Bamford–Stevens reaction
Bamford–Stevens reaction | |
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Named after | William Randall Bamford Thomas Stevens Stevens |
Reaction type | Elimination reaction |
Identifiers | |
Organic Chemistry Portal | bamford-stevens-reaction |
RSC ontology ID | RXNO:0000124 |
The Bamford–Stevens reaction is a
The treatment of tosylhydrazones with alkyl lithium reagents is called the Shapiro reaction.
Reaction mechanism
The first step of the Bamford–Stevens reaction is the formation of the diazo compound 3.[4]
In protic solvents, the diazo compound 3 decomposes to the carbenium ion 5.
In aprotic solvents, the diazo compound 3 decomposes to the carbene 7.
Directed Bamford-Stevens reaction
The Bamford–Stevens reaction has not proved useful for the stereoselective generation of alkenes via
Synthesis of 3-substituted indazoles from arynes and N-tosylhydrazones
N-tosylhydrazones can be used in a variety of synthetic procedures. Their use with arynes has been used to prepare 3-substituted indazoles via two proposed pathways. The first step is the deprotonation of the hydrazone of diazo compounds using CsF. At this point, the conjugate base could either decompose to give the diazo compound and undergo a [3+2] dipolar cycloaddition with the aryne to give the product, or a [3+2] annulation with aryne which would also give the final product. While strong bases, such as LiOtBu and Cs2CO3 are often used in this chemistry, CsF was used to facilitate the in situ generation of arynes from o-(trimethylsilyl)aryl triflates. CsF was also thought to be sufficiently basic to deprotonate the N-tosylhydrazone.[8][9]
N-tosylhydrazones as reagents for cross-coupling reactions
Barluenga and coworkers developed the first example of using N-tosylhydrazones as
The scope of the reaction is wide; N-tosylhydrazones derived from aldehydes and ketones are well tolerated, which leads to both di- and trisubstituted olefins. Moreover, and variety of aryl halides are well tolerated as coupling partners including those bearing both electron-withdrawing and electron-donating groups, as well as π-rich and π-deficient
The mechanism of this transformation is thought to proceed in a manner similar to the synthesis of alkenes through the Bamford–Stevens reaction; the decomposition of N-tosylhydrazones in the presence of base to generate diazocompounds which then release nitrogen gas, yielding a carbene, which then can be quenched with an electrophile. In this case, the coupling reaction starts with the
Moreover, Barluenga and coworkers demonstrated a one-pot three-component coupling reaction of aldehydes or ketones, tosylhydrazides, and aryl halides in which the N-tosylhydrazone is formed in situ. This process produces stereoselective olefins in similar yields compared to the process in which preformed N-tosylhydrazones are used.[10]
Barluenga and coworkers also developed metal-free reductive coupling methodology of N-tosylhydrazones with boronic acids. The reaction tolerates a variety of functional groups on both substrates, including aromatic, heteroaromatic, aliphatic, electron-donating and electron-withdrawing substituents, and proceeds with high yields in the presence of potassium carbonate. The reaction is thought to proceed through the formation of a diazo compound that is generated from a hydrazone salt. The diazo compound could then react with the boronic acid to produce the benzylboronic acid through a boronate intermediate. An alternate pathway consists of the formation of the benzylboronic acid via a zwitterionic intermediate, followed by protodeboronation of the benzylboronic acid under basic conditions, which results in the final reductive product.
This methodology has also been extended to heteroatom nucleophiles to produce ethers and thioethers.[11][12]
A tandem rhodium-catalyzed Bamford-Stevens/thermal aliphatic Claisen rearrangement
A novel process was developed by Stoltz in which the Bamford–Stevens reaction was combined with the
Application to total synthesis
Trost et al. utilized the Bamford–Stevens reaction in their total synthesis of (–)-isoclavukerin to introduce a diene moiety found in the natural product. A bicyclic trisylhydrazone was initially subjected to Shapiro reaction conditions (alkyllithiums or LDA), which only led to uncharacterizable decomposition products. When this bicyclic trisylhydrazone was subjected to strong base (KH) and heat, however, the desired diene product was generated. Moreover, it was shown that olefin generation and the following decarboxylation could be performed in one pot. To that end, excess NaI was added, along with an elevation in temperature to facilitate the Krapcho decarboxylation.[15][16]
References
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