Danishefsky-type diene

Yamamoto et al. were probably the first to report that chiral aluminum(III) catalysts are effective in the cycloaddition reactions of aldehydes [11]. The use of chiral BINOL-AlMe complexes (R)-S was found to be highly effective in the cycloaddition reaction of a variety of aldehydes with activated Danishefsky-type dienes. The reaction of benzaldehyde la with Danishefsky s diene 2a and traws-l-methoxy-2-methyl-3-(trimethylsilyloxy)-l,3-pentadiene 2b affords cis dihydropyrones, cis-3, as the major product in high yield with up to 97% ee (Scheme 4.6). The choice of the bulky triarylsilyl moiety in catalyst (J )-8b is crucial for high yield and the en-antioselectivity of the reaction in contrast with this the catalysts derived from AlMe3 and (J )-3,3 -disubstituted binaphthol (substituent = H, Me, Ph) were effective in stoichiometric amounts only and were less satisfactory with regard to reactivity and enantioselectivity. 

A chiral vanadium complex, bis(3-(heptafluorobutyryl)camphorato)oxovana-dium(IV), can catalyze the cycloaddition reaction of, mainly, benzaldehyde with dienes of the Danishefsky type with moderate to good enantioselectivity [21]. A thorough investigation was performed with benzaldehyde and different activated dienes, and reactions involving double stereo differentiation using a chiral aldehyde. 

Immmium salts constitute a class of generally reactive hetero dienophiles. During the past several years a number of examples have been describe of [4 + 2] cycloadditions of imines with oxygenated dienes under Lewis acid catalysis. - These reactions probably involve intermediate immonium salts which react regio- and often stereo-selectively with these electron-rich 1,3-dienes. Danishefsky and coworkers have provided several instances of this type of process. Equation (18) shows an approach to... 

Intermolecular Diels-Alder reactions are also highly useful for the construction of polycyclic carbocycles in natural product total syntheses. Rawal combined a cyclohexadienone with a Danishefsky-type diene to yield a c -decalin in his total synthesis of platencin. °° Stratakis also generated a cw-decalin upon combination of a quinone dienophile and an acyclic diene during the production of acremine G. Nakamura and Hashimoto employed an intermolecular Diels-Alder reaction for the construction of the G ring in pitmatoxin A. Danishefsky reacted a vinylindene diene with a quinoneketal dienophile to form the tetracyclic framework of fluostatin... 

Chiral scandinm(III)-A, A"-dioxide complexes catalyze enantioselective aza-Diels-Alder reaction of aldimines with Danishefsky-type diene (Scheme 12). The complexes catalyzes the reaction between 1,3-butadiene and aldimines. 

Chiral Lewis acids derived from complexes between copper(I) chloride with phosphino sulfenyl ferrocenes are efficient catalysts for enantioselective aza-Diels-Alder reaction of A-sulfonyl imines with Danishefsky-type dienes (eq 47), and asymmetric conjugate addition of Grignard reagents to cyclic enones (eq 48).136... 

Ito et al. foxmd that this catalyst system gives the best result for the reaction of y-substituted y-butenolide 140c with Kitahara-Danishefsky-type diene giving rise to a key intermediate 172 for synthesis of yonarolide (Scheme 70) [118]. 

In 1988, our group developed the use of BINOL-aluminum complex to catalyze highly enantioselective hetero-Diels-Alder reaction between Danishefsky type dienes and aldehydes (Fig. 9) [50]. Since then, a lot of catalytic asymmetric reactions utilizing this type of mononucleus aluminum catalysts have been developed [6]. 

Danishefsky-type dienes or O-acylation of enones. J. Org. Chem. 2009 74(22) 8882-8885. 

Cycloadditions. The MgBr2-mediated cyclocondensation of a Danishefsky-type diene with chiral a-alkoxy aldehydes affords a... 

The cyclocondensation of Danishefsky s diene 35 with alaninals of type 25, contrary to diene 32, requires neither elevated pressure nor high temperature. The zinc bromide-mediated reaction of 35 with alaninal 25 was followed by acidic workup, resulting in removal of both the trimethylsilyl protection and the ethoxy group [45,46] (Scheme 13). 

Keck [63] and Carreira [64] have independently reported catalytic asymmetric Mukaiyama aldol reactions. Keck et al. also reported the aldol reaction of an a-benzyloxy aldehyde with a Danishefsky s diene. The aldol product was transformed to the corresponding HDA-type product through acid-catalyzed cyclization. In these reactions, the catalyst that is claimed to... 

A very useful intermediate for the attachment of further functionalities to Cgo is obtained by reaction of the fullerene with 2-[(trimethylsilyl)oxy]buta-1,3-diene, followed by hydrolysis of the resulting silyl enol ether under formation of a fullerene-fused cyclohexanone (214) which is reduced to the racemic alcohol ( )-215 (Scheme 1.18).374 Because of their great synthetic potential, silyloxy-substituted dienes, such as Danishefsky diene type systems,375-377 have been widely used in the preparation of fullerene derivatives, mostly in the form of stereoisomeric mixtures.378-383... 

An important discovery in the area of carbonyl cycloadditions is that highly oxygenated 1,3-dienes are excellent 4ir components. These reactions occur at low temperatures with a wide range of aldehydes provided Lewis acid catalysts are used. " " This general type of reaction is shown by the example in equation (81). It was also found by Danishefsky and coworkers that lanthanide shift reagents are elective catalysts for the cycloaddition.An example of one of these cycloadditions is outlined in equation (82). 2 <>... 

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). 

The data in Table 18 summarize observations made for the reaction of a series of different oxygenated dienes with benzaldehyde in the presence of several different catalysts. Danishefsky s diene is only a moderate substrate for this reaction giving the pyrone 378 in 56 % ee. High induction for this substitution pattern can be obtained with the diene 379 and the trixylylsilyl substituted catalyst. An in-depth analysis of the effect of the nature of the silicon substituents on the catalyst were made for the reaction of diene 374. Larger substituents not only increase the amount of asymmetric induction, but also increase the yield, and the diastereoselectivity in favor of the cis product. Other BINOL ligands of type 99 (Sch. 47, R = H, Me, Ph) were examined they would only function stoichiometrically and gave less satisfactory results. 

Keck also investigated asymmetric catalysis with a BINOL-derived titanium complex [102,103] for the Mukaiyama aldol reaction. The reaction of a-benzyloxyalde-hyde with Danishefsky s dienes as functionalized silyl enol ethers gave aldol products instead of hetero Diels-Alder cycloadducts (Sch. 40) [103], The aldol product can be transformed into hetero Diels-Alder type adducts by acid-catalyzed cyclization. The catalyst was prepared from BINOL and Ti(OPr )4, in 1 1 or 2 1 stoichiometry, and oven-dried MS 4A, in ether under reflux. They reported the catalyst to be of BINOL-Ti(OPr% structure. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

Further extension of the reaction pool of Schilf bases 138 was achieved by their reaction with tran -l-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (Danishefsky s diene) to give 2-substituted 5,6-didehydro-piperidin-4-ones 164 [135,136] (Scheme 10.54). The reaction is considered to be a sequence of an initial Mannich reaction between the imine and the silyl enol ether, followed by an intramolecular Michael addition and subsequent elimination of methanol. If the reaction was terminated by dilute ammonium chloride solution, then the Mannich bases 163 could be isolated and further transformed to the dehydropiperidinones 164 by treatment with dilute hydrochloric acid. This result proved that the reaction pathway is not a concerted hetero Diels-Alder type process between the electron-rich diene and the activated imine. The use of hydrogen chloride as a terminating agent resulted in exclusive isolation of the piperidine derivatives 164 formed with... 

As a group, annulation reactions have been exceedingly valuable to the synthetic organic chemist. Unfortunately, processes of this type involving simple alkenes and cycloalkenes are few. However, the facility with which unactivated olefins can be transformed into vinyl sulfones, the high degree to which a, 8-unsaturated sulfones are captured regioselectively by unsymmetrical dienes such as those developed by Danishefsky, and the ease with which reductive desulfonylation can be effected, combine to permit convenient synthetic entry to substituted cyclohexenones. Several representative examples can be found in Table 1. 

The enantioselective total synthesis of the Securienega alkaloid (-)-phyllanthine by S.M. Weinreb et al. involved a stereoselective Yb(OTf)3-promoted hetero Diels-Alder reaction between a cyclic imine dienophile and Danishefsky s diene This was the first example of using an unactivated cyclic imine in this type of cycloaddition. Commonly used Lewis acid catalysts (e.g., SnCb, TiCU, etc.) produced only low yields of the desired cycloadduct. However, it was discovered that ytterbium triflate catalyzed the cycloaddition and afforded the product in 84% yield. Later they also found that the cyclization could occur at high pressure and in the absence of the catalyst, although a slightly lower yield (71%) of the product was obtained. 

Dienes substituted with heteroatoms, X or Y in 145, give allyl (Y in 146) or vinyl (X in 146) derivatives by the Diels-Alder reaction. The heteroatom(s) not only provide latent functionality in the product but also control the regiochemistry of the Diels-Alder reaction itself86. In Danishefsky s vemolepin synthesis87, a compound of type 146 was converted into an enone 147 by hydrolysis since 146 is a 1,3-disub-stituted allyl compounds like the enone precursors in the last section. 

---