A Total Synthesis of (±)‐Codeine by 1,3‐Dipolar Cycloaddition

Erhard, Thomas; Ehrlich, G.; Metz, Peter

doi:10.1002/anie.201007448

Cited by 57 publications

(16 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The excellent selectivity of the epoxidation on the less-hindered face and the stereospecific rearrangement of the resulting α,β -epoxy ketone produced the allylic alcohol 13 as a single isomer. This two-step procedure provides an alternative and efficient approach to transform enone to allylic alcohol derivative in comparision with the previous processes in the total synthesis of morphine 33,49 . Removal of benzyl group of 13 in the presence of electron-rich aromatic ring and disubstituted olefins proved to be a troublesome task.…”

Section: Resultsmentioning

confidence: 96%

“…Synthetically, the efficient introduction of a sterically congested quaternary carbon center, especially in a catalytic fashion, is one of the main challenges in the asymmetric synthesis of (‒)-morphine. Up to now, there are a few methods having been explored to achieve this purpose, for example, Pd-catalyzed Heck reaction by Overman 15 , Trost 17,18 and Hudlicky 19 , C–H insertion by White 16 , radical cyclization by Parker 30 , oxidative coupling by Gaunt 31 , Grewe cyclization by Opatz 32 , and Claisen rearrangement by Metz 11,33 . However, all of these approaches to the formation of the quaternary carbon require the use of chiral precursors, and catalytic enantioselective construction of the key all-carbon quaternary stereocenter from achiral substrates has not been developed.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Enantioselective synthesis of cis-hydrobenzofurans bearing all-carbon quaternary stereocenters and application to total synthesis of (‒)-morphine

Zhang

et al. 2019

Nat Commun

View full text Add to dashboard Cite

(‒)-Morphine, which is selected as an essential medicine by World Health Organization, is widely applied in the treatment of the pain-related diseases. Due to its synthetically challenging molecular architecture and important clinical role, extensive synthetic studies of morphine-type alkaloids have been conducted. However, catalytic asymmetric total synthesis of (‒)-morphine remains a long-standing challenge. Here, we disclose an efficient enantioselective total synthesis of (‒)-morphine in a longest linear sequence of 16 steps. The key transformation features a highly enantioselective Robinson annulation enabled by our spiro-pyrrolidine catalyst to rapidly construct the densely functionalized cis -hydrodibenzofuran framework containing vicinal stereocenters with an all-carbon quaternary center. This asymmetric approach provides an alternative strategy for the synthesis of (‒)-morphine and its analogues.

show abstract

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Enantioselective synthesis of cis-hydrobenzofurans bearing all-carbon quaternary stereocenters and application to total synthesis of (‒)-morphine

Zhang

et al. 2019

Nat Commun

View full text Add to dashboard Cite

show abstract

“…Finally, compound 474 was elaborated to the natural product in few steps (Scheme 55). [118] Jung and co-workers synthesized the broussonone A by using cross-metathesis as a key reaction in their strategy. All attempts to synthesize compound 479 through the Wittig reaction, the cross-metathesis reaction between 477 and 478 with all kinds of reagents were futile.…”

Section: Application In Natural Product Synthesismentioning

confidence: 99%

Molecular Complexity from Aromatics: Recent Advances in the Chemistry of paraQuinol and Masked para‐Quinone Monoketal

Chandra

Patel

2020

ChemistrySelect

View full text Add to dashboard Cite

Synthesis of complex organic molecules from simple, cheap, and readily available starting materials is one of the most challenging and desirable factors in organic synthesis. In the last two decades, various methods have been developed for the de-aromatization reaction of planar aromatics compounds which lead to reactive intermediates like 2,5-cyclohexadienone ketal and para-quinol having a non-planar framework. Recently, there is an upsurge of interest in the development of the chemistry of these intermediates due to their inherent dual electrophilic and nucleophilic character. The presence of diverse functionality makes them important scaffolds and thus these are intensively utilized for the development of methodologies towards the synthesis of the highly functionalized and diverse chemical framework. These synthons have also been used in the total synthesis of many natural products. Interestingly, these are also adaptable for asymmetric synthesis. This review is a summary of the recent development of methods for 2,5-cyclohexadienone ketal and para-quinol synthesis and their application in natural product synthesis.

show abstract

“…4S,4aS,9bR)-9-((1,3-Dioxolan-2-yl)methyl)-6-methoxy-9b-(2-(methylamino)ethyl)-3,4,4a,9b-tetrahydrodibenzo[b,d] furan-4-ol (31) and (4aS,5S,8aR,E)-3-methoxy-11-methyl-4a,5,6,9,10,11-hexahydrobenzo[2,3]benzo-furo[3,4-de] azocin-5-ol (32) carbamate 26 (514 mg, 1.13 mmol) in CH 2 Cl 2 (1 mL) was cooled to 0°C and treated with TFA (0.25 mL) over 10 min. The mixture was stirred for 15 min, concentrated, diluted with saturated aqueous Na 2 CO 3 solution (3 mL), and extracted with CH 2 Cl 2 (3 × 5 mL).…”

mentioning

confidence: 99%

“…4aS,5S,8aR)-3-Methoxy-11-methyl-4a,5,6,9,10,11,12,13octahydrobenzo[2,3]benzofuro[3,4-de]azocin-5-ol (34)…”

mentioning

confidence: 99%

Chemoenzymatic total synthesis ofent-neopinone and formal total synthesis ofent-codeinone from β-bromoethylbenzene*

et al. 2011

View full text Add to dashboard Cite

Formal total synthesis of ent-codeinone and ent-codeine was accomplished via the total synthesis of ent-neopinone attained in 14 steps from β-bromoethylbenzene. The key steps included (i) enzymatic dihydroxylation of β-bromoethylbenzene with E. coli JM109 (pDTG601a), an organism that overexpresses toluene dioxygenase, (ii) a Heck reaction to establish C-13 stereogenic center, (iii) aldol condensation, and (iv) 1,6-conjugate addition of the ethylamino side chain to C-9. Several other modes of construction of the C-9 and C-14 centers were also investigated: Mannich cyclization, and aza-Prins reaction. The synthesis of ent-codeinone was formalized by intersecting Fukuyama’s recently published approach. Experimental and spectral data are provided for all new compounds.

show abstract

A Total Synthesis of (±)‐Codeine by 1,3‐Dipolar Cycloaddition

Cited by 57 publications

References 32 publications

Enantioselective synthesis of cis-hydrobenzofurans bearing all-carbon quaternary stereocenters and application to total synthesis of (‒)-morphine

Enantioselective synthesis of cis-hydrobenzofurans bearing all-carbon quaternary stereocenters and application to total synthesis of (‒)-morphine

Molecular Complexity from Aromatics: Recent Advances in the Chemistry of paraQuinol and Masked para‐Quinone Monoketal

Chemoenzymatic total synthesis ofent-neopinone and formal total synthesis ofent-codeinone from β-bromoethylbenzene*

Contact Info

Product

Resources

About