PTAD

Palladium-catalyzed hydroarylation of sterically hindered PTAD adduct 157 with aryl halides in the presence of triphenylarsine, sodium acetate, and DMSO provides a 1 1 mixture of 170 and 171. The same reaction done with sodium fluoride and formic acid provides mixtures containing 171 as the major product. Apparently, the use of sodium fluoride as a base allows the selective formation of the opening products 171 in good yields (Equation 19). Similarly, the 2,3-phthalazine-l,4-dione adduct 172 provides the corresponding products 173 and 174 (Equation 20) <2002AGE3375>. 

PTAD reacts with cyclopropanaphthalene 352 to give 77% yield of 353 (Equation 49). Attempts to hydrolyze the urazole ring failed <1995T10979>. 

Similar ring-opening reaction leading to a 4 1 mixture of 355 and 356 occurs when cyclopropane derivative 354 is treated at room temperature with PTAD. The products formed are not stable and only the products of their hydrolysis, 357 and 358, respectively, are obtained (Scheme 53) <1996JCM82>. 

While unsubstituted imidazo[l,5- ]pyridine when treated with MTAD and PTAD gives unstable 1 2 adducts, compounds 386 under the same conditions provide good yields of 387 (Equation 54) <1995JHC1525>. 

Reaction of ester 521 with PTAD gives a single adduct 522, formed by the addition of the dienophile syn to the methoxycarbonyl group. In contrast, the free diol 518 provides a mixture of adducts 519 and 520 in a 1 6 ratio. This result can be rationalized by a hydrogen bonding of the hydroxy groups with the dienophile (Scheme 88) <1995J(P1)2647>. 

Ferrocenyl trienes 539 treated with PTAD in benzene at 0 °C form the Diels-Alder monoadducts 540 in virtually quantitative yield (Equation 72) <1999JOM(579)30>. 

Diels-Alder cycloadditions of sila- and germa[3]radialenes 541 with MTAD or PTAD provide the corresponding products 542 (Equation 73) <19930M1996, 1994AG723>. Similarly, phospha derivative 543 with MTAD gives 544 (Equation 74). On the other hand, the same reaction of cyclic 545 with MTAD is slower and the formed reaction mixture contains only small amount of a product probably analogous to 544 and compound 546 as the major product (Equation 75) <2000JA12507>. 

TADs, especially PTAD and MTAD, have also been used in preparation of some stereocontrolled complex libraries <2005JOC6474>. 

Compounds 575, obtained by the Stille coupling reaction, react with PTAD to give high yields of the Diels-Alder products 576 obtained with good to excellent asymmetric induction (Equation 81) <1995SL1264>. 

Dienes 581 and 583 undergo smooth Diels-Alder cycloaddition with a wide range of dienophiles affording the corresponding products. Their reaction with PTAD gives the respective products 582 and 584 with complete Jt-facial selectivity (Equations 82 and 83) <2005CEJ5136>. 

The readily available enantiopure acyclic hydroxy 2-sulfinyl butadiene 585 undergoes a highly face-selective Diels-Alder cycloaddition with PTAD to generate the densely functionalized cycloadduct 586 (Equation 84). The complete reversal of facial selectivity is observed when sulfonyl derivative 587 is treated with PTAD under identical conditions (Equation 85). These results demonstrate that the sulfinyl functionality is not just synthetically useful but also an extremely powerful element of stereocontrol for intermolecular Diels-Alder cycloadditions. On the other hand, the corresponding ( , )-hydroxy-2-sulfinyldienes treated with PTAD affords the cycloadducts in high yield but with moderate 7i-facial selectivity <1998CC409, 2005CEJ5136>. 

Similarly, /V-sulfonyl-protected vinylimidazole 597 reacts with PTAD to provide the cycloaddition reaction product 598 which easily undergoes the retro-Diels-Alder reaction upon heating or with acid treatment. The primary product is easily isomerized using a base to the aromatized condensed imidazole 599 (Scheme 95) <1998TL4561>. 

The alkenylchromone 600 when treated with PTAD in dichloromethane at room temperature affords fused tetracycle 601 in 92% yield (Equation 89) <2002J(P1)2799>. The same treatment of 3-substituted xanthones 602 with PTAD or MTAD gives the corresponding adducts 603 in nearly quantitative yields (Equation 90) <1998J(P1)1547>. Both epimers at C-12a result from a lack of diastereofacial control in the cycloaddition, a feature which is characteristic of the behavior of RTADs with 5-substituted cyclohexa-1,3-dienes <1980JOC5105>. 

The fact that PTAD readily reacts with 5,7-steroidal dienes to form the Diels-Alder adducts, whereas the isomeric 4,6-diene remains unchanged can be used for their separation. Owing to the significant differences in the polarity of these compounds, they can be separated sometimes by simple crystallization <2004JOC8529>. Similarly, the reaction can be used for purification of the 5,7-dienes from other impurities <2005H(65)2107>. 

The Diels-Alder addition of PTAD to 607 in dichloromethane at room temperature is immediate and a mixture of diastereomers 608 and 609 is formed. The diastereomer ratio 92 8 obtained at room temperature is further improved to 97 3 when the reactants are mixed at — 78 °C and then warmed up to room temperature (Equation 91) <2004TL1519>. 

Azabutadiene systems are well-known efficient heterodienes in aza Diels-Alder additions. The presence or absence of substituents especially in the 3-position seems to play an important role in the reactivity of 2-azadienes. For example, compounds 615 with PTAD provide the corresponding products 616 usually in high yields (Equation 92) C1994T12375, 2003H(61)493>. 

Thiolactams 622 treated with carbon suboxide provide mesoionic compounds 623. Their 1,4-dipolar cycloaddition reaction with highly reactive PTAD gives compounds 624, formed by the cycloaddition followed by extrusion of COS, in quantitative yield (Scheme 100) <1995T6651, 1995H(41)1631>. 

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