Prelog-Djerassi lactone, stereoselective synthesis

Note that aldol condensations I, II and III concern the creation of a relative configuration 2,3-syn, which can be easily achieved starting from the (Z)-enolates 74a-74c. Scheme 9.27 summarises the synthesis of 93 and 95, which are equivalent to fragments B and A, respectively. Compound 88 is the abovementioned Prelog-Djerassi lactonic acid 42 which is obtained in optically pure from (>98% ee). On the other hand, for the stereochemical control of the aldol condensation IV a different methodology is necessary whih involves the coupling of two structurally predefined reactants and which will not be discussed here (Scheme 9.28). An important feature of this reaction is that the coordination of Li" " with the oxygen atom at the P-position of the aldehyde 95 is mainly responsible for the observed stereoselection [22e]. 

The BF,-etherate-catalyzed reaction of 1 with the aldehyde 2 provides a short stereoselective synthesis of the Prelog-Djerassi lactonic acid 3. 

Maruyama, K, Ishihara, Y, Yamamoto, Y, A short and stereoselective synthesis of ( )-Prelog-Djerassi lactonic acid. Tetrahedron Lett., 22, 4235-4238, 1981. 

Scheme 8-15 Stereoselective synthesis of the Prelog-Djerassi lactone.

J. Rodriguez et al. have investigated the stereoselective ester dienolate Carroll rearrangement of ( )- and (Z)-allylic (3-keto esters and found a new, attractive approach to the synthesis of the Prelog-DJerassi lactone and related... 

Evans, D. A., Bartroli, J. Stereoselective reactions of chiral enolates. Application to the synthesis of (+)-Prelog-Djerassi lactonic acid. Tetrahedron Lett. 1982, 23, 807-810. 

The aldol addition reaction, and the related crotyl metal additions (section 5.1), have figured prominently in the total synthesis of a number of complex natural products (reviews [48,140-142]). Figure 5.8 illustrates those mentioned in the preceding discussion, along with others selected from the recent literature, with the stereocenters formed by stereoselective aldol addition indicated ( ). For the Prelog-Djerassi lactone and ionomycin, recall (Figure 3.8) that most of the other stereo-centers were formed by asymmetric enolate alkylation. 

Laevoglucosenone provides short, stereoselective routes to chiral synthons leading to (-)-S-multistriatin and (+)-Prelog-Djerassi lactonic acid (84)(see also Vol.16, p.265). The allo-oxiran (85) (obtained from D-glucose) has been used as the chiral control in a synthesis of chrysanthemic acids (86)(Scheme 17), the cyclopropane ring being formed by Wadsworth-Emmons reaction. ... 

Methods for the preparation of optically active compounds have been reviewed. Still and his co-workers recently developed the hydroboration of acyclic 1,4-dienes as a method for the controlled creation of stereocentres. Two groups have now exploited this method in a short synthesis of the Prelog-Djerassi lactone (111). The key step in both routes is the hydroboration-oxidation of (109) to (110) that is highly stereoselective with respect to three of the four stereocentres of (110). 

Chiral boron enolates are effective in enantioselective aldol condensations, a transition-state model being proposed for the moderate chirality transfer exhibited (Scheme 57). ° Diastereoselection with chiral lithium enolates has also been demonstrated by a highly stereoselective synthesis of the Prelog-Djerassi lactonic acid. ... 

Valerolactones.—During a total synthesis of ( )-Malyngolide (120), thermolysis (reflux in cyclohexane) of the epoxy-acid (119) was found to give (120) stereoselectively in 50% yield.A new route to mevalonolactone has been developed which could prove especially useful for the introduction of labels at the C-3 and 3-CH3 positions. Yet another synthesis of the Prelog-Djerassi lactone has been reported. 

Upon lithiation and reaction with electrophiles. In fact, the conversion of (14 R = Me) into (16 R = Me, E = Me) is a crucial step in the synthesis of the (- )-Prelog-Djerassi lactone (18) and gives 97 % of the desired isomer. Another synthesis of the Prelog-Djerassi lactone involves the three- and Cram-selective aldol lactonization of the lithiated aldehyde (19) and the enamine (20) to give the lactone (21), a direct precursor to (18), with 90% stereoselectivity. ... 

Rearrangement of enone 10, shown in Figure 10.4 [6], provided another enone 11, convenient starting material in the stereoselective synthesis of Prelog-Djerassi lactone [7]. 

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