1.3- Butadienes chiral, Diels-Alder reaction

Several highly enantioselective Diels-Alder reactions are known for which the di-enophile does not fit any of the above classes. Corey and coworkers applied the chiral aluminum reagent 36 with a C2-symmetric stilbenediamine moiety (videsu-pra) to the Diels-Alder reaction of maleimides as dienophiles [54] (Scheme 1.68). In most asymmetric Diels-Alder reactions the reactants are usually relatively simple dienes such as cyclopentadiene or monosubstituted butadienes, and unsym-... 

Amino-subsdnued dienes are also important dienophiles in Diels-Alder reactions Recently, chiral and achiral 2-amino-l,3-dienes have been prepared to snidy their reactivity Csee also asymmetric Diels-Alder reaction Section 8 1 2 The reaction of 2,3-diamino-l,3-butadienes v/ith nitrostyrene gives unusual [3t-2 carbocyclization products, 2-aminocyclopentanones, which are not formed by the direct cycloaddidon but derived from the Michael addidon products fsee secdon discussing the Michael addidon Secdon 4 1 3 "... 

Highly functionalized cyclohexenes have been prepared by Diels-Alder reactions of butadienes 1 (Scheme 2.1) and chiral butadienes 2 (Scheme 2.2) with... 

Zamojski A. Chiral (E,E)-l,4-Dialkoxy-l,3-Butadienes. Synthesis, Conformational Studies and Diels-Alder Reactions with Symmetric Dienophiles Chemtracts 2000 13 62-65... 

On the other hand, several examples of chiral sulfonamides derived from ehiral a-amino acids have been successfully employed as ligands for enantio-seleetive Diels-Alder reactions. Thus, Yamamoto and Takasu have easily prepared new chiral Lewis acids from borane and sulfonamides of various ehiral a-amino acids, which were further studied for their abilities to promote the enantioselective Diels-Alder reaction between methacrolein and 2,3-dime-thyl-1,3-butadiene. Since 2,4,6-triisopropylbenzenesulfonamide of a-amino-butyric acid gave the highest enantioseleetivity, this eatalyst was applied to the... 

Optically active /3-ketoiminato cobalt(III) compounds based on chiral substituted ethylenedi-amine find use as efficient catalysts for the enatioselective hetero Diels Alder reaction of both aryl and alkyl aldehydes with l-methoxy-(3-(t-butyldimethylsilyl)oxy)-1,3-butadiene.1381 Cobalt(II) compounds of the same class of ligands promote enantioselective borohydride reduction of ketones, imines, and a,/3-unsaturated carboxylates.1382... 

The domino process probably involves the chiral enamine intermediate 2-817 formed by reaction of ketone 2-813 with 2-815. With regard to the subsequent cy-doaddition step of 2-817 with the Knoevenagel condensation product 2-816, it is interesting to note that only a normal Diels-Alder process operates with the 1,3-bu-tadiene moiety in 2-817 and not a hetero-Diels-Alder reaction with the 1-oxa-l,3-butadiene moiety in 2-816. The formed spirocydic ketones 2-818/2-819 can be used in natural products synthesis and in medidnal chemistry [410]. They have also been used in the preparation of exotic amino adds these were used to modify the physical properties and biological activities of peptides, peptidomimetics, and proteins... 

Nitroalkenes with Chiral Auxiliaries The use of carbohydrates as chiral auxiliary in Diels-Alder reactions for the stereoselective preparation of carbocyclic and heterocyclic chiral rings is well documented.48 For example, D-manno-nitroalkene reacts with 2,3-dimethyl-1,3-butadiene to give a 65 35 mixture of adducts, as shown in Eq. 8.29. The configurations at C-4 and C-5 have been determined to be (4R,5R) and (45,55), respectively. Hydrolysis of the product followed by degradative oxidation of the sugar side chains leads to enantiomerically... 

The double bond of butenolides reacts under Diels-Alder conditions and the resulting chiral bicycles have served as precursors of prostacycline analogs and chrysanthemic acids (250,251). The butenolide 248 was obtained by the procedure described by Ireland et al. (237). A bicyclo[4.3.0] ring system (254) was prepared by Diels-Alder reaction of 248 with butadiene in the presence of aluminum trichloride. Reduction of 254 (LiBH4) yielded the... 

Sudo and Saigo153 reported the application of ds-2-amino-3,3-dimethyl-l-indanol derived l,3-oxazolidin-2-one 231 as a chiral auxiliary in asymmetric Diels-Alder reactions. The TV-crotonyl and TV-acryloyl derivatives were reacted with cyclopentadiene, 1,3-cyclohexadiene, isoprene and 2,3-dimethyl-l,3-butadiene, using diethylaluminum chloride as the Lewis acid catalyst. The reactions afforded the expected cycloadducts in moderate to high yields (33-97%) with high endo selectivities and high de values (92% to >98%). 

Diels-Alder reactions of chiral 1-sulfinyl-l,3-butadienes generally proceed very slowly, which requires the use of either long reaction times or high pressure to complete the reactions166. The reaction between diene 253 and A-methylmaleimide 117 (equation 70), for example, took 20 days in the absence of a Lewis acid and still 6 days when catalyzed... 

Oppolzer and colleagues performed pioneering work on the application of chiral sultam based dienophiles in asymmetric Diels-Alder reactions. The bomanesultam based dienophiles provided excellent de values in the Lewis acid mediated Diels-Alder reactions with a wide variety of dienes179. The efficiency of the simpler toluene-2,a-sultam based dienophiles was also studied180. Chiral auxiliary 282 proved superior to 283 and 284 in the aluminum Lewis acid catalyzed Diels-Alder reactions of its A-acryloyl derivative with cyclopentadiene, 1,3-butadiene and isoprene, affording the adducts with >90% de. 

Chiral boron catalysts had already been widely used in a variety of reactions before they were applied in Diels-Alder reactions220. Boron catalysts were first employed in the Diels-Alder reactions of quinones with electron-rich dienes. Kelly and coworkers221 found that stoichiometric amounts of a catalyst prepared from BH3, acetic acid and 3,3 -diphenyl-l,l/-bi-2-naphthol (344) catalyzed the reaction of 1-acetoxy-l,3-butadiene (341) with juglone (342) to afford cycloadduct 343 with 98% ee (equation 96). The reaction was supposed to proceed via a spirocyclic borate complex in which one face of the double bond of juglone was effectively shielded from attack by the diene. 

Under the influence of 20 mol% of the chiral aluminum complex (S)-26, 2,3-dimethyl-1,3-butadiene adds to ethyl glyoxylate in dichloromethane at —78 °C to room temperature during 20 h to produce a mixture of the cycloadduct 23 (R2 = Et) (73% yield, 97% ee) and the ene product 24 (R2 = Et) (9% yield, 88% ee)17. The analogous aluminum complexes (R)-27 and (S)-27 (Ar = Ph or 3,5-xylyl) (10 mol% in toluene) catalyze the Diels-Alder reaction of benzaldehyde with the diene 28 to give, after the addition of trifluoroacetic acid, the dihydropyrone 29 in 95% ee, accompanied by a small amount of the corresponding fraws-isomer (equation 19)18. 

An extensive review of the hetero-Diels-Alder reactions of 1-oxabuta-1,3-dienes has been published. Ab initio calculations of the Diels-Alder reactions of prop-2-enethial with a number of dienophiles show that the transition states of all the reactions are similar and synchronous.Thio- and seleno-carbonyl compounds behave as superdienophiles in Diels-Alder reactions with cyclic and aryl-, methyl-, or methoxy-substituted open-chain buta-1,3-dienes.The intramolecular hetero-Diels-Alder reactions of 4-benzylidine-3-oxo[l,3]oxathiolan-5-ones (100) produce cycloadducts (101) and (102) in high yield and excellent endo/exo-selectivity (Scheme 39). A density functional theoretical study of the hetero-Diels-Alder reaction between butadiene and acrolein indicates that the endo s-cis is the most stable transition structure in both catalysed and uncatalysed reactions.The formation and use of amino acid-derived chiral acylnitroso hetero-Diels-Alder reactions in organic synthesis has been reviewed. The 4 + 2-cycloadditions of A-acylthioformamides as dienophiles have been reviewed. ... 

A catalytic asymmetric Diels-Alder reaction was developed by using 3-(3-borylpropenoyl)oxazolidin-2-ones 146. In the reactions of butadiene, isoprene, or 2-methyl-l,3-pentadiene and 146, in the presence of a chiral titanium catalyst 147, the cyclohexene derivatives 148 were formed. 

The stereoselective normal electron demand Diels-Alder reaction of chiral 13-diaza-13-butadienes 42, derived from acyclic carbohydrates, with diethyl azodicarboxylate 2 yields the corresponding functionalized l,23,6-tetrahydro-133,4-tetrazines 43. The observed stereoselectivity is markedly dependent on the relative stereochemistry at C-1 3 - Reactions proceed slowly in benzene solution at room temperature, but are greatly accelerated by microwave irradiation <99JOC6297>. 

Enantioselective Diels-Alder reaction,3 The reaction of the chiral acrylate ester 1 with butadiene catalyzed with this Lewis acid followed by hydride reduction gives the alcohol 2 in 70% chemical yield and 86-91% ee. A1C13 and SnCl4 are inferior in terms of either the chemical or optical yield. The product (2) was used for a chiral synthesis of (R)-(- )-sarkomycin (4). 

The hetero-Diels-Alder reaction of activated butadienes with carbonyl compounds is a convenient method for the preparation of precursors of sugars. Up to three chiral centers are created simultaneously. The high-pressure [4 + 2]cycloaddition of l-methoxybuta-1,3-diene 32 to N-mono- and N,N-diprotected alaninals was investigated [42-45]. The Eu(fod)3-mediated reaction of 32 with alaninal 25 gave a mixture of four diastereoisomers, which was then subjected to acidic isomerization, leading to the thermodynamically more stable pair of adducts syn-33 and anti-34, with predominance of the latter isomer (Scheme 12). The N-monoprotected alaninals reacted with a moderate ryn-diastereoselectivity. This method was used in the synthesis of purpurosamines (see Sec. DI.C). 

Currently available chiral Diels-Alder catalysts have major limitations with regard to the range of dienes to which they can be applied successfully. Indeed, most of the reported catalytic enantioselective Diels-Alder reactions involve reactive dienes such as cyclopentadiene, but 1,3-butadiene and 1,3-cyclohexadiene have not been successfully utilized without reactive 2-bromoacrolein. To solve this problem, a new class of super-reactive chiral Lewis acid catalysts has been developed from chiral tertiary amino alcohols and BBr3 [24] (Eq. 8A.13). This type of chiral super Lewis acid works well for a,fj-acetylenic aldehydes [25],... 

Chiral (.S, .S )-diazaaluminolidine catalyst brought about the first highly enantioselective catalytic Diels-Alder reaction of an achiral C2v-symmetric dienophile with an achiral diene. Addition of 2-methoxybutadiene to A-o-tolylmaleimide in the presence of 20 mol % (5,5)-diazaaluminolidine gave rise to the cycloadduct in 98% yield and 93% ee one recrystallization from i-PrOH-hexane furnished the enantiomerically pure compound [57] (Eq. 8A.34). The Diels-Alder reaction of 2-((trimethylsilyl)methyl)butadiene and A-aryimaleimide promoted by this catalyst has been successfully applied to the enantioselective total synthesis of Gracilins B and C [58],... 

Fig. 9.5 The prototypical Diels-Alder reaction is that between 1,3-butadiene and ethene, to form cyclohexene. The Diels-Alder reaction has been used in the synthesis of complex natural products above, methyl 2,4-pentadienoate reacts with 1,4-benzoquinone to form an intermediate in the synthesis of the drug reserpine. In a one-pot reaction two carbon-carbon bonds are made and three chiral centers ( ) are created with the correct relative orientations (i.e. essentially one diastereomer is formed)...

Chiral dienes have proved to be less popular in asymmetric Diels-Alder reactions than their chiral dienophile counterparts. This is primarily a result of the problem of designing a molecule that incorporates a chiral moiety, such as the formation of a chiral isoprenyl ether or vinyl ketene acetal.187-190 In addition, diastereoselectivities often are not high,54 191-199 as illustrated by the cycloaddition of the chiral butadiene 5 with acrolein (Scheme 26.4). Improved stereoselection is observed through the use of double asymmetric induction, although this is a somewhat wasteful protocol.35,54 177 200... 

Recently, Breitmaier et al. [94] showed that in the hetero Diels-Alder reaction of triketones such as indantrione 2-34 and alloxane with the chiral 2-methyl-1-(1-phenylalkoxy)-1,3-butadienes 2-35 a good diastereoselectivity can be obtained. The cycloaddition proceeded regioselectively with increasing facial selectivity in correlation to the steric demand of the alkyl group at the benzylic position in the auxiliary to give the dihydropyran 2-36 as the major and 2-37 as the minor product (Fig. 2-10). 

Chiral aldehydes such as N-protected a-aminoaldehydes and a-alkoxyalde-hydes as well as chiral butadienes derived from sugars by a Wittig reaction have also been used in the hetero Diels-Alder reactions successfully with the inducing stereogenic centers remaining in the obtained cycloadducts. 

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