Diels-Alder reaction, with acylnitroso compounds

Development and application of hetero Diels-Alder reactions with participation of amino acid-derived chiral acylnitroso compounds 98T1317. 

An extensive review of the hetero-Diels-Alder reactions of 1-oxabuta-1,3-dienes has been published. Ab initio calculations of the Diels-Alder reactions of prop-2-enethial with a number of dienophiles show that the transition states of all the reactions are similar and synchronous.Thio- and seleno-carbonyl compounds behave as superdienophiles in Diels-Alder reactions with cyclic and aryl-, methyl-, or methoxy-substituted open-chain buta-1,3-dienes.The intramolecular hetero-Diels-Alder reactions of 4-benzylidine-3-oxo[l,3]oxathiolan-5-ones (100) produce cycloadducts (101) and (102) in high yield and excellent endo/exo-selectivity (Scheme 39). A density functional theoretical study of the hetero-Diels-Alder reaction between butadiene and acrolein indicates that the endo s-cis is the most stable transition structure in both catalysed and uncatalysed reactions.The formation and use of amino acid-derived chiral acylnitroso hetero-Diels-Alder reactions in organic synthesis has been reviewed. The 4 + 2-cycloadditions of A-acylthioformamides as dienophiles have been reviewed. ... 

Similarly, acylnitioso compounds are recognized for their 27r participation in Diels-Alder reactions with dienes and these observations have found substantial application (Chapter 4.2). In addition, recent efforts have detailed the apparent 4ir participation of an acylnitroso compound in a Diels-Alder reaction with a cyclopentadiene that suggests their potentially useful 47r participation in LUMOdiene-controlled Diels-Alder reactions (equation 14). ... 

Acylnitroso compounds are best recognized for their ability to participate as dependable 2ir components of Diels-Alder reactions with dienes, and these observations have found substantial application in the total synthesis of natural products (Chapter 3).81 However, Mackay and coworkers have detailed the isolation of 5,6-dihydro-1,4,2-dioxazine 9a (10%) from the reaction of acylnitroso 7a with cyclopentadiene [Eq. (39)]. ... 

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. 

The nitroso moiety of the N-acylnitroso function is a powerful dienophile and therefore N-acylnitroso compounds are trapped rapidly, especially in an intramolecular reaction, with a diene allowing the Diels Alder reaction to occur also in water, although N-acylnitroso compounds are short-lived in aqueous medium. 

The hetero-Diels-Alder reaction has also utilized dienophiles in which both reactive centers are heteroatoms. Kibayashi reported that the intramolecular hetero-Diels-Alder cycloaddition of chiral acylnitroso compounds, generated in situ from periodate oxidation of the precursor hydroxamic acid, showed a marked enhancement of the trans-selectivity in an aqueous medium compared with the selectivity in nonaqueous conditions (Eq. 12.55).125 The reaction was readily applied to the total synthesis of (—)-pumiliotoxin C (Figure 12.5).126... 

Aliphatic nitroso compounds can be prepared from IV-alkylhydroxylamines by oxidation with bromine, chlorine or sodium hypochlorite in weakly acidic solution, by reaction with potassium dichromate in acetic or sulfuric acid, and by oxidation with yellow mercury(II) oxide in suspension in an organic solvent. Silver carbonate on (Telite has also been used to prepare aliphatic nitroso compounds, such as ni-trosocyclohexane, in high yield from the corresponding hydroxylamines. Aqueous sodium periodate and tetraalkylammonium periodates, which are soluble in organic solvents, are the reagents most commonly used for the oxidation of hydroxamic acids and / -acylhydroxylamines to acylnitroso compounds (40). These compounds are rarely isolated, but are useful as highly reactive dienophiles in the Diels-Alder reaction. ... 

Compound 14 undergoes a retro-Diels-Alder reaction thermally at about 60°C to generate the acylnitroso intermediate which can be trapped by a different diene. Some adducts of acylnitroso compounds with cyclopenta-diene also tend to undergo facile retro-[4 + 2] reactions readily and can... 

C.iii. Nitroso-Type Compounds. Nitroso compounds (R—N=0) show reactivity as dienophiles in Diels-Alder reactions, giving heterocyclic rings. In Kibayashi s synthesis of fasicularin, " for example, hydroxamic acid 180 was treated with tetrapropylammonium periodate in the presence of 9,10-dimethyl-anthracene to give transient acylnitroso compound 181, and the resultant Diels Alder product 182 was formed in 84% yield. In this particular example, the Diels-Alder adduct essentially "protected" the acyl nitroso unit, which was used in a subsequent reaction. 

As our first model we chose N-benzoylnortropane (12) to investigate construction of the tropane ring system based on [4 + 2] nitroso cycloaddition with a 1 3-cycloheptadiene. A search of the literature indicated that only one example of a Diels-Alder cycloaddition of a nitroso compound with a seven-membered ring diene has been reported (ref. 8). In view of this the present study of tropane synthesis was initiated by the examination of the nitroso Diels-Alder reaction of 1 3-cycloheptadiene (7) (Fig. 1). Thus reaction of 7 with the acylnitroso compound 8 generated in situ from benzohydroxamic acid by oxidation with tetrapropyl-ammonium metaperiodate (ref. 9) was carried out at room temperature, affording the [4 +2] cycloadduct 9 in 85% yield. Reduc-... 

The nitroso functionality is a powerful dienophile and N-alkyl- and N-acylnitroso compounds give inter- and intrahetero Diels-Alder reactions easily. The cycloadditions also occur in aqueous medium although some nitroso compounds (i.e. N-acylnitroso derivative) are short-lived in the presence of water. The NO functionality is generated in situ by periodate oxidation of the hydroxylamine group and the cycloaddition with butadienes gives a 1,2-oxazine ring. Scheme 5.16 illustrates the utility of the nitroso Diels-Alder cycloaddition for the synthesis of (—l-swainsonine/ (—)-pumiliotoxin and BCX-1812... 

The normal demand hetero Diels-Alder cycloaddition between nitroso reagents 171 and dienes 172 leads to the formation of 3,6-dihydro-1,2-oxazines 173 via the concomitant stereoselective formations of a C—N and a C O bonds (Scheme 41.36). Several nitroso dienophiles like the a-chloronitroso, arylnitroso, or acylnitroso compounds are known to react efficiently in cycloadditions. Chiral nonracemic chloronitroso and acylnitroso compounds have been developed to achieve diastereoselective nitroso Diels-Alder reactions, and recently Yamamoto and co-workers reported on the first enantioselective-catalyzed cycloaddition with a pyridylnitroso dienophile. ° ... 

Boger and co-workers have recently determined the regioselectivity of acylnitroso compound additions to some 2-substituted 1,3-cyclohex-adienes.5 In the cases of both electron-rich and electron-deficient substituted dienes the same regioisomer predominated by about 3 1 (Scheme 3-IX). It was suggested that the first case is consistent with a normal (HOMOdiene controlled) Diels-Alder process, whereas the second reaction is consistent with either a HOMOdiene or inverse electron demand (LUMOdiene controlled) cycloaddition. 

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