Absolute stereochemistry, reagent

For dihydrodiols derived from substituted benzenes, the key to their significance lies in the availability of two adjacent chiral centers with an established absolute stereochemistry. The dihydrodiol from benzene is, of conrse, the meso compound, although enantiomers produced by subsequent reaction with a chiral reagent are readily separated. There are useful reviews containing nnmerous applications (Carless 1992 Ribbons et al. 1989), many of which involve, in addition, the nse of di-flnoro-, di-chloro-, or di-bromobenzene-2,3-dihydrodiols. 

A 2 1 (- )-90-LAH reagent was employed in the asymmetric synthesis of a cij-diol (91) by reduction of c/j-2-acetoxy-6-phenylcyclohexanone (99,100). Diol 91 is of interest as the tetrahydro derivative of a metabolite obtained from the microbial oxidation of biphenyl. Diol 91 was obtained in 46% e.e. as determined by NMR in the presence of a chiral shift reagent. It was shown to have the absolute stereochemistry (lS,2/ )-dihydroxy-3(S)-phenylcyclohexane by oxidation to ( + )-2-(S)-phenyladipic acid of known absolute stereochemistry. 

The next classes of reagents developed are those for the cyclopropanation of unfunctionalized alkenes. After early attempts at getting high enantioselectivities for the cyclopropanation of /3-methylstyrene using a chiral alcohol (21), bis(iodo)methylzinc, diethylzinc, dichloromethane and a Lewis acid (equation 90) , Shi and coworkers made a major breakthrough when they found that a simple dipeptide (22) derived from valine and proline could be used (equation 91) . However, in either case, the absolute stereochemistry of the cyclopropane has not been determined. 

Yessotoxin (214) is a polyether from the scallop Patinopecten yessoensis and has been implicated in diarrhetic shellfish poisoning (DSP). The structure and partial stereochemistry of yessotoxin were deduced from spectral data [219]. The relative stereochemistry of yessotoxin and the structures of two new analogues, 45-hydroxyyessotoxin (215) and 45,46,47-trinoryessotoxin (216) were also established [220]. The absolute stereochemistry of yessotoxin (214) was determined by NMR spectroscopy using a chiral anisotropic reagent [221]. The absolute configuration at C45 in 45-hydroxyyessotoxin (215), isolated from P. yessoensis, was determined by the use of a modified Mosher s method [222]. 

In a closely related asymmetric reaction, the required absolute stereochemistry at C-4 was established via a Michael addition of a cuprate reagent to a dihydropiperidinone (Scheme 12). The stereochemistry at C-3 was introduced in the form of piperidinone 61, a compound readily available from (5)-glutamic acid. Protection of both the amino and alcohol functionalities was achieved using standard reaction conditions to give 62. Introduction of the A -double bond was accomplished via phenylselenation of the lithium... 

Asymmetric hydroboration followed by oxidation is used to give optically active alcohols. For example, addition of (+)-IpcBH2 to 1-phenylcyclopentene followed by oxidation gives S,2R)-trans-2-phenylcyclopentanol in 100% e.e. (Equation B2.9). The structure of the product alcohol reveals that the homochiral hydroborating reagent encounters fewer unfavourable steric interactions with alkene substituents if it approaches the lower face of the alkene as drawn in Equation B2.9. This preference determines the absolute stereochemistry of the product. (The regiochemistry and relative stereochemistry of the product are determined by fundamental hydroboration characteristics.)... 

While more than a decade has passed since the first reports of reactions with i/2-bound aromatic molecules, this field is still in its infancy compared to the more established field of rj6-arene chemistry. Nevertheless, the general strategy of using a transition metal to render a conjugated re-system more electron-rich is now firmly established. The next phase of development will be marked by a greater focus on practical issues such as less expensive re-basic metal systems, effident control of absolute stereochemistry, and standardization of procedures that allow for easier reagent handling. 

The thiazole-substituted homoallylic alcohol 25 (Scheme 6) is a key intermediate, not only for RCM strategies, but also for other routes. Thiazole aldehyde 4 (Chapter 3) after homologation to enal 24 (90 % yield) [ 11,20) was subjected to asymmetric allylation with allylboron and tin reagents. Interestingly 25 with identical absolute stereochemistry was synthesized by Nicolaou et al. with (+)-IpC2B(allyl) in 96 % yield and > 97 % ee [13, 20], and by Danishefsky et al. with the enantiomeric (—)-Ipc2B(allyl) in 83 % yield and > 95 % ee [11], i.e. in one case an er-... 

A recent report details absolute stereochemical control at levels of up to 75 25 in ene reactions, although typical levels are lower35. This selenium reagent has two identical, chiral sulfur atoms and it is these stereogenic centers that provide for reagent-based control of absolute stereochemistry. 

The optical resolution of racemates 22a, 25a, and 27a was carried out by chromatographic separation of their (4/ ,5S)-MPOT-amide derivatives 22b, 25b, and 27b. The absolute stereochemistry of each pure diastereoisomer was confirmed by comparing the physical data of its derivative with those of the authentic compound in each case. Thus, (4i ,5S)-MPOT (5) proved to be a satisfactory chiral reagent useful for analytical separation and optical resolution of racemic carboxylic acids and amino acids (85JCS(P1)2361). 

Solladie-Cavallo and Tsamo (equation 8) have investigated the addition of Grignard reagents to chiral chromium tricarbonyl complexes of diarylimines (15). Results of these additions are shown in Table 4. While the absolute stereochemistry of the product(s) (39) formed has not been determined, the results... 

Oxazaborolldines have emerged as important reagents for the enantioselective reduction of a variety of prochiral ketones. CBS reduction (chiral oxazaborolidine-catalyzed reduction)of unsymmetrical ketones with diphenyl oxazaborolidine in the presence of BH3 proceeds catalytically to provide alcohols of predicable absolute stereochemistry in high enantiomeric excess. 

Hydroboration of cw-alkenes with these reagents creates new chiral centers. Oxidation of the resultant organoboranes with retention furnishes alcohols of predictable absolute stereochemistry. IPC2BH is perhaps one of the most versatile chiral reagents for laboratory use. A rationalization of the observed stereoselectivities has been proposed. Under similar experimental conditions but using (-t-)-Ipc2BH, hydroboration of cw-2-butene produces the (-h)-(5) alcohol. 

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