Michael-type addition mechanism

Scheme 19.3 Michael-type addition mechanism for nitrile butadiene rubber (NBR) crosslinking [71].

The maleimide group can undergo a variety of chemical reactions, including polymerizations induced by free radicals or anions. Nucleophiles such as primary and secondary amines , as well as thiophenoxides , can react via a classical Michael-type addition mechanism . The maleimide group can also act as a very reactive dienophile and is thns nsed in a variety of Diels-Alder reactions . By varying the natnre of the linkages between the maleimide rings, the physical properties of the bis(maleimide) can be altered. 

Base-induced eliminative ring fission, in which both the double bond and the sulfone function take part, has been observed in thiete dioxides253. The reaction can be rationalized in terms of initial Michael-type addition to the double bond of the ring vinyl sulfone, followed by a reverse aldol condensation with ring opening. The isolation of the ether 270c in the treatment of 6c with potassium ethoxide (since the transformation 267 -> 268 is not possible in this case) is in agreement with the reaction mechanism outlined in equation 101253. 

With any substrate, when Y is an ion of the type Z—CR2 (Z is as defined above R may be alkyl, aryl, hydrogen, or another Z), the reaction is called the Michael reaction (see 15-21). In this book, we will call all other reactions that follow this mechanism Michael-type additions. Systems of the type C=C—C=C—Z can give 1,2, 1,4, or 1,6 addition. Michael-type reactions are reversible, and compounds of the type YCH2CH2Z can often be decomposed to YH and CH2=CHZ by heating, either with or without alkali. 

In an extension of previous work on conjugated enamine carbonyl derivatives, reaction of the pyrazolone 91 with IV.lV-disubstituted hydrazines on heating in an alcohol solvent afforded the hexahydropyrazolo[4,3-Michael-type addition of the alcohol to a pre-formed pyrazolo-diazepine, was excluded <06T8126>. 

In troponoid chemistry cine substitution occurs frequently. In many cases it can be explained by the intermediacy of dehydrotropolone species ( tro-polonyne ) as trapped, for example, by azides (Section II,A,3,h Scheme 34). An alternative mechanism may be a Michael-type addition followed by elimination. The intramolecular cyclizations depicted in Scheme 47 very likely proceed via Michael-type attack (73CRV293, p.351). 

TL1759) from indole, the aldehyde RCHO, and Meldrum s acid could arise from a nucleophilic attack of Meldrum s acid upon the 3-indolylcarbinol by a mechanism analogous to that outlined in Scheme 69. However, it is more probable that the aldehyde reacts initially with Meldrum s acid and that (294) results from a Michael-type addition of indole to the activated ethylene. 

One possible mechanism is the following. The allenyl geminal diester 61, not isolable, is expected to be susceptible to Michael-type addition of Pd(0)L species to... 

Figure 3.3 Mechanism of action of esperamicin A i. Reduction of the trisulfide and Michael-type addition increases the freedom of movement within the enediyne allowing the formation of a diradical intermediate by means of a Bergman cyclisation. When bound to DNA, the diradical abstracts hydrogens from the DNA backbones which are subsequently trapped by oxygen and lead to strand cleavage. The star notes the location of the reactive enediyne functionality of esperamicin Ai.

The unsaturated residues Dha and Dhb are formed by dehydration of serine and threonine residues, respectively, and the thioether linkages Lan and MeLan are generated by intramolecular Michael-type addition of cysteine thiols to the unsaturated sites (e.g., Fig. 3b). These modifications can be performed by either two separate enzymes (LanB and LanC) in class I lantibiotics or a single bifunctional enzyme (LanM) in class II lantibiotics. Typically, proteolysis of the leader sequence is performed by a dedicated protease, either a LanP serine protease (class I) or the cysteine protease domain of a LanT protein (class II). The lanB genes encode large ( 1000 residues) predominantly hydrophilic dehydratases that may be membrane associated. To date, the dehydratase activity of a LanB protein has not been reconstituted in vitro and little is known about the mechanism of catalysis of this group of enzymes. 

As with the normal mechanism of the enzyme, the inactivation starts with Schiff base formation with the enzyme-bound pyridoxal phosphate, followed by removal of an a-proton by an active-site base to form the reactive electrophilic intermediate (82). This then partitions between hydrolysis of the Schiff base linkage, resulting in the keto product (83)and enzyme reactivation, and Michael-type addition of an enzyme active-site nucleophile, resulting in a stable covalently bonded enzyme adduct (84). 

One possible mechanism is the following. The allenyl geminal diester 70 is expected to be susceptible to Michael-type addition of LnPd(O) species to the allenyl sp carbon, resulting in the formation of the palladacyclopropane 71. Insertion of carbon monoxide into 71 and methanolysis afford the triester 72 (Scheme 11-20). The alkene geometry of the product 72 is exclusively E. The high stereoselectivity can be rationalized by assuming that a nucleophilic attack of Pd(0) species on the allenyl sp carbon in 70 takes place from the less-hindered side of a smaller alkyl substituent (R ). Needless to say, in allene 70, the two ester groups are perpendicular to the two substituents Rl and Rg. 

The intermediate of the ElcB mechanism is a carbanion, and thus any factors that stabilise such an ion should favour this mechanism. We have already noted above that on the face of it, elimination reactions are the reverse of addition reactions. However, we also noted that the actual mechanistic pathways involved in elimination reactions were more similar to substitution reactions than addition reactions. This is because normally elimination reactions proceed via a carbonium ion or in a single step that has certain similarities to an SN2 substitution reaction. However, there are also addition reactions that proceed via a carbanion intermediate, for example the Michael-type reaction, in which a carbanion adds to an a,(3-unsaturated carbonyl compound. Indicate the Michael-type addition between the anion formed from the diester of propandioic acid (or malonic acid) and 2-butenal. 

The first prominent catalytic asymmetric Michael-type addition reaction of an organolithium reagent was shown by the reaction of 1-naphthy[lithium with 1-fluoro-2-naphthylaldehyde imine in the presence of 6 to afford the binaphthyls in high ee. Only catalytic amounts of 6 (0.05 mol%) effects the reaction to give 82% ee, in which an enantioselective Michael-type addition-elimination mechanism is operative (Eq. (12.12)) [31],... 

A mechanism for the formation exo-5-morpholinobicyclo[2.2.1]heptan-2-one via a ho-moenolate ion intermediate in a Michael-type addition reaction has been proposed. Michael addition reactions involving secondary amines and a,)S-unsaturated carbonyl compounds have been reported, but this was the first example of such a reaction involving the ho-moenolate ion. ... 

However, other important mechanisms have been observed to play a role in the chemistry of alkenyliodonium compounds Michael-type addition, alkylidenecarbene generation, and p-elimination affording alkynes. 

Propose a mechanism for the following transformation to give compound I. (Hint remember that enones can react with nucleophiles in Michael-type additions.)... 

---