Reduction under Luche conditions

The third cycloaddition substrate explored the feasibility of a vinyl nitro functionality as an activated dipolarophile (98, Scheme 1.9c). Preparation of nitroalkene oxidopyridinium betaine 98 began with silylenol ether 92, which was treated with methoxydioxolane in the presence of Lewis acid catalyst, TrC104, to afford keto dioxolane 93 in 58 % yield [47]. Ketone 93 then underwent a-nitration by treatment with /-BuONCL and KOt-Bu to provide nitro ketone 84 (91 %), which was then converted to the nitroalkene functionality via reduction under Luche conditions to... 

Treatment of 462 with iodine and pyridine leads to a-iodination [208]. Successive reduction under Luche conditions, alcohol silylation, carbonylation of the iodoalkene, reduction of the obtained enal and alcohol silylation leads to 463. Ozonolysis of 463 gives the corresponding keto-aldehyde, which is then transformed into 464 via reductive amination with high diastereoselectivity syn anti> Deprotection delivers (-f)-465 (Scheme 13.107). 

A key step in the preparation of a new gibberellin, GA99, involved the reduction under Luche conditions of a Au -2-one derivative to furnish the critical 2p-stereochemistry.17 While the 2-oxo group in 12 was resistant to reduction, presumably due to in situ ketol formation, the methoxymethyl ester derivative was reduced satisfactorily to the desired 2p-epimer 13 using the combination of CeCU and NaBtU. This combination efficiently and selectively delivered the hydride to the more hindered a-face of the A-ring. This example further demonstrates the propensity for hydride delivery via axial addition under Luche conditions. 

Sodium borohydride is sometimes used in conjunction with CeCl3 (Luche s reagent).70 The active reductants under these conditions are thought to be alkoxyborohydrides. Sodium cyanoborohydride is a useful derivative of sodium borohydride.71 The electron-attracting cyano substituent reduces reactivity and only iminium groups are rapidly reduced by this reagent. 

The synthesis of lincosamine employs a slightly different strategy than that used for NeuAc and KDO. By using aldehyde (130) a precursor to the sugar side chain was installed directly in the cyclocondensation reaction (Scheme 37). Reduction of the carbonyl group of pyrone (131) under Luche conditions, epoxidation of the glycal, and a series of manipulations on the alkene side chain to install the amino alcohol portion gives lincosamine (132). 

The stereoselectivity seen in the reduction of the seven-membered ketone above has proved to be general. This particular result, rationalized by the propensity for pseudoaxial hydride addition under Luche conditions, proved useful in the convergent total synthesis of Gymnocin-A, a polycyclic ether toxin isolated from the red tide dinoflagellate—Karenia mikimotoi.u The Luche reduction was used for the production of allylic alcohol 9 from ketone 8 in 84% yield. Luche conditions were similarly applied to the synthesis of the related polycyclic ether toxin gambierol.12... 

For the synthetic application of this method to Erythrina alkaloids, Anh Tuan and Kim [56] reinvestigated the palladium catalyzed cyclization of the requisite precursor which could be formed from the condensation of ketoester 43 and bromo-arylamine 44. In the reaction, two main products were formed. When the intermediate 45 was treated with Pd(OAc)2 in DBU, an enol intermediate (46) was formed in 30% yield through y-lactam enolate formation followed by cyclization. Some amoimt of the eorresponding ketal compound, the precursor of the enol intermediate, could be obtained if the reaction process was quenched earlier. Treatment of 46 with TsOH in acetone afforded compound 47 in 71% yield. Reduction of the carbonyl compound 47 under Luche condition, affording a mixture of diasteromers in a 2.6 1 ratio, was followed by elimination to afford the known intermediate (48) for erysotramidine (49) in 64% yield. 

The reduction of some substituted divinyl ketones under Luche conditions (sodium borohydride and cerium trichloride) using different alcohols as solvents affords polyenyl alkyl ethers in good yields via rearrangement of allylic cations and nucleophilic attack of the alcohol solvent. ... 

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. 

Aggarwal and Bi proposed the synthesis of 8a-epi-swainsonine (222) from hemiaminal 218 which was prepared from the protected amine 217 in the aza-Achmatowicz reaction as shown in Scheme 42/ The heterocyclic derivative 218 was, under the acidic conditions, transformed into the acetal the carbonyl group was then reduced, under the Luche conditions, providing derivative 219 as practically single isomer. Reduction of the double bond with simultaneous removal of the Cbz group and cleavage of the N,0-acetal afforded piperidine 220 which was easily transformed, via 221, into 8a-epi-swainsonine 222. 

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