Acyloins from Morita–Baylis–Hillman adducts: an alternative approach to the racemic total synthesis of bupropion

Amarante, Giovanni W.; Rezende, Patricia de Souza; Cavallaro, Mayra; Coelho, Fernando

doi:10.1016/j.tetlet.2008.04.040

Cited by 27 publications

(8 citation statements)

References 49 publications

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“…Of those important C-C bond forming reactions, the Baylis-Hillman or Morita–Baylis–Hillman (MBH) reaction is a very useful and versatile one, which combines aldol and Michael reactions in a single step, providing organocatalyzed methylene--hydroxy carbonyl or -methylene--aminocarbonyl compounds. These compounds are very useful multifunctional building blocks in the synthesis of medicinally relevant pharmaceutical compounds [ 1 , 2 ] and natural products [ 3 ]. The interest in this atom-economical reaction has been growing, and good reviews regarding the development and progress using this reaction have been published [ 4 , 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

The Morita-Baylis-Hillman Reaction: Insights into Asymmetry and Reaction Mechanisms by Electrospray Ionization Mass Spectrometry

2009

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This short review presents new insights on the mechanism and online monitoring using electrospray ionization tandem mass spectrometry (ESI-MS/MS) of Morita-Baylis-Hillman (MBH) reactions. MBH reactions are versatile carbon-carbon organocatalyzed bond forming reactions, making them environmentally friendly due to general organocatalysts employed. The organocatalyst behavior, which controls the transition state and thus the enantioselectivities in the obtained products, is very important in the performance of asymmetric MBH transformations. Some recent techniques and advances in asymmetric transformations are reviwed, as well as online reaction monitoring and analysis of the reaction intermediates. The mechanism accepted nowadays is also review through the insights gained from the use of ESI-MS/MS techniques.

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Section: Introductionmentioning

confidence: 99%

The Morita-Baylis-Hillman Reaction: Insights into Asymmetry and Reaction Mechanisms by Electrospray Ionization Mass Spectrometry

2009

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“…Electron‐withdrawing group substituted glyoxal 7p underwent more efficient conversion to the product 9p in better yield (82 %) than the electron donating group substituted α‐dicarbonyl compounds. These results demonstrate that the fast and single‐step synthetic chemistry is applicable to diverse α‐phosphonyloxy ketone analogues, which would be highly useful for manufacturing drug scaffolds in a simple and environmentally benign manner.…”

Section: Methodsmentioning

confidence: 81%

“…Not surprisingly, α‐phosphonyloxy ketones are also of great interest to serve as core structures of synthetic drugs such as prednisolone and oxaprozine drug derived from benzoin, and bupropion drug derived from corresponding acyloin. However, selective synthetic routes to α‐phosphonyloxy ketones are less prevalent over numerous reports on the synthesis of various organophosphates , .…”

Section: Methodsmentioning

confidence: 99%

Fast‐Synthesis of α‐Phosphonyloxy Ketones as Drug Scaffolds in a Capillary Microreactor

et al. 2019

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A simple, room temperature approach for the fast single-step synthesis of α-phosphonyloxy ketone, a drug scaffold, has been developed which involves highly reactive species i.e., 1,2-dicarbonyls that readily react with trialkyl phosphites and formic acids in batch as well as in continuous-flow with the flow rate of 3 ml/min (t R = ∼4 s). The present approach reduced the synthesis time from hours to minutes in batch, which was further lowered to a few seconds precisely controlled by single capillary microfluidics. A wide range of 1,2-dicarbonyl deriva-Continuous-flow microreactors have recently attracted much attention as an important technique for synthesizing organic molecules including drug intermediates/molecules in a very short time under mild reaction conditions. [1][2][3][4] A high surface area to volume ratio in this microfluidic system promotes mass and heat transfer, leading to selectivity and conversion much superior to the levels obtainable by conventional batch processes. [2][3][4] Owing to their many complex issues such as inefficient mixing, non-uniformity in heat, and safety in the scale-up of batch process, in recently, flow approach is more attractive and reliable in both academia and industry. [1,2] Furthermore, high throughput production can be achieved by simply increasing reaction volume with larger dimension of channel, or/and by numbering up microreactor units in parallel. [5,6] In light of the push for continuous manufacturing of pharmaceutical products [7,8] microreactor can be an attractive alternative to the conventional batch process for many of the pharmaceutical products whose world-wide consumption is of the order of tons a year. Therefore, simple and fast continuous-flow methodologies are highly desirable to operate at high flow rate, enabling to satisfy the changing needs of pharmaceutical markets in a safe and environmentally benign, cost-effective manner.On the other hand, the organophosphate chemistry by itself is an interesting area of organic chemistry as well as life science in living organism such as DNA, RNA, ATP and cell membranes. [9] Moreover, various methodologies also reported for [a] Dr. 7730Scheme 4. Control experiments in batch to understand the reaction mechanism.Scheme 5. Plausible reaction mechanism for the synthesis of α-phosponyloxy ketone.

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“…In this approach they performed the MBH reaction of methyl acrylate with 3-chlorobenzaldehyde under sonication. Subsequently, the MBH adduct was transformed to the acyloin derivative (591) which was utilized to prepare bupropion (Scheme 91) [143].…”

Section: Bupropionmentioning

confidence: 99%

Applications of Morita-Baylis-Hillman Reaction to the Synthesis of Natural Products and Drug Molecules

Bhowmik¹,

Batra

2015

COC

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The synthesis of complex natural products from simple and common intermediates has been one of the major goals in synthetic organic chemistry. Toward this objective, if such simple scaffolds are suitably decorated with diverse functional groups they present opportunities not only to synthesize the target compounds but also construct the close analogues to investigate the biological properties. The Morita-Baylis-Hillman (MBH) reaction is an organocatalyzed CC bond forming reaction that leads to multifunctional products thereby offering viable alternatives for employing them for other complexity generating reactions. This property has been extensively utilized for the synthesis of natural products of microbial, animal, terrestrial, and marine origins. Simultaneously, MBH adducts are precursors to several drug molecules or their intermediates. This comprehensive review assimilates applications of the Morita-Baylis-Hillman reaction for the synthesis of different natural products and drug molecules.

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Acyloins from Morita–Baylis–Hillman adducts: an alternative approach to the racemic total synthesis of bupropion

Cited by 27 publications

References 49 publications

The Morita-Baylis-Hillman Reaction: Insights into Asymmetry and Reaction Mechanisms by Electrospray Ionization Mass Spectrometry

The Morita-Baylis-Hillman Reaction: Insights into Asymmetry and Reaction Mechanisms by Electrospray Ionization Mass Spectrometry

Fast‐Synthesis of α‐Phosphonyloxy Ketones as Drug Scaffolds in a Capillary Microreactor

Applications of Morita-Baylis-Hillman Reaction to the Synthesis of Natural Products and Drug Molecules

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