Conjugate Addition−Dipolar Cycloaddition Cascade for the Synthesis of Benzo[a]quinolizine and Indolo[a]quinolizine Scaffolds: Application to the Total Synthesis of (±)-Yohimbenone

Abstract

A highly efficient total synthesis of (+/-)-yohimbenone and a formal synthesis of (+/-)-emetine is described. The key element of the synthesis consists of a conjugate addition-dipolar cycloaddition of 2,3-bis(phenylsulfonyl)-1,3-butadiene with an appropriate oxime. The resulting cycloadducts are cleaved reductively to provide azapolycyclic scaffolds with strategically placed functionality for further manipulation to the target compounds.

Tandem Catalysis: Transforming Alcohols to Alkenes by Oxidative Dehydroxymethylation

“…Diol 8c underwent oxidative dehydroxymethylation and secondary alcohol oxidation to access (+)-yohimbenone 9c . On the basis of this result, we improved our previous synthesis of (+)-yohimbenone 9c by shortening the sequence to two steps. , …”

“…Based on this result, we improved our previous synthesis of (+)-yohimbenone 9c by shortening the sequence to two steps. 5a, 16…”

Breaking and Making of Rings: A Method for the Preparation of 4‐Quinolone‐3‐carb­oxylic Acid Amides and the Expensive Drug Ivacaftor

“…The spectroscopic data were compared with the reported data, and they were found to be identical in all respects. [19] In an alternate route, indolylacetic acid ester 29 [20] was subjected to ozonolysis under the same conditions to yield corresponding quinolone ester 30 [21] in excellent yield (82 %). Ester hydrolysis of compound 30 under basic conditions gave known 4-quinolone-3-carboxylic acid 31 [22] in 94 % yield; this compound was previously converted into Ivacaftor through amine coupling followed by debenzylation.…”

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…178 A total synthesis of (AE)-yohimbenone (439) has been achieved through a conjugate addition-dipolar cycloaddition of 2,3bis(phenylsulfonyl)-1,3-butadiene (440) with oxime as the key step (Scheme 77). 179 A enantioselective formal synthesis of (+)-dihycorynantheine (441) and (À)-dihydrocorynantheol (442) has been accomplished by the synthesis of a known synthetic precursor through a stereoselective cyclocondensation of (S)-tryptophanol with a racemic aldehyde and a stereoselective cyclization of the lactam (Scheme 78). 180 Full details of the recently invented synthesis of 9-methoxysubstituted Corynanthe indole alkaloids, mitragynine (443), 9-methoxygeissoschizol (444) and 9-methoxy-N b -methylgeissoschizol (445), have appeared.…”