Tandem reactions Diels-Alder reaction

A formal transfer of a furan ring was achieved by the tandem intramolecular Diels-Alder reaction and base-catalyzed ring-opening of the adduct [136]. 

Oikawa M, Ikoma M, Sasaki M (2005) Parallel synthesis of tandem Ugi/Diels-Alder reaction products on a soluble polymer support directed toward split-pool realization of a small molecule library. Tetrahedron Lett 46 415-418... 

The key tricyclic intermediate toward the total synthesis of spinosyn A was assembled by W.R. Roush et al. featuring a one-pot tandem intramolecular Diels-Alder reaction and an intramolecular vinylogous Baylis-Hillman cyclization. The cyclization precursor was prepared via the S-G modified HWE reaction. 

Scheme 76. A three-component tandem metathesis/Diels-Alder reaction promoted by second generation Grubbs catalyst to form functionabzed tricycles.

Naruta and coworkers developed a method for the synthesis of an an-thracyclinone tetracyclic moiety based on a Lewis acid-mediated tandem Michael-Diels-Alder reaction of acryloyl quinone with pentadienyltins [165]. Subsequent enantioselective Sharpless epoxidation led to an enantiopure intermediate that was converted into ll-deoxydaunomycinone [166]. In more recent work, they obtained enantiomerically pure 7,ll-deoxydaunomycinone (176) and its analogues by the above strategy using the enantiopure penta-dienyltin derivative 171 [167], which was obtained in six steps from racemic ester 167 [168] (Scheme 34). 

A tandem decarboxylation/Diels-Alder reaction of 5-amino-l-phenyl-4-... 

Sol 1. (i) Tandem ene/Diels—Alder reaction of penta-1,4-diene and maleic anhydride results in the formation of 1 2 adduct. 

A tandem Stille-Diels-Alder reaction to form tricycle 2.174 from vinyl bromide 2.173 was used in a manzamine synthesis (Scheme 2.60). Another aspect of this synthesis is discussed in Scheme 8.66. 

Vosburg DA, Vanderwal CD, Sorensen EJ (2002) A synthesis of (+)-FRl 82877, featuring tandem transannular Diels-Alder reactions inspired by a postulated biogenesis. J Am Chem Soc 124 4552- 553... 

In 2012, Christmann et al. developed an enantioselective tandem oxidation-Diels-Alder reaction of a trienol which constituted the key step in the synthesis of the key decalin subunit of UCS1025A. The first step of this one-pot process was a copper-catalysed oxidation of this trienol into... 

Scheme 7.69 Tandem oxidation-Diels-Alder reaction catalysed by copper catalysis...

Dang Q, Liu Y, Sun Z (2001) A tandem decarboxylation/Diels-Alder reaction of 5-amino-l-phenyl-4-pyrazolecarboxylic acid with 1,3,5-triazines. Tetrahedron Lett 42 8419-8422... 

Soldermann, N. Velker, J. Vallat, O. Stoekli-Evans, H. Neier, R. "Application of the Novel Tandem Process Diels-Alder Reaction/lreland-Claisen Rearrangement to the Synthesis of rac-Juvabione and /ac-EpiJuvabione" Helv. Chim. Acta 2000, 63, 2266-2276. 

SCHEME 45 Tandem intermolecular Diels-Alder reaction/lactonization reaction. 

Since its original report, the StiU-Gennari modified HWE olefination has been widely used in natural product synthesis to access Z-alkenes [18]. One example from the Roush group is shown in Fig. 5, where the olefinatimi reaction was used to provide the conjugated polyene precursor for their key one-pot tandem intramolecular Diels-Alder reaction and vinylogous Baylis-Hilhnan cycUzation [19]. 

Phoenix S, Readdy MS, Deslongchamps P. Total synthesis of (-l-)-cassaine via tandem transannular Diels-Alder reaction. J. Am. Chem. Soc. 2008 130 13989 13995. 

Alkynes substituted with one or two trifluoromethyl groups are also highly reactive dienophiles [9] Indeed, hexafluoro-2-butyne is used increasingly as a definitive acetylenic dienophile in "difficult Diels-Alder reactions. It was used, for example, to prepare novel inside-outside bicycloalkanes via its reaction with cir,trnns -l,3-undecadiene [74] (equation 67) and to do a tandem Diels-Alder reaction with a l,l-bis(pyrrole)methane [75] (equation 68) Indeed, its reactions with pyrrole derivatives and furan have been used in the syntheses of 3,4-bis(tri-fluoromethyl)pyrrole [76, 77] (equation 69) and ],4-bis(trifluoromethyl)benzene-2,3-oxide [78] (equation 70), respectively. 

Scheme 22. Schreiber s approach to dynemicin A system 86 by a tandem Sonogashira coupling/Diels-Alder reaction.

The selectivity for two-alkyne annulation can be increased by involving an intramolecular tethering of the carbene complex to both alkynes. This was accomplished by the synthesis of aryl-diynecarbene complexes 115 and 116 from the triynylcarbene complexes 113 and 114, respectively, and Danishefsky s diene in a Diels-Alder reaction [70a]. The diene adds chemoselectively to the triple bond next to the electrophilic carbene carbon. The thermally induced two-alkyne annulation of the complexes 115 and 116 was performed in benzene and yielded the steroid ring systems 117 and 118 (Scheme 51). This tandem Diels-Alder/two-alkyne annulation, which could also be applied in a one-pot procedure, offers new strategies for steroid synthesis in the class O—>ABCD. 

A domino Diels-Alder reaction (the term was chosen from the well-known game) is a one-pot process involving two or more Diels-Alder reactions carried out under the same reaction conditions without adding additional reagents or catalyst such that the second, third, etc., cycloaddition is the consequence of the functionality generated in the previous reaction. A historical example is illustrated in Equation 1.28 [60]. This type of transformation is sometimes named tandem or cascade, but these terms seem less appropriate for describing a time-resolved transformation. 

A tandem Diels-Alder reaction (the term refers to two operating units that are distinct but working at the same time) would indicate a process involving two distinct Diels-Alder reactions working at the same time (Equation 1.29) [6], and a cascade Diels-Alder reaction would refer to a transformation involving at least two Diels-Alder reactions occurring in sequence, without any reference to the fact that the subsequent reaction is the consequence of the functionality generated in the previous reaction (Equation 1.30) [61]. 

The synthesis of highly substituted rigid tricyclic nitrogen heterocycles via a tandem four-component condensation (the Ugi reaction)/intramolecular Diels-Alder reaction was investigated in both solution and solid phase [24]. The Ugi reaction in MeOH (Scheme 4.2) involves the condensation of furylaldehydes 17, benzylamine 18, benzyl isocyanide 19 and maleic or fumaric acid derivatives 20, and provides the triene 21 which immediately undergoes an intramolecular Diels-Alder reaction, affording the cycloadduct 22 in a diastereoisomeric mixture with high yield. 

Stereoseiective synthesis of decaiines via tandem photooxidation-intramolecular Diels-Alder reactions of bis-furan [104]... 

Enantiomers (M)- and (P)-helicenebisquinones [32] 93 have been synthesized by high pressure Diels-Alder reaction of homochiral (+)-(2-p-tolylsulfo-nyl)-l,4-benzoquinone (94) in excess with dienes 95 and 96 prepared from the common precursor 97 (Scheme 5.9). The approach is based on the tandem [4 + 2] cycloaddition/pyrolitic sulfoxide elimination as a general one-pot strategy to enantiomerically enriched polycyclic dihydroquinones. Whereas the formation of (M)-helicene is explained by the endo approach of the arylethene toward the less encumbered face of the quinone, the formation of its enantiomeric (P)-form can be the result of an unfavourable interaction between the OMe group of approaching arylethene and the sulfinyl oxygen of 94. 

Tietze L. F. Domino-Reactions the Tandem-Knoevenagel-Hetero-Diels-Alder Reaction and Its Application in Natural Product Synthesis J. Heterocycl. Chem. 1990 27 47-69... 

Figure 4.10 Tandem DKR-intramolecular Diels-Alder reaction.

For clarification, individual transformations of independent functionalities in one molecule - also forming several bonds under the same reaction conditions -are not classified as domino reactions. The enantioselective total synthesis of (-)-chlorothricolide 0-4, as performed by Roush and coworkers [8], is a good example of tandem and domino processes (Scheme 0.1). I n the reaction of the acyclic substrate 0-1 in the presence of the chiral dienophile 0-2, intra- and intermolecular Diels-Alder reactions take place to give 0-3 as the main product. Unfortunately, the two reaction sites are independent from each other and the transformation cannot therefore be classified as a domino process. Nonetheless, it is a beautiful tandem reaction that allows the establishment of seven asymmetric centers in a single operation. 

The preparation of resin-bound nitroalkenes via a microwave-assisted Knoevenagel reaction of resin-bound nitroacetic acid with aryl and alkyl substituted aldehydes is reported. The potential of these resin-bound nitroalkenes for application in combinatorial chemistry is demonstrated by a Diels-Alder reaction with 2,3-dimethylbutadiene (Scheme 8.9). It is also used for one-pot three-component tandem [4+2]/[3+2] reactions with ethyl vinyl ether and styrene 46... 

Hetero Diels-Alder reactions using nitroalkenes followed by 1,3-dipolar cycloadditions provide a useful strategy for the construction of polycyclic heterocycles, which are found in natural products. Denmark has coined the term tandem [4+2]/[3+2] cycloaddition of nitroalkenes for this type of reaction. The tandem [4+2]/[3+2] cycloaddition can be classified into four families as shown in Scheme 8.31, where A and D mean an electron acceptor and electron donor, respectively.149 In general, electron-rich alkenes are favored as dienophiles in [4+2] cycloadditions, whereas electron-deficient alkenes are preferred as dipolarophiles in [3+2] cycloadditions. 

Hetero substituted 2-cyclopropylideneacetates are ring-strain activated acrylates, highly reactive dienophiles in Diels-Alder reactions, but also powerful Michael acceptors. The reactivity of these compounds is enhanced by the same strain release in the Diels-Alder cycloadditions as well as in the 1,4-additions, and indeed the borderline between tandem Michael-cyclization and Diels-Alder-type cycloaddition is not well defined in many cases. 

---