Allylmetal reagent

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

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. 

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). 

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. 

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. 

The reactions of allylmetal reagents with carbonyl compounds and imines have been extensively investigated during the last two decades [1], These carbon—carbon bondforming reactions possess an important potential for controlling the stereochemistry in acyclic systems. Allylmetal reagents react with aldehydes and ketones to afford homo-allylic alcohols (Scheme 13.1), which are valuable synthetic intermediates. In particular, the reaction offers a complementary approach to the stereocontrolled aldol process, since the newly formed alkenes may be readily transformed into aldehydes and the operation repeated. 

Indolizidine alkaloids. The key step in a new stereocontrolled synthesis of these alkaloids, such as castanospermine (5), depends upon the diastereoselective reaction of an azagluco aldehyde with allylmetal reagents catalyzed by Lewis acids (12, 21-22). Thus reaction of allyltrimethylsilane with the aldehyde 1 and TiCL, (excess) in CH2C12 at - 85° results in the product 2, formed by selective chelation of the ot-amino aldehydo group with TiCl4. The product can be converted into 5... 

Enantioselective carbonyl allylation is one of the most broadly utilized transformations in synthetic organic chemistry (For reviews on enantioselective carbonyl allylation, see [199-204]). Shortly after the first reports of carbonyl allylation employing isolable aUylboron and allylsUicon reagents by Mikhailov and Bubnov [205] and Hosomi and Sakurai [206], respectively, enantioselective carbonyl allylations were reported by Hoffmann (see footnote 19, [207]). While the design of increasingly effective chiral allylmetal reagents continues 207-220], this... 

Fig. 2 Selected examples of chiral allylmetal reagents for enantioselective carbonyl allylation...

For selected examples of catalytic asymmetric carbonyl allylation employing allylmetal reagents, see [221-224]. 

In addition to the predominant allyl and crotyl reagents, a large nnmber of allylic borane 1 and boronate derivatives 2 (Eq. 1) with varions snbstitnents (R -R" ) have been reported. Interested readers can refer to the comprehensive Tabnlar Snrvey at the end of this monograph, which covers the literatnre np to the end of 2005. Several reviews on allylic boron componnds and other allylmetal reagents and their additions to carbonyl compounds and imines have been written prior to this one," " and these sonrces may be consnlted if a more in-depth historical perspective is desired. 

Table 3 Addition of Allylmetal Reagents to a-Amino Aldehydes124 32331"...

Addition of Organometallic Reagents to I mines 8.8.2.1 Allylmetal Reagents... 

The stereoselective addition of allylmetal reagents to imines is one of the most important reactions in organic synthesis for carbon-carbon bond formation [118, 129] (Scheme 8.59). 

Reaction of Heterosubstituted Allylmetal Reagents with Electrophiles... 

Asymmetric allylation is a valuable method for constructing chiral functionalized structures, and many chiral allylmetal reagents directed toward a high level of asymmetric induction have, therefore, been designed and synthesized. Although for some of these good to excellent enantio- and diastereoselectivity are obtained in reactions with achiral aldehydes, we developed the first novel method for a catalytic process in 1991 [49a]. 

The high yields and the excellent regioselectivities of this hydromagnesation, as well as the versatility of the resultant allylmetal reagents [34,35], make this method valuable in organic synthesis. 

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