Kumulierte Ylide, VI. Eine neue Synthese des (Triphenylphosphoranyliden)ketens, seines Thioanalogen und stabiler Propadienylidentriphenylphosphorane

Abstract

Die Einwirkung von Natrium-bis(trimethyIsilyl)amid (2) auf (Methoxycarbonylmethy1en)triphenylphosphoran (1 a) bzw. sein Dithioanaloges 1 b fiihrt unter @-Eliminierung zu (Triphenylphosphoran-y1iden)keten (3a) bzw. -thioketen (3b). Die analoge Reaktion von 2 mit den (a-Ethoxyally1iden)triphenylphosphoranen 8 liefert die stabilen Propadienylidentriphenylphosphorane 9. Cumulated Ylides, VI')A New Synthesis of (Triphenylphosphoranylidene)ketene, its Thio Analogue, and Stable Propadienylidenetriphenylphosphoranes2)Reaction of sodium bis(trirnethylsilyl)amide (2) with (methoxycarbonylmethy1ene)triphenylphosphorane (la) or its dithio analogue l b leads to @-elimination and formation of (triphenyl-phosphorany1idene)ketene (3a) and -thioketene (3b), respectively. The analogous reaction of 2 with the (a-ethoxyallylidene)triphenylphosphoranes 8 gives rise to the formation of the stable propadienylidenetriphenylphosphoranes 9. A. Heterophosphacumulen-Ylide(Triphenylphosphorany1iden)keten (3a) und -thioketen (3b) lassen sich ausgehend von Hexaphenylcarbodiphosphoran mit C 0 2 bzw. CS2 nach anschlie13ender Thermolyse der Additionsprodukte darstellen 3* 4J. Wir fanden einen wesentlich einfacheren und ergiebigeren Weg zu diesen au13erst reaktionsfahigen Verbindungen ' ).

Chemical Synthesis of the Cardiotonic Steroid Glycosides and Related Natural Products

“…In the event, treatment of 18 with a fluoride source promotes the putative formation of allene oxide Int-I, followed by in situ oxirane hydrolysis and rearrangement to the g-hydroxy-a,b-unsaturated pregnane derivative 19. Catalytic olefin hydrogenation then occurs exclusively from the a face and subsequent installation of the b-oriented butenolide through condensation with the Bestmann reagent [28] completes the synthesis of cardenolide derivative 20, thus constituting a formal synthesis of digitoxigenin, as the conversion of 20 into 1 is known.…”

“…[28] In the presence of the Lewis acid BF 3 ·OEt 2 , a silylated vinyl lithium species attacks the non-enolizable androst-5-en-17-one (15) in 1,2-fashion from the less-hindered a-face, a stereochemical outcome that is well precedented for steroid substrates whose C/D ring fusion is trans. [6] En route to the targeted allene oxide, the diene 16 is chemoScheme 1. a) Concise and stereocontrolled conversion of sarsasapogenin (11) into the 14-hydroxy-androstane (14).…”

“…The b-nitrile 59 was converted to the corresponding 21-hydroxy-20-oxopregnane derivative (61) by a two-step process involving addition of (benzyloxy)-methyllithium followed by palladium-catalyzed hydrogenolytic debenzylation. The now familiar condensation of 61 with the Bestmann phosphoranylidene ketene [28] (see above) and desilylation of the C3 hydroxyl group completed the first total synthesis of (+)-digitoxigenin (1). This work can be considered a historic achievement for its novel and stereocontrolled construction of the 5b,14b-androstane-3b,14-diol skeleton in addition to the creative solutions that were implemented to solve the stereochemical problem of introduction of the 17b-butenolide substituent.…”

“…[28] The first total synthesis of (+)-digitoxigenin by the laboratory of Stork: The first total synthesis of the natural product digitoxigenin (Scheme 3) [35] begins with a four-step conversion of the Wieland-Miescher ketone (30) into the silyl enol ether 45, which is then a-hydroxylated under ozonolysis conditions. Next, the acyloin intermediate 46 is reduced to the corresponding glycol with sodium borohydride and subsequent oxidative diol cleavage leads to the optically active dialdehyde 47.…”

“…Reaction of 97 with the Bestmann reagent [28] followed by selective methanolysis of the C3 acetate provided the cardenolide diol, sarmentogenin acetate (99). Regioand stereoselective Schmidt glycosylation [24a] of 99 with tri-O-acetyl l-rhamnose 1-trichloroacetimidate then delivered a peracetylated intermediate that, upon global deprotection with aqueous hydroxide underwent butenolide ring-opening to the hydroxy-acid salt.…”