Regioselective Annulation of 1,5-Diketones: Access to Functionalized Hagemann’s Esters

Abstract

The synthesis of the ''functionalized'' Hagemann's ester (S)-18 was investigated. The common starting material in these approaches was enamino ester (S,Z)-5, which was prepared through the condensation of keto diester 4 with (S)-1-phenylethylamine. The Michael addition reaction of 5 with methyl vinyl ketone gave the expected adduct (S)-6 with an ee Ն 95%. However, all attempts at annulation of 6 invariably afforded the unwanted cyclohexenone derivatives 7 or 8. The addition of 5 to Nazarov reagent 9 furnished adduct (S)-10 with an ee Ն 95%. The Triton B-induced annulation of 10 unexpectedly gave aldol 11. Depending on the reaction con-

Enantioselective Access to Robinson Annulation Products and Michael Adducts as Precursors

“…A similar strategy has been used to access the functionalized analogs using the vinyl phosphonate 160 (Scheme 43b). [114] Simpler vinyl ketones or Nazarov reagent failed to give this key intermediate in the synthesis of natural compounds. Chiral cyclohexanones such as (+)-dihydrocarvone have been used for the synthesis of (-)-allohedycaryol through the intermediate formation of (+)-α-cyperone (Scheme 44).…”

Asymmetric Michael reaction between a chiral α,β-dimethyl-β-enamino ester and α-substituted acrylates

“…Adducts (S,S)-11a and (S,S)-11b proved to be homogeneous by 1 H and 13 C NMR spectroscopy [including experiments using Eu(FOD) 3 and Eu(hfc) 3 as shift reagents]. For comparison, 11a and 11b were prepared in a nonstereoselective fashion by the addition of methyl methylacetoacetate to acrylates 2a or 2b in the presence of Triton â B.…”

“…These were obtained in good yields (68-75%) and excellent eeÕs (93-96%). 3 As a part of our research directed towards the synthesis of new chiral building blocks, we recently investigated the reaction between the chiral a,b-dimethyl-b-enamino ester 9 and various a-substituted acrylates 2.…”

Asymmetric synthesis of glutamate derivatives

“…Since its discovery in 1985, this methodology as generally been applied to various cyclic systems notably for the synthesis of natural products such as terpenes and steroids, [4][5][6][7][8][9][10][11] but only rarely to acyclic ones. [12][13][14][15][16][17][18] In this paper, we explore the Michael reaction between acyclic chiral β-enaminoesters exhibiting various alkoxy groups and various olefins, the effect of Lewis acid on the reactivity and the enantioselectivity of this reaction will be explored.…”