Nucleophilic carbonyl addition variations

TABLE 1.5 Linear free energy relationships for addition to carbonyl groups variation in nucleophile. ... 

Nucleophilic additions to carbonyl groups lead to alcohols which on dehydration, furnish alkenes70,71. This two-step protocol has been extremely useful for diene and polyene synthesis with wide variation in the carbonyl substrate and the nucleophilic addendum. Diene synthesis using aldol-type condensation as well as phenyl sulphonyl carbanion (the Julia reaction) are also discussed in this section. 

The most useful methods for the formation of C-C bonds are based on the addition of C-nucleophiles to carbonyl compounds. Among the many variations of this basic scheme phosphorus ylides, capable of olefinating aldehydes or ketones in a single step, have proven to be exceedingly valuable reagents in organic synthesis. 

Ab initio calculations at the HF/6-31G level have been used to explore energy changes, structural variation, and electron density shifts during jr-face selective addition of substituted acetylide ions to cyclohexanone and cyclohexanethione. Charge polarization of the jr-bond on approach of the nucleophile is such that the carbonyl carbon becomes considerably electron deficient for most of the reaction path (and may... 

The addition of RLi and other nucleophiles to carbonyl functions in general proceeds via one of the two possible reaction pathways, polar addition (PL) and electron transfer (ET)-radical coupling (RC) sequence (equation 5). Current reaction design for the synthetic purpose of additions of common nucleophiles to aldehydes and ketones is mostly based on the polar mechanism, but apparently the ET process is involved in some reactions of, for example, Grignard reagents Mechanistically there are three possible variations the PL pathway, the ET rate-determining ET-RC route and the RC rate-determining ET-RC route. 

A variation of GTP, referred to as aldol GTP, involves polymerization of a silyl vinyl ether initiated by an aldehyde [Sogah and Webster, 1986 Webster, 1987]. Both initiation and propagation involve nucleophilic addition of the vinyl ether to the aldehyde carbonyl group with transfer of the trialkyl silyl group from vinyl ether to the carbonyl oxygen (Eq. 5-82). The reaction has similar characteristics as GTP. The product is a silated poly(vinyl alcohol) (PVA), which can be hydrolyzed by acid to PVA (Eq. 5-83). 

Several useful variations of the tetracarbonyliron dianion-alkyl halide reactions are known. These employ the iron complex stoichiometrically, however. Since the dianion is much more nucleophilic than the alkyliron monoanion, the reaction can easily be stopped at the monoalkylated stage. Carbonylation or addition of another good ligand such as triphenylphos-phine to the monoalkylated complexes produces monoacyliron anions. Pro-... 

One method of deciding between Mechanisms I and II is to look at the trend of a in acid-catalyzed additions of various nucleophiles to a carbonyl group.26 It follows from the reacting bond rules that in true general acid catalysis (Mechanism I), the sensitivity of the rate to acidity of the catalyst, and therefore also a, should decrease as the species adding is made more nucleophilic. The reason is that this variation will cause the change in reaction coordinate shown in... 

Jencks (1972, 1969b) has proposed a model which maintains the significance of a as a measure of transition state structure and yet provides a very elegant rationalization of the fact that linear Br nsted plots are often obtained over large reactivity ranges, both by variation in catalyst pKa and substrate reactivity. Jencks noted that the acid catalysed nucleophilic addition to carbonyl compounds (21) yielded linear Br nsted plots (in apparent violation of the reactivity-selectivity principle) yet as the basicity of the nucleophile N was increased the Br nsted slope decreased (in agreement with the... 

Many variations of this route involve the formation of the 2,3-bond of a thiophene by the 2-carbon atom acting as a nucleophilic center in an intramolecular addition to a carbonyl or a cyano group . Examples are shown in Schemes 88 <2002TL257> and 89 <2003T1557>. 

Nucleophilic additions to aldeliydcs and ketones have two genera) variations, as shown in Figure 19.2. In one variation, the tetrahedral intermediate is protonated by water or acid to give an alcohol as the final product in the second variation, tlie carbonyl oxygen atom is itrotonated and then eliminated as HO or H2O to give a product witli a C=Nu bond. 

Most reactions of carbonyl groups occur by one of four general mechanisms nucleophilic addition, nucleophilic acyl substitution, alpha substitution, am carbonyl condensation. These mechanisms have many variations, just a alkene electrophilic addition reactions and 8 2 reactions do, but the varia tions are much easier to learn when the fundamental features of the mechanisms are understood. Let s see what the four mechanisms are and what kinds of chemistry carbonyl groups undergo. 

Ft, Tr, Bu) [45a]) or failure to obtain any sort of sensible FER at all (e.g. nucleophilic addition to a carbonyl group concerted with PT [47], cf. HYW [38]) probably indicates that the TSs involve structural features not present in either the reactants or products [48]. This type of behavior sometimes manifests itself in terms of large variations in Marcus intrinsic barriers [6c]. 

Abstract This chapter deals with the facial selectivity of nucleophilic additions to carbonyl compounds. This is explained using models such as the Cram s model, Anh-Felkin modification of Cram s model, Houk s transition structure model, Houk s electrostatic model, Cieplak s a —> cr model, and cation coordination model. The intricacies, variations, and predicted selectivities of these models are elaborated with examples. It has been argued that the Cieplak s cr > cr model is applicable to only those reactions that proceed through product-like transition structures. Using the cation coordination model, the facial selectivities of a number of substrates, including the better anrf-selectivity of endo,endo-2,3-die hyl-l -norbomanone in comparison to that of en[Pg.71]

The reactions of P-donor nucleophiles with the metal carbonyl cluster Rh4COi2 have been studied over a considerable time period.It is widely accepted that the reaction is associative. This latest investigation is aimed at quantifying the effects of the electronic and steric properties of the nucleophiles upon the kinetic parameters. A rapid substitution reaction step using an excess of the nucleophile was monitored by SF spectrophotometry. Second-order rate constants were obtained from the variation of the pseudo-first-order rate constants with nucleophile concentration. Contributions to these constants from the properties steric effect, TT-activity, and, in addition, an aryl effect of the nucleophiles were assessed in a multi-parameter equation. The outcome is a successful understanding of the relative reactivities of many P-donors toward the rhodium cluster. The data were also represented by a three-dimensional potential energy surface. 

This chapter focused upon reactions at unsaturated centers alkenes, alkynes, arenes, and carbonyls. A large variety of additions and eliminations was examined. The complexity in the examples showed how diverse the possibilities are for additions and eliminations to such centers. One can have electrophilic, nucleophilic, and radical pathways for almost all reaction classes, and the dominant product depends upon the structures of the reactants and the experimental conditions. You should now be able to write the electron pushing for the standard reaction mechanisms (El, E2, SeAr, etc.), as well as be able to predict and examine experimentally the variations that are possible. Given this background on unsaturated centers, we turn our attention to reactions that occur at saturated centers, which is the first major topic of the next chapter. 

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