Regioselectivity Switch: Gold(I)-Catalyzed Oxidative Rearrangement of Propargyl Alcohols to 1,3-Diketones

Hashmi, A. Stephen K.; Wang, Tao; Shi, Shuai; Rudolph, Matthias

doi:10.1021/jo301381z

Cited by 143 publications

(49 citation statements)

References 47 publications

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“…In this Account, I will discuss our results based both on intramolecular alkyne oxidation and on intermolecular oxidation, with the latter being the focus. I am, however, obligated to point out here that many other researchers including Liu, 17−22 Toste, 23 Shin, 24,25 Zhang, 26−28 Davies, 29−31 Gagosz, 32 Hashmi, 33,34 Li, 35 and Liu 36 have also made outstanding contributions in this field, which will not be discussed due to the nature of this Account.…”

Section: Introductionmentioning

confidence: 99%

A Non-Diazo Approach to α-Oxo Gold Carbenes via Gold-Catalyzed Alkyne Oxidation

2014

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For the past dozen years, homogeneous gold catalysis has evolved from a little known topic in organic synthesis to a fully blown research field of significant importance to synthetic practitioners, due to its novel reactivities and reaction modes. Cationic gold(I) complexes are powerful soft Lewis acids that can activate alkynes and allenes toward efficient attack by nucleophiles, leading to the generation of alkenyl gold intermediates. Some of the most versatile aspects of gold catalysis involve the generation of gold carbene intermediates, which occurs through the approach of an electrophile to the distal end of the alkenyl gold moiety, and their diverse transformations thereafter. On the other hand, α-oxo metal carbene/carbenoids are highly versatile intermediates in organic synthesis and can undergo various synthetically challenging yet highly valuable transformations such as C–H insertion, ylide formation, and cyclopropanation reactions. Metal-catalyzed dediazotizations of diazo carbonyl compounds are the principle and most reliable strategy to access them. Unfortunately, the substrates contain a highly energetic diazo moiety and are potentially explosive. Moreover, chemists need to use energetic reagents to prepare them, putting further constrains on operational safety.In this Account, we show that the unique access to the gold carbene species in homogeneous gold catalysis offers an opportunity to generate α-oxo gold carbenes if both nucleophile and electrophile are oxygen. Hence, this approach would enable readily available and safer alkynes to replace hazardous α-diazo carbonyl compounds as precursors in the realm of gold carbene chemistry.For the past several years, we have demonstrated that alkynes can indeed effectively serve as precursors to versatile α-oxo gold carbenes. In our initial study, we showed that a tethered sulfoxide can be a suitable oxidant, which in some cases leads to the formation of α-oxo gold carbene intermediates. The intermolecular approach offers excellent synthetic flexibility because no tethering of the oxidant is required, and its reduced form is not tangled with the product. We were the first research group to develop this strategy, through the use of pyridine/quinolone N-oxides as the external oxidants. In this manner, we can effectively make a C–C triple bond a surrogate of an α-diazo carbonyl moiety in various gold catalyses. With terminal alkynes, we demonstrated that we can efficiently trap exclusively formed terminal carbene centers by internal nucleophiles en route to the formation of cyclic products, including strained oxetan-3-ones and azetidin-3-ones, and by external nucleophiles when a P,N-bidentate ligand is coordinated to gold. With internal alkynes, we generated synthetically useful regioselectivities in the generation of the α-oxo gold carbene moiety, which enables expedient formation of versatile enone products. Other research groups have also applied this strategy en route to versatile synthetic methods. The α-oxo gold carbenes appear to be more electrophilic...

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Section: Introductionmentioning

confidence: 99%

A Non-Diazo Approach to α-Oxo Gold Carbenes via Gold-Catalyzed Alkyne Oxidation

2014

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“…This strategy circumvents the use of hazardous and potentially explosive α-diazo ketone precursors [3] and has led to the development of various efficient synthetic methods by us [1, 4] and others [5] based on their intramolecular trapping. The intermolecular counterpart, likely of exceptional synthetic utilities, however, proves to be very challenging due to the highly electrophilic nature of the carbene center, and is often plagued by over oxidation, reactions with solvents, [4b, 4g] and intractable side reactions.…”

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confidence: 99%

Optimizing P,N‐Bidentate Ligands for Oxidative Gold Catalysis: Efficient Intermolecular Trapping of α‐Oxo Gold Carbenes by Carboxylic Acids

2013

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Steric Bulk or Conformation Control? Optimization of P,N-bidentate ligands reveals the importance of conformation control in the development of highly efficient intermolecular trapping of reactive α-oxo gold carbene intermediates. While a pendant piperidine ring offers suitable steric bulk, fixing its conformation to provide better shielding to the highly electrophilic carbene center turned out to be crucial for the excellent reaction efficiency. A generally highly efficient and broadly applicable synthesis of carboxymethyl ketones from readily available carboxylic acids and terminal alkynes is developed under exceptionally mild reaction conditions.

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“…Selective synthesis of β-diketones by oxidative rearrangement of alkynols A-D in the presence of IPrAuNTf 2 was reported in [38]. The catalyst was prepared directly from IPrAuCl and AgNTf 2 in CH 2 Cl 2 , and 4-methylpyridine N-oxide was used as oxidant (Scheme 28).…”

Section: Alkynols In the Synthesis Of β-Diketonesmentioning

confidence: 99%