Nucleophilic additions multiple bonds conjugated

The previous sections dealt with reactions in which the new carbon-carbon bond is formed by addition of the nucleophile to a carbonyl group. Another important method for alkylation of carbon nucleophiles involves addition to an electrophilic multiple bond. The electrophilic reaction partner is typically an a,(3-unsaturated ketone, aldehyde, or ester, but other electron-withdrawing substituents such as nitro, cyano, or sulfonyl also activate carbon-carbon double and triple bonds to nucleophilic attack. The reaction is called conjugate addition or the Michael reaction. 

The complexes of sulfur trioxide with various nucleophiles (dioxane, pyridine etc.) are mild sulfonating reagents. Unlike other complexes of sulfur trioxide, dimethyl sulfide-sulfur trioxide readily adds to conjugated multiple bonds. Consequently, not only the sulfo group but also the dimethyl sulfide group add at the multiple bond. The reactions of dimethyl sulfide-sulfur trioxide complex with butadiene, isoprene and 2,3-dimethylbutadiene take place as conjugated l,4- -additions of dimethyl sulfide and sulfonate groups at the double bonds of the diene (equation 103).124... 

A general type of chemical reaction between two compounds, A and B, such that there is a net reduction in bond multiplicity (e.g., addition of a compound across a carbon-carbon double bond such that the product has lost this 77-bond). An example is the hydration of a double bond, such as that observed in the conversion of fumarate to malate by fumarase. Addition reactions can also occur with strained ring structures that, in some respects, resemble double bonds (e.g., cyclopropyl derivatives or certain epoxides). A special case of a hydro-alkenyl addition is the conversion of 2,3-oxidosqualene to dammara-dienol or in the conversion of squalene to lanosterol. Reactions in which new moieties are linked to adjacent atoms (as is the case in the hydration of fumarate) are often referred to as 1,2-addition reactions. If the atoms that contain newly linked moieties are not adjacent (as is often the case with conjugated reactants), then the reaction is often referred to as a l,n-addition reaction in which n is the numbered atom distant from 1 (e.g., 1,4-addition reaction). In general, addition reactions can take place via electrophilic addition, nucleophilic addition, free-radical addition, or via simultaneous or pericycUc addition. 

L. Miginiac, Nucleophilic Additions to Conjugated Carbon-Heteroatom Multiple Bonds O, S, N, in Handbook of Grignard Reagents (G. S. Silverman, P. E. Rakita, Eds.), Marcel Dekker Inc., New York, 1996, 391-396... 

Nucleophilic Addition to Conjugated Carbon-Carbon Multiple Bonds... 

The addition reactions take place at a carbon-carbon multiple bond, or carbon-hetero atom multiple bond. Because of this peculiarity, the addition reactions are not common as the first step in pyrolysis. The generation of double bonds during pyrolysis can, however, continue with addition reactions. The additions can be electrophilic, nucleophilic, involving free radicals, with a cyclic mechanism, or additions to conjugated systems such as Diels-Alder reaction. This type of reaction may explain, for example, the formation of benzene (or other aromatic hydrocarbons) following the radicalic elimination during the pyrolysis of alkanes. In these reactions, after the first step with the formation of unsaturated hydrocarbons, a Diels-Alder reaction may occur, followed by further hydrogen elimination ... 

In alkenyl- and alkynylcarbene complexes the addition of nucleophiles to the carbene carbon competes with the addition to the 3-carbon of the conjugated C-C multiple bond. [17] The regioselectivity of the addition of amines to alkynylcarbene complexes is temperature dependent 1,2-addition is favoured by lower temperatures. [17c] Enolates turned out to be efficient C-nucleophiles for Michael addition reactions to unsaturated metal carbenes. The product distribution may depend on steric factors as shown in Scheme 7 for the addition of different enolates to alkenylcarbene complex 10. The less bulky acetone enolate 11 adds to the carbene carbon protonation of the primary addition product results in demetalation and in the formation of a mixture of isomeric enones 12. In contrast, the more bulky cyclopentanone enolate 13 adds to the less shielded vinylic position. 

Regiochemistry is ordinarily not a concern in the addition of nucleophiles to structures having carbon-heteroatom multiple bonds that are not conjugated with carbon-carbon double or triple bonds, because only 1,2-addition is expected. If the addition creates a new chiral center, however, then stereoisomeric addition products can be formed. Considerable interest in this area was sparked by a report by Cram that nucleophilic addition to ketones having chiral a carbon atoms gave unequal yields of the possible diastereomeric adducts. For example, addition of ethyllithium to the methyl ketone (+ )-92 gave primarily the erythro product (+ )-93. 

Since these early groundbreaking studies, the field of conjugate addition reactions has experienced noteworthy advances. The reactions constitute a vital method for the formation of new bonds f to carbonyl groups. Multiple innovative approaches to effect diastereoselective [21, 27-36] and enantio-selective [34—47] conjugate additions of a wide variety of nucleophiles to an equally large spectrum of acceptors have appeared. These form the greater part of the discussion in this chapter (Sections 12.2-12.7), followed by sections on conjugate reductions (12.8) [32, 38] and recent advances in enantioselective Stetter reactions (12.9) [41, 48, 49]. 

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