Carbon nucleophiles acceptors

The l ,J -DBFOX/Ph-transition metal aqua complex catalysts should be suitable for the further applications to conjugate addition reactions of carbon nucleophiles [90-92]. What we challenged is the double activation method as a new methodology of catalyzed asymmetric reactions. Therein donor and acceptor molecules are both activated by achiral Lewis amines and chiral Lewis acids, respectively the chiral Lewis acid catalysts used in this reaction are J ,J -DBFOX/Ph-transition metal aqua complexes. 

In addition to enolate ions, other kinds of carbon nucleophiles also add to a jjS-iinsaturated acceptors in Michael-like reactions. Among the most important such nucleophiles, particularly in biological chemistry, are enamines, which are... 

The conjugate addition of a carbon nucleophile to an a./3-unsiituratcd acceptor is known as the Michael reaction. The best Michael reactions take place between unusually acidic donors (/3-keto esters or /3-diketones) and unhindered n,/3-unsaturated acceptors. Knamines, prepared by reaction of a ketone with a disu Instituted amine, are also good Michael donors. 

Early investigations of additions of soft carbon nucleophiles to simple Michael acceptors like ethyl sorbate date back to the beginning of the 20th century. Already in 1906, Vorlander and coworkers4-6 described additions of malonate anion whereas ethyl sorbate provided the 1,6-addition product6 (equation 2), the 1,4-adduct was obtained from methyl 5-phenyl-2,4-pentadienoate4 (equation 3). Thus, it seems that the regioselectivity... 

As in the case of addition reactions of carbon nucleophiles to activated dienes (Section HA), organocopper compounds are the reagents of choice for regio- and stereoselective Michael additions to acceptor-substituted enynes. Substrates bearing an acceptor-substituted triple bond besides one or more conjugated double bonds react with organocuprates under 1,4-addition exclusively (equation 51)138-140 1,6-addition reactions which would provide allenes after electrophilic capture were not observed (cf. Section IV). 

As demonstrated in Section m.A, activated enynes with an acceptor group at the triple bond react with carbon nucleophiles under 1,4-addition exclusively the same is... 

Direct coupling of carbon nucleophiles with 1,3-dinitrobenzene is promoted by ultraviolet irradiation in the presence of quaternary ammonium fluorides, which can act not only as the base to generate the carbon nucleophile, but also as a proton transfer agent in the rearomatization step [83], The dinitrobenzene acts as the electron acceptor in the photochemical step. No reaction occurs in the absence of the fluoride and, surprisingly, although simple ketones, nitriles, esters and fl-kcto esters react, pentan-2,4-dione does not. 

Transition metal carbene complexes have broadly been classified into Fischer-type and Schrock-type carbene complexes. The former, typically low-valent, 18-electron complexes with strong 7t-acceptors at the metal, are electrophilic at the carbene carbon atom (C ). On the other hand, Schrock-type carbene complexes are usually high-valent complexes with fewer than 18 valence electrons, and without n-accepting ligands. Schrock-type carbene complexes generally behave as carbon nucleophiles (Figure 1.4). 

Also alkynylcarbene complexes can react as Michael acceptors with nucleophiles, forming 1,3-dien-l-ylcarbene complexes (Figure 2.17). Both carbon nucleophiles, such as, e.g., enamines [246-249], and non-carbon nucleophiles, such as imidates [250], amines [64,131,251], aliphatic alcohols [48,79,252], phenols [252], and thiols [252] can add to the C-C triple bond of alkynylcarbene complexes. Further reactions of the C-C triple bond of alkynylcarbene complexes include 1,3-dipolar [253,254], Diels-Alder [64,234,238,255-258] and [2 -i- 2] cycloadditions [259 -261], intramolecular Pauson-Khand reactions [43,262], and C-metallation of ethynylcarbene complexes [263]. 

Carbon-centered nucleophiles are those compounds or intermediates which contain an electron-rich carbon atom and thus are capable of donating an electron pah from that carbon atom to an electrophile. The electron pair that is donated is found in a filled orbital in the nucleophilic carbon and the electrons are not tighdy bound. Donation to the electrophilic carbon occurs by overlap of the filled orbital of the donor with an unfilled orbital of the acceptor. The most common carbon nucleophiles fall into three main classes ... 

Having defined the types of commonly used carbon nucleophiles and carbon electrophiles, it would seem that if you react any of the carbon nucleophiles (electron donors) with any of the carbon electrophiles (electron acceptors), then a carbon-carbon bond should be formed. While this is theoretically true, it is unworkable from a practical point of view. If, for example, a carbanion nucleophile was reacted with a cationic electrophile, it is unlikely that the desired carbon-carbon bond formation would be detected, even after the smoke cleared. Or if a silyl enol ether nucleophile was reacted with an a, /f-unsaturated ester, no reaction could be observed to take place in any reasonable time frame. 

F. F. Fleming, Q. Wang, Unsaturated Nitriles Conjugate Additions of Carbon Nucleophiles to a Recalcitrant Class of Acceptors, Chem. Rev. 2003, 103, 2035-2077. 

Besides the Michael addition of heteroatomic nucleophiles initiating cyclocondensations, acceptor substituted unsaturated systems can also be reacted with carbon nucleophiles stemming from aldehydes in the sense of an umpolung, generally referred to as the Stetter reaction [244-246]. This process is organocatalytic and furnishes in turn 1,4-dicarbonyl compounds, intermediates that are well suited for Paal-Knorr cyclocondensations giving rise to furans or pyrroles. Among numerous heterocycles furans and pyrroles have always been the most prominent ones since they constitute important classes of natural products [247-249], of synthetic... 

In addition ta molate iona. other kinds of carbon nucleophiles add unaatarated acceptors in th Michael reaction greatly extending the usefulness ami versatility of the procew. Among (he most important such nucleophiles are eruimines- Recall from Section 19 9 that enamines are reedily prepared by reaction between a ketone and a socondary amine ... 

When carbon nucleophiles carrying a leaving group at the a-position are allowed to react with Michael acceptors, the resultant intermediate anions will be capable of undergoing an intramolecular displacement to produce cyclopropanes (equation 85). Some reactions described in Section III. A may actually proceed in this way. 

Route (u) could use a Michael acceptor together with a suitable one carbon nucleophile such as MeOCH2MgCl. Route (i) could have formaldehyde as the electrophile and a suitably protected and activated derivative for the nucleophile such as. .. 

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