Allylmetals

Allylic metal compounds useful for further transformations can be prepared by Pd-catalyzed reactions of allylic compounds with bimetallic reagents. By this transformation, umpolung of nucleophilic 7r-allylpalladium complexes to electrophilic allylmetal species can be accomplished. Transfer of an allyl moiety from Pd to Sn is a typical umpolung. 

The nucleophilic addition of unsubstituted and carbon- or hetero-substituted allylmetals to carbonyl compounds is a straightforward step in addition to the C-C bond formation, the introduction of further functionality to the molecule is achieved. 

For a successful application in synthesis, several problems have to be solved regioselectivity, whether the C-C bond is formed with the 1- or 3-position in an unsymmetrical ambident anion, EjZ selectivity in the formation of the double bond, and simple diastereoselectivity, since two new stereogenic centers are created from prostereogenic compounds. Further, different types of induced stereoselectivity or enantioselectivity may be required. Allylmetals with a wide choice of substituents are accessible by various methods (Sections D. 1.3.3.3.1.-10.). 

The action of a (constitutionally and configurationally homogeneous) 1,3-disubstituted allylmetal on a prostereogenic carbonyl compound can give rise to up to four racemic diastereomers with the relative configurations (Z)-anti, (Z)-syn, (E)-anti and (E)-syn of one particular regioisomer. 

The intention of this section is to assist the potential user to choose the optimal allylmetal reagent in carbonyl addition reactions. 

Furthermore, being a member of the family of nonprostereogenic allylmetals, 2-(alkoxy- or alkylaminocarbonyl)-2-propenyl reagents offer the possibility of introducing the a-methylene-propanoic acid /f-enolate to aldehydes. 

Alkyl-substituted allylmetals 1 usually cover the synthon A. Since oxidative cleavage of the C-C double bond in the products formed can be readily achieved, such reagents are often used as equivalents for the appropriate cnolatc synthons B and C or /1-hydroxycarbonyl anions D. Subsequent hydroboration extends their scope on y-hydroxyalkyl anions E. 

Allylmetal reagents which hear alkyl or aryl groups at both termini are stereogenic and usually add aldehydes w ith a high degree of reagent-induced stereoselectivity (Section D.3.3.1.5.1.). Some of these reagents have been prepared in enantiomerically enriched form and used in enantioselective synthesis. Table 4 collects some representative examples. 

For the stereoselective construction of a structural unit of type 1 from aldehydes or ketones, the synthon 2 is required. It is delivered by the /-hetero-substituted allylmetal (E)- or (Z)-3 with allylic inversion. 

Allyl anion synthons A and C, bearing one or two electronegative hetero-substituents in the y-position are widely used for the combination of the homoenolate (or / -enolate) moiety B or D with carbonyl compounds by means of allylmetal reagents 1 or 4, since hydrolysis of the addition products 2 or 5 leads to 4-hydroxy-substituted aldehydes or ketones 3, or carboxylic acids, respectively. At present, 1-hetero-substituted allylmetal reagents of type 1, rather than 4, offer the widest opportunity for the variation of the substitution pattern and for the control of the different levels of stereoselectivity. The resulting aldehydes of type 3 (R1 = H) are easily oxidized to form carboxylic acids 6 (or their derivatives). 

Table 6. Synthons and Reagents for Carbonyl Addition to y-, at,y- and y,y-IIetero-Substituted Allylmetals...

Investigation of the configurational stability of allylmetals 2a, prepared by means of Rieke metals from geometrically pure l-chloro-2-decenes 1 a in THF, showed that the (Z)- and (ZT)-lithium, -sodium, and -potassium derivatives preserve the configuration of the precursors to a preparatively useful extent below — 90°C, — 50°C, and >0°C, respectively. For the pairs of 3,7-dimethyl-2,6-octadienyl derivatives (Z)- and ( )-2b, which differ less in their thermodynamic stability, the respective temperatures are — 60 °C, — 40 °C and >0°C124. 

A large number of publications appeared on these aspects5, but most of these studies did not address stereochemical questions. In most cases, a given synthetic problem can be better solved by other allylmetals. Grignard reagents have some importance as intermediates for the preparation of allylboronates (Section D.1.3.3.3.3.2.1.), allylsilanes (Section D.1.3.3.3.5.2.L), allyl-stannanes (Section D. 1.3.3.3.6.2.1.1.), or allyltitanium derivatives (Section D.I.3.3.3.8.2.). 

Allylboron compounds have proven to be an exceedingly useful class of allylmetal reagents for the stereoselective synthesis of homoallylic alcohols via reactions with carbonyl compounds, especially aldehydes1. The reactions of allylboron compounds and aldehydes proceed by way of cyclic transition states with predictable transmission of olefinic stereochemistry to anti (from L-alkene precursors) or syn (from Z-alkene precursors) relationships about the newly formed carbon-carbon bond. This stereochemical feature, classified as simple diastereoselection, is general for Type I allylorganometallicslb. 

Allylsilanes are readily available by silylation of allylmetal reagents. If the allylmetal reagent is unsymmetric, mixtures of regioisomers are usually obtained1,8. 

Symmetric allylstannanes are readily available by stannylation of allylmetal reagents3,4. 

Lewis acids, particularly the boron trifluroride diethyl ether complex, are used to promote the reaction between allyl(trialkyl)- and allyl(triaryl)stannanes and aldehydes and ketones52-54. The mechanism of these Lewis acid promoted reactions may involve coordination of the Lewis acid to the carbonyl compound so increasing its reactivity towards nucleophilic attack, or in situ transmetalation of the allyl(trialkyl)stannane by the Lewis acid to generate a more reactive allylmetal reagent. Which pathway operates in any particular case depends on the order of mixing of the reagents, the Lewis acid, temperature, solvent etc.55- 58. 

As a result of additional 1.3-diaxial interactions, involving the C-l position of the allylmetal moiety in the chair transition state 7, a boat transition state 8 has been proposed, to provide amine 6. 

Mechanistic Discussion. For the mechanism of the metal-mediated allylation reaction in aqueous media, Li proposed a carbanion-allylmetal-radical triad (Figure 8.1) in which the specific mechanism of the... 

A mechanistic picture which reconciles the experimental results is given in Scheme 24. It is assumed that both the heteroatom and the double bond of the allyl halide compete for an electrophilic metal carbene. Heteroatom attack yields a metalated ylide 129, which may go on to ylide 131 by demetalation and/or to allylmetal complex 130. Symmetry-allowed [2,3] rearrangement of 131 accounts for product 132, and metal elimination from 130 gives rise to products 132 and 133, corresponding to [2,3] and [1,2] rearrangement, respectively, as well as haloacetate (if R3 = CHc ). 

Metal-mediated and -catalyzed [3 + 2 + 2]-higher-order cycloaddition reactions have also proved to be viable and mechanistically novel methods for the synthesis of seven-membered rings. The reported [3 + 2 + 2]-cycloadditions of allyliridium (Equation (30)),139 -allylcobalt (Scheme 47),140 and allylmanganese (Equation (31 ))141 complexes with alkynes involve the reaction of preformed allylmetal complexes with two separate alkynes, leading to a cycloheptadiene-metal complex. 

Etherification with 7r-Allylmetals Generated from Allylic Alcohol Derivatives 657... 

Although transition metal-catalyzed allylic alkylation has become one of the most powerful methods in chemical synthesis, the formation of ether bonds using this process has been slow to evolve.119-121 The main reasons for this disparity are the lower nucleophilicity and higher basicity of oxygen nucleophiles, particularly those derived from aliphatic alcohols, compared to their carbon or nitrogen analogs. However, this notion has rapidly been revised, as recent advances in the O-allylation area have largely addressed the issue of the reactivity mismatch between the hard alkoxide and the soft 7r-allylmetal species to provide a considerable body of literature. 

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