[2678-54-8] · C6H12O2 · Ketene Diethyl Acetal · (MW 116.18)
(inverse electron demand Diels-Alder reactions; thermal and photochemical [2 + 2] cycloadditions; naphthoquinone and anthraquinone synthesis; Paterno-Büchi photocycloadditions)
Physical Data: bp 68 °C/100 mmHg, 84-86 °C/200 mmHg.
Solubility: sol THF, ether, benzene; decomposes in water, ethanol.
Form Supplied in: liquid, not commercially available.
Preparative Method: reaction of 2-bromo-1,1-diethoxyethane with potassium t-butoxide in t-butanol.1
Handling, Storage, and Precautions: storage in an alkaline glass bottle dusted with potassium t-butoxide is recommended.
Ketene diethyl acetal undergoes Diels-Alder reactions with various electron deficient dienes especially heterodienes such as a,b-unsaturated aldehydes and ketones (eq 1),2 acylketenes (eq 2),3 triazines,4 acyliminium ions (eq 3),5 and azodicarboxylates.6 The Diels-Alder adducts often undergo further reaction, as in the case of cycloaddition of ketene diethyl acetal to 2-pyrones which undergo Diels-Alder reaction followed by retro-Diels-Alder reaction and elimination to allow rearomatization to produce good yields of substituted aromatics (eq 4).7
Diethyl ketene acetal readily reacts with fumarate8 and acrylate esters (eq 5)9 in highly regioselective thermal [2 + 2] cycloadditions to give cyclobutanone acetals, and with propiolate esters10 to provide cyclobutenone acetals (eq 6), in good yield. Reaction with aryl isocyanates can provide substituted b-lactams (eq 7),11 but isocyanates with stabilizing groups on the nitrogen generally give ring opened products.12 Dichloroketene undergoes thermal [2 + 2] cycloaddition with the ketene acetal followed by ring opening (eq 8).13
One of the most common uses of ketene diethyl acetal has been in [2 + 2] photocycloadditions with enones.14 This is a highly regioselective process which provides access to cyclobutanone acetals in high yields (eqs 9-11).15-17 These intermediates can serve as important synthetic building blocks. One example which displays some asymmetric induction has been reported (eq 12).18
The reaction of diethyl ketene acetal with benzo- and naphthoquinones to prepare naphtho- and anthraquinones respectively has been widely studied (eqs 13 and 14).19-21 The yields vary depending on the substitution of the quinone, and benzofurans are sometimes byproducts.22 A similar reaction has been carried out on pyridinium salts.23
Ketene diethyl acetal reacts with various ketones in the Paterno-Büchi reaction to produce substituted oxetanes in modest yields (eqs 15 and 16).24-26 More electrophilic carbonyls tend to give higher yields.
Ketene diethyl acetal has been used in the palladium-catalyzed orthoester Claisen rearrangement of allylic alcohols (eq 17)27 and in reaction with phenyl selenocyanate (eq 18).28
Michael T. Crimmins
University of North Carolina at Chapel Hill, NC, USA