Highly diastereoselective synthesis of spiro[tetrahydrothiophene-3,3′-pyrazol] with an all-carbon quaternary stereocenter via [3 + 2] cascade Michael/Michael cyclization catalyzed by DABCO

ABSTRACT

The diastereoselective formation of spiro[tetrahydro thiophene-3,3′-pyrazol] derivatives has been achieved via a Michael/Michael cyclization reaction. The reaction was performed using trans-ethyl 4-mercapto-2-butenoate 1 with various 4-benzylidene-5-methyl-2-phenylpyrazolones 2 catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) in toluene at 0 °C. The reaction proceeds rapidly and affords the corresponding spiro[tetrahydrothiophene-3,3′-pyrazol] derivatives in excellent yields and moderate to excellent diastereoselectivities (up to 98% yield and >20:1 dr).

GRAPHICAL ABSTRACT

KEYWORDS:

• Cascade Michael/Michael cyclization
• DABCO
• diastereoselective synthesis
• spiro[tetrahydrothiophene-3,3′-pyrazol]