180961-72-2

Upstream product

• 444575-93-3 (R)-(-)-1-phenyl-1-(2-methylphenoxy)-2-propene 
• 66583-43-5 (+)N-methyl-ephedrine methiodide 
• 33603-90-6 (2Z)-2-bromo-3-phenyl-2-propenal 
• 104-55-2 3-phenyl-propenal 
• 2665-12-5 tris(2-methylphenyl) borate 
• 106760-61-6 (R)-(+)-2-Phenyloxetane 
• 77118-87-7 (S)-1-Phenyl-3-buten-1-ol 
• 80735-94-0 1-Phenyl-3-buten-1-ol 
• 104713-12-4 (R)-1-phenylprop-2-en-1-ol 
• 321-98-2 (1S,2R)-(+)-ephedrine 

Downstream Products

• 105314-52-1 (R)-tomoxetine 

Relevant academic research and scientific papers

One-pot sequential asymmetric hydrogenation of β-aryl-β-aryloxy acroleins

A one-pot sequential asymmetric hydrogenation of β-aryl-β-aryloxy acroleins has been realized for the preparation of chiral 3-aryl-3-aryloxy alcohols with excellent yields and good enantioselectivities. This methodology can be employed in new synthetic routes for the synthesis of fluoxetine, atomoxetine, and related analogues.

Regio- and stereoselective ring opening of enantiomerically enriched 2-aryl oxetanes and 2-aryl azetidines with aryl borates

(Chemical Equation Presented) The regioselective ring opening of 2-aryl-substituted four-membered heterocyclic rings with phenols, including catechol, was achieved by the use of aryl borates in mild and neutral reaction conditions without the aid of any transition metal catalysts. While β-alkyl azetidines were found not to be reactive, optically active N-tosyl azetidines gave the corresponding β-aryloxy amines in a racemic form, thus indicating the considerable carbocationic character of the transition state. The introduction of a hydroxyl group in the azetidine ring (i.e., an azetidinol), able to anchor the aryl borate and to direct the subsequent nucleophilic delivery, was shown to determine the ring-opening process with predominant inversion of configuration. When enantiomerically enriched 2-aryl oxetanes were used, the reduced extent of racemization observed (up to 93:7 er) was rationalized by an intramolecular delivery through a six-membered transition state, giving β-aryloxy alcohols with a predominant retention of configuration (i.e., a syn-stereoselective ring opening). The aryloxy alcohols obtained, endowed with suitable functionalities, can be cyclized to give access to enantiomerically enriched 2-aryl-1,5-benzodioxepins.

A stereospecific ruthenium-catalyzed allylic alkylation

Good regioselectivity and chirality transfer for aryl-substituted allyl units is achieved in allylic alkylations with a wide range of nucleophiles by using the highly active ruthenium catalyst 1. This method provides a route to antidepressants such as (-)-fluoxetine from (S)-ephedrine (see scheme; Cp* = η5-C5Me5, TBAT = tetrabutylammonium triphenyldifluorosilicate).

An efficient chemoenzymatic route to the antidepressants (R)-fluoxetine and (R)-tomoxetine

(S)-1-Phenyl-3-buten-1-ol (1), prepared in high optical purity by enzymatic resolution of the racemate, is a convenient building block for the synthesis of (R)-fluoxetine (7a) and (R)-tomoxetine (7b). Compound 1 was converted to the title drugs by etherification with appropriate phenols under Mitsunobu conditions, ozonolysis of the terminal double bond, mesylation of the resulting alcohol and substitution with methylamine.