Tetrahydroisoquinoline‐Based N‐Oxides as Chiral Organocatalysts for the Asymmetric Allylation of Aldehydes

Abstract

The short synthesis of a series of novel chiral N-oxide organocatalysts and their evaluation in the asymmetric allylation reaction of aromatic and α-β-unsaturated aldehydes with allyltrichlorosilane is reported. These readily modifiable organocatalysts are the first of their kind based on the tetra-

Crystal structure of (S)-benzyl 3-(benzylcarba-moyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, C25H24N2O3

“…The title compound is a precursor to chiral ligands involving a tetrahydroisoquinoline backbone applied by our group to both metal-and organo-catalysis [5,6]. Crystal strcuture analysis of the title compound shows that the N-contaning six membered ring of dihydroisoquinoline is in distorted boat conformation as opposed to its N-methylated analogue which adopted a boat conformation [7].…”

Crystal structure of 3-(benzhydrylcarbamoyl)-2-benzyl-6,7-dimethoxy-1- phenyl-1,2,3,4-tetrahydroisoquinoline 2-oxide, C38H36N2O4

“…We have recently reported the useofsimilar TIQ derivativesas organocatalysts for the asymmetric allylation of aldehydes [4]. The N-oxide orientates syn (on the sameside) to the amide hydrogen-bond donor substituent and is stabilized by an intramolecular hydrogen bond O×××H=1.85 Å. Fromthe crystal structure it is evident that the N-containing six membered ring assumesah alfchair conformation [(Q) =0 .5193(12))Å ,q=4 8.77(14)°, f = 357.37(19)°].…”

“…The N-oxide orientates syn (on the sameside) to the amide hydrogen-bond donor substituent and is stabilized by an intramolecular hydrogen bond O×××H=1.85 Å. Fromthe crystal structure it is evident that the N-containing six membered ring assumesah alfchair conformation [(Q) =0 .5193(12))Å ,q=4 8.77(14)°, f = 357.37(19)°]. We have previouslyr eported similar conformationsfor TIQ based N-oxideorganocatalysts [4]. …”

Mechanistic Dichotomy in the Asymmetric Allylation of Aldehydes with Allyltrichlorosilanes Catalyzed by Chiral Pyridine N‐Oxides

“…In parallel, we have developed novel pyridine‐derived N ‐monooxides12d, 28–31 and demonstrated their superior enantio‐ and diastereoselectivity in the allylation and crotylation of various aldehydes. Hoveyda then reported on the first “non‐pyridine‐type” N ‐monooxide derived from proline,32 and Govender made use of the N ‐oxides derived from tetrahydroisoquinolines 27d. Chiral, Lewis basic sulfoxides,33 sulfonamides,34 phosphine oxides, such as BINAPO (2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthalene‐ P , P′ ‐dioxide),28e, 35 and dinitrones36 have also been shown to catalyze or mediate the allylation reaction 37…”