Claisen rearrangement reductive

Stille and co-worker developed an attractive route to aza-Claisen precursors. Allylamine reacted with 2-methylpropanal (isobutyraldehyde), for example, to give allylimine 658. When this reacted with 2-methylpropanoyl chloride, N-acyl derivative 659 was produced (94% overall yield from allylamine) and reduction with LiAlH4 give a 98% yield of the tertiary amine, 660. Stille found that conversion of the amine to the ammonium salt by treatment with HCl led to clean conversion to 661 in 82% yield via a [3,3]-sigmatropic rearrangement (an aza-Claisen rearrangement). Reduction of the iminium salt led to an 81% yield of 662 from 661. Stille and co-workers also found that Lewis acids as well as HCl react with the allyl enamine precursor to facilitate the aza-Claisen rearrangement. 2... 

Claisen rearrangement, 1194-1195 dehydration, 622 elimination reactions, 393 oxidation, 625-626 radical reactions, 243-244 characteristics of, 162-164 comparison with laboratory reactions, 162-164 conventions for writing, 162. 190 energy diagram of, 161 reduction, 723-725 reductive animation, 932 substitution reactions, 381-383 Biological reduction, NADH and, 610-611... 

Hydroxyalkyl)porphyrins,84-85 I07b 109 easily accessible from porphyrins by Friedel-Crafts acylation and subsequent reduction, undergo a stereoselective Claisen rearrangement with N,N-dimethylacetamide dimethyl acetal. The substitution pattern and the stereochemical arrangement of the derived chlorins match those of naturally occurring chlorins9 (see Section 1.2.1.2.). 

Single isobacteriochlorin stereoisomers even in enantiomcrically pure form can be obtained230 when the Claisen rearrangement is performed with the pure hematoporphyrin stereoisomers23d which can be prepared by stereogenic enantioselective reduction from diacetyl deuteroporphyrin dimethyl ester. 

Morken et al. developed a reductive Claisen rearrangement of substituted allyl acrylates. The reaction of ( )-hex-2-enyl acrylate 175 was catalyzed by [Rh(COD)Cl]2 (0.25 mol %) and Me-DuPhos (0.5 mol %) with C MeSiH in benzene at 22 °C to give y,8-unsaturated ester 176 with high diastereoselect-ivity, 11 1 (Scheme 46) [80]. The reaction was carried out on a 10 g scale to provide a 70% yield of 176. This reaction was applied to allylic ester 177 to provide 178, which is a key intermediate in the total synthesis of inos-tamycin [24],... 

An intramolecular nitrone 1,3-dipolar cycloaddition reaction to give 46 from 45 followed by reductive N-O bond cleavage afforded a stereoselective synthesis of the tetrahydro 177-1-benzazepines 47 the nitrone precursors 44 were prepared in turn by a Claisen rearrangement from an IV-allylamine <06SL2275>. 

Shortly after these results were published, Giguere and coworkers reported dramatic reductions in reaction times in other MW-assisted syntheses, including Diels-Alder, Claisen rearrangements and ene reactions [2]. These reactions were also performed at elevated pressures, but sealed glass vessels (inside a bath packed with ver-miculite) were used rather than Teflon. 

Allyl acrylates have been reacted with the combination of ClMe2SiH/ [(cod)RhCl]2/Me-DuPHOS (l,2-bis(2,5-dimethylphospholano)benzene) to bring about reduction of the ,/l-unsaturated ester followed by a Claisen rearrangement to the y,8-unsaturated carboxylic acid (Eq. 293)474 Other silanes did not perform as well in this sequence. 

Several applications of this methodology are known. For the determination of the relative configuration of the stereocenter and the axial chiral unit of 71, the product of a diastereoselective ester enolate Claisen rearrangement of 70, with AgBF4 a cycli-zation to 72 was initiated. Then the carboxylic acid was reduced to alcohol 73 and the position of the substituents was investigated by NMR and by the use of NMR shift-reagents (Scheme 15.16) [32], Control experiments ensured the stereospecifi-city of the cyclization and the reduction step. There are further examples of this strategy [33]. 

Selective protection of the primary alcohol gave 138 (P=TBDMS), which was then esterified with ( )-3-hexenoic acid to produce the key intermediate 139 for cyclization. Ireland ester-enolate Claisen rearrangement and hydrolysis produced a protected hydroxyacid, which, after reduction of the acid and deprotection of the alcohol, yielded meso diol 128 more quickly and efficiently than in the previous synthesis. The meso diol was then converted to the racemate of the lactol pheromone 130 as previously described. 

Simple aromatic aza-Claisen rearrangement without charge acceleration by addition of an acid required other activating factors to enable the reaction to be run at acceptable temperatures. The reduction of ring strain was found to serve as a useful promoter to induce aromatic aza-Claisen rearrangement [21]. 

An elegant ring expansion methodology has been developed by Paquette [699] (Figure 3.41). This synthetic sequence is based on the double methylenation of an a-(acyloxy)aldehyde to give an allyl vinyl ether, which undergoes (reductive) Claisen rearrangement when treated with trialkylalanes. 

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