Vitamin E side chain

An elegant example of a stereo relay in a nonrigid system employed a chiral vinyl lactone 430 For the relay to be completely successful (i) the ionization of the vinyl lactone must occur from one conformation, (ii) the intermediate ir-allylpalladium complex must retain its stereochemistry, and (iii) the nucleophile must attack regioselectively at the carbon of the allyl system distal to the incipient carboxylate. This distal transfer of chirality was achieved as shown in equation (346). This same process has been utilized in a synthesis of an optically active vitamin E side chain from D-glucose.431... 

The rigidity of the allene and its facile formation were imaginatively exploited in a synthesis of the vitamin E side chain alcohol, in which an overall transfer of 1,4 to 1,5 acyclic stereoselection process was achieved (Scheme 8).162... 

Chenevert, R. Desjardins, M. Enzymatic desymmetrization of meso-2,6-dimethyl-l,7-heptanediol. Enantioselective formal synthesis of the vitamin E side chain and the insect pheromone tribolure. /. Org. Chem. 1996, 62, 1219-1222. 

Heathcock, C.H., Finkelstein, B.L., Jarvi, E.T., Radel, PA. and Hadley, C.R. (1988). 1,4-and 1,5-Stereoselection by sequential Aldol addition to a,6-unstaurated aldehydes followed by Claisen rearrangement. Application to total synthesis of the vitamin E side chain and the archaebacterial C40 diol. J. Org. Chem., 53,1922-1942. 

Yamamoto reported an efficient asymmetric synthesis of the Vitamin E side chain 44.6 in which the key step was an Sn2 reaction of the C2-symmetric dioxolane 44 3 with trimethylaluminium [Scheme 2.44].1<>0 The reaction was slow at -15 °C but delivery of the methyl group was highly diastereoselective (dr -98 2) giving the dioxolane 44 5. 

The vitamin E side chain can be prepared stereoselectively by addition to an homochiral vinyl lactone (equation 62). The product is the result of selective anti addition. 

A stereocontrolled synthesis of the vitamin E side chain alcohol was achieved in an elegant fashion (equation 121) allowing mutation from a 1,4- to a 1,5-acyclic stereoselection process applicable also to the optically active series . 

This domino Wacker-Heck reaction is the key step of this total synthesis. In the presence of catalytic amounts of Pd(OTFA)2, the chiral ligand (S,S)-Bn-BOXAX (5) and j -benzoquinone (13) as reoxidant, phenol 19 first undergoes an intramolecular enantioselective Wacker oxidation and then reacts with methyl vinyl ketone (9) in a Heck reaction to afford chroman 22 with part of the vitamin E side chain in 84 % yield with 97 % ee. 

Tietze and coworkers developed a new total synthesis of vitamin E (1) using a novel enantioselective domino Wacker Heck process as the key step. This allows the formation of the chroman framework 22 with the required i -configuration at the stereogenic center C-2 in 97 % ee with concomitant introduction of part of the vitamin E side chain in 84 % yield. Condensation with (3i )-3,7-dimethyloctanal (21), synthesized from 7 -citronellol (20), followed by reaction with methyl lithium and hydrogenation completed the synthesis. 

Reaction of reagent (27) with crotonaldehyde provides a syn aldol, which is transfoimed by a four-step sequence including a Claisen rearrangement into (35 equation 55). Aldol (36), obtained from (27) and acrolein, was converted via propionate (37) into (38), a building block for the vitamin E side chain (equation 56). The strategy of parlaying the 1,2 relative stereochemistry obtainable from the aldol reaction into 1,5 relative stereochemistry by use of a Claisen rearrangement has also been used to prepare the C40 archaebacterial diol and one of its stereoisomers. ... 

This methodology has been used in the synthesis of the vitamin E side chain (Table 7, entry 6) starting from D-glucose81. 

Complete chirality transfer is observed in the left to right vitamin E side chain synthesis starting from (S )-chromanylacetaldehyde (15)389. 

A left to right synthesis of the a-tocopherol (vitamin E) side chain was realized via the ester enolate procedure with 1,4-chirality transfer starting with alcohol 15 as the substrate443. 

In a similar set of reactions a 86.14 mixture of the stereoisomeric alcohols 18 and 16 was obtained from diol 17182. For a right to left" synthesis of the vitamin E side chain see p 3371. 

Figure 4.22. Natural products synthesized by asymmetric 1,4-addition of cuprates to esters citronellic acid [124] California red scale pheromone [129] mycolipenic acid (W. Oppolzer T. Godel, unpublished, quoted in [130]) the alleged norpectinatone [128] vitamin E side chain (W. Oppolzer R. Moretti, unpublished, quoted in [ 130]) southern com rootworm pheromone...

Chirality transfer via 7r-allyl palladium complexes is observed during a synthesis of an optically active vitamin E side chain (Scheme 32). ° The optically active lactone (40) is prepared from D-glucose stereospecific alkylation of the corresponding ir-allyl palladium complex occurs when the nucleophile attacks... 

Helmchen G, Schmierer R. A total synthesis of enantiomerically pure vitamin E side chain using a chiral propionate syn-thon. Tetrahedron Lett. 1983 24 1235-1238. 

The use of DIBAL-H in the presence of the zirconium catalyst 141 leads to a hydroalumination reaction and provides access to functionalized aluminum reagents that have been employed in subsequent carboalumination reactions (Scheme 13.20) [82]. Negishi employed this feature to introduce the two stereogenic centers in an elegant synthesis of the vitamin E side chain 151. 

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