Reduction Ireland-Claisen rearrangement

Scheme 9.16 Domino reductive conjugate reduction/Ireland-Claisen rearrangement.

Schkeryantz and Pearson (59) reported a total synthesis of ( )-crinane (298) using an intramolecular azide-alkene cycloaddition (Scheme 9.59). The allylic acetate 294 was first subjected to an Ireland-Claisen rearrangement followed by reduction to give alcohol 295, which was then converted into the azide 296 using Mitsunobu conditions. Intramolecular cycloaddition of the azide 296 in refluxing toluene followed by extrusion of nitrogen gave the imine 297 in quantitative yield. On reduction with sodium cyanoborohydride and subsequent reaction with... 

Chelated Ireland-Claisen Rearrangement of 4,4,4-Trifluorobut-2-enyl Methoxyacetates 12 to Acids 13, and Reduction to 2-Methoxy-3-(trifluoromethyl)alk-4-en-1-ols 14 General Procedure 44... 

The C27-C38 segment 208 was prepared from D-galactal 227 (O Scheme 26). The silyl ether, prepared from 227, was selectively benzylated, and the resulting C3-alcohol was desilylated and propanoylated to afford 228. After the Ireland-Claisen rearrangement of 228, carboxylic acid 229 was subjected to iodolactonization followed by reductive removal of iodine to give y-lactone 230. This was converted to the C27-C38 segment 208. 

Dehydration and reduction of the resulting cyclohexenone under Luche s conditions gave the corresponding allylic alcohol. Esterification with an acid representing the C39 to C26 part of rapamycin gave compound 389. Finally, Ireland-Claisen rearrangement gave the branched-chain cyclohexane 390. 

Claisen rearrangement The Ireland-Claisen rearrangement Stereoselective Reduction of p-Hydroxy Ketones... 

Ireland-Claisen rearrangement of 81, followed by methylation, afforded the intermediate 82 as a single stereoisomer. DIBAL reduction to the aldehyde and successive Wollemberg homologation afforded the key nitro-olefin 83. 

In 1991, the Danishefsky group disclosed the synthesis of the C-28-C-49 subunit of rapamycin utilizing the combination of the Perrier carbocyclization reaction and an Ireland-Claisen rearrangement (see Section 12.3.3. Scheme 12.21T The Perrier carbocyclization of 5-enopyranoside 86, prepared from 2-deoxy-d-glucose derivative (Section 12., Scheme 12.2ST followed by elimination of the p-hydro group gave cyclohexenone 152 tScheme 12.40T Luche reduction of 152 afforded cyclohexenol 83 stereoselectively. Condensation of 83 with carboxylic acid 84, prepared from (i )-3-(benzylojg )-2-methylpropanal, provided ester 82 in 75% yield. 

An iterative Claisen rearrangement starting from allylic ester 38 was used in the synthesis of the tocopherol side chain 42 and pine sawfly pheromones (Scheme 5.2.12) [24]. Ireland-Claisen rearrangement of (Z)-allylic ester 38 and in situ reduction of the silyl ester afforded alcohol 39 as a single product Completion... 

Corey et al. have reported the synthesis of a 5-lactone, an intermediate in their early synthesis of the key intermediate 74 of atractyligenin 73, via lactonization of a 5-hydroxy acid [51] (Scheme 14). Corey-Bakshi-Shibata reduction of enone 68 under optimized conditions in the presence of freshly prepared catalyst 69 afforded alcohol 70 in 88 % enantiomeric excess. A fluoride-induced destannylation of 70 gave seco-acid 71, which was lactonized using W-(3-dimethylaminopropyl)-W -ethylcarbodiimide hydrochloride (EDC) and 4-(dimethylamino)pyridine (DMAP) to provide lactone 72. This intermediate was then elaborated to the key intermediate 74 via alkylation and Ireland-Claisen rearrangement. 

Ariza et al. utilized the TST-RCM in conjunction with the Ireland-Claisen rearrangement to facilitate the total synthesis of (—)-phaseolinic acid (Scheme 8.3) [14]. The C2-symmetrical silaketal 6 was prepared in 58% overall yield using an adaptation of the protocol described by Evans and Murthy [13], which employed enantiomerically enriched propargylic alcohols to form the symmetrical bis-alkoxysilane rather than allylic alcohols. Selective reduction of the his-alkyne with Lindlar catalyst, followed by RCM with catalyst [Ru]-I, afforded the silaketal... 

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. 

Claisen-Ireland rearrangement of 239 followed by DIBALH reduction gives a mixture of syn and anti isomers 240 (equation 194)34-347. In a similar manner, orthoester Claisen rearrangements of 241 give stereoselectively the corresponding chiral allylsilanes 242 (equation 195)348. 

The Ireland contribution to nonactic acid synthesis, outlined in Scheme 4.32, involves a selective silyl ketene acetal formation and Claisen rearrangement in the key step. D-Mannose (209) was readily converted in a straightforward manner to dihydrofuran 212 via 210 and 211 in 36% overall yield. Esterification of the free alcohol with propionyl chloride followed by the an enolate Claisen rearrangement afforded a mixture (89 11) of tetrahydrofuryl propionates 213 after catalytic reduction. 

An electrochemical oxidative decarboxylation in combination with an ester enolate Claisen rearrangement was reported by Wuts et al. (Scheme 5.2.26) [51]. A variety of allylic esters such as 97 was subjected to an Ireland-Qaisen rearrangement, and the resulting acids (98) obtained were submitted to electrolytic decarboxylation in a divided cell to afford ketals 99. The use of the divided cell was necessary to suppress side reactions such as alkene reduction. 

Ireland and co-workers, in their synthesis of the prostanoid skeleton, have described the use of the ester enolate modification of the aliphatic Claisen rearrangement to produce the cyclopentane ring C-8—C-12 bond, viz. (74) ->(75). Conversion of the silyl ester (75) into the lactone (76), with a trace of acid, followed by reduction with DIBAL and aldol cyclization, then led to the prostanoid (77) (Scheme 20). 

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