Stereocontrolled Total Syntheses of Isodomoic Acids G and H via a Unified Strategy

Abstract

Marine neuroexcitatory compounds isodomoic acids G and H were efficiently synthesized from a common intermediate using a silicon-based cross-coupling reaction. Dividing each target compound into the core fragment and the side-chain fragment enabled the synthesis to be convergent. The trans-2,3-disubstituted pyrrolidine core fragment was accessed through a diastereoselective rhodium-catalyzed carbonylative silylcarbocyclization reaction of a vinylglycine-derived 1,6-enyne. A stereochemically divergent desilylative iodination reaction was developed, converting of the cyclization product to both E-and Z-alkenyl iodides, which would eventually lead to isodomoic acid G and isodomoic acid H, respectively. The late stage alkenylalkenyl silicon-based cross-coupling reaction uniting the core alkenyl iodides and the side-chain alkenylsilanol was achieved under mild conditions. Finally, two mild deprotections afforded the target molecules.

Ethylene Transposition: Ruthenium Hydride Catalyzed Intramolecular trans-Silylvinylation of Internal Alkynes

“…The majority of work in this area has focused on hydrosilylation chemistry. − Recently, a number of ruthenium catalyzed protocols have emerged for the synthesis of trisubstituted olefins using an intramolecular hydrosilylation of alkynes. − These complementary routes to trisubstituted vinylsilanes are inherently limited due to the mandatory inclusion of a hydrogen atom into the product alkene. Subsequent studies on silylcarbonylation and silylcyanation of alkynes have been described to circumvent this limitation. − Specifically, Ojima and Denmark have studied the silylformylation of alkynes and found that five- and six-membered rings could be formed readily in this reaction. − Silylformylation and silylcyanation reactions afford the syn -alkene isomers selectively. Intermolecular versions of silylcarbocyclization reactions also afford the syn -isomers. − We have recently reported that vinyl-silicon tethers can be used to control both the regio- and stereochemistry in the silylvinylation of pendent alkynes with acrylates …”

Scalable Total Syntheses and Structure–Activity Relationships of Haouamines A, B, and Their Derivatives as Stable Formate Salts

“…Asymmetric reduction of 9 a and 9 b with [Rh(cod)( R , R )‐DiPAMP]]BF 4 (cod=1,5‐cyclooctadiene, DiPAMP=1,2‐bis[(2‐methoxyphenyl)phenylphosphino]ethane) (1 mol %) and one‐pot removal of the Cbz group with 10 % Pd/C under a hydrogen atmosphere afforded amines 11 a and 11 b . The tosylation and subsequent propargylation of the crude sulfonamides under Mitsunobu reaction conditions, as reported by Tsunoda, afforded esters 12 a and 12 b in high yields with a small optical purity loss (93 and 94 % ee , respectively) . Reduction of methyl esters with diisobutylaluminum hydride (DIBAL) at −98 °C yielded aldehydes 7 a and 7 b (Scheme ), which immediately participated in the next “anti‐Wacker”‐type cyclization without further purification.…”

From Alkynes to Heterocycles through Metal-Promoted Silylformylation and Silylcarbocyclization Reactions

“…of TBAF•3 H 2 O as additive, in THF at room temperature: both electron rich and electron poor aryl iodides gave the coupling products in good yields (Scheme 26). More recently, the same research group applied standard silylcarbocyclization to a highly functionalized allyl propargyl amine, i.e., N-tosyl-N-methylpropargyl-(L)-vinylglycine methyl ester, as a key step for the total synthesis of isodomoic acids G and H, two kainoid amino acid derivatives isolated from red alga Chondria armata with well recognized properties as neuroexcitatory agents [78,79].…”