Stereogenic center absolute configuration

In order to prove the utility of this method and to ascertain the absolute configuration of the products, (S)-alanine has been enantioselectively prepared. The key step is the addition of methyllithium to the AjA -dimethyl hydrazone acetal 4c, derived from diol 3c. In accordance with 13C-NMR investigations it can therefore be assumed that all major diastereomers resulting from the addition of organolithium reagents to hydrazone acetals 4a-c derived from diols 3a, 3b or 3c (Table 3, entries 1 -6) have an S configuration at the newly formed stereogenic center. 

Natural products are valuable substrates for further transformations, especially if they contain one or more stereogenic centers of defined absolute configuration. One of the most frequently used natural products in this respect is the monoter-pene a-pinene (6/3-43), which has also been restructured using domino processes. Mehta and coworkers [241] have used the alcohols 6/3-44, easily accessible from a-pinene (6/3-43), for a ROM/RCM reaction to give 6/3-45 and 6/3-46, which were... 

WIN 64821 (10) and (—)-ditryptophenaline (11) syntheses [7], not only effectively differentiated the two amide moieties but also most importantly marked the first in a series of stereochemical transfer steps in which the stereochemistry of the constituent L-amino acids was relayed to ultimately define each of the relative and absolute stereochemical configurations at all eight stereogenic centers found in the target compound. Finally, /V-methylation of the base-sensitive amide in 77 % yield using methyl iodide and potassium carbonate in acetone completed the 5-step synthesis of our key tetracyclic bromide monomer starting from commercially available amino acid derivatives. 

Some generic structures of /3-amino acids are shown in Fig. 6.40. Since, in /3-amino acids, two C-atoms separate the amino and carboxylate groups, there are two possible locations for attachment of a single side chain (i.e., /32 and /33), or even two or more side chains (e.g., /32,3 and /32,2,3, respectively). In a /3-peptide, these symbols can be used as prefixes, e.g., the /33/32-dipeptide in Fig. 6.40 becomes /33-HAla- /32-HVal for R=Me and R = i-Pr. The stereodescriptors (R) and (S) should be used to specify the absolute configuration at the stereogenic centers. The same rules apply to y-amino acids and y-peptides. 

The P-atom in sarin (9.84), soman (9.85), and tabun (9.87) is a stereogen-ic center, allowing for stereoselective enzymatic hydrolysis [162], This aspect has been extensively investigated for soman, which exists as four stereoisomers by virtue of the presence of a second stereogenic center (C-atom). These stereoisomers are usually designated as C(+)P(-), C(-)P(+), C(+)P(+), and C(-)P(-), where C(+/-) refers to the 1,2,2-trimethylpropyl moiety and P(+/ ) to the P-atom. Such a nomenclature may be convenient but has no implication for the absolute configuration. The C(+)P( ) and Cf-)P(-) epimers are the more active toward acetylcholinesterase and, hence, the more toxic ones. In contrast, the C(+)P(+) and C(-)P(+) epimers are preferentially hydrolyzed... 

A more traveled route to the absolute configuration represented by cyclohexa-1,4-diene 8 involves Birch reduction-alkylation of benzoxazepinone 9.2.5 heterocycle is best prepared by the base-induced cyclization of the amide obtained from 2-fiuorobenzoyl chloride and (5)-pyrrolidine-2-metha-nol. o The molecular shape of enolate 10 is such that the hydrogen at the stereogenic center provides some shielding of the a-face of the enolate double bond. Thus, alkylation occurs primarily at the 3-face of 10 to give 11 as the major diastereomer. The diastereoselectivity for alkylation with methyl iodide is only 85 15, but with more sterically demanding alkyl halides such as ethyl iodide, allyl bromide, 4-bromobut-1-ene etc., diastereoselectivities are greater than 98 2. 

Three years later. List and coworkers extended their phosphoric acid-catalyzed dynamic kinetic resolution of enoUzable aldehydes (Schemes 18 and 19) to the Kabachnik-Fields reaction (Scheme 33) [56]. This transformation combines the differentiation of the enantiomers of a racemate (50) (control of the absolute configuration at the P-position of 88) with an enantiotopic face differentiation (creation of the stereogenic center at the a-position of 88). The introduction of a new steri-cally congested phosphoric acid led to success. BINOL phosphate (R)-3p (10 mol%, R = 2,6- Prj-4-(9-anthryl)-C H3) with anthryl-substituted diisopropylphenyl groups promoted the three-component reaction of a-branched aldehydes 50 with p-anisidine (89) and di-(3-pentyl) phosphite (85b). P-Branched a-amino phosphonates 88 were obtained in high yields (61-89%) and diastereoselectivities (7 1-28 1) along with good enantioselectivities (76-94% ee) and could be converted into... 

Tbe compounds were characterized throughout detailed spectroscopic, spectrometric and chemical analyses. The absolute configuration at the stereogenic centers in compounds 4, 5, 12 and 16 was established by applying the Mosher ester methodology. Furthermore, the structures of coumarins 4, 5 and 10 were confirmed by X-ray analysis. 

The absolute configuration of 41 at the stereogenic centers at C-2, C-7, C-8 and C-9 was determined following the same procedure as for compound 40. The tri-/>-bromobenzoate 41c, whose ten-membered ring conformation ( mmx = 67.34 kcal/mol) resembled those of 40, 41A, 40a and 41a showed a typical split CD and this established the chirality of the 7-OBrBz/8-OBrBz as being positive. Therefore, herbarumin II (41) was characterized as (2i , IS, 85, 9i )-2,7,8-trihydroxy-9-propyl-5-nonen-9-olide (41). 

The conformation and absolute configuration at the stereogenic centers in herbarumin III (42) were established following the same general strategy as for herbarumins I (40) and II (41). 

DHPMs obtained through a Biginelli reaction contain a stereogenic center, and the absolute configuration has a considerable influence on the biological activity. Indeed, the two individual enantiomers may perform different or even opposite... 

DHAP-dependent aldolases produce 2-keto-3,4-dihydroxy adducts with high control of the configuration of the two newly formed stereogenic centers. However, while it can be assumed that the absolute configuration at C3 is independent on the acceptor used in the reaction, the configuration of the stereocenter generated from the addition to the aldehyde (C4 position) in some cases may depend on the structure and stereochemistry of the acceptor [6]. 

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