A Catalyst‐Directed Remote Stereogenic Center Switch During the Site‐Selective Aldol Desymmetrization of Cyclohexanone‐Based Diketones. Issue 23 (9th November 2016)

• Record Type: Journal Article
• Authors: Nugent, Thomas C.; Spiteller, Peter; Hussain, Ishtiaq; Hussein, Hussein Ali El Damrany; Najafian, Foad Tehrani
• Is Part Of: Advanced synthesis & catalysis. Volume 358:Issue 23(2016)
• Page Start: 3706
• Page End: 3713
• Publication Date: 2016-11-09
• Subjects: aldols -- desymmetrization -- diketones -- epimer switch -- organocatalysis -- site-selectivity; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201600833
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: Site‐selectivity, differentiating members of the same functional group type on one substrate, is an emerging tactic for shortened advanced building block and biomolecule synthesis. Despite its potential, site‐selectivity remains less studied and especially so for ketone‐based substrates. During this work ketone site‐selectivity has been coupled with the chiral amine‐catalyzed aldol desymmetrization of 4‐keto‐substituted cyclohexanones, allowing three stereogenic centers to form in the aldol product while leaving the acyclic ketone unreacted. Unique here, compared to all previous 4‐substituted cyclohexanone desymmetrizations, is the first access to synthetically useful quantities of an epimeric (remote stereogenic center) aldol product. To demonstrate the value of these aldol products, we show their elaboration into eight keto‐acetonide and one keto‐lactone products. All compounds were isolated as single diastereomers and in high ee (≥96%). These efforts represent the first full characterization of aldol products with type III, Figure 2, relative stereochemistry, regardless of the enantiomer formed. Abstract :