Brønsted Acid Catalyzed Conjugate Addition of Thiocarboxylic Acids to in situ-Generated (aza-)ortho-Quinone Methides

doi:10.6023/cjoc202411004J

Abstract

An efficient Brønsted acid catalyzed conjugate addition of thiocarboxylic acids to in situ-generated ortho-quinone methides (o-QMs) and aza-ortho-quinone methides (aza-o-QMs) has been reported. The reaction has the advantages of broad substrate scope, mild reaction conditions, easy operation and excellent yield. This study provides a new synthetic methodology for the efficient construction of structurally diverse thioesters under mild conditions.

Key words: ortho-quinone methides, aza-ortho-quinone methides, thiocarboxylic acids, conjugate addition

Cite this article

Xiu Xue, Huier Yang, Zeshen Huang, Ming Lang, Wenfeng Liu. Brønsted Acid Catalyzed Conjugate Addition of Thiocarboxylic Acids to in situ-Generated (aza-)ortho-Quinone Methides[J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2968-2982.

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Fig. & Tab. 8

Scheme 1. Background and reaction design

Entry	Cat.	Solvent	Yield^b/%	Entry	Cat.	Solvent	Yield^b/%
1	A	CH₂Cl₂	>99	9	A	CH₃CO₂Et	47
2	B	CH₂Cl₂	48	10	A	CH₃COCH₃	39
3	C	CH₂Cl₂	Trace	11	A	CH₃C₆H₅	88
4	D	CH₂Cl₂	99	12	A	ClC₆H₅	94
5	E	CH₂Cl₂	95	13	A		Trace
6	F	CH₂Cl₂	73	14	A		Trace
7	G	CH₂Cl₂	Trace	15	—	CH₂Cl₂	0
8	A	CH₃CN	54

Table 1. Optimization of reaction conditionsa

Scheme 2. Substrate scope of o-hydroxybenzyl alcohols

Scheme 3. Substrate scope of thiocarboxylic acids

Scheme 4. Reaction of o-aminobenzyl alcohols with thiocarboxylic acids

Scheme 5. Practicality of the reactions (a) Gram-scale synthesis of 3a and 6a; (b) synthetic transformation of compound 3a.

Scheme 6. Control experiment

Scheme 7. Proposed mechanism of the reaction

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