Nucleophilic addition to carbonyl compound

Alkyl substituents accelerate electrophilic addition reactions of alkenes and retard nucleophilic additions to carbonyl compounds. The bonding orbital of the alkyl groups interacts with the n bonding orbital, i.e., the HOMO of alkenes and raises the energy (Scheme 22). The reactivity increases toward electron acceptors. The orbital interacts with jt (LUMO) of carbonyl compounds and raises the energy (Scheme 23). The reactivity decreases toward electron donors. 

These reactions comprise nucleophilic SN2 substitutions, -eliminations, and nucleophilic additions to carbonyl compounds or activated double bonds, etc. They involve the reactivity of anionic species Nu associated with counterions M+ to form ion-pairs with several possible structures [52] (Scheme 3.4). 

Nucleophilic Additions to Carbonyl Compounds Saponification of hindered aromatic esters... 

Dunitz (180) has collected X-ray crystallographic data for carbonyl compounds that possess nucleophilic atoms in proximity to C=0, and has postulated that such molecules can be used as models for the incipient transition state (reaction coordinate) for the nucleophilic addition to carbonyl compounds. Atrop-isomeric compounds have the potential, by providing a variety of such data, for understanding the incipient transition states. For example, the interaction found in the 1,4-dimethoxy-9-(2-acyloxyethyl)triptycenes (130) can be viewed as a model for SN2 type reactions where the acyloxy group is the leaving group and the methoxy is the nucleophile. In an extreme case of this sort, cyclization actually takes place. Such an example has been reported (181). 

The most important application of organolithium reagents is their nucleophilic addition to carbonyl compounds. One of the simplest cases would be the reaction with the molecule CO itself, whose products are stable at room temperature. Recently, it was shown that a variety of RLi species are able to react with CO or f-BuNC in a newly developed liquid xenon (LXe) cell . LXe was used as reaction medium because it suppresses electron-transfer reactions, which are known to complicate the reaction . In this way the carbonyllithium and acyllithium compounds, as well as the corresponding isolobal isonitrile products, could be characterised by IR spectroscopy for the first time. 

Nucleophilic addition to carbonyl compounds or imines are classified based on the nucleophilicity of the nucleophile and/or electrophile. 

Nucleophilic Addition to Carbonyl Compounds and -Unsaturated Carbonyl Compounds.—Although the reactions of 17-oxo-steroids with various carbanion reagents are reported to have varying success/ the use of alcohols or DMF as solvents appears to facilitate the Wittig-Horner reaction/ For example, the ketone (97) was converted with (Et0)2P0CHC02Et into the E-ethyl ester (98) in... 

Carbonyl hydration has been extensively studied primarily because it serves as a model for a number of important reactions, nucleophilic additions to carbonyl compounds foremost around them. While for most common carbonyl compounds the equilibrium lies far to the left (in favor of the carbonyl compound), it is possible to find compounds where the reverse is true. Because there are ample experimental data, it should be possible to identify structural and/or other characteristics which drive the equilibrium one way or the other. Alternatively, quantum chemical models can be employed. 

A formal asymmetric nucleophilic addition to carbonyl compounds is achieved by Trost and his co-workers in the allylic alkylation of acylals of alkenals. An excellent enantioselectivity is observed in this alkylation. The starting acylals are easily prepared by the Lewis-acid catalyzed addition of acid anhydrides to aldehydes, by use of Trost s ligand 118 (Scheme 13), where various carbon-centered nucleophiles are available (Scheme l4),101,101a-10lc Asymmetric synthesis of some natural products is achieved according to this procedure. 

Allyl- and vinylsilane chemistry was one of the first areas of reagent synthesis impacted by CM methodology. Allylsilanes are commonly employed in nucleophilic additions to carbonyl compounds, epoxides, and Michael acceptors (the Sakurai reaction) vinylsilanes are useful reagents for palladium-coupling reactions. As the ubiquitous application of CM to this substrate class has recently been described in several excellent reviews, this topic will not be discussed in detail, with the exception of the use of silane moieties to direct CM stereoselectivity (previously discussed in Section 11.06.3.2). 

Electronic and conformational effects on jt-facial stereoselectivity in nucleophilic additions to carbonyl compounds have been studied by the use of RHF/3-21G and RHF/6-31G methods ". Figure 10 shows a comparison of predicted and experimental selectivities for methyl Grignard additions. Satisfactory agreement of the ratios of anti and equatorial attacks of MeMgX on the carbonyl carbon atoms was reported. 

Lefour, J.-M. and Loupy, A. (1978) The effect of cations on nucleophilic additions to carbonyl compounds carbonyl complexation control versus ionic association control. Application to the regioselectivity of addition to a-enones. Tetrahedron. 34. 2597. 

Coordinated nitrogen donor atoms can be involved in chelate-forming template reactions by virtue of nucleophilic addition to carbonyl compounds. An early and rather specific example does not allow the possibility of elimination following the addition step (equation 46).171 More recent work on ruthenium(III) and osmium(III) results in the formation of a-diimine chelate rings... 

The rates of nucleophilic additions to adamantanone have been studied in an attempt to determine the structure of the transition states of nucleophilic additions to carbonyl compounds in general. The kinetic analysis suggests that the transition states of borohydride reductions of ketones are product-like while for bisulfite additions the transition states are reactant-like 367). A similar analysis 36 ) of data obtained for photo-initiated oxetane formation (trans-dicyanoethylene + carbonyl compound) 3681 indicates a reactant-like transition state. 

Hydroboration of allenes 65 with pinacolborane in the presence of Pt(DBA)2 and a trialkylphosphine provides either the allyl boronate 66 or the vinyl boronate 67 regioselectively, depending on the stereoelectronic factors of the phosphine employed (Equation 2) <1999CL1069>. Allyl and vinyl boronates are synthetically important because of their ability to undergo nucleophilic addition to carbonyl compounds as well as transition metal-catalyzed cross-coupling. 

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... 

Following this review, we will consider the largest and most versatile group of alcohol syntheses nucleophilic additions to carbonyl compounds. 

III. NUCLEOPHILIC ADDITION A. Nucleophilic Addition to Carbonyl Compounds... 

Wu, Y. D. Houk, K. N. Electronic and conformational effects on Jt-facial stereoselectivity in nucleophilic additions to carbonyl compounds, J. Am. Chem Soc. 1987, 908-910. 

Wong, S. S. Paddon-Row, M. N. The importance of electrostatic effects in controlling 7i-facial stereoselectivity in nucleophilic additions to carbonyl compounds An ab initio MO study of a prototype chelation model, J. Chem. Soc. Chem. Commun. 1991, 327-330. 

Oxathiane (12) has been shown to be an efficient chiral auxiliary in the nucleophilic addition to carbonyl compounds, ... 

This chapter includes examples of aliphatic nucleophilic substitution at both sp and sp centers, aromatic nucleophilic substitution, E2 elimination, nucleophilic addition to carbonyl compounds, 1,4-addition to a, -unsaturated carbonyl compounds, and rearrangements promoted by base. 

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