SAMP/RAMP hydrazone method

Figure 2-3. Synthetic scope of the SAMP/RAMP-hydrazone method.

Bestmann et al.166) used the SAMP/RAMP-hydrazone method very successfully in their synthesis of both enantiomers of methylsubstituted pheromone analogues (150) of Lepidopetra species Manestra brassicae (R = n-C4H9), Argyrotaenia velu-tinana, Ostrinia nubilalis and Tortrix viridana (R = C2HS). 

ElectrophiHc substitutions with carbon and hetero electrophiles a to the carbonyl group of aldehydes and ketones are among the most important synthetic operations. Such regio-, diastereo-, and enantioselective substitutions can be carried out efficiently with the SAMP/RAMP hydrazone methodology [3]. For cases where virtually complete asymmetric inductions could not be attained, an alternative approach based on a-silylated ketones 2 was developed [4]. They can be prepared easily from ketones 1 in high enantiomeric purity (ee > 98%) by asymmetric carbon silylation employing the SAMP/RAMP hydrazone method (Fig. 1.1.1). After the introduction of various electrophiles via classical enolate chemistry with excellent asymmetric inductions, the desired product ketones 3... 

Since only a few asymmetric syntheses are known [55], we developed an efficient asymmetric synthesis of (S,S,R)-(-F)-2-epi-deoxoprosopinine ](S,S,R)-87] employing the SAMP/RAMP hydrazone method as key steps [56]. Scheme 1.2.19 describes our retrosynthetic analysis, showing that the title alkaloid can be syn-... 

Dieter Enders, Helmut Kipphardt, and Peter Fey 183 ASYMMETRIC SYNTHESES USING THE SAMP-/RAMP-HYDRAZONE METHOD (S)-(+)-4-METHYL-3-HEPTAN0NE... 

The three-step procedure described here, using inexpensive, commercially available starting materials and the chiral auxiliary SAMP, Illustrates the synthetic utility of the "SAMP-/RAMP-hydrazone method".18 It is remarkable that the classical electrophilic substitution of a conformationally flexible, acyclic ketone 1 (S)-4 occurs with virtually complete asymmetric... 

Table I. Optically Active Carbonyl Compounds and Amines Prepared by Asymmetric Synthesis Using the SAMP/RAMP Hydrazone Method... 

Enders D, Bockstiegel B (1989) Enantioselective alkylation of 2,2-dimethyl-l,3-dioxan-5-one using the SAMP-/RAMP-hydrazone method. Synthesis... 

The synthetic utility of the SAMP/RAMP hydrazone method is demonstrated in particular in the stereoselective alkylation of aldehyde and ketone SAMP/RAMP hydrazones. A great number of natural products have been synthesized using this method, like the principal alarm pheromone of the leaf cutting ant Atta texana (eq 1), the C(l)-C(15) segment of FK 506 (eq 2) the amino acid MeBMT (eq 3), and (-)-methyl kolavenate (eq 4). ... 

The aggregation pheromone of the rice and maize weevil was synthesized by aldol reaction of an enantiomerically pure a-silyl ketone, obtained by the SAMP/RAMP hydrazone method,with various aldehydes (eq 8). ... 

The utility of the SAMP/RAMP hydrazone method in diastereo- and enantioselective Michael additions was demonstrated in the synthesis of 5-oxo esters " (eq 9), -lactones (eq 10), 0x0 diesters and dinitriles, heterocyclic compounds (eq 11), MIRC (Michael initiated ring closure) reactions, and 2-substituted 4-oxo sulfones. ... 

Enders, D, Jegelka, U, l,3-Dioxan-5-one as C3-building block for the diastereo- and enantioselective synthesis of C5- to Cg-deoxy sugars using the SAMP-/RAMP-hydrazone method. Tetrahedron Lett., 34, 2453-2456, 1993. 

Figure 3.10 illustrates several natural products which have been synthesized using this methodology. These include a number of insect pheromones as well as the sesquiterpene eremophilenolide and the antibiotic X-14547A. The latter two compounds have multiple stereocenters but the asymmetric alkylation using the SAMP-RAMP hydrazone method produces one stereocenter which is then used to direct the selective formation of the others. 

Enders and co-workers developed a highly enantioselective synthesis of 4-aryl-dihydro-2-quinolones by combining enaminone chemistry and asymmetric Michael additions with the SAMP/RAMP-hydrazone method. As shown in Scheme 125, the cyclic 1,3-diketones 457 are transformed into... 

Through chemoselective esterification of the primary hydroxy group of the 2-ketoses to the corresponding (S)-3,3,3-trifluoro-2-methoxy-2-phenylpropionic acid [(S)-MTPA] esters [17], we opened an easy and reliable way to determine the diastereomeric and enantiomeric excess by NMR spectroscopy. In addition, by correlation with our SAMP-/RAMP-hydrazone method, the absolute configurations can be assigned [16]. 

The FDP-aldolase catalyzed DHAP-addition to glyoxylic acid, examined in detail by Wandrey and Bossow-Berke under continuous flow reaction conditions [18], required the determination of the relative and absolute configuration. Employing the SAMP-/RAMP-hydrazone method, the aldol reaction of 1 with benzyl glyoxylate afforded a doubly protected adduct, which was deprotected with trifluoroacetic acid anhydride (TFAA) and subsequent debenzylation with H2/ Pd-C to give the final product, identical with the enzyme product. The independent chemical synthesis and the enzymatic route are compared in scheme 4. It... 

Scheme 6. Diastereo- and enantioselective synthesis of protected, C2- symmetric ketodiols using the SAMP-/ RAMP-hydrazone method...

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