An efficient asymmetric catalytic hydrogenation of 4-aryl coumarins, preparation of a key intermediate in the synthesis of a class of endothelin receptor antagonists

Rawat

et al. 2019

Applied Organom Chemis

Polyaniline coated on particles of celite is used as support to load palladium catalyst. This heterogenized Celite•PANI•Pd system, is used as an efficient catalyst for chemoselective hydrogenation reactions. The catalyst is characterized by usual spectral, analytical techniques and studied for hydrogenation reactions at ambient conditions. The mild reaction conditions allow the control over the reactions and excellent selectivity is achieved in number of conversions. Hydrogenation of a carbon–carbon double bond was favored over other polar π‐bond systems, while labile functional groups such as benzyl ether, benzyl esters, cyano, nitro and halogen remained unaffected. Primary amines were converted to N,N‐dimethyl amines with formaldehyde, the double bond of coumarin was selectively hydrogenated without opening of the lactone functionality.

Section: Resultsmentioning

confidence: 99%

Celite‐Polyaniline supported palladium catalyst for chemoselective hydrogenation reactions

Rawat

et al. 2019

Applied Organom Chemis

“…(3)], is the key intermediate in several asymmetric syntheses of ( R )‐tolterodine,24a–c the active ingredient of the commercial antimuscarinic drug Detrol ® , and 4 j is the precursor of the potent endothelin antagonists SB‐209670 and SB‐217242 [Eq. (4)] 24e,f, , …”

Section: Methodsmentioning

confidence: 99%

Catalytic Asymmetric Addition of Meldrum’s Acid, Malononitrile, and 1,3‐Dicarbonyls to ortho‐Quinone Methides Generated In Situ Under Basic Conditions

Caruana

Mondatori

Corti

et al. 2015

Chemistry A European J

112

A new approach to the utilization of highly reactive and unstable ortho-quinone methides (o-QMs) in catalytic asymmetric settings is presented. The enantioselective reactions are catalysed by bifunctional organocatalysts, and the o-QM intermediates are formed in situ from 2-sulfonylalkyl phenols through base-promoted elimination of sulfinic acid. The use of mild Brønsted basic conditions for transiently generating o-QMs in catalytic asymmetric processes is unprecedented, and allows engaging productively in the reactions nucleophiles such as Meldrum's acid, malononitrile and 1,3-dicarbonyls. The catalytic transformations give new and general entries to 3,4-dihydrocoumarins, 4H-chromenes and xanthenones. These frameworks are recurring structures in natural product and medicinal chemistry, as testified by the formal syntheses of (R)-tolterodine and (S)-4-methoxydalbergione from the catalytic adducts.

Advanced Synthesis & Catalysis

“…The most interesting approach would be an asymmetric hydrogenation of coumarin 12, directly leading to the desired dihydrochromen-2-one 7. [7] However, this pathway to tolterodine was abandoned because of difficulties of preparing coumarin 12 from simple starting materials by Pechmann condensation. [8] Some years ago, Clark et al reported a novel enantioselective synthesis of highly enantioenriched 3-arylindanones via three consecutive, base-induced [1,5]-suprafacial sigmatropic rearrangements of the corresponding 3-arylindenol, easily available by catalytic asymmetric methyloxazaborolidine (Me-CBS) reduction of the indenone.…”

Section: Resultsmentioning

confidence: 99%

Catalytic Asymmetric Total Synthesis of the Muscarinic Receptor Antagonist (R)-Tolterodine

Hedberg

Andersson

2005

A convenient and high yielding method for the preparation of (R)-tolterodine, utilizing a catalytic asymmetric Me-CBS reduction was developed. Highly enantioenriched (R)-6-methyl-4-phenyl-3,4-dihydrochromen-2-one (94% ee) was recrystallized to yield practically enantiopure material (ee > 99%) and converted to (R)-tolterodine in a four-step procedure. The configuration of the crucial stereocenter was preserved during the synthesis and the obtained product was identified by chiral HPLC to be the (R)-tolterodine enantiomer.