Camphor Diels-Alder reaction

Chiral heterocyclic compounds containing vicinal oxygen and nitrogen atoms were achieved by an asymmetric Diels-Alder reaction [111] of chiral acylnitroso dienophiles 111. The latter were prepared in situ from alcohols 110, both antipodes of which are available from camphor, and trapped with dienes (Scheme 2.46). Both the yield (65-94 %i) and diastereoisomeric excess (91-96%) were high. 

For acrylates, or type I reagents, applied in asymmetric Diels-Alder reactions, several chiral auxiliaries such as menthol derivatives, camphor derivatives,16,3 and oxazolidinones4 are available. Carbohydrate compounds have also been reported as chiral auxiliaries in a recent publication, although the stereoselectivity was not good.5 Here are examples in which asymmetric Diels-... 

Camphor sultam derivatives have proved to be effective chiral auxiliaries in many different types of asymmetric reactions. As shown in Scheme 5-44, chiral camphor sulfam can be applied in the synthesis of (—)-pulo upone precursor 151 using an intramolecular Diels-Alder reaction. A Wittig reaction of 148 with 147 connects the chiral auxiliary to the substrate, and subsequent intramolecular Diels-Alder reaction via transition state 150 affords product 151. Compound 151 already has the stereochemistry of (—)-pulo upone 153.72... 

Asymmetric Diels-Alder reactions have also been achieved in the presence of poly(ethylene glycol)-supported chiral imidazohdin-4-one [113] and copper-loaded silica-grafted bis(oxazolines) [114]. Polymer-bound, camphor-based polysiloxane-fixed metal 1,3-diketonates (chirasil-metals) (37) have proven to catalyze the hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene. Best catalysts were obtained when oxovanadium(lV) and europium(III) where employed as coordinating metals. Despite excellent chemical yields the resulting pyran-4-ones were reported to be formed with only moderate stereoselectivity (Scheme 4.22). The polymeric catalysts are soluble in hexane and could be precipitated by addition of methanol. Interestingly, the polymeric oxovanadium(III)-catalysts invoke opposite enantioselectivities compared with their monomeric counterparts [115]. 

Also the use of moisture stable ionic liquids as solvents in the Diels-Alder reaction has been carried out, and in all examples an enhanced reaction rate was observed [182,183]. The application of pyridinium-based ionic liquids allowed the utilization of isoprene as diene [184]. The chiral ionic liquid [bmim][L-lactate] was used as a solvent and accelerated the reaction of cyclopentadiene and ethyl acrylate, however, no enantiomeric excess was observed [183]. In addition several amino acid based ionic liquids have been recently tested in the Diels-Alder reaction. Similar exo. endo ratios were found but the product was obtained as racemate. The ionic liquids were prepared by the addition of equimolar amounts of HNO3 to the amino acids [185]. Furthermore, an enantiopure imidazolium salt incorporating a camphor motive was tested in the Diels-Alder reaction. No enantiomeric excess was found [186]. 

The hetero-Diels-Alder reaction of homochiral camphor-derived thiabutadienes has given, for the first time, optically active bornene ring-fused dihydrothiopyrans with high diastereoselectivity (Scheme 53) <2000H(53)1685>. The exo endo- t2X o varied with the nature of substituent, varying from 91 9 (X = CH2, R = R = H) to 1 99 (X = CO,... 

It was clear that 1 would be derived from a Diels-Alder adduct. There has been a great deal of work in recent years around the development of enantioselective catalysts for the Diels-Alder reaction, but the catalysts that have been developed to date only work with activated dienophile-diene combinations. For less reactive dienes, it is still necessary to use chiral auxiliary control. One of the more effective of those was the known camphor-derived tertiary alcohol, so that was used in this project. Diels-Alder cycloaddition of the diene 4 with the enantiomerically-pure enone 5 led to the adduct 6 with high diastereocontrol. Oxidative cleavage led to the acid 7, which was carried on to the bis-enone I. 

The reagent has one handicap only (+)-pulegone is readily available. Consequently, Oppolzer and coworkers2 have examined a number of chiral alcohols, derived from various monoterpenes, in which the hydroxyl group is similarly shielded. The endo, e/.r-diphenylmethylisoboraeol (2), obtained from ( + )-camphor, and the enantiomer, obtained from ( —)-camphor, are almost as effective as 1 as chiral adjuncts in this Diels-Alder reaction. 

Racemic camphor can be produced by total synthesis from 1,1,2-trimethylcyclopentadiene and vinyl acetate through a Diels-Alder reaction (Scheme 5.8).40 Currently, about three-fourths of the camphor sold in the United States are produced synthetically, and most is in the racemic form.41... 

Carbonyl compounds have also been used as electrophiles with the intermediate 719 to afford a-allenic alcohols758,783 788 1016 1030,1033-1051 and, after hydrolysis, the corresponding hydroxy enones1034 1037 1051. The chiral acrylate equivalent endo-2-acryloylisoborneol (726), used in metal-free Diels-Alder reactions, has been prepared by reaction of (-El-camphor with compound 7191039 (Scheme 190). 

Chiral metal alkoxides M(OR)4 have been developed as asymmetric variants of ordinary Lewis acids, such as A1C13 and ZrCU, and are used as catalysts for selective carbon-carbon bond formation. Thus, starting from bidentate l,l -bi-2-naphthol derivatives (BINOL) and SnCU, a series of chiral tin(iv) aryloxides 221 (Figure 7) was prepared and successfully applied to the enantioselective Diels-Alder reaction <2006TL873>. Similar silocanes obtained from menthone- or camphor-derived 2,2 -biphenols have been obtained and their configuration was analyzed by NOE differential spectroscopy (NOEDS) <1997JOC7156>. 

Camphor-10-sulfonic acid (1) is available in large quantities in both enantiomeric forms. In only 3 steps the cyclic sulfonamide 2 (sultam) can be synthesized, which can be acylated with acid chlorides after deprotonation with sodium hydride (Scheme 1) [1, 2]. The resulting amides 3 are considerable more reactive towards nucleophiles than the corresponding carboxylic esters and the a,/ -unsaturated derivatives undergo, with excellent selectivities, Diels-Alder reactions or Michael additions under mild conditions. Al-... 

DIELS-ALDER REACTIONS Allylidenecy-clopropane. 1 -Bromo 2-chlorocyclopro-pene. 2-Bromomethy -3-(trimethylsilylme-thyObutadiene. Camphor-10-sulfonlc acid. 

By using chiral auxiliary groups derived from phenylmenthol or camphor, Lewis acid catalyzed Diels-Alder reactions gave an easy access to enantiomerically pure carbamate alcohols38,39. For example, the enantiomerically pure cycloadduct from cyclohexadiene and chiral IV-sulfinyl carbamate could be transformed into the bicyelic carbamate with complete transfer of chirality. 

Zwanenburg and coworkers have examined the diastereoselectivity of chiral sulfme systems in Diels-Alder reactions. In one case, a-chlorosulHne (195) derived from camphor reacts with 2,3-dimethy(butadiene via attack on the sulfme conformer indicated in equation (103) to afford adduct (196) as a single diastereomer. 

Diastereoselective acylnitroso Diels-Alder reactions were performed using enantiopure hydroxamic acids derived from camphor and a-amino acids as chiral auxiliaries (Equation 90) <1997JOC3806, 1998T10537, 2003TL4571>. 

This is a Diels-Alder reaction in which 25 as the dienophile and 26 as the diene form a new cyclohexene ring. In terms of the electron demand this is a normal Diels-Alder reaction with an electron-rich diene 26 and an electron-poor dienophile 25. The use of a chiral camphor-derived auxiliary means that only one diastereomer is obtained in 70 % yield. The reaction proceeds via the endo transition state 38 with the auxiliary blocking one side of the dienophile. 

Optically pure sultams have been used by Oppolzer as chiral auxiliaries in various asymmetric transformations, including Diels-Alder reaction, aldoliza-tion, conjugate addition, his-hydroxylation, and catalytic hydrogenation [42,43]. In the literature, the most commonly used chiral sultam is derived from camphor (Oppolzer s sultam). The ready access to 80 and other chiral sultams from the Diels-Alder cycloadducts could further expand the scope of their use as chiral auxiliaries in asymmetric synthesis. 

The in situ photochemical generation of 1,2-dithioketones and -aldehydes including dithioglyoxal, 3,3-dimethyl-2-thioxobutanethial, and camphor dithioquinone was confirmed by the subsequent trap of the 1,2-dithiocarbonyl compounds in [4 + 2] cycloadditions. The 1,2-dithioketones and 1,2-dithioaldehydes exhibited a preference for 4ir participation in inverse electron demand (LUMOdlene controlled) Diels-Alder reactions with electron-rich dienophiles (Scheme 8-X).37... 

USE Manuf resins in organic synthesis as the diene in the Diels-Alder reaction producing sesquiterpenes, synthetic alkaloids, camphors. 

Asymmetric Diels-Alder reaction, ene reaction, hydrogenation, halogenaflon by means of dwal olelin, such as camphor derivative 1 or 2. 

In an original publication which describes the addition of diphenylmethyl chloride to the enolate of ( + )-camphor [( + )-2] and subsequent reduction, it was claimed that the endo, tWoalcohol 24 was formed in such a reaction sequence23. However, other authors found the exo.e.xo-alcoho]24 using the same procedure, and attributed this to possible differences in the reaction and/or work-up methods which were not described precisely in the original article. The alcohols 24 thus obtained were used for the formation of chiral enol ethers and esters used as dienophiles in Diels - Alder reactions (Section D. 1.6.1.1.1.2.2.1.). 

OTHER COMMENTS, used in organic synthesis as the diene in the Diels-Alder reaction producing synthetic alkaloids and camphors useful as the starting materials for synthetic prostaglandin, chlorinated insecticides, and formation of cyclopentadienyl iron dicarbonyl dimer also used in manufacture of resins. 

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