Controlled Carbonyl Addition Reactions

Furthermore, during the reaction of 2 (R = Bn) with enolsilane 1 in presence of SnCU, alcohol 5 was obtained as by-product in significant yield. 

Propose a reasonable reaction pathway to explain the formation of 5. 

Aldehyde 2 has a nicely positioned P-oxygen that may be able to coordinate the metal. Within this premise, the stereochemical outcome of the reaction would depend on the ability of the metal to coordinate both, the carbonyl oxygen and the P-oxygen, or just the carbonyl oxygen alone. 

Application of this model to aldehyde 2 results in conformation 10 fliat would lead to aldols 3 (Fig. 19.2). Compounds 3 are called Felkin products. This is the situation for the tin-promoted reaction. Therefore it is not necessary to proceed for the reaction with SnCU, as the simplest model perfectly explains the observed dia-stereoselectivity. 

The reaction with Me2AlCl follows a different pathway. If we apply the Felkin-Anh s model in this case the situation has to be entirely analogous to that depicted 

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Ketone 13 possesses the requisite structural features for an a-chelation-controlled carbonyl addition reaction.9-11 Treatment of 13 with 3-methyl-3-butenylmagnesium bromide leads, through the intermediacy of a five-membered chelate, to the formation of intermediate 12 together with a small amount of the C-12 epimer. The degree of stereoselectivity (ca. 50 1 in favor of the desired compound 12) exhibited in this substrate-stereocontrolled addition reaction is exceptional. It is instructive to note that sequential treatment of lactone 14 with 3-methyl-3-butenylmagnesium bromide and tert-butyldimethylsilyl chloride, followed by exposure of the resultant ketone to methylmagnesium bromide, produces the C-12 epimer of intermediate 12 with the same 50 1 stereoselectivity. 

The completion of the synthesis of the polyol glycoside subunit 7 requires construction of the fully substituted stereocenter at C-10 and a stereocontrolled dihydroxylation of the C3-C4 geminally-disub-stituted olefin (see Scheme 10). The action of methyllithium on Af-methoxy-Af-methylamide 50) furnishes a methyl ketone which is subsequently converted into intermediate 10 through oxidative removal of the /j-methoxybenzyl protecting group with DDQ. Intermediate 10 is produced in an overall yield of 83 % from 50) , and is a suitable substrate for an a-chelation-controlled carbonyl addition reaction.18 When intermediate 10 is exposed to three equivalents of... 

M. T. Reetz, Structural, Mechanistic, and Theoretical Aspects of Chelation-Controlled Carbonyl Addition Reactions, Ace. Chem. Res. 1993, 26, 462M68. 

Usefid reviews address alkyl zirconocene catalysts for the pol)mierisation of silanes to poly silanes by a a-bond metathesis mechanism, chiral titanates as promoters in aldol reactions, and MeTiCl3 as a reagent for chelate-controlled carbonyl addition reactions. 5 xhe reactions of terminally functionalized alkenes with zirconocene hydrides are reviewed. Thermochemical studies show that while the bond dissociation enthalpies of Zr—C6H13 and Zr— CgHjj in zirconocene systems are comparable, the insertion of cyclohexene into the Zr—bond is more exothermic than the insertion of hexene. 

Reetz MT. Strucmral, mechanistic, and theoretical aspects of chelation-controlled carbonyl addition reactions. Acc. Chem. Res. 1993 26 462 8. 

There are a number of powerful synthetic reactions which join two trigonal carbons to form a CC single bond in a stereocontrolled way under proper reaction conditions. Included in this group are the aldol, Michael, Claisen rearrangement, ene and metalloallyl-carbonyl addition reactions. The corresponding transforms are powerfully stereosimplifying, especially when rendered enantioselective as well as diastereoselective by the use of chiral controller groups. Some examples are listed in Chart 20. 

Carbonyl-addition reactions continue to be the speciality of the French group interested in germylphosphines. Thus the germaphospholan (68) adds to aldehydes to give diastereomeric products (69).62 Steric factors are believed to control the mode... 

M. T. Reetz, Chelation or non-chelation control in addition reactions of chiral a- and (3-alkoxy carbonyl compounds, Angew. Chem. Int. Ed. Engl 23 556 (1984). 

Chelation or Non-chelation Control in Addition Reactions of Chiral a and B-Alkoxy Carbonyl Compounds"... 

O CONTENTS Introduction to Series An Editor s Foreword, Albert Padwa. Introduction, Timothy J. Mason. Historical Introduction to Sonochemistry, D. Bremner. The Nature of Sonochemical Reactions and Sonoluminescence, M.A. Mar-guli. Influence of Ultrasound on Reactions with Metals, B. Pugin and A.T. Turner. Ultrasonically Promoted Carbonyl Addition Reactions, J.L. Luche. Effect of Ultrasonically Induced Cavitation on Corrosion, W.J. Tomlinson. The Effects of Ultrasound on Surfaces and Solids, Kenneth S. Suslick and Stephen J. Doktycz. The Use of Ultrasound for the Controlled Degradation of Polymer Solutions, G. Price. 

The most intensely studied aldol addition mechanisms are those beUeved to proceed through closed transition structures, which are best understood within the Zimmerman-Traxler paradigm (Fig. 5) [Id]. Superposition of this construct on the Felkin-Ahn model for carbonyl addition reactions allows for the construction of transition-state models impressive in their abiUty to account for many of the stereochemical features of aldol additions [50a, 50b, 50c, 51]. Moreover, consideration of dipole effects along with remote non-bonding interactions in the transition-state have imparted additional sophistication to the analysis of this reaction and provide a bedrock of information that may be integrated into the further development and refinement of the corresponding catalytic processes [52a, 52b]. One of the most powerful features of the Zimmerman-Traxler model in its application to diastereoselective additions of chiral enolates to aldehydes is the correlation of enolate geometry (Z- versus E-) with simple di-astereoselectivity in the products syn versus anti). Consequently, the analyses of catalytic, enantioselective variants that display such stereospecificity often invoke closed, cyclic structures. Further studies of these systems are warranted, since it is not clear to what extent such models, which have evolved in the context of diastereoselective aldol additions via chiral auxiliary control, are applicable in the Lewis acid-catalyzed addition of enol silanes and aldehydes. 

The class of ene reactions involving a carbonyl compound as the enophile, which we refer to as the carbonyl-ene reaction [8c], constitutes a useful synthetic method for the stereo controlled construction of carbon skeletons using a stoichiometric or catalytic amount of various Lewis acids (Scheme 1) [9,10]. From the synthetic point of view, the carbonyl-ene reaction should, in principle, constitute a more efficient alternative to the carbonyl addition reaction of allylmetal... 

Angew Int 23 556 (1984) (chelation and non-cheladon control in addition reactions of chiral - and / -alkoxy carbonyl compounds) 30 49 (1991) (enandoselectivity)... 

Another factor that affects stereoselectivity of carbonyl addition reactions is chelation If an a or p substiment can form a chelate with a metal ion involving the carbonyl oxygen, the stereoselectivity is usually governed by the chelated conformation. Complexation between a donor substituent, the carbonyl oxygen, and the Lewis acid can establish a preferred conformation for the reactant, which then controls reduction. Usually hydride is delivered from the less sterically hindered face of the chelate. 

Up to this point, we have considered cases in which there is a single major influence on the stereo- or enantioselectivity of a reaction. We saw examples of reactant control of facial selectivity, such as 1,2- and 1,3-asymmetric induction in carbonyl addition reactions. In the preceeding section, we considered several examples in which the chirality of the catalyst controls the stereochemistry of achiral reagents. Now let us consider cases where there may be two or more independent influences on stereoselectivity, known as double stereodijferentiation For example, if a reaction were to occur between two carbonyl compounds, each having an a-stereocenter, one carbonyl compound would have an inherent preference for R or S product. The other would have also have an inherent preference. These preferences would be expressed even toward achiral reagents. 

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