Luche allylation

Luche allylation (13, 298). One unusual feature of Luche allylation of aldehydes is the use of H20/THF as solvent. More recently Wilson and Guazzaroni1 have effected this allylation with ally halides and zinc dust in an aqueous NH4CI solution with a solid organic support in place of THF. The support can be reverse-phase C-18 silica gel (Custom Chem. Laboratories), biobeads SX8 (Bio-Red), or OV-101 on... 

J.-L. Luche, 1978) to give allylic alcohols. L1AIH4 itself tends to reduce the C = C double bond. 

Schemes 28 and 29 illustrate Curran s synthesis of ( )-hirsutene [( )-1]. Luche reduction58 of 2-methylcyclopentenone (137), followed by acetylation of the resulting allylic alcohol, furnishes allylic acetate 138. Although only one allylic acetate stereoisomer is illustrated in Scheme 28, compound 138 is, of course, produced in racemic form. By way of the powerful Ireland ester enolate Clai-sen rearrangement,59 compound 138 can be transformed to y,S-unsaturated tm-butyldimethylsilyl ester 140 via the silyl ketene acetal intermediate 139. In 140, the silyl ester function and the methyl-substituted ring double bond occupy neighboring regions of space, a circumstance that favors a phenylselenolactonization reac-...

Luche found that tin-mediated allylations can also be performed through ultrasonic radiation, instead of using aluminum powder and hydrobromic acid to promote the reaction.82,83 The use of a saturated aqueous NH4C1/THF solution, instead of water/THF, dramatically increased the yield. When a mixture of aldehyde and ketone was subjected to the reaction, highly selective allylation of the aldehyde was achieved. 

Luche s conditions [71] for the reduction of 124 delivered the unstable allylic alcohol (134), which was quickly treated with TBSCl and EtsN to afford 135 in 70% yield for the two steps (Scheme 31). This 5-step reaction sequence from 125 proved to be usable in sizable quantity ( 20 g) and it also offered the advantage of starting with a simple and commercially available chiral moiety (S-glycidol). 

The total synthesis of several amaryllidaceae alkaloids including that of narciclasine was accomplished in the laboratory of T. Hudlicky. The C2 stereochemistry was established by a two-step sequence Luche reduction of the a,(3-unsaturated cyclic ketone followed by a Mitsunobu reaction. The ketone was first mixed with over one equivalent of CeCIs in methanol and then the resulting solution was cooled to 0 °C, and the sodium borohydride was added. In 30 minutes the reaction was done, and the excess NaBH4 was quenched with AcOH. The delivery of the hydride occurred from the less hindered face of the ketone and the allylic alcohol was obtained as a single diastereomer. 

During the final stages of the total synthesis of (-)-subergorgic acid by L.A. Paquette and co-workers, the transposition of a tricyclic enone was needed. The enone was exposed to the Luche conditions and an 85 15 mixture of diastereomers was obtained. In order to achieve this level of diastereoselectivity, the reaction temperature had to be lowered to -50 °C instead of the usual 0 °C. The major product was formed via the exo attack of the carbonyl group by the hydride. The allylic alcohol was later converted to the corresponding sulfoxide followed by a Mislow-Evans rearrangement to the isomeric allylic alcohol. 

Luche reduction Reduction of enones to the corresponding allylic alcohols using CeCl3/NaBH4. 268... 

Various functionalized allylic halides have been used under the Luche conditions. Thus, 2-bromomethyl acrylate reacted with carbonyl compounds to give a-methylene-y-butyrolactones after acidic treatment of the alcoholic intermediate [102]. The reaction of ciimamyl chloride with aldehyde, unlike cinnamyl bromide which led to phenyl propene leaving the aldehyde unchanged [103], gave the diastereoisomeric y-products whereas the reaction with ketones gave mixtures of a- and y-products [104]. In the presence of zinc dust, l-chloro-3-iodopropene yielded the corresponding chlorohydrin when reacted with aldehydes or ketones under aqueous conditions. In this way, further treatment with base gave vinyl oxiranes whereas zinc in the presence of aqueous HBr led to (E)-buta-1,3-dienes (Scheme 21) [1051. 

This zinc-promoted reaction has been used with a variety of carbonyl compounds. Thus, the Luche conditions were applied in a synthesis of (-1-)-muscarine using an aldehyde derived from ethyl lactate [109]. Allyl halide condensation onto a-ketoamides of proline benzyl ester gave good diastereoselec-tivity when performed in the presence of zinc dust and pyridinium p-toluene-sulfonate in a water/THF mixture. In this way, a-hydroxy ketones were obtained with good enantioselectivity after removal of the chiral auxiliary [110]. Reactions of allyl bromide under the Luche conditions with y-aldo esters afforded y-hydroxy esters, which were converted in a one-pot reaction to y-allyl-y-butyro-lactones (Scheme 22) [111]. 

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. 

The Luche reduction involves a selective 1,2-reduction of a,p-unsaturated aldehydes and ketones using sodium borohydride in combination with cerium(III) chloride, resulting in the formation of allylic alcohols.1... 

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... 

Luche conditions have also found synthetic utility in the preparation of steroid derivatives such as the shark repellent pavoninin-5 and aragusterol H, an antiproliferative agent.38 During the synthesis of pavoninin-5, the intermediate enone 32 is reduced to the enantiopure allylic alcohol 33 in 98% yield. p-Delivery of the hydride is rationalized by blocking of the a-face by the bulky chlosterol side chain. Additionally, the flattened D-ring reduces the steric hindrance of the C-18 methyl group. 

This reaction was first reported by Luche in 1985. It is the modification of the initial aqueous allylation of carbonyl compounds (in 1983) via the intermediacy of tin in the presence of a catalytic amount of hydrobromic acid (HBr), to the zinc mediated allylation of carbonyl compounds using ultrasonic irradiation in saturated aqueous NH4CI/THF solution. Thus the new reaction condition is referred to as the Luche reaction. In parallel, Li" and Chan extended the Barbier-Grignard-type reaction to successfully proceed in aqueous media and contributed to the new area called green chemistry. ... 

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