Hetero-Diels-Alder reaction acyl phosphonates

The copper complex of these bis(oxazoline) compounds can also be used for hetero Diels-Alder reactions of acyl phosphonates with enol ethers.43 5 A favorable acyl phosphonate-catalyst association is achieved via complexation between the vicinal C=0 and P=0 functional groups. The acyl phosphonates are activated, leading to facile cycloaddition with electron-rich alkenes such as enol ethers. The product cyclic enol phosphonates can be used as building blocks in the asymmetric synthesis of complicated molecules. Scheme 5-36 shows the results of such reactions. 

TABLE 9.20. ENANTIOSELECTIVE HETERO-DIELS-ALDER REACTIONS OF a,P-UNSATURATED ACYL PHOSPHONATES... 

Evans has reported that the cationic C2-symmetric chiral Lewis acid Cu(ll)bis(oxazoline) complex promotes the hetero-Diels-Alder reaction of 0 ,/3-unsaturated acyl phosphonates with enol ethers to give the cycloadducts with excellent ee (Scheme 52). As well as simple dihydropyrans, various fused bis-dihydropyrans are also reported <1998JA4895, 2000JA1635>. 

The chiral bis(oxazoline)/Cu(II) complex with OTf or SbFg as a counter anion effectively promotes the enantioselective hetero Diels-Alder reaction of enol ethers with acyl phosphonates to give chiral enol phosphonates as synthetically useful chiral building blocks [64] (Eq. 8A.40). 

Inverse electron demand hetero-Diels-Alder reactions of acyl phosphonates or a-keto ester heterodienes and enol ethers are also catalyzed by (5, iS )-t-Bu-box complexes. High levels of enantioselectivity are obtained with y-alkyl-, -aryl-, -alkoxy-... 

Copper Lewis acids have also found utility in hetero-Diels-Alder reactions. In these transformations the Lewis acid can activate either the diene or the dienophile and both types of reaction have been reported. Evans et al. have evaluated unsaturated acyl phosphonates [95] and acyl esters (amides) [87] as dienes in hetero-Diels-Alder reactions. The reactions proceed with excellent chemical efficiency and high stereoselectivity with as little as 0.2 mol % of the catalyst (Sch. 50). The reaction tolerates a variety of substituents on the diene and the dienophile. A square-planar model 226 wherein the phosphonate and the carbonyl groups form a chelate with copper, and addition occurring from the less hindered face, accounts for the selectivity observed. It is interesting to note that the reaction of 185 with phosphonate 228 gives 230, an inverse-electron-demand product, in preference to the normal Diels-Alder adduct 229. This unusual reaction pathway has been attributed to the electron-withdrawing capacity of the phosphonate group. 

Evans, D.A., and Johnson, J.S., Catalytic enantioselective hetero Diels-Alder reactions of a,P-unsat-urated acyl phosphonates with enol ethers, J. Am. Chem. Soc., 120, 4895, 1998. 

The hetero-Diels-Alder reactions of acyl phosphonates with c-rich dienes, such as Danishefsky s diene and Brassard s diene, produced glycosyl-type phosphonates in moderate to good yields. The indium(III)-catalysed hetero-Diels—Alder reaction of a Brassard-type diene with aliphatic aldehydes produced /l-methoxy-y-methyl-a, -unsaturated (5-lactones in good yields (86%) and with high diastereo- and enantio- 0 selectivities. ... 

Chiral copper Lewis acids have also found broad utility in a variety of hetero Diels-Alder reactions. Examples in which the copper Lewis acid activates either the diene or dienophile component have been reported. Evans and coworkers utilized Cu(II)/BOX catalysts in hetero Diels-Alder reactions using unsaturated acyl phosphonates (272) or acyl esters as dienes (Scheme 17.62, Equation 17.8)... 

A range of substituents on the diene and the dienophile are tolerated and reactions proceed in high yields with high enantioselectivities. The authors have proposed a square-planar model (275) with acyl phosphonate or acyl ester coordinated to the Cu(II)/t-Bu-BOX (13) complex to account for the observed stereoselectivity. Stavenger and Schreiber also applied this approach to enan-tioselective hetero Diels-Alder reactions in a diversity-oriented synthesis of a library of dihydropyrancarboxamides [89]. Jorgensen and coworkers also reported Cu(II)/bisoxazoline-catalyzed hetero Diels-Alder reactions employing acyl esters... 

A bifunctional squaramide catalyst (460) has been utilised in the efficient and highly regio- and stereoselective synthesis of optically active dihydropyran phosphonates (457) by dual activation of both substrates used in the reaction. Thus, the hetero-Diels-Alder reaction of aliphatic and aromatic a,p-unsaturated acyl phosphonates (455) and a,(3-unsaturated aldehydes (456) afforded dihydropyran derivatives (457) in good yields ranging from 52% to 84% and up to 92% ee. The potential of the reaction has been also demonstrated by transformation of the products (457) into valuable and complex synthons (458) and (459) bearing five stereogenic centers (Scheme 138). ... 

Polat-Cakir and Demir have prepared glycosyl type phosphonates (744) and (745) via hetero Diels-Alder (HDA) reactions of acyl phosphonates... 

---