An Efficient Synthesis of the Fully Elaborated Isoindolinone Unit of Muironolide A

Abstract

An efficient stereocontrolled construction of the fully substituted isoindolone subunit of muironolide A is described. The approach is centered on the intramolecular Diels-Alder reaction between the enol form of the β-keto amide and an α β γ δ-unsaturated ester, followed by the installation of the cyclohexene double bond.

Stereoselective Synthesis of Pyrans from Epoxyalkenes: Dual Catalysis with Palladium and Brønsted Acid

“…The epoxyalkene diastereomer 20 or 21 was obtained from the corresponding Z - or E -dienyl alcohol 15 or 17 (Scheme ). Specifically, Cu-catalyzed carbomagnesiation of propargyl alcohol ( 13 ) with methylmagnesium bromide followed by quenching with elemental iodine provided ( Z )-3-iodo-2-methylprop-2-en-1-ol ( 14 ), , and subsequent Pd-catalyzed Kumada coupling with vinylmagnesium bromide gave ( Z )-2-methyl-2,4-pentadien-1-ol ( 15 ). , A complementary sequence of steps, namely Sonogashira coupling of propargyl alcohol and vinyl bromide to pent-4-en-2-yn-1-ol ( 16 ), followed by Cu-catalyzed carbomagnesiation yielded exclusively ( E )-2-methyl-2,4-pentadien-1-ol ( 17 ). , Sharpless asymmetric epoxidation of each dienyl alcohol 15 or 17 provided the corresponding epoxyalkenyl alcohol 18 or 19 . The primary alcohols were then blocked as TBDPS ethers, completing the synthesis of epoxyalkene diastereomers 20 and 21 .…”

The chemistry of isoindole natural products

“…Just recently, the group of Zakarian reported another approach to the fully elaborated isoindolinone core of 204 [154]. …”

Toward the Synthesis of Muironolide A: Synthesis and Structure of Heteroleptic Lanthanide–Terpyridine Complexes with 2‐Oxo Amides

“…[6] A key feature of the synthesis plan is the stereoselective construction of the isoindolinone subunit of 1 by an intramolecular Diels-Alder (IMDA) reaction, in which the β-oxo amide performs as a surrogate of the diene via its enol form. [7,8] We previously reported that with substrate 5 the IMDA reaction is successful under thermal conditions (110°C, 60 h) giving rise to the expected cyclization product in 60 % yield with very high diastereoselectivity (Scheme 1b). [7] However, for an application in the total synthesis of 1, control of the absolute stereochemistry must also be exercised.…”

“…[7,8] We previously reported that with substrate 5 the IMDA reaction is successful under thermal conditions (110°C, 60 h) giving rise to the expected cyclization product in 60 % yield with very high diastereoselectivity (Scheme 1b). [7] However, for an application in the total synthesis of 1, control of the absolute stereochemistry must also be exercised. In a preliminary investigation described herein, we discovered that the IMDA reaction could be accelerated with a 1 ples of nonsymmetric heteroleptic complexes of lanthanides with β-oxo carbonyl compounds, which reveal several structural properties that could be exploited in the development of catalytic reactions with lanthanides.…”