Efficient asymmetric syntheses of naturally occurring lignan lactones using catalytic asymmetric hydrogenation as a key reaction

Stereoselective Hydrogenation ofCCBonds: Application to Drug and Natural Product Synthesis

“…226,227 The enantioselective hydrogenations of 140 were carried out at 30 C for 40 hours in methanol in the presence of Et 3 N under 1 atm of hydrogen using 0.2 mol% of a neutral Rh(I)-complex as a precatalyst, which was prepared in situ from (S,S)-MOD-DIOP and 1/2[Rh(COD)Cl] 2 in methanol. 228 After the workup, hydrogenation product (R)-141 was obtained in almost quantitative yields and enantioselectivity (up to 93-95% ee). Optical purity can be improved by a single recrystallization of hydrogenated products from isopropyl ether to give enantiopure (R)-arylmethylsuccinic acids (R)-141 with up to 99% ee.…”

“…The (R)-141 has been successfully applied for the stereoselective syntheses of (þ)-collinusin, (À)-deoxypodophyllotoxin, and (þ)-neoisostegane. 228 Isomeric nonproteinogenic amino acids (S)-(2)-acromelobic acid and (S)-(2)-acromelobinic acid ,229,230 which differ in the attachment of the a-amino acid side chain on the pyridone ring, were isolated from the fruit bodies of poisonous mushroom (Clitocybe acromelalga) found in Japan, and they are the source of a variety of potent neuroexcitatory nonproteinogenic amino acids related to the kainoid family. 231 Adamczyk and co-workers set out to develop a straightforward access to enantioenriched (S)-(À)-acromelobinic 232 and (S)-(À)-acromelobic 233 acids to achieve elaboration of asymmetric hydrogenation of dehydroamino acid derivatives 145 and 147 (Scheme 29.10).…”

Advances in the Synthesis of Aryltetralin Lignan Lactones

“…Reflecting the control obtained in electrophilic additions to enolates derived from β-substituted butyrolactones, a popular approach has been to develop enantioselective syntheses of this versatile intermediate and then elaborate this to the aryltetralin lactone skeleton. The initial asymmetric centre has been established in a number of ways including by asymmetric hydrogenation of succinates [42] (Scheme 8, a), C-H insertion of diazo esters, [43] (Scheme 8, b) and enolate alkylation [44] (Scheme 8, c). In this context it is pertinent to note that Pelter has demonstrated that the three-component coupling reaction of enantiomerically pure 5-menthyloxyfuranone proceeded with complete diastereoselectivity (see Scheme 1,b).…”

“…Saponifica- Scheme 10. tion of the D ring followed by reduction and recyclisation afforded the desired 1,2-cis stereochemistry, albeit as a mixture of lactone stereoisomers 62 and 63 (Scheme 11). [42] Scheme 11.…”

“…[49] Elimination to apopodophyllotoxin is possible and related reductions in this series have previously been demonstrated to provide the desired 1,2-cis,2,3-trans stereochemistry (vide supra). [42,54,72] The ∆ 1,2 unsaturated skeleton can also be accessed from the C1 ketone through enol triflate formation and Suzuki-Miyaura cross coupling (Scheme 27c). [89] A particularly elegant approach, which simultaneously establishes the D-ring lactone and introduces the C1 aryl group, involves a tandem radical cyclisation-radical translocation sequence (Scheme 28).…”