Cyclopentadienes Lewis acid promoted

The ene reaction of fuUerene (C o) with 3-methylene-2,3-dihydrofuran gives an easily isolated addition product in good yield <96JOC2559>. There is a continuous need for chiral acrylate esters for asymmetric Diels-Alder reactions with high diastereoselectivity. Lewis acid promoted Diels-Alder reactions of acrylate esters from monobenzylated isosorbide 28 (or isomannide) and cyclopentadiene provided exclusively e db-adducts with good yields and high diastereoselectivity <96TL7023>. 

Diels-Alder Cycloadditions (AUcene -+ Six-Membered Cycloadduct). lV-Acryloyl-a-methyltoluene-2,a-sultam (3a) participates in highly endo and C(a)-re ir-face selective Lewis acid promoted Diels-Alder reactions with Cyclopentadiene, 1,3-Butadiene, and Isoprene (eq 2 and Table 1). These levels of induction compare favorably with most alternative auxiliaries, including the 10,2-camphorsultam. However, V-crotonyl-a-methyltoluene-2,a-sultam (ent-3b) reacts with cyclopentadiene with only mod-... 

The four possible transition-state structures for the Lewis acid-promoted Diels-Alder reaction of cyclopentadiene with propynal are depicted in Fig. 7. In the chiral Lewis acid-promoted reaction, the enantiomeric excess of an adduct originates in the enantiofacial selectivity of cyclopentadiene, which has prochiral reactive centers. The enantioselective pathway presupposes three characteristics (i) the chiral Lewis acid must sterically shield one enantioface of the coordinated propynal because the open acetylenic jr-face in the chiral catalyst-dienophile complex approaches one face of... 

In Lewis acid-promoted Diels-Alder reactions of cyclopentadiene with the acrylate of (iS )-ethyl lactate, good diastereofacial and endolexo selectivity are obtained with SnCU (84 16 endolexo = 18 1) and TiCU (85 15 endolexo = 16 1) [104]. It is interesting to note that boron, aluminum, and zirconium Lewis acids give the opposite diastereofacial selectivity (33 67 to 48 52). 

As another example, the Diels-Alder reaction of 2-0-acryloyl derivative of methyl 4,6-di-O-benzyl-3-0-(f-butyldimethylsilyl)-a-D-glucopyranoside 117, prepared from methyl a-D-glu-copyranoside 96, with cyclopentadiene, was explored under thermal or Lewis acid-mediated conditions [94] (O Scheme 31). Under thermal (rt) conditions, the 2-0-acryloyl ester 117 provided one endo-addvLCi 118R with moderate endo/exo selectivity (74 26) and good r-facial selectivity (de = 82%). Under Lewis acid-promoted conditions, another enclo-adduct 118S was a predominant product with good jt-facial selectivity. 

A third approach to brefeldin A by Greene dealt with a version of the second synthesis designed to provide optically active 161, as shown in Scheme 1.39. Enantiomerically pure alcohol (S)-( -i- )-240, obtained via resolution of the derived phthalate mono ester with brucine, was acylated with acryloyl chloride to afford 241. Lewis acid promoted Diels-Alder reaction of 241 and cyclopentadiene then led to a 75% yield of diastereomers 242a (endo) and 242b (exo) in a 97 3 ratio. 

Excellent selectivities were observed in Lewis acid-promoted Diels-Alder reactions. In general, cyclopentadiene or 1,3-butadiene were chosen as dienes (see, table column 4). Anthracene and other dienes, as for example (5) or (6), were examined in isolated cases as indicated in the following table. 1-Acetoxy-1,3-butadienes (5) and diene (6) were employed in natural product syntheses furnishing the desired cycloadducts as single diastereomers. 

Excellent selectivities were observed in Lewis acid-promoted Diels-Alder reactions of chiral alkylidene malonates (D), fumarates (C) and allenic esters (G) with cyclopentadiene (see, column 3 in die table below). 

Moderate selectivities were observed in non-catalyzed and Lewis acid-promoted aza Diels-Alder reactions of non-activated imines with cyclopentadiene and 1,3-butadienes. 

In the first Corey prostaglandin synthesis we saw the use of an acyl anion equivalent . Now we will see another application of the equivalency concept , use of a real reactant that, after some functional group manipulations, can be used to accomplish a transformation that could not be accomplished otherwise. Let s look at the tactics that were ultimately used by the Corey group. Sodium cyclopentadienide was alkylated with chloromethyl methyl ether to provide 37. Chloromethyl methyl ether is extremely reactive and thus, this reaction could be accomplished at a low temperature, below the temperature at which 37 isomerizes to cyclopentadienes 38 and 39. Cyclopentadiene 37 was then reacted with an excess of 2-chloroacrylonitrile, an extremely reactive dienophile. Under the influence of Lewis acid promotion (copper tetrafluoroborate) this diene-dienophile pair underwent cycloaddition, to give 40 at temperatures where diene isomerization did not occur. Although 40 was obtained as a mixture of endo and exo diasteromers, it is notable that the dienophile approached 37 from the sterically least... 

Chiral aluminum catalyst 2, prepared from Et2AlCl and a Vaulted biaryl ligand, is reported to be an effective Lewis acid catalyst of the Diels-AIder reaction between methacrolein and cyclopentadiene, affording the adduct in 97.7% ee [4] (Scheme 1.2). Although the Diels-AIder reaction with other a,/ -unsaturated aldehydes has not been described, that only 0.5 mol% loading is sufficient to promote the reaction is a great advantage of this catalyst. 

It is believed that clay minerals promote organic reactions via an acid catalysis [2a]. They are often activated by doping with transition metals to enrich the number of Lewis-acid sites by cationic exchange [4]. Alternative radical pathways have also been proposed [5] in agreement with the observation that clay-catalyzed Diels-Alder reactions are accelerated in the presence of radical sources [6], Montmorillonite K-10 doped with Fe(III) efficiently catalyzes the Diels-Alder reaction of cyclopentadiene (1) with methyl vinyl ketone at room temperature [7] (Table 4.1). In water the diastereoselectivity is higher than in organic media in the absence of clay the cycloaddition proceeds at a much slower rate. 

Oppolzer sultam-like chiral auxiliary (e.g., Xc in 304) has been studied in Diels-Alder cycloaddition reactions (Scheme 43) <2003JP0700>. The TiCU-promoted reaction of dienophile 304 and 1,3-cyclopentadiene 305 in DCM is complete within 18h and excellent diastereoselectivity of product 306 is observed. The same reaction in the absence of Lewis acid provides product 306 in very low yield. However, switching to trifluoroethanol as the solvent, the cycloaddition reaction proceeds to completion, albeit with slightly diminished levels of diastereoselectivity for Diels-Alder adduct 306. Surprisingly, the use of hexane as the solvent affords the opposite (23, J 31-diastereomer of 306 as the major product. 

Diels-Alder catalyst.2 The acrylates (4) of three chiral alcohols (1-3) have been found to undergo asymmetric Diels-Alder reactions with cyclopentadiene (equation I) in the presence of a Lewis acid catalyst. For this purpose, catalysts of the type TiCl2(X2) are superior to TiCl4 because they do not promote polymerization of the acrylate. The final products (6) all have the enrfo-orientation the configuration (R) or (S) depends upon the chiral alcohols. Those derived from 1 all have (S)-configuration ... 

Diphenyl-BINOL-derived chiral aluminum reagents are prepared in situ by addition of Ethylaluminum Dichloride or Diethylaluminum Chloride to 3,3 -diphenyl-BINOL. These chiral aluminum reagents promote the enantioselective Diels-Alder reaction of cyclopentadiene with the oxazolidone dienophile (eq 14). Endo products are obtained with a high level of asymmetric induction (>90% ee) however, a stoichiometric amount of the Lewis acid is required. The preparation and use of a C3 symmetric BINOL-derived boronate has been reported (eq 15). BINOL-B(OAr)3 complexes have recently been developed for the asymmetric Diels-Alder reaction with imines (eq 16). ... 

Chiral titanium and aluminum Lewis acids (465), prqrared in situ from (463) at (464), promote the addition of cyclopentadiene to N-acryolyl- and N-crotonoyl-oxazolidinones (466) (Scheme 110, Table... 

Figure 7. Four possible transition structures in the Diels-Alder reaction of propynal and cyclopentadiene promoted by Lewis acid. ML = Lewis acid.

The asymmetric Diels-Alder reaction of optically active acrylate and cyclopentadiene is promoted by Et2AlCl as a Lewis acid giving the endo adduct preferentially with moderate diastereoselectivity the use of MAD once again enhances diastereo-selectivity (Sch. 131) [170]. 

In 1979, Koga and coworkers disclosed the first practical example of a catalytic enantioselective Diels-Alder reaction [44] promoted by a Lewis acidic complex, presumed to be menthoxyaluminum dichloride (1), derived from menthol and ethylaluminum di chloride, whose structure remains undefined [45]. This complex catalyzed the cycloaddition of cyclopentadiene with acrolein, methyl acrylate, and methacrolein with enantioselectivities as high as 72% ee. Oxidation of 2 (predominantly exo) followed by recrystallization actually lowered the ee ... 

Finally, acyclic primary alcohols have proved to be less efficient than cyclic secondary alcohols28, even with bulky anchoring substituents. Ethyl lactate, when employed as a chiral auxiliary for the acrylate 15, results in an inversion of the sense of induction according to the nature of the Lewis acid used to promote its addition to cyclopentadiene (9)29. 

A one-step Lewis acid-catalysed intermolecular 4- -3-cycloaddition of aromatic a,)3-unsaturated aldehyde and ketones (105) with epoxides (106) formed seven-membered oxacycles (107) under mild conditions (Scheme 34).The effect of oxygen-, sulfur-, and halogen-substituents on the reactivity of nitrogen-stabilized oxyallyl cations in 4- -3-cycloaddition reactions has been extensively investigated. Aza-oxyallyl cationic intermediates react with cyclopentadiene and furan via an aza-4 -I- 3-cycloaddition reaction to form bicyclic cycloadducts in moderate yields. The intramolecular formal 4- -4-cycloaddition of conjugated enynes with an e-deflcient cyclobutene (108) yielded a strained six-membered cyclic allene (109) that isomerized to a 1,3-cyclohexadiene (110). This intermediate underwent a thermal or acid-promoted six-electron electrocyclic ring opening to yield a 2,4,6-cyclooctatrienone (111) (Scheme 35). ... 

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