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This communication describes the synthesis of new bis-oxazoline chiral ligands (SPIROX) derived from the C2-symmetric spirocyclic scaffold (SPIROL). The readily available (R,R,R)-SPIROL (2) previously developed by our group was subjected to a three-step sequence that provided key diacid intermediate (R,R,R)-7 in 75% yield. This intermediate was subsequently coupled with (R)- and (S)-phenylglycinols to provide diastereomeric products, the cyclization of which led to two diastereomeric SPIROX ligands (R,R,R,R,R)-3a and (R,R,R,S,S)-3b in 85% and 79% yield, respectively. The complexation of (R,R,R,R,R)-3a and (R,R,R,S,S)-3b with CuCl and Cu(OTf)2 resulted in active catalysts that promoted the asymmetric reaction of α-diazopropionate and phenol. The resultant O–H insertion product was formed in 88% yield, and with excellent selectivity (97% ee) when ligand (R,R,R,R,R)-3a was used.
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Exploration of chiral diastereomeric spiroketal (SPIROL)-based phosphinite ligands in asymmetric hydrogenation of heterocycles
New and readily available chiral SPIROL-based diphosphinite ligands (SPIRAPO) have been prepared and employed for iridium-catalyzed asymmetric hydrogenations of quinolines, quinoxalines and 2 H -1,4-bezoxazin-2-ones. While the structurally similar ( R , R , R )-SPIRAPO and ( R )-SPINOL-based phosphinites were not the best ligands for these transformations, the ( S , R , R )-diastereomer of SPIRAPO was found to be highly effective ligand for the reduction of 20 different heterocyclic systems with loadings as low as S/C = 10 000. This dearomatizative hydrogenation provided direct access to optically active tetrahydroquinolines in high enantioselectivities (up to 94% ee) and excellent yields (up to 99%), and was used to generate 1.75 g of natural alkaloid (−)-( R )-angustureine. This protocol was subsequently extended to achieve asymmetric hydrogenation of quinoxalines and 2 H -1,4-benzoxazin-2-ones in good to excellent enantioselectivities.
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- Award ID(s):
- 1350060
- PAR ID:
- 10337722
- Date Published:
- Journal Name:
- Chemical Communications
- Volume:
- 56
- Issue:
- 60
- ISSN:
- 1359-7345
- Page Range / eLocation ID:
- 8432 to 8435
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d0cc03088k
