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. 2023 Oct 20;88(20):14396-14403.
doi: 10.1021/acs.joc.3c01304. Epub 2023 Sep 28.

Carboxylate Catalysis: A Catalytic O-Silylative Aldol Reaction of Aldehydes and Ethyl Diazoacetate

Saara Riuttamäki  1 , Anton Bannykh  1 , Petri M Pihko  1
Affiliations

Carboxylate Catalysis: A Catalytic O-Silylative Aldol Reaction of Aldehydes and Ethyl Diazoacetate

Saara Riuttamäki et al. J Org Chem. .

Abstract

A mild catalytic variant of the aldol reaction between ethyl diazoacetate and aldehydes is described using a combination of N,O-bis(trimethylsilyl)acetamide and catalytic tetramethylammonium pivalate as catalyst. The reaction proceeds rapidly at ambient temperature to afford the O-silylated aldol products in good to excellent yield, and the acetamide byproducts can be removed by simple filtration.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Examples of Aldol-Type Reactions between Ethyl Diazoacetates and Aldehydes
Scheme 2
Scheme 2. Substrate Scope of the TMAP-Catalyzed O-Silylative Aldol Reaction
Scheme 3
Scheme 3. Stereochemical Assignment of 5n
Conditions: (a) 1% HCl, THF, 0 °C, 84%; (b) H2, PtO2 (10 mol %), AcOH (cat.), EtOAc, rt., 73%; (c) HF–pyridine (20 mol %), MeCN–H2O, 0 °C, 81%; (d) 2,2-dimethoxypropane, (+)-CSA (10 mol %), Me2CO, rt.
Scheme 4
Scheme 4. Experiments To Probe the Reaction Mechanism
Reaction conditions for control experiment: (a) (i) EDA (1 equiv, 0.08 M), BSA (2 equiv), TMAP (1 mol %), Bn2O (1 equiv), CD3CN (600 μL), rt. (ii) 1a (1 equiv, 0.06 M), EDA (1 equiv), BSA (2 equiv), Bn2O (1 equiv), CD3CN (600 μL), rt. (iii) 1a (1 equiv, 0.07 M), EDA (1 equiv), BSA or BSTFA (2 equiv), TMAP (0.1 mol %), Bn2O (1 equiv), CD3CN (600 μL), 25 °C. (iv) 1a (1 equiv, 0.37 M), EDA (0.9 equiv), BSA (2 equiv), TMAP (2 mol %), trichloroethylene (1.1 equiv), CD3CN (537 μL), 25 °C. (v) 1b (1 equiv, 0.07 M), 4a (1 equiv), BSA (2 equiv or none), TMAP (0.1 mol %), Bn2O (1 equiv), CD3CN (600 μL), 25 °C.
Scheme 5
Scheme 5. Proposed Catalytic Cycle of the Carboxylate-Catalyzed Silylative Aldol Reaction Involving a Probase Mechanism
See this image and copyright information in PMC

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