Crotylmetal reagent

Figure 11-5. Mechanisms of allylation reactions of type II crotylmetal reagents with internally chelated aldehydes.

Hoffmann (with aldehydes 55a,c and d), Mulzner (with aldehyde 55b) and Wuts (with aldehyde 55e) subsequently reported similar findings in the crotylation reactions of a-heteroatom-substituted aldehydes with the ( )- and (Z)-crotylmetal reagents (Tables 11-3 and 11-4) [68-70]. These data, together with the results summarized in Table 11-2, clearly demonstrate that steric effects play a larger role in determining reaction diastereoselectivity than do. stereoelectronic effects. 

The 4,5-anti diastereomer (formally the Felkin product) predominates when the aldehyde a-heteroatom substituent is larger than the aldehyde R group with both the ( )- and (Z)-crotylmetal reagents (see aldehydes 55b and 55c, Tables 11 -3 and 11-4). However, when the R substituent is larger than the heteroatom, X, as is the case with aldehyde 55e, the ( )-crotylboronate reagent strongly favors formation of the 4,5-syn adduct 57e, formally the anti-Felkin product (Table 11-3). 

Table 11-3. Reactions of a-heterosubstituted aldehydes with ( )-crotylmetal reagents.

The stereochemical outcome of the reactions of a-alkoxy aldehydes with Type 1 (Z)-crotylmetal reagents can be rationalized through the competition between transition states 65 and 66, which lead to the 4,5-anti and 4,5-5yn adducts, 59 and 60, respectively (Fig. 11-9) [67], The Comforth [71] transition state 65 is favored when R is sterically larger than X since, in this transition state, R occupies the least sterically demanding position, anti to the forming C-C bond. Conversely, transition state 66 should be favored when X is much larger than R. 

Figure 11-9. Reactions of a-heteroatom aldehydes with (Z)-crotylmetal reagents.

The crotylation reactions of a-methyl chiral aldehydes (e.g. 97) with Type II crotylmetal reagents can give up to four products (e.g., 105-108). The syn,syn- A-duct 106 and the 3,4-.vyn-4,5-anh diastereomer 107 can be obtained with useful levels of diastereoselectivity via the reaction of 97 with the achiral ( )- and (Z)-crotyltri-u-butylstannanes 10 under appropriate conditions (Table 11-8) [53]. 

From these examples it is clear that the principles of acyclic stereocontrol that govern the allylation reactions of achiral Type II allyl- and crotylmetal reagents with chiral aldehydes can be used to excellent advantage in the stereoselective synthesis of natural products. In the following section, the factors that influence the stereoselective formation of cyclic compounds in the ring-closing allylation reaction are discussed and selected synthetic applications are reviewed. 

The synthesis and use of tartrate-modified allylboronate 1 was first reported by Roush and co-workers in 1985. The synthesis and use of the corresponding (E)- and (. -crotylboronate reagents 2 and 3 was published by Roush and co-workers shortly thereafter. The ease of synthesis, stability and efficient reactivity of these reagents offers advantages over many other allyl- and crotylmetal reagents. Roush and co-workers have extensively explored the enantioselective allylations with achiral aldehydes as well as the... 

In reactions of a-methyl chiral aldehydes with (.. -enolates and Type (2)-crotylmetal reagents like 3, the anti-Felkin addition product is favored due to unfavorable syn-pentane interactions in the Felkin transition state. Thus, in the matched reaction, the (S,5)-3 reagent reacts with aldehyde 40a to provide the anh, syn-dipropionate 45 with 95 5 selectivity. The stereochemical outcome of the reaction can be rationalized by anti-Felkin transition state H, where the nucleophile must approach near the methyl substituent. The mismatched reaction between aldehyde 40b and (R,R)-3 provides a mixture of dipropionates where the syn,syn-dipropionate 46 is only modestly favored (64 36 = sum of all other diastereomers). Transition state I, that rationalizes the formation of the major product, is less favorable as the nucleophile must approach the carbonyl carbon past the larger R substituent. 

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