Regioselective Base-Free Intermolecular Aminohydroxylations of Hindered and Functionalized Alkenes

Abstract

Regioselective base-free intermolecular aminohydroxylations of functionalized trisubstituted and 1,1-disubstituted alkenes employing benzoyloxycarbamate 3a and catalytic OsO(4) are described. In all cases, the more substituted alcohol isomer is favored. Sluggish reactions could be promoted by gentle heating, the use of amine ligands, or increased catalyst loadings. A competitive rearrangement was observed with a secondary allylic alcohol substrate. The adducts serve as useful precursors to dehydroamino acids.

Diastereoselective Osmium‐catalyzed Vicinal Oxyamination of Acyclic Allylic Alcohol Derivatives

“…4,[9][10][11][12] High regioselectivity in the oxyamination reaction would significantly simplify product analysis of the diastereomeric mixtures. In the absence of ligand control, the intermolecular oxyamination of unsymmetrically substituted alkenes by pre-formed nitrogen sources typically gives high selectivity for products where the nitrogen adds to the less substituted end of the double bond.…”

“…3,4 The recent development of pre-formed nitrogen sources has improved the efficiency, chemoselectivity and control of the osmiumcatalyzed oxyamination reaction. The development of nontethered pre-formed nitrogen sources has further expanded the scope of this process, [9][10][11][12] and includes the introduction of N-(4-chlorobenzoyloxy)carbamates which allow for the enantioselective intermolecular oxyamination of mono-and di-substituted alkenes in the presence of cinchona alkaloidderived chiral ligands. The development of nontethered pre-formed nitrogen sources has further expanded the scope of this process, [9][10][11][12] and includes the introduction of N-(4-chlorobenzoyloxy)carbamates which allow for the enantioselective intermolecular oxyamination of mono-and di-substituted alkenes in the presence of cinchona alkaloidderived chiral ligands.…”

“…Advances include the development of the intramolecular Tethered Aminohydroxylation (TA) reaction 5 of carbamates 6,7 and amides 8 that provides secure control over regioselectivity. 9,10 We recently reported the development of N-(4-tosyloxy)carbamates as pre-formed nitrogen sources in the osmium-catalyzed vicinal oxyamination reaction of a range of mono-, di-and tri-substituted alkenes. 9,10 We recently reported the development of N-(4-tosyloxy)carbamates as pre-formed nitrogen sources in the osmium-catalyzed vicinal oxyamination reaction of a range of mono-, di-and tri-substituted alkenes.…”

Osmium-Catalyzed Vicinal Oxyamination of Alkenes by N-(4-Toluenesulfonyloxy)carbamates

“…The lower reactivity associated with higher levels of alkene substitution has also been recently highlighted for N-(4-chlorobenzoyloxy)-carbamates in the intermolecular oxyamination reaction. 11 In the case of the intramolecular TA variants involving preformed nitrogen sources, the proximity effects largely override this lower reactivity. 6,8,9 The regioselectivity of the oxyamination reaction was strongly influenced by alkene substitution.…”

Bulky Dehydroamino Acids Enhance Proteolytic Stability and Folding in β-Hairpin Peptides

“…The requisite azlactone dipeptides were synthesized as shown in Table 1. Coupling of Alloc-protected amino acids 3 with racemic β-OHVal-OEt ( 4a ) 24 or racemic β-OHEnv-OEt ( 4b ) 23 furnished dipeptides 5 . In contrast to our prior work, the use of rigorously purified samples of 4b enabled EDC•HCl and HOBt to be employed in couplings instead of the more expensive COMU.…”