264277-66-9

Upstream product

• 80783-99-9 3-phenyl-N-methoxy-N-methylacrylamide 
• 1226876-03-4 N-methoxy-N-methyl-3-oxo-3-phenylpropanamide 
• 33401-74-0 ethyl (3R)-3-hydroxy-3-phenylpropionate 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 

Downstream Products

• 202744-51-2 (-)-(S)-1-hydroxy-1-phenyl-3-heptanone 
• 5381-93-1 (4S)-4-hydroxy-4-phenylbutan-2-one 

Relevant academic research and scientific papers

Stereodivergent Synthesis through Catalytic Asymmetric Reversed Hydroboration

The control of chemo-, regio-, diastereo-, and enantioselectivity is a central theme in organic synthesis. The capability to obtain the full set of stereoisomers of a molecule would significantly enhance the efficiency for the synthesis of natural product analogues and creation of chiral compound libraries for drug discovery. Despite the tremendous progress achieved in the field of asymmetric synthesis in the past decades, the precise control of both relative and absolute configurations in catalyst-controlled reactions that create multiple stereocenters remains a significant synthetic challenge. We report here the development of a catalyst-controlled hydroboration with hitherto unattainable selectivity. The Rh-catalyzed hydroboration of α, β-unsaturated carbonyl compounds with pinacolborane proceeds with high levels of regio-, diastereo-, and enantioselectivities to provide a hydroboration product with two vicinal stereocenters. Through the appropriate choice of substrate geometry (E or Z) and ligand enantiomer (S or R), all the possible diastereoisomers are readily accessible. The boron-containing products underwent many stereospecific transformations, thus providing a strategy for collective stereodivergent synthesis of diverse valuable chiral building blocks.

Synthesis of Enantiomerically Pure β-Hydroxy Ketones via β-Keto Weinreb Amides by a Condensation/Asymmetric-Hydrogenation/Acylation Sequence

An established route to enantiomerically pure β-hydroxy ketones proceeds through the asymmetric hydrogenation of β-keto esters, an ester/amide exchange, and the use of the resulting β-hydroxy amide for the acylation of an organometallic compound. We shortened this route by showing that β-keto Weinreb amides are hydrogenated with up to 99 % ee in the presence of [Me2NH2]+{[RuCl(S)-BINAP]2(μ-Cl)3}–(0.5 mol-%) at room temp./5 bar. These Weinreb amides were prepared by seemingly obvious yet unprecedented condensations of lithiated N-methoxy-N-methylacetamide with carboxylic chlorides (51–87 % yield). The resulting β-hydroxy Weinreb amides were used for the acylation of organolithium and Grignard reagents. They thus gave enantiomerically pure β-hydroxy ketones (28 examples). A selection of these compounds gave anti-1,3-diols after another C=O bond hydrogenation, or syn-1,3-diols by a Narasaka–Prasad reduction.

Isoquinoline-based chiral monodentate N-heterocyclic carbenes

C1-symmetric isoquinoline-based chiral diaminocarbene ligands (MIQ) have been developed to block three quadrants of the metal coordination sphere, complementing C2-symmetric biisoquinoline-based ligands (BIQ). MIQ-Cu complexes catalyzed conjugate borylation of various α,β-unsaturated amides in good yields (82-99%) and enantioselectivities (75-87% ee).

Synthesis of anti-l,3-Diols through RuCl3/PPh3-Mediated Hydrogenation of β-Hydroxy Ketones: An alternative to organoboron reagents

Hydrogenation of enantioenriched β-hydroxy ketones promoted by the catalyst generated in situ from commercially available and inexpensive RuCl 3 and PPh3 under hydrogen pressure allowed the efficient preparation of a variety of anti1