Epimeric center

The effect of substituents at the a-carbon of the enone on the stereoselectivity was examined on compounds 270, with the stereogenic center located at the alkenyl side chain. Crimmins and DeLoach122 found that the stereoselectivity encountered upon irradiation of 270 depends on the degree of steric hindrance associated with the ester group linked to the double bond. The ratio of the two epimeric centers at the C-9 position varied from 13 1 (R = Me) to 17 1 (R = Et), then 20 1 (R = i-Pr). These results demonstrate that steric effects play an important role in controlling the stereofacial selectivity in these and related systems. Fragmentation of the photoproduced four-membered ring and simple transformations afforded synthesis of ( )-pentalene 274, (i)-pentalenic acid 275 and (i)-deoxypentalenic acid 276 (Scheme 59). 

Numerous examples of stereospecific reactions in the gas phase are reported in the mass spectrometric literature [1,2]. Many if not most of them, however, deal with relatively rigid systems, e.g., 1, or polyfunctional molecules such as derivatives of tartaric acid [6] the latter gave rise to the first chirality effect observed in mass spectrometry [7]. For stereogenic centers linked by flexible alkyl chains, however, diastereoisomeric differentiation in ion fragmentation is often poor. Two epimers of the aminoalkanol 2, for example, show quite small differences in their mass spectra whereas these differences increase if the two centers are linked by cyclization upon formation of 3 as indicated in Scheme 2 with the epimeric center being marked by an asterisk [8]. 

Figure 2 Environmental arsenic compounds referred to in text and tables by structure number. Carbons marked represent epimeric centers where both diastereoisomers have been identified as natural products.

Several stereochemical labels have been developed for diastereomers. Epimers are diastereomers that differ in configuration at only one of several chiral centers. The chiral center at which the difference in configuration occurs is said to be the epimeric center. Structures 69 and 70 are epimeric at C4. Anomers are epimers in the carbohydrate series that differ only at the... 

If the ketone function is adjacent to a hydrogen-bearing asymmetric center, the compound can undergo epimerization. In steroids with a normal skeletal configuration (8/3, 9a, 14a) there is no detectable epimerization at C-8 or C-9 during the exchange of and 11- ketones. 

A classic diagnostic use of such stereochemical requirements, due to Ruzicka, is the ring contraction induced in natural products containing the 4,4-dimethyl-5a-3 -ol system (94). The epimeric, axial 3a-alcohols (95) dehydrate without ring contraction. Barton suggested that it is necessary for the four reacting centers (hydroxyl, C-3, C-4, C-5) to be coplanar for ring contraction to occur, and this is only the case with the 3)5-alcohol. 

Photolytic epimerizations of this type would represent a potentially useful method of direct inversion of chiral centers. However, competition by numerous other intramolecular processes vide infra) frequently renders its more general utilization less practical. 

The success of intramolecular conjugate additions of carbon-centered radicals in multifunctional contexts is noteworthy. Compound 57 (see Scheme 10), prepared by an interesting sequence starting from meto-toluic acid (54) (see 54 > 55 > 56 > 57), can be converted to the highly functionalized perhydroindane 58 through an intramolecular conjugate addition of a hindered secondary radical.21-22 This radical cyclization actually furnishes a 6 1 mixture of perhydroindane diastereoisomers, epimeric at C-7, in favor of 58 (96 % total yield). It should be noted that a substantially less strained cis-fused bicyclo[4.3.0] substructure is formed in this cyclization. 

When a cold (-78 °C) solution of the lithium enolate derived from amide 6 is treated successively with a,/ -unsaturated ester 7 and homogeranyl iodide 8, intermediate 9 is produced in 87% yield (see Scheme 2). All of the carbon atoms that will constitute the complex pentacyclic framework of 1 are introduced in this one-pot operation. After some careful experimentation, a three-step reaction sequence was found to be necessary to accomplish the conversion of both the amide and methyl ester functions to aldehyde groups. Thus, a complete reduction of the methyl ester with diisobutylalu-minum hydride (Dibal-H) furnishes hydroxy amide 10 which is then hydrolyzed with potassium hydroxide in aqueous ethanol. After acidification of the saponification mixture, a 1 1 mixture of diastereomeric 5-lactones 11 is obtained in quantitative yield. Under the harsh conditions required to achieve the hydrolysis of the amide in 10, the stereogenic center bearing the benzyloxypropyl side chain epimerized. Nevertheless, this seemingly unfortunate circumstance is ultimately of no consequence because this carbon will eventually become part of the planar azadiene. 

Another route to enantiomcrically pure iron-acyl complexes depends on a resolution of diastereomeric substituted iron-alkyl complexes16,17. Reaction of enantiomerically pure chloromethyl menthyl ether (6) with the anion of 5 provides the menthyloxymethyl complex 7. Photolysis of 7 in the presence of triphenylphosphane induces migratory insertion of carbon monoxide to provide a racemic mixture of the diastereomeric phosphane-substituted menthyloxymethyl complexes (-)-(/ )-8 and ( + )-( )-8 which are resolved by fractional crystallization. Treatment of either diastereomer (—)-(/J)-8 or ( I )-(.V)-8 with gaseous hydrogen chloride (see also Houben-Weyl, Vol 13/9a, p437) affords the enantiomeric chloromethyl complexes (-)-(R)-9 or (+ )-(S)-9 without epimerization of the iron center. 

Photochemical oxygen transfer reactions involving sulfoxides have also been documented. For example, a photochemical rearrangement of 2-nitrophenyl phenyl sulfoxide to 2-nitrosophenyl phenyl sulfone224, and the inverse photoconversion of o-methylbenzoic acid225 have been reported. Finally, photochemical epimerizations of the sulfoxide centers... 

Pentenomycin (33), a highly oxygenated cyclopentenoid with a quaternary chiral center (Scheme 6), was prepared by a similar reaction sequence [29]. The RCM precursor 31 was prepared in eight steps from D-mannose via iodo compound 29 and aldehyde 30 (1 1 diastereomeric mixture). RCM of 31 led to the epimeric cyclopentenols 32. 

Initial attempts to effect addition of allyltrimethylsilane with compound 132 under conditions developed in Kishi s C-glycoside work were plagued by epimerization of the acetal center subsequent to the coupling event, providing 133 as a 1 1 mixture of diastereomers (Eq. 21). Boons reported that acetal... 

---