Dienophiles, phosphonation

The strongly dienophilic N-enoyl compounds (363) are readily prepared by direct -acylation (NaH, RCOCl or MeaAl, RC02Me) or via phosphonates (364) by means of a modified Wittig-Homer reaction. 

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. 

A novel sterically congested cliv-like receptor for dicationic quests, incorporating a hindered cyclophane possessing chiral spirobiindanol phosphonate and phosphate units (32) has been synthesised P-Nitrosophosphates (33) have been obtained and used as new N-O hetero-dienophiles in the Diels-Alder type reaction with a few selected 1,3-dienes to give highly functionalized cycloadducts (34). The latter can be directly transformed by... 

The phosphonodithioformate (336) has been used as an interesting hetero-dienophile in the Diels-Alder reactions with different dienes. A selective radical desulfanylation of the cycloadducts (337) using BusSnH leads to new (3,6-dihydro-2H-thiopyran-2-yl) phosphonates (338)(Scheme 90). ... 

Dienophilic reactivity has been observed in the Diels-Alder additions of esters of (2-methyl-l-propenyl)phosphonic acid to cyclopentadiene... 

A more readily available Fe-complex for asymmetric Diels-Alder reaction is from chiral hydrobenzoin.Dienophiles derived from f7/ ,61 )-l-pivaloyloxyspiro[4.4]nonan-6-ol 5 give chiral adducts on reaction with dienes. A representative of axially chiral dienophiles is 65 which gives Diels-Alder reactions with high endo- and diastereoselectivity. An access to dihydropyranyl ethers by the hetero-Diels-Alder reaction, C2-syiiunetric Cu(II) complexes such as and yttrium tri[(7 )-l,l -binaphth-2,2 -diyl]phosphonate are... 

Rudinskas, A.J., and Hullar, T.L., Phosphonic acid chemistry. Part 1. Synthesis and dienophilic properties of diethyl 2-formylvinylphosphonate and diethyl 2-formylethynylphosphonate, J. Org. Chem., 41, 2411, 1976. 

Dangyan, Y.M., Panosyan, G.A., Voskanyan, M.G., and Badanyan, S.O., Reactions of unsaturated compounds. Part 88. Vinylallenic phosphonates in cycloaddition reactions with unsymmetric dienophiles, Zh. Obshch. Khim., 53, 61, 1983 J. Gen. Chem. USSR (Engl. Transl.), 53, 47, 1983. 

It has recently been demonstrated in our own laboratory that negatively substituted olefins of the type known as dienophiles react smoothly with phosphite, phosphonite, and phosphinite esters in the presence of a suitable proton donor (123,127). With the use of phenol for this purpose, reactions are exceptionally clean and high yields may be realized. Some representative examples are included in Table I. While ethanol or methanol are often satisfactory substitutes for phenol, the yields of phosphonate are generally lower and side reactions often occur, possibly due to the lessened efficiency of alcohol as a protonating agent. Yields of phosphonate for reactions in ethanol are indicated in brackets in Table I. Thus, in addition to the expected phosphonate from reaction of acrylamide and triethyl phosphite in ethanol, there were also ob-... 

The simplest mechanism consistent with the experimental facts is depicted for 2-cyclopentenone in equation 12. While initial attack by the phosphorus reagent at the carbonyl (eqs. 13 and 14) is conceivable, subsequent rearrangement of phosphorus from oxygen to carbon via a phosphorane intermediate is not possible, due to the restricted geometry of the intermediate in equation 13. Since only the 7-ketocyclopentyl-phosphonate ester (72%) and none of the enol phosphate ester (eq. 13) or hydroxyphosphonate ester (eq. 14) were detected in the product, attack by phosphorus is exclusively at the terminal carbon atom of the conjugated system. It is reasonable to assume that a similar mechanism holds for the majority of dienophiles. 

Reactions and Properties of Phosphonic and Phosphinic Acids and their Derivatives.-The diastereoisomers of 3-benzyl-4-isopropyl-2-vinyl-l,3,2-oxazaphospholi-dine 2-oxide, derived from valinol, react as dienophiles with cyclopentadiene to give the 1 1 adducts (467). The (2. 45) and (2S.4S) compounds each give mixtures of cmio and... 

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... 

The trienamine-catalysed asymmetric Diels-Alder cycloaddition reaction of 2,4-dienals (77) with chiral phosphorous dienophiles (78) produced densely functionalized phosphonocyclohexene adducts (79) with excellent enantioselectivity (up to 99% ee) and good to high diastereoselectivity (up to >99 1) (Scheme 22). The thermal Diels-Alder reaction of l-phosphono-(3,4)-disubstituted-1,3-butadienes with maleimides and 4-phenyl-l,2,4-triazoline-3,5-dione produced polycyclic phosphonic acid derivatives. ... 

Phosphonate-substituted dienophiles exert a powerful directive influence in the Diels-Alder reaction, and the first of two examples reported this year which illustrates the effect is the reaction of the butenone (222) with either isoprene or acetoxybutadiene, giving products (223) and (224) respectively rather than those of the opposite regiochemistry usually found in such reactions. The dienophile (Et0)2P(0)CsCC0aEt has also been found to be highly regiospecific in Diels-Alder reactions, and has been applied to the synthesis of a number of aromatic phosphonates such as (225). ... 

Acetylenes activated by perfluoroalkyl and dialkyl phosphonate groups also show high reactivity as dienophiles (Scheme 4.6) [436]. 

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