Diastereomeric diols

Scheme 24.3 The preparation of diastereomeric diols from D-mannitol.

Regio- and stereoselective dihydroxylation of dienes functionalized at the allylic position with a benzene sulfone group has been reported42. Osmylation of dienic sulfones 33, a potential key synthon for forskolin, occurred exclusively on the A6-7 double bound and preferentially from the a-face of the traws-fused bicyclic molecule, presumably due to a combination of steric and electronic factors (equation 25). While the reaction of diene sulfones proceeded sluggishly under catalytic conditions, treatment of 33a with a stoichiometric amount of OSO4 resulted in quantitative yield of diastereomeric diols 34a and 35 in a 9 1 ratio, respectively. Protecting the hydroxy group of the dienol as its t-butyldimethylsilyl ether (33b) affords diol 34b exclusively. 

Treatment of the /3-keto ester 220 with sodium ethoxide at elevated temperature triggered off an epoxide ring opening by / -elimination that was followed by the desired Knoevenagel condensation to afford the tricyclic product 206 (Scheme 34). The enone moiety in the intermediate 221 did not show a propensity for deprotonation and, therefore, the ketone carbonyl function of the enone moiety was available for a Knoevenagel condensation. The reduction of the p-keto ester (206) to the corresponding diol was the next objective. Treatment of the TES-protected -keto ester (TES-206) with DIBAH afforded the diastereomeric diols 222 and 223 in a moderate diastereoselec-tivity in favour of the undesired diastereomer 222. The diastereomers were separated and the undesired diastereomer 222 was epimerized to 223 by a sequence that consists of Mitsunobu inversion and benzoate ester reduction [98, 99]. 

Attack of the solvent led primarily to the N-acetyliminoquinol 54 and lesser amounts of the ort/io-acetamidophenol, 55. The intermediate 54 was detected by HPLC, UV and H NMR if R = 4-CHj, but it decomposed to generate 57, 58, and 59 as shown in Scheme 24." The diastereomeric diols 56a,b were also detected, and the kinetics of their decomposition showed that they were formed reversibly from 54. The methoxy analogues of 54 and 56a,b were isolated and characterized by Gassman and Granrud during the methanolysis of 45h. These species decomposed into the methoxy analogues of 58 and 59. ... 

Epoxidation of allylic and homoallylic alcohols The diastereomeric diols la and lb posess both allylic and homoallylic hydroxyl groups. Oxidation of the... 

Diarylheptanoids from Zinziber officinale, the common ginger, the gingerones A, B, and C (49-51), as well as isogingerone B (52) were isolated by Endo and his coworkers in 1990 (42). Later Kikuzaki et al. isolated additional components, such as 53, the demethyl derivative of 49, further (5)-hexahydrocurcumin (42), from which 49 can be derived by dehydration (43). It is noteworthy that apart from the diastereomeric diols (S,S)-45 and (R,S)-4S, arising from the reduction of 42, the corresponding acetates, 54 and 55, could also be isolated (44). The same authors later described two more diarylheptanoid acetates (56, 60) and a series of racemic P-hydroxyketones (57-59) (45). Considering that P-hydr-oxyketones readily eliminate water, it cannot be excluded that the enones 49-53 are artefacts. 

The first total synthesis of the marine dolabellane diterpene (+)-deoxyneodolabelline was achieved in the laboratory of D.R. WilliamsJ In the final step of the synthetic sequence, the oxidation of a secondary alcohol functionality of a 1,2-diol to the corresponding a-hydroxy ketone was required. Such 1,2-diols are known to be unstable under most oxidation conditions, and often glycol cleavage is observed. Indeed, when Dess-Martin and Ley oxidations were tried, the substrate suffered carbon-carbon bond cleavage. However, under the Swern oxidation conditions, the desired a-hydroxy ketone was isolated in a 65% yield. Interestingly, the substrate was a mixture of four inseparable diastereomeric diols (obtained in a McMurry reaction), which gave two easily separable ketone products, one of which was the natural product. 

The use of ammonia generates other types of data. When the adduct ion [M + NH4] is stable the measurement of the ratio MH /M -t- NH4] gives direct access to the distinction between diastereomeric diols, for example, the cyclopentane and cyclohexane diols [37,38]. This behavior is due to slight variations of proton affinity, in these cases certainly resulting from the possibility of forming hydrogen bonds (Table 2). 

Negative ionization is also very sensitive to stereochemical effects. Winkler and Stahl [38] were thus able to differentiate diastereomeric diols. More recently, we [65] were able to distinguish diastereomeric dipeptides R-R and R-S by the variations in the abundance of losses of benzyl radical and of acetamide (Fig. 7). 

For example, the dihydroxylation of the steroid derivative 30 using 0s04.py-ridine gave a 1 8 mixture of diastereomeric diols in favour of the unnatural isomer 32 [91].UsingDHQD-CLB,a4 l ratio in favor ofthe natural isomer 31 could be obtained (Scheme 17). 

Nakane and Hutchinson have further shown that the aldol step in this cyclization is stereoselective as well as regioselective. Treatment of (39) with Hunig s base, acetic anhydride and 4-(A, A -dimethyl-amino)pyridine (DMAP), followed by sodium borohydride reduction of the intermediate P-hydroxy aldehyde, gives diol (40) in 48% yield no diastereomeric diols were detected (equation 102). 2i... 

With a formal total synthesis of coriolin (3) accomplished, we turned our attention toward hypnophilin (4). In practice, it was found that treatment of enone 59 with LDA in THF at -78 °C, followed by trapping of the resulting enolate with formaldehyde at -30 °C, led to a mixture of the diastereomeric diols 60 in 85% yield (Scheme 4). The mixture was treated with tosyl chloride and pyridine in dichloromethane at room temperature TLC analysis revealed that some dienone 39 was formed even under these reaction conditions. After 4 days, tosylation of the primary hydroxyl group was complete and the elimination reaction was... 

Eremophilane sesquiterpenes are not widely distributed in Eremophila species. In fact, the only other example so far known is the aldehyde (70) which occurs in E. rotundifolia (66). The structure of 70 was deduced largely from H- and C-nmr spectral data and, the absolute, stereochemistry by correlation with eremophilone. The keto aldehyde was reduced with sodium borohydride-cerium trichloride to give a mixture of diastereomeric diols. The major compound was assigned the 9a-configuration. The derived diacetate, on treatment with lithium-diethylamine, gave mainly the 9-allylic alcohol which was oxidised to eremophilone with Collin s reagent. 

Suggest reagents and conditions for the synthesis of the two diastereomeric diols syn and anti 10. 

Some of the earliest work in this area was reported by Blechert, who prepared the diastereomeric diols 13.1.1 416) and 13.1.2 417). Both compounds were reported as being able to inhibit the depolymerization of tubulin, but the level of this activity was not reported. An even more simplified set of analogs was prepared by Fuji and Kohno and their collaborators these investigators prepared the analogs 13.1.3-13.1.8, in which the alkyl chain comprised two to seven carbons 418) none of these compounds showed any promising tubulin inhibitory activity. 

The substrate-specific reduction was rationalized by an activating intramolecular hydrogen bond present only in the two reacting diastereomers. The diastereomeric diols 153 (dr = 2.9 1) were further reacted to provide lactone 154, which closely resembles the guaianolide family of natural products. 

Aromatic aldehydes have been allylborated with l,6-bis(dipropylboryl)hexa-2,4-diene (80) the reaction is highly diastereoselective, giving only two diastereomeric diols. ... 

Currently, only one example of a fully-conjugated indeno[2,l- ]fluorene is known and its existence at this time remains unofficial (Shimizu and Tobe, 2011, private communication). Tobe et al. synthesized the molecule in a near identical manner in which 115 was made - IF dione 17 was reacted with 2 equiv. mesitylmagnesium bromide to form diastereomeric diols 133. Further reaction with SnCl2 in the presence of trifluoroacetic acid yielded 10,12-dimesitylindeno [2,l-6]fluorene 134 (Scheme 39). Little is known about this molecule in terms of optoelectronic or stmctural properties. Due to the presence of the two s-cis diene linkages, however, 134 is considerably less stable than its [1,2-b] and [1,2-a] counterparts. 

The ketonic alkaloid hypecorinine, C20H17O6N, Vmax 1690 and 1630 cm (5.92 and 6.14 fi) was obtained from several sources, including Corydalis incisa Pers. (Fumariaceae). The characteristic instability of the molecule toward acid was indicative of the presence of an aminoketal function. Lithium aluminum hydride reduction of hypecorinine gave rise to a pair of diastereomeric diols 5 and 6 identified as bicucullinediol and adlumidinediol, respectively. This chemical interrelation, coupled with the absence of hydroxyl absorption in the IR spectrum of the alkaloid confirmed the structure assigned ... 

In a more recent paper,Vankar and Ansari presented an approach to dihydroxymethyl dihydroxypiperidines. The representative synthesis (shown in Scheme 2) was initiated from derivative 8, prepared from the protected D-glucal. Oxidative cleavage of the double led to dicarbonyl compound 9 which, after reduction, provided diastereomeric diols 10 and 11 in the ratio 1.4 1. Isomer 10 was transformed into the corresponding pyrrolidine 13 in a sequence of reactions involving mesylation and Sn2... 

In the first step, vinyhnagnesium bromide is a powerful nucleophile and can attack the epoxide in a ring-opening reaction (attacking the less substituted carbon) to afford an alcohol. This alcohol is subsequently converted to an ether via a Williamson ether synthesis. Dihydroxy lation of the terminal alkene with catalytic OSO4 in the presence of NMO gives a mixture of diastereomeric diols. 

---