Danishefsky diene

Danshefsky s diene [19] is the 1,3-butadiene with amethoxy group at the 1-position and a trimethylsiloxy group at the 3-position (Scheme 18). This diene and Lewis acids extended the scope of hetereo-Diels-Alder reactions with aldehydes [20], This diene reacts with virtually any aldehyde in the presence of Lewis acids whereas dienes usually react with only selected aldehydes bearing strongly electron accepting a-substituents. There are two (Diels-Alder and Mukaiyama aldol) reaction pathways (Scheme 18) identified for the Lewis acids catalyzed reactions of Danishefsky diene with aldehydes [21, 22]. The two pathways suggest that these reactions occur on the boundary between the delocahzation band (the pericyclic... 

In a related reaction, the Danishefsky diene 1434 cyclizes with ethyl pyruvate 1435 in the presence of catalytic amounts of the asymmetric Lewis acid catalyst 1436, at -72 °C in THF, to give the Diels-Alder adduct 1437, in 85% yield and 91% ee, and the ring-opened product 1438, which cyclizes, however, with triflic acid to give 1437 [11] (Scheme 9.9). 

Chloro-2-cyclopropylideneacetate (4) is one of the most studied and reactive dienophiles. It reacts readily with open-chain dienes, like 2,3-dimethylbutadiene (35), at room temperature to yield 41 (79%) (Scheme 7) or Danishefsky diene 42 to give exclusively the regioisomer 43 [15] (Scheme 8). 

The reaction of 4-chloro-7-nitrobenzofurazan 232 with the electron-rich Danishefsky diene provides a new and efficient access to a series of functionalized hydroxynaphthofurazans (Scheme 61) <2001TL7571>. 

Kobayashi and his team have utilized a catalytic system similar to that used in their development of a Zr-catalyzed Mannich reaction (Schemes 6.27—6.29) to develop a related cycloaddition process involving the same imine substrates as used previously (Scheme 6.35) [105]. As the representative examples in Scheme 6.35 demonstrate, good yields and enantioselectivities (up to 90% ee) are achieved. Both a less substituted version of the Danishefsky diene (—> 110) and those that bear an additional Me group (e. g.— 111) can be utilized. Also as before, these workers propose complex 89, bearing two binol units, to be the active catalytic species. 

Scheme 6.35. Zr-catalyzed enantioselective addition of Danishefsky dienes to o-hydroxyphenylimines the structure of the purported chiral catalyst (89) is also shown.

As far as catalytic enantioselective cycloadditions to imines are concerned, the only non-Zr-catalyzed process is a Cu-catalyzed protocol reported by Jorgensen (Eq. 6.22) [112]. It should be noted, however, that high enantioselectivities are attained only with highly substituted versions of the Danishefsky diene. 

Danishefsky dienes [98] cycloadd to Cjq in refluxing toluene or benzene [5, 38, 99-101]. The diene 103 adds in 60% yield to Cjq to give the desilylated ketone 104 [5,101]. Acid-catalyzed methanol elimination then furnishes the enone 105 in 82% yield (Scheme 4.17). As already described, this enone can be reduced by DIBAL-H to the corresponding alcohol for further functionalization. The same a,(3-un-saturated alcohol can also be obtained in better yield by Diels-Alder reaction of Cg0 with butadiene, followed by oxidation with singlet oxygen to the allylic hydroperoxide and PPhj reduction to the desired alcohol [101]. This sequence yields the allylic alcohol in 53%, starting from Cjq without the need of isolating intermediates. 

Treatment of the intermediate silylenolefher, obtained by reaction of 106 with CgQ, with SiOj and triethylamine leaves the methoxy group and yields a mixture of the two isomers 107 and 108 (Scheme 4.18) [99, 100], This reaction can be carried out either photochemically or thermally. Because the trans-product 107 is the major product under both thermal and photochemical conditions, the mechanism of this addition is concluded to proceed stepwise. The first step is probably an electron transfer from the Danishefsky diene to CgQ. At least for the photochemical pathway this electron-transfer step could be proven [100]. 

A difluorinated analogue of the Danishefsky diene has been prepared by reductive defluorination with Mg(0) of an a,/i-unsaturated trifluoromethylketone. Its use in a hetero-Diels-Alder reaction (including asymmetric version) can lead to oxygen- and nitrogen-containing heterocycles (Figure 2.25)." ... 

ZnCl2 was also used for a hetero-Diels-Alder reaction of 192 with Danishefsky diene. The dihydropyranone was obtained in 61% yield and good diastereoselectivity (Equation 59) <1998T14573>. 

The reaction of carbohydrate-derived imines with the Danishefsky diene, ( )-1 -methoxy-3-(trimethylsilyloxy)butadiene, to form heterocycles via the open-chain adducts (for assignment, see pp 456 and 478)130. 

Determination of the configuration at the newly created stereogenic center in heterocycles 29a and 29b (obtained from imines 28a and 28b and the Danishefsky diene, p416) byconversion to the alkaloids ( -anabasine (31 a) and (S)-coniine (31b), respectively, through a reaction sequence involving removal of the auxiliary, as discussed on p 45613°,... 

New possibilities in hetero-Diels-Alder condensation have been opened by the introduction of highly active l-methoxy-3-trimethylsilyloxy-, 4-benzoyIoxy-l-methoxy-3-trimethylsilyloxy-, and 2-acetoxy-l-alkoxy-3-trimethylsilyloxy-l,3-butadienes ( Danishefsky dienes, 5). These compounds readily react under atmospheric pressure, in the presence of Lewis acids, with normal aldehydes (e.g., acetaldehyde, benzaldehyde, furfural) to furnish 2,3-disubstituted or 2,3,5-trisubstituted derivatives of 2,3-dihydro-4H-pyran-4-one 7 capable of readily functionalizing to sugars (Scheme 5) [26]. This approach... 

Diels-Alder reactions.2 This diene provides an alternative to l-methoxy-3-trimethysilyloxy-1,3-butadiene (Danishefsky diene) in Diels-Alder reactions. Examples ... 

The polymer-bound Mn and Cr complexes were used as catalysts for epoxidations of six phenyl-substituted olefins with m-CPBA/NMO and for dihydropyranone formation from the Danishefsky diene and aldehydes. There are several remarkable features of the novel immobilized salens ... 

As far as the first category of reactions is concerned, a nice and representative example deals with the addition of several analogs of Danishefsky dienes to give the functionalized fullerene-fused cyclohexanones [86], as shown in Scheme 5. The presence of the carbonyl group makes this system suitable for further chemical transformations, leading to useful materials in nanotechnological areas. 

In contrast, the Hoveyda and Snapper groups reported the efficient catalysis of silver acetate complexes of imine 204.86 These authors first established the superior performance of IV-ort/zo-methoxyaniline-substituted imines in the reaction with Danishefsky diene 195. Because of the modular nature of ligand 206, optimization of its structure could be achieved by surveying a combinatorial library of amino acid derivatives. The /-isoleucine para-methoxyaniline conjugate 206 proved the best. This ligand facilitated full conversion within 2-3 h with high yield and enantioselectivity (Scheme 2.53). 

The DielsAlder reaction of 4//-pyran-4-one 451 with Danishefskys diene gives cycloadduct 452 <1996H(43)745>. 

The hetero-DielsAlder reaction (hDA) using iminium species has been commonly used for the synthesis of reduced pyridines and pyridones . The aza-1,3-butadiene 107 was employed in hDA reaction to synthesize the key intermediate 108 in the total synthesis of the pyridine-based natural product piericidin (Scheme 60) <2005JA15704>. The reaction of Danishefskys diene with N-functionalized imine 109 in the presence of (A)-BINOL zinc complex has been utilized to produce 4-piperidones 110 in moderate to high enantioselectivity (Scheme 61) <2004SL711>. 

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... 

Addition of the Danishefsky diene derivative (l ,3Z)-l-methoxy-2-methyl-3-[(trimethylsilyl)oxy]penta-l,3-diene 216 (Scheme 1.19), was shown by Mikami, Fukuzumi, and co-workers to proceed in a stepwise process,... 

Scheme 1.19. Diastereoselective addition of a Danishefsky diene derivative (216) to (V,o- The product distribution is indicative of a stepwise reaction, because the major diastereoisomer (( )-217) obtained after hydrolysis of the silyl enol ether function of the primary adduct cannot result from a concerted [4 + 2] cycloaddition.

The B-alkylated CAB catalyst (3) is easily prepared in situ by mixing a 1 1 molar ratio of tartaric acid derivative and phenyl-boronic acid in dry propionitrile at room temperature for 0.5 h. The hetero Diels-Alder reaction of aldehydes with Danishefsky dienes is promoted by 20 mol % of this catalyst solution at —78 °C for several hours to produce dihydropyranone derivatives of high optical purity (eq 9). 

A chiral Lewis acid prepared in situ from magnesium iodide and (/ ,f )-DPEN efficiently catalyzes asymmetric aza-Diels-Alder reaction of a methyl glyoxylate/p-anisidine derived imine with the Danishefsky diene to give the cyclic adduct in 97% ee (eq 11). ... 

One of the most popular dioxygenated dienes is l-methoxy-3-trimethylsilyloxy-1,3-butadiene (109), the so-called Danishefsky diene (Scheme 30). The elegant application of this and related polyoxygen-ated dienes in synthesis was reviewed in 1981. ° [4 + 2] Cycloadditions of diene (109), wifo typical electron-poor dienophiles, display increased reactivity and legiochemical control owing to die synergism of die two oxygen atoms. Acidic hydrolysis of the initial cycloadducts readily affords cyclohexenones, phenols or cyclohexadienones (c/. Action 4.1.2, Schemes 12, 17,18 and 21). A pertinent example is the... 

We have developed a stable CAB 2 (R = aryl) complex that can be prepared in situ by mixing tartaric acid derivative and arylboronic acid at room temperature. In contrast with 2, R = H, which is both air- and moisture-sensitive, the B-alkylated catalyst 2, R = aryl or alkyl, is stable and can be stored in closed containers at room temperature (Eq. 39). A solution of the catalyst (20 mol %) is effective in catalyzing the hetero Diels-Alder reaction of aldehydes with a Danishefsky diene to produce dihydro-pyrone derivatives of high optical purity (up to 98 % ee) (Eq. 40) [39]. The extent of asymmetric induction is largely dependent on the structure of the boronic acid. In general, bulky phenylboronic acid (R = 2,4,6-Me3CeH2, o-MeOC6H4) results in excellent asymmetric induction. 

The Brpnsted acid-assisted chiral Lewis acid (BLA) 28, prepared from a 1 2 molar ratio mixture of a trialkylborate and optically pure binaphthol, is also an excellent chiral promoter for the aza Diels-Alder reaction of imines with Danishefsky dienes (Eqs 44 and 45). Enantioselectivity and double diastereodifferentiation in reactions employing chiral 28 are slightly better than those using chiral 27 [41]. 

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