Allylmetal reagents, reactions aldehydes

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. 

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... 

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 analysis of open transition states in the chelate-controlled allylation reactions of a- and ff-alkoxy aldehydes with Type II allylmetal reagents is much simpler (Fig. 11-5). In these cases, only the synclinal transition state 21 and the antiperiplanar transition state 22 are considered as viable possibilities. Other possible transition states have been eliminated because of the perceived requirement that... 

Reactions of Achiral Type I and Type III Allylmetal Reagents with Chiral Aldehydes... 

In the reactions of Type II allylmetal reagents with chiral aldehydes, y -alkoxy substituents on the aldehyde can exert a strong influence on the reaction, much more so than in reactions of Type I allylmetal reagents. Reetz and co-workers reported that the BF3-OEt2-catalyzed allylation reaction of the /f-benzyloxy aldehyde 130 with allyltrimethylsilane 131 is selective for the, 3-anti diol 132 (Eq. (11.7)) [92]. Evans and co-workers sub.sequently rationalized this result by invoking tran-... 

As the size of the allylmetal reagent increases, 1,2-induction plays an increasingly important role. This is illustrated in Eqs. (11.10) and (11.11), where the ( -silyloxyallyl)stannane 113 gives high levels of stereoselectivity for the Felkin dia-stereomer 141 with the 2,3-anti aldehyde 135, but poor diastereoselectivity for the Felkin diastereomer 143 with the 2,3-syn aldehyde 138 (ratio = 59 32 9) [93]. Note that in this case the Felkin isomer 143 predominates vs the preferential formation of the anti-Felkin isomer in Eq. (11.9), thus highlighting the role of the steric demands of the reagent in determining the overall reaction stereoselectivity. 

The ( -y-(silyl) allyl boronates 47 and 48 were subsequently introduced in order to access more highly oxygenated aldehyde addition products. For example, the allylic silane addition products can undergo subsequent oxidation to provide 1,2- and 1,4-diol products. The allylsilane products are also allylmetal reagents Roush and co-workers have demonstrated their ability to undergo addition reactions with Lewis acid activated aldehydes to form tetrahydrofuran products. ... 

If the presence of sensitive functional groups poses problems of chemoselectivity in the use of hard allylmetal reagents, allylboronate derivatives can also be accessed by transmetallation of allyltin species with boron halides [29], This approach was used by Corey in the synthesis of chiral bis(sulfonamido)boron reagents (Section 6.3.1.3) [30]. Recently, Williams and co-workers employed this mild approach to synthesize the highly functionalized allylboron reagent 9, which was employed in a key aldehyde allylboration reaction en route to the total synthesis of leucasdandrolide A (Equation 5) [31]. 

Another variation on the reaction involves Lewis acid exchanges with the BusSn moiety to form transient allylmetal species which then add to the aldehyde through a cyclic transition state (Eq. 3) [4]. These additions proceed under mild conditions owing to the strong affinity of the electron-deficient metal of the allylic MX , reagent for the carbonyl oxygen. 

Finally, the allylmetal aldehyde addition can also operate under the influence of stereocontrolling reagents, in particular, chiral Lewis acids and related activators (Eq. (10.6)). In these cases the stereochemical influence on the steric course of the reaction is due to a non-covalently bound agent that is found in neither the educts or products. Thus, the term external stereoselection will be used to describe the enantiofacial outcome at the newly formed stereogenic centers. 

In the following Sections we review the reactions of chiral allylmetal and allenylmetal reagents and their application to the synthesis of complex natural products. These reagents are useful for the enantioselective allylation of achiral aldehydes... 

The allylation reactions of carbonyl compounds catalyzed by chiral Lewis acids represent a powerful new direction in allylmetal chemistry. Yamamoto and coworkers reported the first example of the catalytic enantioselective allylation reaction in 1991, using the chiral (acyloxy)borane (CAB) catalyst system (see below) [288]. Since then, several additional reports of the catalytic allylation reaction have appeared. To date, the most effective catalyst systems reported for the enantioselective reaction of aldehydes and Type II allyl- and crotylstannane and silane reagents include the Yamamoto CAB catalyst and catalysts complexes composed of various Lewis acidic metals and either the BINOL or BINAP chiral ligands [289-293]. Marshall and Cozzi have recently reviewed progress in the enantioselective catalytic allylation reaction [294, 295]. 

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