Chiral starting materials

Weiland-Mischeler Ketone (chiral starting material)... 

Novel Synthetic Methods. Mote recendy, several novel syntheses of iZ-biotin, starting from a variety of chiral starting materials, have been... 

Methodology for the enantioselective synthesis of a broad range of chiral starting materials, by both chiral catalytic and controller-directed processes, is rapidly becoming an important factor in synthesis. The varied collection of molecules which are accessible by this technology provides another type of chiral S-goal for retrosynthetic analysis. 

Walden inversion (Section 8.4) Originally, a reaction sequence developed by Paul Walden whereby a chiral starting material was transformed to its enantiomer by a series of stereospecihc reactions. Current usage is more general and refers to the inversion of conhguration that attends any bi-molecular nucleophilic substitution. 

Finally, there is the enantioselectivity of the 1,3-dipolar cycloaddition reactions. This chapter is limited to describing only the metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions that involve non-chiral starting materials. The only fac-... 

An enantioselective aldol reaction may also be achieved with non-chiral starting materials by employing an asymmetric Lewis acid as catalyst ... 

In the selection of suitable chiral starting materials for the total synthesis of amphotericin B (1) and amphoteronolide B (2), the recognition of subtle symmetry in the targets played a crucial role. 

Besides high effectiveness in the diastereoselective control of nucleophilic addition reactions, another major goal in the design of chiral auxiliaries is the use of readily available, chiral starting materials. The hexahydro-l//-pyrrolo[l,2-c]imidazole derivatives 9a-e are examples which use the inexpensive amino acid L-proline (7) as starting material. 

The raw materials from which di-D-fructose dianhydrides can be obtained in appreciable yield are readily available from comparatively inexpensive agricultural feedstocks. Thus, these compounds are attractive as chiral-starting materials for chemical synthesis. Their stability to acid and heat, and their relative rigidity, because of the conformational constraints covered here, are also features that might be exploited during syntheses.119 A series of variously substituted di-D-fructose dianhydrides has been prepared,119 starting from 6,6 -dideoxy-6,6 -di-halosucroses. The properties of these and other derivatives of di-D-fructose dianhydrides are summarized in Tables XIV-XX. Two of these derivatives, 48 and 56, exhibit thermotropic liquid-crystal properties.119... 

The first (+)-discodermolide synthesis was completed by Stuart Schreiber s group at Harvard University and is outlined in Scheme 13.68. This synthesis was carried through for both enantiomers and established the absolute configuration of the natural material. The retrosynthetic plan outlined in Scheme 13.67 emphasizes the stereochemical triads found at C(2)-C(4), C(10)-C(12) and C(18)-C(20) and was designed to use a common chiral starting material. Each of the segments contains one of the stereochemical triads. 

Enantiospecific syntheses of amino derivatives of benzo[ ]quinolizidine and indolo[2,3- ]quinolizidine compounds have also been achieved via A-acyliminium ion cyclization reactions, as an alternative to the more traditional Bischler-Napieralski chemistry (see Section 12.01.9.2.2). One interesting example involves the use of L-pyroglutamic acid as a chiral starting material to construct intermediates 240 via reaction with arylethylamine derivatives. Diisobutylaluminium hydride (DIBAL-H) reduction of the amide function in 240 and subsequent cyclization and further reduction afforded piperidine derivatives 241, which stereoselectively cyclized to benzo[ ]quinolizidine 242 upon treatment with boron trifluoride (Scheme 47) <1999JOC9729>. 

A similar strategy served to carry out the last step of an asymmetric synthesis of the alkaloid (—)-cryptopleurine 12. Compound 331, prepared from the known chiral starting material (l )-( )-4-(tributylstannyl)but-3-en-2-ol, underwent cross-metathesis to 332 in the presence of Grubbs second-generation catalyst. Catalytic hydrogenation of the double bond in 332 with simultaneous N-deprotection, followed by acetate saponification and cyclization under Mitsunobu conditions, gave the piperidine derivative 333, which was transformed into (—)-cryptopleurine by reaction with formaldehyde in the presence of acid (Scheme 73) <2004JOC3144>. 

A great number of natural compounds have been employed as chiral starting materials for asymmetric syntheses. Table 1-2 classifies such inexpensive reagents. 

TABLE 1-2. Inexpensive Chiral Starting Materials and Resolving Agents86... 

Enzyme-catalyzed reactions can provide a rich source of chiral starting materials for organic synthesis.2 Enzymes are capable of differentiating the enantiotopic groups of prochiral and mew-compounds. The theoretical conversion for enzymatic desymmetrization of mew-compounds is 100% therefore enzymatic desymmetrization of mew-compounds has gained much attention and constitutes an effective entry to the synthesis of enantiomerically pure compounds. 

I n addition to the direct oxidation of simple amides, indirect oxidations of amides have proven useful for synthesizing chiral starting materials. Such reactions are often employed when direct electrolyses... 

Atorvastatin, an antihypercholesterolemic agent, is a synthetic drug that was initially produced in kilogram quantities using an 11-step chemical route. The iy -l,3-diol-con-taining side chain was produced from the chiral starting material, isoascorbic acid (Scheme 1.25). ... 

We have recently discovered that phosphoramidite 18 is also an excellent ligand for copper-catalyzed kinetic resolution of chiral 2-cyclohexenones (Scheme 7.15). Chiral 2-cyclohexenones are attractive building blocks for a variety of natural products, but their synthesis usually requires multistep routes from chiral starting materials [65]. The development of the new kinetic resolution was the product of two impor-... 

Diazotization of AAs proceeds via the corresponding a-hydroxy acids to oxiranes. From chiral starting material chiral oxiranes are obtained with retention of configuration. This synthetic principle is generally applicable (79T1601 89TL5505). 

Money T, Camphot A chiral starting material in natutal ptoduct synthesis, Nat Prod Rep 2 25 >-2 3, 1985. 

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