Efficient Acyclic Stereocontrol Using the Tethered Aminohydroxylation Reaction

Abstract

[reaction: see text] The tethered aminohydroxylation (TA) of acyclic allylic carbamates has been achieved in a stereospecific and stereoselective manner. Unusually high levels of stereocontrol were observed in the oxidation of 1,1-disubstituted substrates.

Recent Developments in Methodology for the Direct Oxyamination of Olefins

“…[27] The reaction also delivers the requisite amino alcohol motif in moderate yields and excellent diastereoselectivities with highly substituted olefins.…”

“…It was also established that these robust reaction conditions are highly diastereoselective for the stereospecific anti-addition of heteroatoms across the double bond, thereby providing a complementary approach to the syn-tethered aminohydroxylation reaction developed by Donohoe and co-workers. [26][27][28][29] The following year, Stahl and Liu employed an analogous catalytic system to the intermolecular introduction of phthalimide (HNPhth) 55 and acetate functionalities onto a range of terminal allylic, homoallylic and enol ethers 54 (Scheme 22). [46] Aminoacetates 56 were delivered with complete regioselectivity.…”

Tethered Aminohydroxylation Reaction and Its Application to Total Synthesis

“…This type of substrate had been used extensively in the 1 st Generation TA reaction to access syn-amino alcohols. [11] The application of aroyloxycarbamate reoxidants in these systems afforded a significant increase in the yield of the reaction with lower catalyst loading, as illustrated by the reaction of the olefins 25 and 27 (Scheme 8). In both cases the allylic aroyloxycarbamates allowed the utilisation of just 1 mol-% of potassium osmate and formed amino alcohols 26 (80 %) and 28 (78 %) in higher yielding, cleaner reactions.…”

The Influence of Exocyclic Stereochemistry on the Tethered Aminohydroxylation Reaction

“…[4,5] Recent developments obviate the need for generating in situ reoxidants (typically N-halocarbamates) by employing bench-stable mesitoyloxycarbamates as starting materials, in which the nitrogen is introduced at the correct oxidation state to complete the catalytic cycle, thus delivering higher-yielding, cleaner reactions with lower catalyst loadings. This strategy has been applied successfully in the highly diastereoselective formation of amino alcohols from both cyclic and acyclic carbamates [9,10] and amides [8] in which the stereogenic center in the starting material is positioned on the Keywords: allylic compounds · aminohydroxylation · chirality · heterocycles · stereoselectivity Abstract: A new strategy that employs an exocyclic stereocenter to effect diastereocontrol in the tethered aminohydroxylation (TA) reaction is applied to the stereoselective synthesis of a range of amino alcohols in good to excellent yields, and with anti selectivities of up to 20:1. This strategy has been applied successfully in the highly diastereoselective formation of amino alcohols from both cyclic and acyclic carbamates [9,10] and amides [8] in which the stereogenic center in the starting material is positioned on the Keywords: allylic compounds · aminohydroxylation · chirality · heterocycles · stereoselectivity Abstract: A new strategy that employs an exocyclic stereocenter to effect diastereocontrol in the tethered aminohydroxylation (TA) reaction is applied to the stereoselective synthesis of a range of amino alcohols in good to excellent yields, and with anti selectivities of up to 20:1.…”

“…[6][7][8] Although chiral ligands do not induce enantioselectivity in the TA, the stereochemical course of the reaction can be directed by a stereocenter in the starting material. This strategy has been applied successfully in the highly diastereoselective formation of amino alcohols from both cyclic and acyclic carbamates [9,10] and amides [8] in which the stereogenic center in the starting material is positioned on the Keywords: allylic compounds · aminohydroxylation · chirality · heterocycles · stereoselectivity Abstract: A new strategy that employs an exocyclic stereocenter to effect diastereocontrol in the tethered aminohydroxylation (TA) reaction is applied to the stereoselective synthesis of a range of amino alcohols in good to excellent yields, and with anti selectivities of up to 20:1. The influence of the reaction conditions and substrate parameters on the level of diastereocontrol is described.…”