Divergent Stereocontrol of Acid Catalyzed Intramolecular Aldol Reactions of 2,3,7-Triketoesters: Synthesis of Highly Functionalized Cyclopentanones

Abstract

The intramolecular acid catalyzed aldol cyclization of 2,3,7-triketoesters formed from ζ-keto-α-diazo-β-ketoesters provides highly functionalized cyclopentanones with good diastereoselectivity in high overall yields via kinetically controlled and stereodivergent catalytic processes. Lewis acid catalysis gives high selectivity for the 1,3-anti tetrasubstituted cyclopentanones, whereas Brønsted acid catalysis produces the corresponding 1,3-syn diastereomer.

Highly Enantioselective Carbonyl–Ene Reactions of 2,3‐Diketoesters: Efficient and Atom‐Economical Process to Functionalized Chiral α‐Hydroxy‐β‐Ketoesters

“…We have previously proposed Lewis acid activation of the central carbonyl of 2,3‐diketoesters through a bidentate coordination with the more basic keto group rather than with the carboxylate group,9b and our current data provides further evidence for this claim. If the [Cu{( S , S )‐ t Bu‐box}](SbF 6 ) 2 catalyst undergoes bidentate coordination with the 2,3‐diketoester 3 in a square‐planar complex,13 so that the central carbonyl oxygen atom and the adjacent keto carbonyl are bound ( 8 ), the approach through the Si face is sterically hindered by the tert ‐butyl substituent of the box ligand, thus allowing olefin approach from only the Re face, and thus generates the S enantiomer (Figure 2).…”

Traditional and New methods for the Preparation of Diazocarbonyl Compounds

“…They performed a Lewis acid-catalyzed Mukaiyama aldol addition of methyl 3-(trialkylsilanyloxy)-2-diazo-3-butenoate with aromatic and aliphatic aldehydes as well as the asymmetric version using AgF/(R)-BINAP as catalyst or using dibutylboron triflate in a high diastereoselectivity reactions with α-diazoβ-ketopentanoate (Doyle et al 2005, Kundu and Doyle 2006, Zhou and Doyle 2010. Moreover, Doyle's group explored the Mukaiyama−Michael reactions with α,β-enones (Liu et al 2008, Truong et al 2012, and Mannich reactions with nitrones and hydrazones (Xu et al 2011(Xu et al , 2012. More recently, they developed an efficient approach for a Lewis acid mediated coupling reaction of enoldiazo compounds and propargyl acetates to afford a diverse series of alkynyl-tethered diazoketones that undergo a metal-catalyzed carbene metathesis cascade reactions (Qian et al 2013).…”

Vicinal Tricarbonyl Compounds: Versatile Building Blocks for Natural Product Synthesis

“…The intramolecular aldol reaction of 2,3,7-triketo esters gives access to highly substituted cyclopentanones (i.e., 44 and 45). 25 The 2,3,7-triketo ester 41 used for cyclisation was prepared from enol diazoacetate 40 via Mukaiyama-Michael reaction followed by oxidation with DMDO and dehydration under reduced pressure (Scheme 8). According to whether a Brønsted or Lewis acid was used in the subsequent cyclisation step, the syn- (44) or anti-product (45) was obtained selectively.…”