Biomimetic total synthesis of steroids VI. Stereospecific synthesis of 19‐nor‐8α‐steroids and 11α‐alkyl derivatives

Groen, Marinus B.; Hindriksen, B.; Zeelen, F. J.

doi:10.1002/recl.19821010404

“…Initially, tetracycle 9 was transformed into a 3.5:1 mixture of epoxides 10a/10b by reaction with m-CPBA in 91 % yield. [18] For the last step, that is, a Lewis acid catalyzed rearrangement of the epoxy group to the carbonyl group, only epoxide 10a with the desired stereochemistry was used. This step proved to be more complicated than reported and envisioned.…”

Section: Resultsmentioning

confidence: 99%

Enantioselective Synthesis of (–)‐Methoxyestrone

Betík

¹

,

Kotora

²

2011

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Enantioselective synthesis of unnatural (–)‐methoxyestrone in 12 steps from the commercially available tetralone based on the formation of a chiral bicyclic intermediate having the A–B steroid ring framework was accomplished. The crucial synthetic step comprised the enantioselective conjugate addition of vinylmagnesium bromide to a chiral imine formed from a trisubstituted cyclic α,β‐unsaturated aldehyde with >98 % ee, giving rise to the stereoselectively substituted building block possessing the A–B steroid rings. Further steps included the construction of the side chain containing the triple bond, and the obtained enyne was subjected to a Pauson–Khand reaction that furnished stereoselectively an intermediate tetracyclic ketone. Further functional group transformations yielded the target compound.

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Hydrazide‐Catalyzed Polyene Cyclization: Asymmetric Organocatalytic Synthesis of cis‐Decalins

Plamondon

¹

,

Warnica

²

,

Kaldre

³

et al. 2019

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Polyene cyclizations offer rapid entry into terpenoid ring systems. Although enantioselective cyclizations of (E)‐polyenes to form trans‐decalin ring systems are well precedented, highly enantioselective cyclizations of (Z)‐polyenes to form the corresponding cis‐decalins have not been reported. Here, we describe the first application of iminium catalysis to the initiation of polyene cyclizations. Ethyl 1,2‐diazepane‐1‐carboxylate catalyzes the cyclization of polyenes bearing enal initiators. Moreover, chiral bicyclic hydrazides catalyze the cyclizations of (Z)‐polyene substrates to form cis‐decalins with enantioselectivities of up to 97:3 er. DFT calculations suggest the catalysts promote the reaction by stabilizing positive charge as it develops during the bicyclization.

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Hydrazide‐Catalyzed Polyene Cyclization: Asymmetric Organocatalytic Synthesis of cis‐Decalins

Plamondon

¹

,

Warnica

²

,

Kaldre

³

et al. 2019

View full text Add to dashboard Cite

Polyene cyclizations offer rapid entry into terpenoid ring systems. Although enantioselective cyclizations of (E)‐polyenes to form trans‐decalin ring systems are well precedented, highly enantioselective cyclizations of (Z)‐polyenes to form the corresponding cis‐decalins have not been reported. Here, we describe the first application of iminium catalysis to the initiation of polyene cyclizations. Ethyl 1,2‐diazepane‐1‐carboxylate catalyzes the cyclization of polyenes bearing enal initiators. Moreover, chiral bicyclic hydrazides catalyze the cyclizations of (Z)‐polyene substrates to form cis‐decalins with enantioselectivities of up to 97:3 er. DFT calculations suggest the catalysts promote the reaction by stabilizing positive charge as it develops during the bicyclization.

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Biomimetic total synthesis of steroids VI. Stereospecific synthesis of 19‐nor‐8α‐steroids and 11α‐alkyl derivatives

Cited by 8 publications

References 29 publications

Enantioselective Synthesis of (–)‐Methoxyestrone

Enantioselective Synthesis of (–)‐Methoxyestrone

Hydrazide‐Catalyzed Polyene Cyclization: Asymmetric Organocatalytic Synthesis of cis‐Decalins

Hydrazide‐Catalyzed Polyene Cyclization: Asymmetric Organocatalytic Synthesis of cis‐Decalins

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