Lewis acid catalyzed reaction 4 + 2 cycloaddition

The Lewis acid-catalyzed reaction of nitrone 21 with ethyl vinyl ether 22 (Scheme 8.8) was also investigated for BH3 and AlMe3 coordinated to 21 [32]. The presence of BH3 decreases the activation energy for the formation of 23 by 3.1 and 4.5 kcal mol to 9.6 kcal mol for the exoselective reaction and 11.6 kcal-mol for the endo-selective reaction, respectively, while the activation energy for the formation of 24 increases by >1.4 kcal mol , compared to those for the uncatalyzed reaction. The transition-state structure for the BH3-exo-selective 1,3-dipolar cycloaddition reaction of nitrone 21 with ethyl vinyl ether 22 is shown in Fig. 8.19. 

Optically active norbornene derivatives [26] have been prepared by cycloaddition of hexachlorocyclopentadiene with /-menthylacrylate and /-menthylallyl-ether (Equation 2.9). Low levels of enantiomeric excess have been obtained in the thermal processes, whereas Lewis acid catalyzed reactions (BF3, BBr3, AICI3, SnCU, DCM, 40-80 °C) gave better results. 

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

Because of their previous findings that a,/l-unsaturated thioesters were more reactive than their ester counterparts in Diels-Alder reactions85, Hart and coworkers86 performed a systematic study of the cycloaddition reactions of a,/l-unsaturated thioesters and a,ft-unsaturated selenoesters with several dienes. Thermal reactions were compared with Lewis acid catalyzed reactions at room temperature (equation 28 and Table 2). The results clearly demonstrated that use of a Lewis acid enhanced the regioselectivity (entries 1 vs 2, 3 vs 4, 5 vs 6 and 7 vs 8) as well as the endo (with respect to the thioester or selenoester group) selectivity (entries 5 vs 6 and 7 vs 8). 

Lewis acid catalyzed reaction of oximes 172 (equation 113) with divinyl ketone (173) provided l-aza-7-oxabicyclo[3.2.1]octan-4-ones 174 through a sequential Michael addition and [3 + 2] cycloaddition. The reaction occurred with complete stereoselectivity giving the same product with both cis- and frawi-oximes . 

A chelating enone employed in a Lewis acid catalyzed nitrone cycloaddition reaction should result in a rate enhancement. The first example of such catalysis... 

The thermal reaction produced 5 and 6 in a 3 2 ratio but the Lewis acid-catalyzed reaction gave a 1 1 ratio. We could not separate the two cycloadducts, but based the indicated constitution on analysis of the mass spectrum and lH NMR spectrum of the mixture of the two compounds. The stereochemistry was assigned on the basis that the Diels-Alder reaction is normally suprafacial-suprafacial18 and that for other cycloaddition reactions of levoglucosenone (2) the addition anti to the 1,6-anhydro bridge is favored.13 15... 

Tetrahydro-2-pyridones are also produced by a [4+2] cycloaddition of l-aza-2-siloxydiene with simple dienes in a Lewis acid-catalyzed reaction (Equation 142) <2004S2222>. In an analogous manner, hydrazone derivatives have been in aza-[4+2] cycloadditions with reactive dienophiles which can be trapped with aldehydes to form highly functionalized piperidines (Scheme 88) <2004AGE2001, 2004JOC8429>. 

A wide range of variously substituted thiochromans has been obtained from the readily accessible ot-(benzotriazo-lyl)methyl thioethers by their Lewis acid-catalyzed reaction with styrenes. Initial loss of the benzotriazole unit generates a thionium cation which undergoes an efficient cationic cycloaddition to the alkene. The reaction, which generally proceeds with high diastereoselectivity, is considered to occur in a stepwise manner rather than as a concerted [4++2] process (Scheme 174) <2001JOC5595>. 

Lewis acid catalyzed reactions of allenes with alkenes generally give cyclobutanes rather than ene adducts. AlCb catalyzed reactions of alkylallenes with alkenes give alkylidenecyclobutanes. Similarly, AICI3 catalyzed reactions of alkynes with alkenes give cyclobutenes. These reactions are believed to occur by stereospecific cycloaddition of the alkene with the vinyl cation formed by complexation of AICI3 to the allene or alkyne. 

One of the most effective approaches to implementing the Diels-Alder participation of 1-oxa-1,3-butadienes is through the use of an intramolecular [4 + 2] cycloaddition reaction.A select set of thermal and Lewis acid-catalyzed intramolecular cycloaddition reactions of unactivated and electron-rich alkenes with a,P-unsaturated aldehydes and ketones has been detailed. Two examples of the poorly matched intramolecular Diels-Alder reaction of an a,P-unsaturated aldehyde (4 ir component) with an a, 3-unsaturated amide (2ir component) have proven successful (190-160 °C) and may be attributed to the entropic assistance provided by the intramolecular reaction. These observations have been applied in... 

Dienes are also amenable for activation by copper Lewis acids (Sch. 41) [79]. The intramolecular Diels-Alder reaction of 176 under thermal conditions gave all the possible isomers. In contrast, the Cu(I) promoted reaction gave the isomer 177 as a major product, with minor amounts of 180. Copper(II) Lewis acids were less efficient in the cycloaddition. It is also worth noting that the Lewis acid-catalyzed reaction proceeds at a much lower temperature. 

There are two different modes of cyclizations in hetero [4+2] cycloadditions involving Danishefsky s diene 1) concerted (pericyclic) and 2) stepwise. When carbonyl compounds are reacted with Danishefsky s diene, the stepwise pathway is often referred to as the Mukaiyama aldol reaction pathway. The concerted process is called the Diels-Alder pathway. The mode of cyclization in the case of Lewis acid catalyzed reactions depends on the Lewis acid itself and whether it is present in stoichiometric or catalytic amounts. The Mukaiyama aldol pathway has been... 

Pyrone derivatives containing a 2-pyridyl substituent at C3 can undergo Lewis-acid catalyzed DA cycloadditions with electron-rich dienophiles. Shown in Scheme 30 is the ZnBrj catalyzed cycloaddition of 100 with BVE. After 48 hours at -20 °C, the reaction afforded endo-cycloadduct 102 as only product in 81% yield. 

With the achievement of high stereochemical control resulting from nearly exclusive endo topography in the Lewis acid catalyzed reactions interest next turned to the effect of chiral Lewis acid complexes on the enantiofacial selectivity of the cyclocondensation reaction. For example, consider the cycloaddition of benzaldehyde to diene (8) under the influence of a chiral catalyst. Assuming a pericyclic reaction mode and high endo selectivity, a mixture of two possible products can result. Compound (64) is desig-... 

The auxiliary-controlled, noncatalyzed [4 + 2] cycloaddition of homodienophiles has been thoroughly studied and the results are often compared with Lewis acid catalyzed reactions (see Section 1.6.1,1.1.2.2.2.). A very interesting version of dienophiles bearing a chiral auxiliary are chiral vinylic sulfoxides in which the chirality results from the dissymmetric sulfur atom. The first example studied is the Diels-Alder reaction of ( + )-(/ )-4-methylphenyl vinyl sulfoxide (1) with cyclopentadiene (2), in which four possible diastereomers 3-6 are obtained in an endojexo ratio of (5 + 6)/(3 + 4) 64 36. The diastereomers are further separated the (2 /J)-isomers (3 and 5) being favored. Desulfuration produces pure ( + )- or (-)-dehydronorcamphor. 

The reported thermal [4 + 2] cycloaddition of arylmethylenemalon-dialdehydes with electron-rich olefins including enol ethers, ketene acetals, enamines, and cyclopentadiene (benzene, 25°C) or their Lewis acid-catalyzed reaction with simple olefins including isobutylene and 1,1-diphenylethylene (Znl2 catalyst, benzene, 25°C) further illustrates the Diels-Alder rate acceleration accompanying the substitution of an ,/3-unsaturated aldehyde with a C-3 electron-withdrawing group [Eq,... 

The structures of l-aza-2-siloxydienes 176, prepared by silylation of a,P-unsaturated amides, were rigorously proven. A study of the Lewis acid-catalyzed reactions of 176 with simple dienophiles showed that the [4+2] cycloaddition products 177 did form, along with several... 

Non-chloroaluminate ILs, which are in general poor nucleophiles, have proven to be attractive alternative media for Lewis acid catalyzed reactions. ILs may have a reaction rate accelerating effect, and they may improve selectivity and facilitate catalyst recovery. This is the case for scandium triflate catalyzed Diels-Alder cycloaddition [8,9], three-component (aldehyde, aniline, triethylphosphite) synthesis of a-aminophosphonates [10], Claisen rearrangement and cyclization reactions [11], or Friedel-Crafts reactions [12, 13]. 

Hetero Diels-Alder cycloaddition reactions are of great importance in organic chemistry for the synthesis of six-membered heterocyclic ring systems. " In the past heterodienophiles and -dienes with one or more oxygen, nitrogen or sulfur atoms have been examined in thermal and Lewis acid-catalyzed reactions. " ... 

Thermal and Lewis acid-catalyzed reactions of 1-thia-l,3-dienes with chiral a,P-unsaturated carboxylic acid derivatives lead to thiopyrans. The cycloadditions of chiral a,p-unsaturated oxazolidinones in the presence of aluminum Lewis acids lead to encouraging stereoselectivities. Cleavage of the chiral auxiliaries was achieved by treatment with LiAlHi. 

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