1.3- Diene-2-amines

Die bei der Reduktion mil Natriumboranat gebildeten 1,2-Dihydro-pyridine konnen als Dien-amine zu Diels-Alder-Addukten dimerisieren6. 

En-amine und Dien-amine werden durch Ameisensaure reduziert, wobei in Dien-ami-nen zumeist eine C=C-Doppelbindung hydriert wird. Da zusatzlich oft lsomerisierung eintritt, entstehen meist Produktgemische (s.ds. Handb. Bd. V/lc, S. 874). 

Dienes with Chiral Auxiliaries The use of dienes with the chiral auxiliary attached to the C-l position of the dienes is the most popular in asymmetric Diels-Alder reactions.59 In 1980, Trost reported high asymmetric induction in the Diels-Alder reaction using l-(S)-0-methylmandeloxy-l,4-butadiene59a However, the result obtained by Trost et al. has remained unique for more than a decade, at least in terms of enantioselectivity. The asymmetric Diels-Alder reaction of chiral diene-amines with nitroalkenes gives aminocyclohexenes with good diastereoselectivity (Eq. 8.37).60 The development in the area of chiral dienes is slow it may be due to the difficulty of preparing these compounds. 

The ultraviolet spectra 27,28 exhibit, in agreement with the general postulate of Braude et al.2%-30 a bathoehromic shift to 225-235 m/j. caused by the auxochromic action of the nitrogen-free electron pair. This shift is approximately the same as that caused by introduction of a conjugated double bond, and is increased by further conjugation with other multiple bonds, e.g. in diene-amines prepared from A -3-oxosteroids.31,32 Spectral maxima (at 280-285 mfi, e 19,000-26,000) point to the conjugation of three mobile electron pairs but cannot decide the position of the double bonds the molecular extinction coefficient indicates a transoid (5) rather than cisoid arrangement (e.g. 6).33... 

In general, the excited radicals shown have been found to possess enhanced donor/acceptor properties, especially in interactions with such quenchers as oxygen, dienes, amines, and halides. To date, the most well-characterized intermolecular processes are charge (electron) transfer reactions between excited diphenyl-methyl radicals and electron donors and acceptors. Thus, excited 132 reacts with methyl benzoates and benzyl bromides (Schemes 23 and 24) with rates that increase with the increasing electron withdrawing ability of substituents on the... 

Ethanol 2-[Ethyl-(2,7-octadienyl)-amino]- E18, 1039 (1,3-Dien + Amin)... 

The ting-closing metathesis of functionalized linear dienes, diene-ethers, diene-amines, etc., leads to a variety of cyclic alkenes and heterocycles [16] (eq. (8)). 

But this has an essential restriction some of the used vinamidinium salts (7) are sensitive and may be decomposed by treatment with strong base, e.g., sodium me-thoxide. Especially such salts possessing methyl or methylene groups at odd-numbered, electron-dificient positions of the vinamidinium system tend toward complex self-condensations a proton abstraction to a diene amine may occur, followed by attack of the unaltered ion ... 

The azulene (156) slowly condenses with (7a) to the red-violet azulene diene-amine (157) and cyclization occurs at 150-200°, giving in 58% yield by a 70% conversion a mixture of the expected l,2-dihydrodicyclopenta(e,f-k,l)heptalene (158) and the azupyrene (159), formed by simultaneous dehydrogenation74. Treatment of the mixture with chloranil in benzene leads quantitatively to the pure (159), bronze-shining, black plates, mp. 257-259° (subl.). 

The synthesis of ( )-yohimbone by Grieco and Fobare illustrates the use of an allylsilane to terminate an iminium ion initiated polyene cyclization. The o/E-ring system of the target alkaloid was assembled by treating diene amines (114) with formaldehyde and CF3CO2H in aqueous THF to give (115) in good yield. Only the rrans-hydroisoquinoline stereoisomer was produced (Scheme 42). 

The ethyl ester of (.S l-pyroglutamic acid (,S)-32 was applied for the preparation of dien-amines used as chiral dienes in enantioselective Diels-Alder reactions (Section D.l.6.1.1.1.1.5.1.). Thus, acrolein or methacrolein reacted with the auxiliary under acidic catalysis to form the corresponding dienamines 31. 

In terms of catalyst development, studies by Otsuka and Tani led the way with a (+)-D10P-modified cobalt catalyst (Kagan, 1972). [126] Diethylneryl-amine could be converted, in 23 % yield and with an enantiomeric excess of 32 %, to the corresponding enamine of citronellal. However, concomitantly a dien-amine was produced in quantities which were not insignificant. 

S.4.4.5. -Substituted Cyclohexenone Derivatives. Inspired with the dien-amine catalysis developed by Jprgensen and co-workers [138], Melchiorre and coworkers [139] found that the chiral primary amine salts 142 could selectively activate the 7-position of ummodified cyclic a,(3-unsaturated ketones through dienamine catalysis (Scheme 5.70). The direct vinylogous Michael addition of p-substituted... 

As previously mentioned, Rawal and co-workers [35,45] reported the first example of asymmetric catalytic HDA based on hydrogen bonding activation in 2003. They found that the relatively simple diol, TADDOL 52, catalyzed the reaction between diene amine 76 and aldehydes 75 to give hemiaminals 77 (Scheme 6.17). Further treatment of the crude product with acetyl chloride resulted in elimination of the amine to give optically active pyranones 78 in good yields and excellent ee. 

The use of enamine catalysis in the enantioselective a-functionalization of carbonyl compounds has been reviewed, including aldol, Mannich, and alkylation processes," and a short review has examined enantioselective a-alkylation of aldehydes Benzodithiolylium tetrafluoroborate (133) is a water-stable salt and can be added enantioselectively to aldehydes at the a-position in the presence of simple chiral organocatalysts, giving the corresponding alcohol. The sulfurs can be readily cleaved with H2/Raney Ni, rendering the process a formal tf-methylation of aldehydes." a ,/3-Unsaturated aldehydes undergo enantioselective a- and y-alkylation via dien-amine activation, using a diarylprolinol TMS ether as catalyst." ... 

The inhibitors act as ligands, blocking the hydrosilylation reaction by coordination to the metal center, but vmder conditions employed for cure, they release the active catalyst. The numerous vmsaturated organic compounds, such as esters, alcohols, ketones, sulfoxides, phosphines, phosphites, nitriles, azodicarbonyl compounds, triazoline, dienes, amine N-oxides, hydroperoxides, and others, are known and have been reported as platinum catalyst inhibitors during the cure of silicon rubber through addition processes (3,4). The unsaturated diesters (e.g., maleates and fumarates) are the most important and commonly used platinum inhibitors in industrial curing processes and have been described in many articles and patents. 

A full paper detailing the preparation and chemical properties of diphenylthiiren 1-oxide has appeared.The reactions of thiiren 1,1-dioxides with a-metallated isocyanides and lithium azide have been reported. The latter leads to a new heterocyclic system (69). Dimethyl- and diphenyl-thiiren 1,1-dioxides are reported to react with the 1,3-dipoles (70) and (71) to give (72) or (73) respectively. In the case of (71) and diphenylthiiren 1,1-dioxide, (74) is also formed. The Diels-Alder reaction with a diene-amine, but not the structure of the product, is mentioned in the same report. 

Grignard coupling with the methiodide of the diene-amine (57), derived from 2-methylpyridine (56), offers an interesting new synthesis of Z,F-1,3-dienes (58), many of which are pheromones e.g. from Hedya ochroleucana) (Scheme 13). The corresponding E,E-1,3-diene (59) may also be obtained from (57) by using the modified Polonovski reaction to effect the Z ->E isomerization. 

Keywords 1,2-Diaza-1,3-dienes, amines, isocyanates, ethanol, room temperature, sequential three-component reaction, aza-Michael reaction, one-pot synthesis, functionalized 1,3,5-trisubstituted hydantoins... 

A less explored mode of activation within aminocatalysis is the so-called dien-amine catalysis [37]. In this case it is an a,P-unsaturated carbonyl compound with a proton in the y position suitable for deprotonation that after condensation with a chiral amine provides a reactive nucleophile, but now two activated positions are available, making possible both a- and y-functionahzation of the substrate. This vinylogous enamine can also act as an electron-rich diene. Work published in this area is very scarce to date, and only a few ejamples of its application in total synthesis have appeared in recent years (+)-palitantin [38], a-tocopherol [39], a pungent constituent of black cardamom [40], and (R)-rotundial [41] (Figure 44.3). 

Structure (Scheme 3.9). A mechanism that has been proposed is shown in Scheme 3.10. Intermediate 60 was formed upon activation of phytal 56 by dien-amine catalysis. Subsequently, an intermolecular aldol reaction between phytal 56 and aldehyde 55 occurred in the presence of catalyst 57. Finally, the tricyclic core structure 58 was built after the adjacent phenol group captured the newly formed iminium ion 61 via an oxa-Michael reaction. The cascade product desired was obtained in 58% yield with 97% diastereomeric excess. The total synthesis of natural product a-tocopherol was achieved through a four-step chemical synthesis. 

One synthetic approach to perhydrohistrionicotoxin yielded as the major product the racemic 2,7-epimer (Scheme XXXI) (75). Several unsuccessful or relatively unsuccessful routes to perhydrohistrionicotoxin have been discussed by Corey and Balanson (70). An approach involving the Mannich reaction did not afford the desired spiro-compound but instead yielded a diene amine (Scheme XXXII). The methylated eneamine on acid treatment also did not afford the desired spiro-product but instead another diene amine. A route involving an ultimate Michael addition of an amine function (Scheme XXXIII, reaction F ) did not yield perhydro-... 

Only 16 years have elapsed since Grubbs and Fu reported that Schrock s molybdenum catalyst ([Mo-I[) could be used to induce efficient cyclization of functionaHzed a,a)-diene-amines. Since then, a wide range of RCM reactions to form the nitrogen heterocyclic products have been reported, including applications in the synthesis of natural products. These applications have been greatly facihtated by the advent... 

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