In the reaction between cyclohexanone and β-nitrostyrene sketched below, the base proline is derivatized and works in conjunction with a protic acid such as "p"-toluenesulfonic acid:  Syn addition is favored with 99% ee. In the transition state believed to be responsible for this selectivity, the enamine (formed between the proline nitrogen and the cycloketone) and β-nitrostyrene are co-facial with the nitro group hydrogen bonded to the protonated amine in the proline side group. A well-known Michael reaction is the synthesis of warfarin from 4-hydroxycoumarin and benzylideneacetone first reported by Link in 1944:  Several asymmetric versions of this reaction exist using chiral catalysts. In the Mukaiyama–Michael addition the nucleophile is a silyl enol ether and the catalyst usually titanium tetrachloride:  The research done by Arthur Michael in 1887 at Tufts University was prompted by an 1884 publication by Conrad & Kuthzeit on the reaction of "ethyl 2,3-dibromopropionate" with "diethyl sodiomalonate" forming a cyclopropane derivative (now recognized as involving two successive substitution reactions). Michael was able to obtain the same product by replacing the propionate by "2-bromacrylic acid ethylester" and realized that this reaction could only work by assuming an addition reaction to the double bond of the acrylic acid. He then confirmed this assumption by reacting diethyl malonate and the ethyl ester of cinnamic acid forming the very first Michael adduct:  In the same year Rainer Ludwig Claisen claimed priority for the invention. He and T. Komnenos had observed addition products to double bonds as side-products earlier in 1883 while investigating condensation reactions of malonic acid with aldehydes. However, according to biographer Takashi Tokoroyama, this claim is without merit.