the Sharpless AA reaction on a series of functionalized pent-2-enoic acid ester substrates demonstrate that the opposite regioselectivity afforded using PHAL and AQN ligands results from a change in substrate orientation with respect to the catalyst. Two distinct ligand binding domains within the catalyst have been proposed that undergo attractive interactions with the substrates. Selective access to each of the four potential regio- and stereo-isomeric AA products could be achieved through the appropriate choice of ligand and substrate. These results have been applied toward the efficient stereoselective synthesis of naturally occurring and regioisomeric 3- and 4-aminosugar derivatives.     

The asymmetric aminohydroxylation route to GABOB and homoserine derivatives

The 4-nitrophenyl ether is an efficient directing group in the asymmetric aminohydroxylation reaction of homoallylic ether derivatives. Either regioisomeric product can be obtained with useful levels of enantioselectivity allowing for the short enantioselective synthesis of GABOB and homoserine derivatives. A model based on substrate-catalyst interactions is presented to explain the regio- and enantioselectivity of the aminohydroxylation reactions.     

Copper-catalyzed enantioselective Henry reactions of alpha-keto esters: an easy entry to optically active beta-nitro-alpha-hydroxy esters and beta-amino-alpha-hydroxy esters

The catalytic enantioselective Henry reaction of alpha-keto esters with nitromethane has been developed. The reaction conditions have been optimized by the screening of different chiral Lewis acids, solvents, and bases, and it was found that the copper(II)-tert-butyl bisoxazoline complex in combination with triethylamine catalyzed a highly enantioselective reaction giving optically active beta-nitro-alpha-hydroxy esters in high yields and with excellent enantiomeric excesses. The scope of the reaction is demonstrated by the reaction of a variety of different alpha-keto esters. The catalytic enantioselective Henry reaction of beta,gamma-unsaturated-alpha-keto esters proceeds as a 1,2-addition reaction exclusively, in contrast to the uncatalyzed reaction where both the 1,2- and 1,4-addition products are formed. It is demonstrated that the beta-nitro-alpha-hydroxy esters can be converted into, e.g., Boc-protected beta-amino-alpha-hydroxy esters in high yields and without loss of optical purity. The mechanism for the reaction is discussed, and it is postulated that both the alpha-keto ester and nitromethane/nitronate is coordinated to the metal center during the reaction course.     

Tethered aminohydroxylation using acyclic homo-allylic sulfamate esters and sulfonamides as substrates

Homo-allylic sulfamate esters and sulfonamides are shown to be useful substrates for the tethered aminohydroxylation (TA) reaction. The sulfamate esters undergo the TA reaction delivering 1,2,3-oxathiazinane products whereas the sulfonamides give 1,2-thiazinane products. A range of acyclic homo-allylic sulfamate esters were prepared and subjected to the TA reaction to establish the scope of the process. Nucleophilic ring-opening reactions of the 1,2,3-oxathiazinane products are also described.     

Remote steric effect on the regioselectivity of Sharpless asymmetric dihydroxylation

Studies on the regioselectivities for the Sharpless asymmetric dihydroxylation (AD) of conjugated dienoates, trienoates, dienones and dienamides are described. Excellent regioselectivities were obtained in straight chain dienoates, all trienoates, ketones and amides. The remote branched iso-propyl and tert-butyl groups of dienoates greatly lowered the normally excellent regiocontrol. This observation is rationalized in terms of substrate conformational changes, and the steric interaction between the branched methyl group of iso-propyl or tert-butyl groups and the ethyl group on the (DHQD)₂PHAL ligand.     

Application of Sharpless asymmetric dihydroxylation to thienyl- and benzothienyl acrylates and crotonates

Optimized conditions for the catalytic asymmetric dihydroxylation have been applied to thiophene and benzothiophene containing acrylates and crotonates to afford the corresponding diols in good overall yields and good to excellent enantiomeric excess. The products obtained were revealed to be useful intermediates in peptidomimetic synthesis.     

Novel synthesis of CP-734432, an EP4 agonist, using Sharpless asymmetric dihydroxylation

A novel and efficient asymmetric route to CP-734432, a lactam analog of PGE2, that shows selective agonism against the EP4 receptor subtype, is reported herein. The key steps include a Heck coupling to introduce the aryl ring at C-16 and a highly diastereoselective Sharpless asymmetric dihydroxylation to set the C-15 center.     

Osmylated macroporous resins: safe,highly efficient and recyclable catalysts for asymmetric aminohydroxylation of olefins

Osmylated macroporous resins displayed excellent catalytic performances in the asymmetric aminohydroxylation of olefins and, moreover, these resins were easily recovered and reused without any significant decrease in catalytic efficiencies.     

Sharpless Asymmetric Aminohydroxylation: Scope,Limitations, and Use in Synthesis

As a valuable methodology for organic synthesis , asymmetric aminohydroxylation (AA)—the catalytic and asymmetric conversion of alkenes into enantiomerically enriched N‐protected amino alcohols—has become established in a remarkably short period of time. Examples of the types of products that can be synthesized easily on a reasonably large scale and in enantiomerically pure form are shown in the picture.     

Scalable synthesis of enantiomerically pure syn-2,3-dihydroxybutyrate by Sharpless asymmetric dihydroxylation of p-phenylbenzyl crotonate

An efficient four-step synthetic route to the useful chiral building block (2R,3S)-dihydroxybutyric acid acetonide in >95% ee is detailed. The sequence is readily scaled, requires no chromatography, and allows for efficient recycling of p-phenylbenzyl alcohol, an expedient for enantio- and diastereoenrichment by recrystallization.     

Formal asymmetric enone aminohydroxylation: organocatalytic one-pot synthesis of 4,5-disubstituted oxazolidinones

A formal asymmetric organocatalytic aminohydroxylation reaction of enones has been achieved via an aziridination-double S(N)2 sequence. As a part of the reaction design, the generated amino alcohol products are isolated as the corresponding oxazolidinones in good yields and excellent stereoselectivities.