Chiral precursor

With strategic bond guidance, it is easy to find 2-Gp transform disconnections even if neither FG of an effective retron is present. In the case of the bridged aldehyde 160, recognition of the strategic bond shown (in bold face) keys FGI processes in both directions from the bond, which successfully establish the aldol retron leading to molecular disconnection by a sequence of aldol and Michael transforms, to generate a simple chiral precursor.31... 

Figure 10.35 Stereoselective generation of chiral precursors for the synthesis of the lichen macrolactone (+)-aspicillin and the macrolide antibiotic pentamycin using FruA catalysis.

Reactions of nitro compounds with chiral imines have only recently been described. Either chiral 1-phenylethylamine (auxiliary) or the glyceraldehyde acetonide aldehyde was used as the chiral precursors of the imines 66 and 68, which reacted with 3-mesyloxynitropropane to give the 3-nitropyrrolidines dl)-67 and 69, respectively, with good diastereoselectivity. In fact, both products were obtained (almost) exclusively as trans diastereomers with high level of asymmetric induction, but the configurations of the newly formed stereocenters were not determined [44] (Scheme 13). N-Boc imines can be formed... 

Furthermore, iterative approaches are useful methods to construct polyhydroxy chains with 1,2- or 1,3-diol units of any length as chiral precursors for the synthesis of complex natural products [57] because automated synthesis becomes feasible. A preparation of trans-fused polytetrahydropyranes as structural unit for polycyclic ether biotoxines by repeated reaction sequences was recently named reiterative synthesis [58]. 

From the atomic to the macroscopic level chirality is a characteristic feature of biological systems and plays an important role in the interplay of structure and function. Originating from small chiral precursors complex macromolecules such as proteins or DNA have developed during evolution. On a supramolecular level chirality is expressed in molecular organization, e.g. in the secondary and tertiary structure of proteins, in membranes, cells or tissues. On a macroscopic level, it appears in the chirality of our hands or in the asymmetric arrangement of our organs, or in the helicity of snail shells. Nature usually displays a preference for one sense of chirality over the other. This leads to specific interactions called chiral recognition. 

A neat synthesis of the chiral 10,ll-dibenzo[ / thiepine 79 from the chiral precursor 78 has been described. Cyclisation of the lithiated intermediate was mediated via reaction with sulfur W.v(i mid azole) <06OBC2218>. 

Amination. Three laboratories2-4 have reported use of esters of azodicarbox-ylic acid for amination of chiral substrates to provide a synthesis of optically active a-hydrazino and a-amino acids. The di-r-butyl ester is particularly useful because the diastereoselectivity improves with increasing size of the ester group, and in addition these esters are hydrolyzed by TFA at 25°. Two laboratories21 used the lithium enolates of chiral N-acyloxazolidones (2) as the chiral precursors. A typical procedure is outlined in equation (I). Thus reaction of the lithium enolate of 2... 

Reactions of acetal derivatives of aldonolactones involving the lactone carbonyl group or used as chiral precursors in the synthesis of noncarbohydrate natural products are discussed in later sections. 

Carbene-mediated methylenation of aldonolactones provides a direct route to 1-methylene sugars, which may be used as intermediates for the preparation of furanoid or pyranoid C-glycosyl compounds, or chiral precursors for the synthesis of natural products. 

Elements of this synthesis were used as the foundation for a clever synthesis of both enantiomers from a single chiral precursor 49, with a Diels-Alder reaction comprising the key step [64]. The critical concept was the recognition that the Diels-Alder reaction of 49 could proceed through two different transition states (Scheme 7), with the product from one transition state (50a) being the tricyclic alkene 44 which had been readily converted to the desired product 48 in the synthesis of the racemate (see above). The second transition state (50b) would provide intermediate 51 that, with slightly different synthetic manipulations, could be converted to the other enantiomer of 48. The full synthesis has been described in Vol. 1, Chap. 1, and so will not be reiterated here. 

Monofunctionalized and difunctionalized Ru(ll) coordination complexes can be used as enantiomerically pure building blocks and can be cross-coupled to diastereochemically pure multi-Ru(ll) complexes. The enantiomerically pure [(bpy)2Ru(3,8-diethynyl-l,10-phenanthroline)] (PF6)2 (45), [(bpy)2Ru(3-ethynyl-l,10-phenanthroline)] (PF6)2 (44),and [(bpy)2Ru(3-bromo-l,10-phen-anthroline)] (PF6)2 (46) were isolated in their A and A forms. Chiral precursor... 

The preparation of fluorinated catechols and phenols and particularly fluori-nated derivatives of the catecholamines and aminoacids has led to the search for methods which do not induce racemization of chiral precursors. Benzaldehydes and alkoxybenzaldehydes are considered as latent phenols and catechols respec-... 

Sugars are often used as chiral precursors for the synthesis of optically active compounds, because they are readily available in large quantities and they are relatively inexpensive. The major restriction is that only the D-se-ries of sugars is usually available. An exception is arabinose, which is an attractive chiral source since both enantiomers are commercially available. 

Stereospecific synthesis, starting from chiral precursors, has been exploited in many different ways (91, 92). Apart from the usual demands incurred during synthetic work, symmetry considerations (49, 50, 56-59, 91) impose an additional constraint upon the design and synthesis of chiral crown compounds. Generally speaking, it is desirable to prepare... 

Among the 1,4-di-O-substituted-L-threitol derivatives (Figure 14a) the one that has found most use in chiral crown ether synthesis is the 1,4-dibenzyl ether. Not only has it provided (88, 106, 107) a ready entry into the chiral tetrasub-stituted 18-crown-6 derivatives ll-31 to ll-34, but it has also proved to be a usehil chiral precursor for the preparation of chiral disubstituted 9-crown-3 (107), 12-crown-4 (108), 15-crown-5 (108), and 18-crown-6 (109) derivatives l-57, l-58, l-59, and l-60, respectively. In the preparation of l-S8 the base-promoted cyclization with triethylene glycol ditosylate is best carried out (108) with a... 

Thus, the (R)-glycidol (R)-897 was transformed to ethyl (S)-6-benzyloxy-3-methyl-4(E)-hexenoate (S)-899 via addition of acetylide followed by spontaneous isomerization, stereoselective reduction, and Claisen-Johnson rearrangement. The chiral ester (S)-899 was converted to (R)-4-methyl-6-phenylthiohexanol (R)-902. The primary alcohol (R)-902 was then transformed to the terminal acetylene (R)-904, a common intermediate for the synthesis of carbazoquinocins A (272) and D (275). Chain elongation of (R)-904 by two carbon atoms led to (R)-905, the chiral precursor for carbazoquinocin D (275) (639) (Scheme 5.116). 

Dihydropyrimidinones can be reduced by hydrogenation over palladium on charcoal, as demonstrated by the synthesis of the tetrahydropyrimidinone 534 from the chiral precursor 533 <1996TA2233, 1999JOC8668, 2004HCA1016>. 

Many syntheses of chiral allenes of high enantiomeric purity start from chiral precursors, notably propynyl compounds, with the central chirality being converted into allene axial chirality by a mechanism-controlled reaction. 

The prochiral ketones (63) were reduced with (57) at low temperature in high chemical (82-97 %) and optical (31-96%) yields90) to the (S)-alcohols (64). The chiral precursor or (57) can be recovered. 

The three most interesting routes identified between 1990 and 1995 are compared in Table 12.2 in terms of manufacturing costs, investment, environmental impact, and complexity. Although chiral chromatography is relatively complex compared to diastereomeric salt crystallization or synthesis from a chiral precursor, these figures are clearly in favor of the MCC process, mainly because of manufacturing costs and environmental impact. 

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