Acylnitroso

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

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. 

Table 4.15 Diels-Alder reactions of acylnitroso compounds...

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. 

N-Acylnitroso compounds 4 are generated in situ by periodate oxidation of hydroxamic acids 3 and react with 1,3-dienes (e.g. butadiene) to give 1,2-oxazines 5 (Scheme 6.3). The periodate oxidation of 4-O-protected homo-chiral hydroxamic acid 6 occurs in water in heterogeneous phase at 0°C, and the N-acylnitroso compound 7 that is generated immediately cyclizes to cis and tranx-l,2-oxazinolactams (Scheme 6.4) [17a, b]. When the cycloaddition is carried out in CHCI3 solution, the reaction is poorly diastereo-selective. In water, a considerable enhancement in favor of the trans adduct is observed. 

The acylnitroso approach has been used for the enantioselective syntheses of (—)-swainsonine and (—)-pumiliotoxin C [17d] (Scheme 6.5). 

Vogt P. E., Miller M. J. Development and Applications of Amino Acid-Derived Chiral Acylnitroso Hetero Diels-Alder Reactions Tetrahedron 1998 54 1317 1348 Keywords nitroso and acylnitroso dienophlles, befero-Dlels-Alder reaction... 

Aoyagi, S., Tanaka, R., Naruse, M., Kibayashi, C. (1998) Total Synthesis of (—)-Epibatidine Using an Asymmetric Diels-Alder Reaction with a Chiral N-Acylnitroso DienophUe. Journal of Organic Chemistry, 63, 8397-8406. 

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... 

The source of alcohol 50 is most probably acid-catalysed hydrolysis of 49 to the nitrosocarbonylbenzene intermediates 51, which, like acid chlorides, react with water to give benzoic acids 52 (Scheme 1 pathway (i)).159 Acylnitroso intermediates 51 were trapped as the Diels Alder adducts 53 in reactions in CH3CN/H20 and in the presence of cyclopentadiene. In CH3CN/10% H280, 53 was enriched in lsO... 

Acylnitroso compounds 197 (R = Me, Ph or Bn) react in situ with 1-methoxycarbonyl-1,2-dihydropyridine to yield solely the bridged adducts 198 quantitatively. On the other hand, 1 1 mixtures of the regioisomers 199 and 200 were formed from the nitroso-formates 187 (R = Me or Bn) (equation 110)103. The chiral acylnitroso compounds 201 and 202, which are of opposite helicity, add to cyclohexadiene to give optically active dihydrooxazines in greater than 98% diastereomeric excess (equations 111 and 112)104. Similarly, periodate oxidation of the optically active hydroxamic acid 203 in the presence of cyclopentadiene, cyclohexa-1,3-diene and cyclohepta-1,3-diene affords chiral products 204 (n = 1, 2 and 3, respectively) in 70-88% yields and 87-98% de (equation 113)105. 

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. ... 

After being converted into the hydroxamic acid, A-protected L-Pro was transformed in situ into the acylnitroso dienophile, which underwent cycloaddition with cyclohexadiene to give the bicyclic cycloadduct 108 (or its mirror image) (89TL7061). 

Due to the restricted availability of nitroso components, it more convenient to prepare acylnitroso compounds in situ from iV-acyl or Af-carbamoyl hydroxylamines with NaI04 (equation 100) . Subsequent deprotection results in an Af-unsubstituted dihydro-1,2-oxazine cycle. The reaction is also commonly employed for intramolecular cyclo-additions ". ... 

A new method of generation of acylnitroso compounds is the photochemical cleavage of... 

Zu einer weiteren Diels-Alder-Cyclisierung (intramolekular) einer doppelt ungesattigten Acylnitroso-Verbindung mit Folgereaktionen (z. B. Synthese von 3-Butyl-5-methyl-hexa-hydroindolizin) s. Lit.3. 

The outcome of this reaction can be rationalized by oxygen transfer from a transient intermediate (118 or an oxaziridine) to 1,3-DIBF [but see 89H(29)263]. Trapping of acylnitroso compounds yields similar products [81 JCS(P1)3250]. A similar ring-opening reaction has been observed when diarylalkylidencyclopropenes were reacted with 1,3-DIBF (93TL3131). Without citing [89H(29)263] C Moinet and co-workers reported a... 

V-Acylhydroxylamines are oxidized to the interesting intermediates acylnitroso compounds by the action of Dess-Martin periodinane.59... 

Pseudomonas putida mediated cis-dihydroxylation of bromo or chlorobenzene supplied the requisite chiral starting material 44 for a second synthesis of (+)-7-deoxynarciclasine reported by Hudlicky [18,19]. Subsequent to protection of the diol as the acetonide45 (Scheme 8), its cycloaddition reaction with the N-acylnitroso compound derived from benzyl-N-hydroxycarbamate 46 by in situ oxidation, occurred with complete regio and stereospecificity togive the bromo adduct 47. In a similar fashion, the chloro compound 48 was obtained. 

Another route to ( )-retronecine, together with its C-7 epimer ( )-heliotridine (21), has been described by Keck and Nickell.9 This synthesis depends upon the transfer of an acylnitroso moiety, generated from the Diels-Alder adduct (15) with dimethylanthracene.10 Addition of the lithium enolate of this adduct to the unstable dienal (14), formed as shown in Scheme 4, gave an alcohol (16). 

A new synthesis of ( )-crinane (13) (Scheme 2) may be applicable to Amaryllidaceae alkaloids.5 Key features of the synthesis are the preparation of the acid (10) by Claisen rearrangement of the allylic acetate (9) and intramolecular ene reaction of a protected acylnitroso-enophile (11) to give the cyclic hydroxamic acid (12). 

Enantioselective total syntheses of (-)-6-epitrehazolin and (+)-trehazolin were achieved by the synthesis of 275, which began with an asymmetric heterocycloaddition between [(benzyloxy)methyl]cyclopentadiene (263),108 prepared from thallous cyclopentadienide, and the acylnitroso compound arising from in situ oxidation of (,S )-mandelohydroxamic acid (264) with tetrabutylammonium periodate. Cycloaddition led to a mixture of 265 and its diastereomer (Scheme 35).109 The inseparable mixture was reduced to afford cyclopentenes 266 and 268 in 40% and 11 % overall yields, respectively, from thallous cyclopentadienide. Catalytic osmylation of 266 favored syn addition, while the osmylation of diacetate 267 was more selective and nearly quantitative, affording, after acetylation, compounds 270 and 269 in >5 1 ratio. 

A type 2 intramolecular /V-acylnitroso Diels-Alder reaction of hydroxamic acid 177 followed by catalytic hydrogenation of the double bond was employed for the synthesis of substituted bridged bicyclic derivative 178, as a single diastereomer (Scheme 75 <2002OL2637>). Cleavage of the N-O bond was performed by reduction with Na(Hg) amalgam and provided m-3,7-disubstituted azocane 9, as a single isomer in 80% yield. 

Aliphatic nitroso compounds can be prepared from IV-alkylhydioxylamines oxidation widi bromine, chlorine or sodium hypochlorite in weakly acidic solution, reaction with potassium dichromate in acetic or sulfuric acid, and by oxidation widi yellow mercury(II) oxide in suspension in an organic solvent. Silver carbonate on Celite has also been used to prepare aliphatic nitroso compounds, such as ni-trosocyclohexane, in high yield from the corresponding hydroxylamines." Aqueous sodium periodate and tetraalkylanunonium periodates, which are soluble in organic solvents, are the reagents most commonly used for the oxidation of hydroxamic acids and IV-acylhydroxylamines to acylnitroso compounds... 

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