Efficient and Practical Syntheses of Enantiomerically Pure (S)‐(−)‐Norcryptostyline I, (S)‐(−)‐Norcryptostyline II, (R)‐(+)‐Salsolidine and (S)‐(−)‐Norlaudanosine via a Resolution‐Racemization Method

Abstract

Four racemic tetrahydroisoquinolines (RS)‐(±)‐1–4 were prepared from homoveratrylamine via amidation, Bischler‐Napieralski reaction and the subsequent reduction. The enantiomerically pure tetrahydroisoquinolines (S)‐ (−)‐norcryptostyline I [(S)‐(−)‐1], (S)‐(−)‐norcryptostyline II [(S)‐(−)‐2], (R)‐(+)‐salsolidine [(R)‐(+)‐3] and (S)‐(−)‐norlaudanosine [(S)‐(−)‐4] were then obtained in 45%, 40%, 41% and 38% yields, respectively, via resolution of the racemic compounds (RS)‐(±)‐1–4 with half equivalent of chiral acids. In addition, the enantiomerically enriched compounds (R)‐(+)‐1, (R)‐(+)‐2, (S)‐(−)‐3 and (R)‐(+)‐4 from the mother liquors were efficiently racemized via a one‐pot redox method in almost quantitative yields.

Racemization of Secondary‐Amine‐Containing Natural Products Using Heterogeneous Metal Catalysts

“…If Ir/C was used as a catalyst, all (±)‐ 1 was rapidly converted into imine, whereas with Pt/Al 2 O 3 (T94) the rate of dehydrogenation was considerably slower. If separately prepared imine was added to the Pt‐catalyzed racemization reaction of ( S )‐ 1 , a significant decrease in the reaction rate was observed (Figure ).…”

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

“…The tert -butyl hypochlorite ( t- BuOCl) reagent is also used regularly, but is similarly expensive, wasteful and hazardous [ 14 , 19 – 21 ]. On the other hand sodium hypochlorite (NaOCl) is an inexpensive byproduct of chlorine manufacture, and offers a safer, greener source of electrophilic chlorine for producing N -chloramines [ 11 , 14 , 22 ]. Reaction times can, however, be long [ 14 , 23 – 24 ], and yields low [ 25 ].…”

Photocatalytic C–H silylation of heteroarenes by using trialkylhydrosilanes

“…To further demonstrate the utility of our strategy, a new synthetic route towards the synthesis of benzylisoquinoline alkaloids norcryptostyline I–II was developed (Scheme 8G). These two naturally occurring target compounds were readily assembled via a modular synthetic approach in 52–56% yields (overall yields of three steps), which provides an alternative efficient method for the synthesis of this class of natural products 46,47…”