Recent Developments in Methodology for the Direct Oxyamination of Olefins

Abstract

1,2-Amino alcohols are high-value, versatile functional groups that are found in scores of biologically active molecules and other interesting synthetic targets such as ligands and auxiliaries. Given their prominent position within organic compounds of import, it is no surprise to note that many routes have been developed to access this motif and there are many different starting points from which a synthetic chemist might embark on a synthesis. However, one particular approach stands out from the others, and this is the direct conversion of an alkene to a vicinal amino alcohol derivative (oxyamination). Research in this field has been particularly active in recent years and many interesting new methodologies have been reported. The purpose of this review is to give the reader a tour of the methods that have emerged in the last few years so one can appreciate the myriad of different metals and reagents that can accomplish the oxyamination of alkenes. There are still many challenges to be overcome and, herein, we also outline the areas that are ripe for further development and which bode well for the future.

Intramolecular Aminocyanation of Alkenes by NCN Bond Cleavage

“…[1] Recent successes include forming new CÀN bonds in conjunction with vicinal CÀC, [2,3] CÀO, [4] CÀN, [5] CÀH, [6] or CÀX [7] bonds. These alkene aminofunctionalization reactions represent a unique strategy for the synthesis of valuable nitrogencontaining heterocycles.…”

“…These compounds are versatile precursors to the biologically and pharmacologically important b-amino acids. [13] To our surprise, the well-developed strategies for alkene aminofunctionalization [2][3][4][5][6][7] have only recently been applied to the introduction of cyano groups onto the alkene double bond. In 2013, Xiong, Li, Zhang, and co-workers reported the first example of alkene aminocyanation.…”

Hydroxyamination of Olefins Using Br-N-(CO2Me)2

“…Amino alcohols are found in many natural products, such as myriocin, bestatin, and cytoxazone. 1 They are also used as ligands in asymmetric synthesis and found in numerous bioactive molecules. 1 There have been many methods developed to prepare the amino alcohol functional group; however, they often require multistep procedures.…”

“…3 Therefore, alternative direct and indirect methods for hydroxyamination reactions are still required to access the amino alcohol motif. 1,4 …”

Tethered Aminohydroxylation: Synthesis of the β-Amino Acid of Microsclerodermins A and B

“…1,2 However, one drawback to alkene aminohydroxylation is the unpredictable regiochemical outcome; this can be highly dependent on the nature of the alkene substrate. 2 We recognized that tethering the nitrogen source to an allylic alcohol would ensure complete control of regioselectivity in a subsequent osmium catalyzed aminohydroxylation, a tethered aminohydroxylation (TA). Since our early reports, 3 we have disclosed significant improvements to the process through discovery of new nitrogen reoxidants for TA, using N -sulfonyloxycarbamates 4 and N -aroyloxycarbamates.…”