Catalysis hetero-Diels-Alder

The final class of reactions to be considered will be the [4 + 2]-cycloaddition reaction of nitroalkenes with alkenes which in principle can be considered as an inverse electron-demand hetero-Diels-Alder reaction. Domingo et al. have studied the influence of reactant polarity on the reaction course of this type of reactions using DFT calculation in order to understand the regio- and stereoselectivity for the reaction, and the role of Lewis acid catalysis [29]. The reaction of e.g. ni-troethene 15 with an electron-rich alkene 16 can take place in four different ways and the four different transition-state structures are depicted in Fig. 8.16. 

Togni A., Pastor S. D. Cooperativity of Chirality in Homogeneous Catalysis The Gold(I)-Catalyzed Aldol Reaction and the Vanadium(IV)-Catalyzed Hetero-Diels-Alder Cycloaddition Chirality 1991 3 331-340... 

Bolm et al. [108] prepared a C2-symmetric bis (sulfoximine) as ligand for the copper-catalyzed hetero-Diels-Alder reaction. The stereogenic sulfur atom being located near the AT-coordinating atom, these structures were assumed to be promising for asymmetric catalysis. Their Hgand (79 in Scheme 43) was synthesized by palladium-catalyzed N-aryl imination from 1,2-dibromobenzene and (S)-S-methyl-S-phenylsulfoximine with Pd2dba3 in 70% yield. 

The presence of a small amount of water was found beneficial for several asymmetric hetero-Diels-Alder reactions. The asymmetric catalysis... 

Evans et al. (219, 220) examined the use of electron-poor heterodienes as partners in cycloadditions with electron-rich alkenes under copper catalysis. In particular, a,p-unsaturated acylphosphonates and keto-esters afford hetero-Diels-Alder adducts in high selectivities when treated with enol ethers in the presence of catalysts 269c and 269d. 

Diels-Alder Reactions The organocatalytic Diels-Alder reaction of a,P-unsaturated carbonyl compounds can be performed either via iminium (see Section 11.3) or enamine catalysis. The first highly selective enamine-promoted cycloaddition reaction was reported by Jprgensen and coworkers, who developed an amine-catalyzed inverse-electron-demand hetero-Diels-Alder (HDA) reaction (Scheme ll.lOa). ... 

Because a comprehensive discussion of the transition state of hydrogen-bond catalysis will be presented by Berkessel in Chapter 3, the hydrogen bond catalyzed hetero Diels-Alder reaction of butadiene with carbonyl compounds will be discussed briefly here. Huang and Rawal reported that the hetero Diels-Alder reaction of aminodiene with aldehyde exhibited significant solvent effects (Scheme 2.7) [15]. The reaction in CHCfi was accelerated 30 times in comparison with that in THF, while that in i-PrOH was accelerated 630 times. They proposed that the Diels-Alder reaction was promoted by the hydrogen-bond activation of aldehyde. This finding resulted in the development of TADDOL catalyst [3]. 

TADDOL-Promoted Enantioselective Hetero-Diels-Alder Reaction of Danishefsky s Diene with Benzaldehyde-Another Example for Catalysis by Cooperative Hydrogen Bonding... 

The initial work on the asymmetric [4-1-2] cycloaddition reactions of A -sulfinyl compounds and dienes was performed with chiral titanium catalysts, but low ee s were observed <2002TA2407, 2001TA2937, 2000TL3743>. A great improvement in the enantioselectivity for the reaction of AT-sulfinyl dienophiles 249 or 250 and acyclic diene 251 or 1,3-cyclohexadiene 252 was observed in the processes involving catalysis with Cu(ll) and Zn(ii) complexes of Evans bis(oxazolidinone) (BOX) ligands 253 and 254 <2004JOC7198> (Scheme 34). While the preparation of enantio-merically enriched hetero-Diels-Alder adduct 255 requires a stoichometric amount of chiral Lewis acid complex, a catalytic asymmetric synthesis of 44 is achieved upon the addition of TMSOTf. 

The development and application of catalytic enantioselective 1,3-dipolar cycloadditions is a relatively new area. Compared to the broad application of asymmetric catalysis in carbo- and hetero-Diels-Alder reactions (337,338), which has evolved since the mid-1980s, the use of enantioselective metal catalysts in asymmetric 1,3-dipolar cycloadditions remained almost unexplored until 1993 (5). In particular, the asymmetric metal-catalyzed reactions of nitrones with alkenes has received considerable attention during the past 5 years. 

The reaction of diphenylketene with an azadiene was reported to produce piperidinones <99SL1379>. An intramolecular hetero-Diels-Alder of the activated azadiene 65 was carried out either by heating or with catalysis <99TL7211,99TL7215>. 

Sanders and coworkers have extended the use of these cyclic porphyrin systems in the catalysis of acyl-transfer reactions [15] and hetero-Diels-Alder reactions [16]. 

In this transformation two new C-C-rr-bonds are formed from three different components. The enantioselectivity of this reaction is generally low (< 5%). With cyclic ketones the corresponding products were obtained as single diastereomers. It is proposed that this reaction involves a Knoevenagel-hetero-Diels-Alder sequence where proline utilizes both iminium and enamine catalysis (Scheme 9.20). 

An intramolecular hetero-Diels-Alder reaction of activated azadienes gives rise to the fused tetrahydropyridines by heating or catalysis (Equation 139) <1999TL7211, 1999TL7215>. 

Inanaga et al. have reported the preparation of the new chiral Yb(III) phosphate complex 180 (Figure 43), which is an efficient catalyst for asymmetric hetero-Diels-Alder reactions of 181 with aromatic aldehydes and/or a,P-unsaturated aldehydes. 2,6-Lutidine is found to be an effective additive to obtain high enantioselectivities.98 Another asymmetric catalysis for hetero-Diels-Alder reaction was reported by Mikami et al.99 An illustrative example is shown in Figure 44, wherein the interesting effects of water as an additive were observed to increase not only the enantioselectivity but also the chemical yield. 

A.K. Unni, Asymmetric Catalysis of Hetero-Diels-Alder Reactions Through Hydrogen Bonding. PhD Thesis, The University of Chicago, Chicago, IL, June 2005. 

The hetero-Diels-Alder reaction between sulfinyl diene 152a and ethyl gly-oxalate [149] has also been reported. (Scheme 89). In the presence of LiCl04,the endo adducts 185 are predominant, but under Eu(fod)3 or ZnCl2 catalysis the exo adducts 186 are the major ones. The endo/exo selectivity is rather moderate, and the 7r-facial selectivity is low in all cases. 

A remote sulfinyl group has also been used to control the stereoselectivity of the hetero-Diels-Alder reaction of the carbonyl group of furfural [176]. Reaction of sulfoxide 236 with Danishefsky s diene in the presence of Ln(OTf)3 (Ln = Yb, Nd, and Sm) yielded cycloadducts 237a and 237b with high de (93-99%). When reactions were conducted under Eu(thd)3 catalysis, the stereoselectivity of the reaction was dramatically inverted (Scheme 107). The influence of the catalysts in the stereoselectivity is not discussed. 

In addition to these intramolecular [2+2+2] cycloadditions, intramolecular [4+2] cycloaddition of yne-enones 29 leading to fused pyrans 30 has been achieved by means of the ruthenium catalysis with a cationic complex, CpRu(MeCN)3PF6 (Eq. 15) [24], Such hetero Diels-Alder cycloaddition was considered to proceed via an oxaruthenacycle 31. 

Ooi, T. Maruoka, K. Hetero-Diels-Alder and Related Reactions. In Comprehensive Asymmetric Catalysis Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds. Springer Heidelberg, 1999 Vol. 3, pp 1237-1254. 

Desimoni and Righetti have been thoroughly investigating the effect of solvents, acid catalysis and salts on hetero Diels-Alder and ene reactions of 1-oxa-1,3-butadienes for a long time [ 154-156]. Recently, for the cycloaddition of 2-154 and ethyl vinyl ether 2-83 in the presence of lithium perchlorate in different solvents as diethyl ether, acetonitrile, acetone, methanol, iso-propanol to give... 

A major problem in the reaction of a,/3-unsaturated carbonyl compounds and alkenes proves to be the competition between hetero Diels-Alder and ene reactions. Intramolecular cycloadditions of 1,6- and 1,7-dienes with ester and cyano groups at the double bond yield the ene product nearly exclusively, but with alkylidene- and benzylidene-ketoesters and 1,3-diketones the Diels-Alder reaction is preferred under thermal conditions, however under Lewis acid catalysis also ene reactions occur [12]. 

However, activation with suitable substituents is not the only method to make 1-aza-1,3-butadienes react in aza Diels-Alder reactions. Nevertheless, Lewis acid catalysis has not yielded good results in this area of hetero Diels-Alder chemistry. Interestingly, Lewis and Bronsted acids promote a [3 + 2] cycloaddition process instead of the aza Diels-Alder reaction upon addition of a,/ -unsatura-ted hydrazones to quinones [249],... 

Lewis acid catalysis, apparently dispensible due to the very high reactivity of nitroso dienophiles, has not yet been investigated although such a study has been suggested by Streith and Defoin [8]. Thus, examples of asymmetric catalysis lack completely in this area of hetero Diels-Alder chemistry. Nevertheless, cycloadditions involving nitroso dienophiles have reached an advanced level concerning stereoselectivity and therefore much attention has been paid towards the preparation and application of chiral, enantiopure dienophiles and dienes for these reactions. 

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