Hetero-Diels-Alder adducts

Fig. 8.6 The calculated transition-state structure for the reaction of acrolein with butadiene leading to formation of vinyldihydropyran by a hetero-Diels-Alder adduct catalyzed by BH3 using a RHF/3-21G basis set [6]...

The mechanism for the hetero-Diels-Alder reaction of benzaldehyde 9 with the very reactive diene, Danishefsky s diene 10, catalyzed by aluminum complexes has been investigated from a theoretical point of view using semi-empirical calculations [27]. The focus in this investigation was to address the question if the reaction proceeds directly to the hetero-Diels-Alder adduct 11, or if 11 is formed via a Mukaiyama aldol intermediate (Scheme 8.4) (see the chapter dealing with hetero-Diels-Alder reactions of carbonyl compounds). 

The reaction was studied in the absence, and presence, of (MeO)2AlMe as a model catalyst for the BINOL-AlMe system. The change in relative energy for the concerted hetero-Diels-Alder reaction, and formation of the hetero-Diels-Alder adduct 11 via a Mukaiyama aldol reaction, is shown in Fig. 8.13. The conclusion of the study was that in the absence of a catalyst the concerted reaction is the most... 

The structures along the reaction path in Fig. 8.13 are outlined in Fig. 8.14 starting with benzaldehyde activated by (MeO)2AlMe in the reaction with Danishefsky s diene 10 leading to the transition-state structure for the formation of the al-dol-like intermediate, and finally the formation of the hetero-Diels-Alder adduct. 

Transilion-state structure lor ton nation ot hetero-Diels-Alder adduct... 

Amino alcohols are also good substrates for aziridination under Mitsunobu conditions. The rfs-1,4-amino alcohols 48, obtained by reductive cleavage of the nitrogen-oxygen bonds of the hetero Diels-Alder adducts 47, underwent syn-SN2 -type displacement on treatment with PPh3 and DEAD to give cyclic vinylaziridines 49 (Scheme 2.15) [27]. 

Reactive unsaturated nitroso compounds such as 1112 can also be readily prepared from a-halooximes such as 1111 on treatment with powdered Na2C03 in diethyl ether to give, in the presence of enoltrimethylsilyl ether 1113 or strained olefins such as norbomene and other dienophiles, hetero-Diels-Alder adducts such as 1114 and 1115 in moderate yields [150-155] (Scheme 7.47). 

A similar strategy can also be used in a seven-step procedure of preparation of 3/3,25-dihydroxy-cholesta-5,7-diene from ergosterol giving a total yield of 30%. The 3-hydroxy function of ergosterol is protected as /-butyldimethylsilyl ether before the 5,7-diene system is treated with l,4-dihydrophthalazine-l,4-dione. In this case, the key step is a very mild method for the cleavage of the hetero Diels-Alder adduct using lithium naphthalenide <1999S1331>. 

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. 

Various substituted unsaturated acylphosphonates participate in highly dias-tereoselective and enantioselective cycloadditions with vinyl ethers, Eqs. 177 and 178. It is intriguing to note that catalysts [(.V,.Y)-f-Bu-box]Cu (OTf)2 (269c) and [(.V,.S )-Ph-box]Cu (OTf>2 (269d) possessing the same sense of chirality afford opposite antipodes of the cycloadduct in comparable selectivities. Cyclopentadiene was found to react with acylphosphonates to give a mixture of the normal Diels-Alder adduct and the inverse electron demand hetero-Diels-Alder adduct (35 65), Eq. 179. This result may be contrasted with crotonylimide, which furnishes the normal demand Diels-Alder adduct exclusively. 

A few examples of hetero-Diels-Alder adducts have been reported [75-81]. A thio-chroman-fused fuUerene adduct was synthesized by the reaction of o-thioquinone with CgQ in o-dichlorobenzene at 180 °C [77]. The obtained cyclic sulfide 84 (Figure 4.4) can be oxidized to the corresponding sulfoxide and sulfone with m-chloroperoxybenzoic acid. Reaction of azadienes with Cgg leads to hetero Diels-Alder adducts such as, for example, 85 (Figure 4.4) [79]. The tetrahydropyrido[60]-fullerene 85 is formed in refluxing o-dichlorobenzene. 

The H NMR spectra of two diastereomeric hetero-Diels-Alder adducts 43 has been obtained (Figure 10) <2004JOC7198>. The diastereotopic a-protons of the sulfonamide (C-6) fall in the range of 3.4—3.5 ppm, while the C-3 protons occur around 4.6 ppm. Both and C-5 vinylic hydrogens occur in the characteristic region for double-bond protons. 

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. 

A -sulfinylacetamide 297 in greater than 90% yield when a catalytic amount of methyltrioxorhenium is employed. Futhermore, the hetero-Diels-Alder adduct is highly soluble in both chlorinated and ethereal solvents. A detailed investigation of the retro-Diels-Alder reaction of 298 by thermogravimetric analysis revealed an onset temperature of 120 °C and complete conversion of bicycle 298 to pentacene 296 at 160 °C, which are temperatures compatible with the polymer supports typically used in electronics applications. The electronic properties of these newly prepared OTFTs are similar to those prepared by traditional methods. Later improvements to this chemistry included the use of A -sulfinyl-/< r/-butylcarbamate 299 as the dienophile <2004JA12740>. The retro-Diels-Alder reaction of substrate 300 proceeds at much lower temperatures (130 °C, 5 min with FlTcatalyst 150 °C, Ih with no catalyst). 

Reaction of 6-nitro[l,2,3]oxadiazolo[4,5- ]pyridine-l-oxide 8 under Diels-Alder conditions resulted in the formation of several adducts, a normal Diels-Alder adduct, a hetero-Diels-Alder adduct, and a di-adduct, which is believed to arise from the minor dinitroso tautomer of 8 unfortunately, no yields were reported for these products (Equation 5) <2000JOC7391>. 

Cyclocondensation of 2-siloxy dienes and aldehydes is catalyzed by 1 mol % of a soluble lanthanide complex, Eu(hfc)3, and gives the hetero-Diels-Alder adduct in up to 58% ee (Scheme 107) (263). Upon treat-... 

Due to the longer lifetime of the arene radical ration in the SSIP, 37 undergoes isomerization to 38 yielding after return electron transfer and collapse of the reactive intermediates the Hetero Diels Alder adducts 40 and 41 in a. ratio of ra. 1 2.5. There is also experimental evidence for some participation of an ion pair annihilation leading directly to 40 and 41. 

Sulfinyl dienes and vinyl sulfoxides have rarely been used in asymmetric hete-ro-Diels-Alder reactions [145]. The first example was reported in 1992 and describes an intramolecular cycloaddition using a heterodiene bearing a chiral sulfinyl group [146a]. In this paper, the conversion of a-p-tolylsulfinyl a,ft-unsaturated ketone 176 (prepared by Knoevenagel reaction of 3-methylcitronellal and (S)-p-toluenesulfinylacetone) into the hetero-Diels-Alder adducts 177... 

A number of selenium heterocycles are prepared utilizing carbon-selenium double bonds as 271 dienophilic intermediates for [4+2] cycloadditions. However, Koketsu et al. reported a novel hetero Diels-Alder reaction wherein selenoazadienes 353 serve as 47t components. Accordingly, compound 353 reacts with dimethyl acetylenedicarboxylate to yield 4-selenazolone 354. The proposed mechanism involves the formation of hetero Diels-Alder adduct 355, which is converted into 4-selenazolone 354 following purification on silica gel. Protonation of cycloadduct 355 presumably affords the selenoamidine 356, which is converted into 357 by nucleophilic recyclization <03H(60)1211>. 

Section 1.1.3.3 Formation of 1-vinyl-2-alkylcyclohexanes from 1,7-dienes. Narasaka demonstrated that the chiral titanium alkoxide prepared from TiCl2(OPr )2 and (213) catalyzes the asynunetric intramolecular ene reaction of oxazolidinone (212) in Freon 113 at 0 °C to give 63% of ene adduct (214) in >98% enantiomeric excess and 25% of the hetero Diels-Alder adduct. ... 

Ruthenium(II) complexes may also be used to oxidize N-Boc hydroxylamine in the presence of tert-butylhydroperoxide (TBHP) to the corresponding nitroso dieno-phile, which is subsequently trapped by cyclohexa-1,3-diene to give the hetero Diels-Alder adduct (Entry 1, Scheme 10.26) [51]. A triphenylphosphine oxide-stabilized ruthenium(IV) oxo-complex was found to be the catalytically active species. Use of a chiral bidentate bis-phosphine-derived ruthenium ligand (BINAP or PROPHOS) result in very low asymmetric induction (8 and 11%) (Entry 2, Scheme 10.26). The low level of asymmetric induction is explained by the reaction conditions (in-situ oxidation) that failed to produce discrete, stable diastereomerically pure mthenium complexes. It is shown that ruthenium(II) salen complexes also catalyze the oxidation of N-Boc-hydroxylamine in the presence of TBHP, to give the N-Boc-nitroso compound which can be efficiently trapped with a range of dienes from cyclohepta-1,3-diene (1 h, r.t., CH2CI2, 71%) to 9,10-dimethylanthracene (96 h, r.t., CH2CI2,... 

Yamamoto and Maruoka demonstrated that ATPH can discriminate between structurally similar aldehydes, thereby facilitating selective functionalization of the less-hindered aldehyde carbonyl [163]. Treatment of an equimolar mixture of valeralde-hyde (149) and cyclohexanecarbaldehyde (150) with ATPH (1.1 equiv.) in CH2CI2 at -78 °C, then addition of Danishefsky s diene gave hetero-Diels-Alder adduct 151 and 152 in the ratio > 99 1. It is worthy of note that the complexed aldehyde could react with the diene only. The reaction gave relatively low chemoselectivity with other types of Lewis acid (ratio of 1517152 6.2 1 with (Pr 0)2Ti2Cl2 5 1 with McsAl 3.7 1 with MAD 2 1 with TiCU 1.3 1 with BF3-OEt2). This emphasizes that the cavity of ATPH plays an important role in differentiating between the reactivities of the two different aldehydes. In a similar manner, the aldol reaction of a mixture of 149 and 150 was effected with ATPH to furnish 4-hydroxy-2-octanone (153) without formation of 154 (Sch. 122). 

There have been a few reports of new [4+2] cycloaddition reactions including reaction of the 2-alkylidene-l,3-benzoxathiole dioxides 149, formed as shown in Section 4.10.5.1, with diene 150 to give products 151 (Equation 39), and this is how compound 57 was prepared <1996AP361>. The chiral 4,5-diaryl-2-methylene-l,3-dioxolanes 152 have been reacted both with formylcyclohexenones 153 (Equation 40) and 2-acetylaminomethylene-l,3-diones 154 (Equation 41) to give the corresponding hetero-Diels-Alder adducts <1999T12907, 2003T341>. 

Similarly (Scheme 42) (82JOC1302), oxidation of hydroxamic acid 313 in the presence of 9,10-dimethylanthracene gave an 82% yield of the hetero Diels-Alder adduct 314. This product was decomposed in refluxing toluene to afford a quantitative yield of the ene adduct 315. The cyclic hydroxamic acid 315 was converted to the corresponding lactam (316) by TiClj reduction. The... 

The modified organoaluminum reagent, BINAL, can be used as a chiral Lewis acid catalyst in the asymmetric hetero-Diels-Alder reaction [41]. Reaction of various aldehydes with activated dienes under the influence of catalytic BINAL (5-10 mol%) at -20 °C gave, after exposure of the resulting hetero-Diels-Alder adducts to tri-fluroacetic acid, predominantly c/v-dihydropyrone in high yield with excellent enan-tioselectivity. 

Cycloaddition of enaminone carboxaldehyde (formylenaminone) with a vinyl ether leads to pyrans as hetero-Diels-Alder adducts . The stereochemistry is dependent on the substituents of the N-acyl group and on the reaction temperature (equation 227). 

Yamamoto and Maruoka also reported a conceptually new method of in situ generating the chiral catalyst 12 for asymmetric hetero-Diels-Alder reactions by discrimination of the racemic 12 with a chiral ketone [ 16]. As shown in Scheme 7, sequential treatment of ( )-12 (0.1 equivalent) with d-3-bromocamphor (0.1 equivalent), the diene 10a (1.05 equivalent), and benzaldehyde (1 equivalent) at -78 °C in CH2CI2 and stirring of the mixture at this temperature for 3 h afforded the hetero-Diels-Alder adducts 14 and 15, after acidic workup, in 78% and 19% yields, respectively. The optical yield of the major cis isomer 14 was 82%. Although the extent of asymmetric induction is not as satisfactory as that with optically pure 12, one recrystallization of the cis adduct 14 of 82% ee from hexane gave the essentially pure 14 (>98% ee with 60% recovery), thereby enhancing the practicability of this method. 

The hetero-Diels-Alder adduct thus obtained by the use of (S)-22a can readily be converted not only to monosaccharides but also to the lactone portion 24 of mevinolin or compactin in a short step as shown in Scheme 12. 

Ketone silyl enol ethers react with derivatives of diacyl azo compounds at room temperature245 or on heating242,243 (see also Eq. 82) as well as enantio-selectively under the influence of silver trifluoromethanesulfonate and BINAP (Eq. 93)244 or copper bis(oxazoline) complexes (Eq. 94). The latter is proposed to proceed via a formal hetero Diels-Alder adduct.252 Ketones themselves react with azodicarboxylic esters either thermally246,389,390 or in the presence of potassium carbonate390 but yields are low. Higher yields can be achieved with LDA,391 394 (see also Eq. 88), LiHMDS,395,396 or KOBu-r325 as the bases. Aryl diazonium... 

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