Dipropionate adducts

The BF OEta-catalyzed addition of crotyltri-n-butylstannane 10 (a 55 45 mixture of E- and Z-isomers was used in this experiment) to the ff-silyloxy aldehyde 97b furnishes the 5yn,.v> u-dipropionate adduct 106 with 95 5 diastereoselectivity. 

The tartrate-derived crotylboronate reagents are most useful in the context of double asymmetric reactions with chiral aldehydes [118, 203]. Equations (11.16)-(11.19) demonstrate the utility of ( )-219 and (Z)-213 in the synthesis of dipropionate adducts 105-108. 

Reaction of the /y-benzyloxy-o-methyl chiral aldehyde 97a with (/ )-crolylsi-lanes 217 (R = H, Et) under catalysis by TiC affords the ann,antt-dipropionate adduct 362 (Eq. (11.29)). The diastereoselectivity in this reaction is best explained by anti S e addition of the chiral crotylsilane to the least hindered face of the fi-alkoxy aldehyde chelate, as shown in the synclinal transition state 363. Finally, the anri.syn-dipropionate 364 may be obtained as the major adduct when aldehyde 97a is treated under the same conditions with the enantiomeric crotylsilane reagents (5)-217 (Eq. (11.30), R=Me, Et). This adduct should arise from the antiperiplanar transition state 365, where the anti S e facial selectivity of the crotylsilane reagent and the facial bias of the chiral aldehyde are maintained. In these cases, the factors that dictate the utilization of the synclinal vs the antiperiplanar transition states are (1) the requirement that a small substituent (H) occupy the position over the chelate ring, (2) that C-C bond formation occurs anti to the sterically demanding a-methyl group of the aldehyde and (3) the requirement for an anti Se mechanism, which dictates the stereochemistry of C(5) of the adducts 362 and 364. 

In a related manner, -keto imide 25 also functions as a versatile dipropionate reagent with three different stereoselective aldol reactions being reported by the Evans group (Scheme 9-9). Both syn aldol isomers, 26 and 27, are available from either the titanium or tin(II) enolates [14] and the anti adduct 28 can be accessed using the dicyclohexyl boron enolate [15], While a chiral auxiliary is present, it is the ketone a-stereocenter that controls the r-facial selectivity in these aldol reactions. 

In our synthesis, iterative aldol reactions of dipropionate reagent (R)-18 allowed for the control of the C3-C10 stereocenters (Scheme 9-72) [89]. Hence, a tin-mediated, syn aldol reaction followed by an anti reduction of the aldol product afforded 270. Diol protection, benzyl ether deprotection and subsequent oxidation gave aldehyde 271 which reacted with the ( )-boron enolate of ketone (/ )-18 to afford anti aldol adduct 272. While the ketone provides the major bias for this reaction, it is an example of a matched reaction based on Felkin induction from the... 

The TBS-protected (S)-a-methyl-j5-alkoxy aldehyde 97b reacts with the (R,R)-( )-crotylboronate 219 to give the syn,anf -dipropionate 108b as the major adduct... 

In reactions of a-methyl chiral aldehydes with achiral (Z)-crotylboronates, the anti-Felkin adduct (cf. 107b) is favored (for further discussion see Section 11.2) [3, 65]. In the double asymmetric reaction of 97b and (S,S)-213, the anti,syn-di-propionate 107b is obtained with high selectivity (selectivity=95 5). The stereochemistry of 107b is consistent with product formation via the matched anti-Felkin transition state 247. Finally, the, vyn,5y -dipropionate 106c is obtained as the major product from the mismatched reaction of the TBDPS-protected aldehyde 97c with (f ,R)-(Z)-213 this reaction, however, is not sufficiently stereoselective to be synthetically useful (selectivity = 64 36). The mismatched transition state... 

Reaction of the same aldehyde 97c with enantiomeric crotylsilanes (5)-217 (R=Me, Et) results in preferential formation of the syn,nnft-dipropionates 359. These adducts can arise either through the Felkin synclinal transition state 360 or the Felkin antiperiplanar transition state 361 (Eq. (11.28)). In the reactions of aldehyde 97c with both the (R)- and (S)-crotylsilane reagent 217, the major products result from crotylsilane addition to the aldehyde via the normally favored Felkin orientation in the transition state. The chirality of the crotylsilane and the stereo-electronic preference for anti S e addition then dictate the facial selectivity of the crotylsilane reagent, which is translated into the stereochemistry of the C(5) methyl substituent of the product. 

Dipropionates are available through the reaction of the (. -and (2)-crotylboronates 2 and 3 with a-methyl-P-hydroxy aldehydes. The syn,anti-dipropionate 43a emerges as the major product with 97 3 selectivity from the matched crotylation reaction of aldehyde 40a with (R,R)-2. This is the intrinsically favored adduct, and its formation can be rationalized via the Felkin transition state F. The antAanh-dipropionate 44b is the major adduct (selectivity = 90 10) of the mismatched reaction of aldehyde 40b and 2. Its formation can be rationalized via anti-Felkin transition state G and is an example of a reagent-controlled reaction. 

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