Elimination reactions lithium enolate synthesis

The same elimination strategy was used for the synthesis of the natural product (i )-(-)-dysidazirine 15 as is shown in Scheme 10 [23]. The requisite aziri-dine ester was prepared by treatment of sulfimine 19 with the lithium enolate of methyl bromoacetate. This reaction is a Darzens-type condensation leading to czs-M-sulfinylaziridine ester 20. The elimination of sulfenate was accomplished in the same manner as mentioned above (see Scheme 9). The natural product 15 (see Fig. 1) was obtained in 42% yield. Attempts to prepare azirinomycin 14 in a similar fashion all failed [23]. 

The study of Fuji et al. shows that the addition of lithium enolate 75 to ni-troamine 74 is readily reversible quenching conditions are thus essential for getting a good yield of product 76. An equilibrium mixture of the adducts exists in the reaction mixture, and the elimination of either the prolinol or lactone moiety can take place depending on the workup condition (Scheme 2-34). A feature of this asymmetric synthesis is the direct one pot formation of the enantiomer with a high ee value. One application of this reaction is the asymmetric synthesis of a key intermediate for indole type Aspidosperma and Hun-teria alkaloids.68 Fuji69 has reviewed the asymmetric creation of quaternary carbon atoms. 

The final step in a recent synthesis of cannabichromene (2) is the aromatization of the cyclohexenone ring of 1. Reagents used for this purpose also attack the double bond in the side chain, but the desired reaction was effected by treatment of the lithium enolate of 1 with benzeneselenenyl chloride followed by selenoxide elimination in the presence of 3,5-dimethoxyaniline.5... 

Aspects of the synthesis, structure and reactivity of lithium enolates 553 2. By elimination reactions... 

Lithium enolates can be used directly in aldol reactions, even with enolisable aldehydes, a simple example6 being the synthesis of the enone 32. The ketone 15 forms mostly the less substituted lithium enolate which condenses 29 with butanal to give aldol 31 in reasonable yield. Elimination is usually carried out in acid solution. 

Among the ethers of prolinol, (5)-2-methoxymethylpyrrolidinc [SMP, (S)-10] has found most applications. It is readily prepared from prolinol by the normal sodium hydride/iodo-methane technique9,13 (sec also Section 2.3. for O-alkylations of other amino alcohols) and is also commercially available. An improved synthesis from proline avoids the isolation of intermediates and gives the product (which is highly soluble in water) by continuous extraction14. SMP has been used as the lithium salt in deprotonation and elimination reactions (Section C.) and as an auxiliary for the formation of chiral amides with carboxylic acids, which in turn can undergo carbanionic reactions (Sections D.l.3.1.4., D.l. 1.1.2.. D.l. 1.1.3.1., in the latter experimental procedures for the formation of amides can be found). Other important derivatives are the enamines of SMP which are frequently used for further alkylation reactions via enolates (Sections D.l.1.2.2.. where experimental procedures for the formation of enamines are... 

In the synthesis of aspyrone (994), an antibiotic isolated from the culture broth of Aspergillus species, lactaldehyde 990 supplies the asymmetric centers of the epoxide in the side chain (Scheme 134). The molecule is assembled convergently by addition of the lithium enolate of D-rhamnose-derived a-phenylseleno- -lactone 991 to aldehyde 990. After an initial aldol-type reaction, the intermediate alkoxide displaces tosylate to provide epoxide 992 with >99.8% stereoselectivity. Peroxide-induced elimination of phenylselenide furnishes TBS-protected aspyrone 993 in 61% overall yield from 990. 

Nitroalkenes react with lithium dianions of carboxylic acids or with hthium enolates at -100 °C, and subsequent treatment of the Michael adducts with aqueous acid gives y-keto acids or esters in a one-pot operation, respectively (Eq. 4.52).66 The sequence of Michael addition to nitroalkenes and Nef reaction (Section 6.1) provides a useful tool for organic synthesis. For example, the addition of carbanions derived from sulfones to nitroalkenes followed by the Nef reaction and elimination of the sulfonyl group gives a,P-unsaturated ketones (Eq. 4.53).67... 

The protection of an a, p-unsaturated ketone by a conjugate addition strategy is the subject of our last example but it does not involve the use of an 0,0-acetal. During a synthesis of the cockroach pheromone Periplanone B. Still needed to perform a copper(I)-mediated Sn2 reaction on the allylic acetate 37.1 [Scheme 2.37], In order to prevent competing addition to the a, p-unsaturated ketone, it was protected temporarily by conjugate addition of trimethylstannyl-lithium and trapping of the intermediate enolate with chlorotrimethylsilane. The desired Sn2 reaction was then performed on the adduct 37.2 and the a.p-un-saturated ketone recovered by oxidation of the C-Sn bond to a C-OH using m-chloroperbenzoic acid. Concomitant destruction of the labile enol ether and -elimination of water returned the a, p-unsaturated ketone 373. 

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