Chemoselectivity as a Delineator of Cuprate Structure in Catalytic 1,4‐Addition of Diorganozinc Reagents to Michael Acceptors

Welker, Matthias; Woodward, Simon; Veiros, Luı́s F.

doi:10.1002/chem.200903310

Cited by 19 publications

(10 citation statements)

References 55 publications

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“…(b) Interconversion/coexistence of phosphoramidite copper complexes [Cu 2 X 2 L 4 ], [Cu 2 X 2 L 3 ], and [CuXL] 3 with [Cu 2 X 2 L 3 ] as the proposed precatalyst of the ACA reaction . (c) Monomeric in Cu, but bimetallic transmetalation intermediate and a π-complex, which essentially agrees with [Cu 2 X 2 L 3 ] calculated theoretically …”

Section: Introductionsupporting

confidence: 79%

Elusive Transmetalation Intermediate in Copper-Catalyzed Conjugate Additions: Direct NMR Detection of an Ethyl Group Attached to a Binuclear Phosphoramidite Copper Complex

2014

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Copper-catalyzed asymmetric conjugate addition reactions are a very powerful and widely applied method for enantioselective carbon-carbon bond formation. However, structural and mechanistic insight into these famous reactions has been very limited so far. In this article, the first direct experimental detection of transmetalation intermediates in copper-catalyzed reactions is presented. Special combinations of (1)H,(31)P HMBC spectra allow for the identification of complexes with chemical bonds between the alkyl groups and the copper complexes. For the structural characterization of these transmetalation intermediates, a special approach is applied, in which samples using enantiopure ligands are compared with samples using enantiomeric mixtures of ligands. It is experimentally proven, for the first time, that the dimeric copper complex structure is retained upon transmetalation, providing an intermediate with mixed trigonal/tetrahedral coordination on the copper atoms. In addition, monomeric intermediates with one ligand, but no intermediates with two ligands, are detected. These experimental results, in combination with the well-known optimal ligand-to-copper ratio of 2:1 in synthetic applications, allow us to propose that a binuclear transmetalation intermediate is the reactive species in copper-catalyzed asymmetric conjugate addition reactions. This first direct experimental insight into the structure of the transmetalation intermediate is expected to support the mechanistic and theoretical understanding of this important class of reactions and to enable their further synthetic development. In addition, the special NMR approach presented here for the identification and characterization of intermediates below the detection limit of (1)H NMR spectra can be applied also to other classes of catalyses.

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Section: Introductionsupporting

confidence: 79%

Elusive Transmetalation Intermediate in Copper-Catalyzed Conjugate Additions: Direct NMR Detection of an Ethyl Group Attached to a Binuclear Phosphoramidite Copper Complex

2014

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“…Dithioacetal functionalities are very useful protecting, stabilizing and promoting groups in organic synthesis, due to their easy deprotection to the corresponding aldehydes and ketones under acidic conditions. [96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114] Because a strong bond can be easily formed between a catalytic metal and the sulfur atom, it is usually difficult to render the metal-involved reactions of dithioacetals catalytic. In addition, dithioacetals are sensitive to acids, the organic transformations of dithioacetals via C-S bond cleavage are usually carried out by means of strong base catalysts as well as Brønsted acids.…”

Section: Catalytic C-s Cleavage In Dithioacetalsmentioning

confidence: 99%

Transition-metal mediated carbon–sulfur bond activation and transformations

2013

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C-S bond activation, cleavage and transformations by means of transition metal compounds have recently become more and more important in the petroleum industry and synthetic chemistry. Homogeneous transition metal compounds have been investigated in order to provide the fundamental insight into the C-S bond cleavage in problematic organosulfur compounds such as thiophene, benzo- and dibenzothiophene derivatives. Rendering transition-metal mediated reactions with organosulfur compounds catalytic may provide promising routes to deep hydrodesulfurization of petroleum feedstocks, and offer potentially useful synthetic protocols for cross-couplings and biomimetic organic synthesis. During the last few decades increasing work was documented on C-S bond activation and transformations by means of transition metal compounds. This review summarizes the recent advances in C-S bond cleavage via the insertion of transition metals into the inert C-S bonds of these problematic organosulfur compounds, and transition-metal mediated C-S bond transformations via C-S activation through cross-couplings of thioesters, ketene dithioacetals, sulfonyl chlorides, and other diverse organosulfur compounds.

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“…Although Michael reactions of unsubstituted benzoquinone monoketals have previously been explored,, the conjugate addition reaction of highly electron‐rich Michael acceptors, in particular benzoquinone monoketal 2a , is a long‐standing problem , . Baran and co‐workers solved this matter by searching for the appropriate ketal protecting group .…”

Section: Discussionmentioning

confidence: 99%

Synthesis of (+)‐Antroquinonol and Analogues by Using Enantioselective Michael Reactions of Benzoquinone Monoketals

Hsu

Fang

2016

Eur J Org Chem

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(+)‐Antroquinonol is an anticancer agent that was first isolated from the rare mushroom Antrodia cinnamomea, which is indigenous to Taiwan. In this study, (+)‐antroquinonol is synthesized from benzoquinone monoketals by using an enantioselective Michael reaction as the strategic step followed by an alkylation, reduction, hydrolysis of a ketal, and inversion of configuration sequence of reactions. Because the enantioselective Michael reaction to the electron‐rich 2,3,4,4‐tetramethoxycyclohexa‐2,5‐dien‐1‐one was problematic, the reaction was facilitated by introducing an electron‐withdrawing chloro group to replace the methoxy substituent at the C‐2 position. Upon treatment with K2CO3 in MeOH in the final step, the chloro substituent was then replaced by the methoxy group concurrently with the inversion of configuration at C‐6 to afford (+)‐antroquinonol in a one‐pot operation. This modular type of synthetic method can also be applied to efficient total syntheses of other antroquinonol analogues that contain the 4‐hydroxycyclohex‐2‐enone core by starting from their corresponding benzoquinone monoketals.

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Chemoselectivity as a Delineator of Cuprate Structure in Catalytic 1,4‐Addition of Diorganozinc Reagents to Michael Acceptors

Cited by 19 publications

References 55 publications

Elusive Transmetalation Intermediate in Copper-Catalyzed Conjugate Additions: Direct NMR Detection of an Ethyl Group Attached to a Binuclear Phosphoramidite Copper Complex

Elusive Transmetalation Intermediate in Copper-Catalyzed Conjugate Additions: Direct NMR Detection of an Ethyl Group Attached to a Binuclear Phosphoramidite Copper Complex

Transition-metal mediated carbon–sulfur bond activation and transformations

Synthesis of (+)‐Antroquinonol and Analogues by Using Enantioselective Michael Reactions of Benzoquinone Monoketals

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