Chiral carbocycles, synthesis

A unique member of the seven carbon carbaketose family, namely hept-2-uloseptanosylamine 342, was assembled by Mandal [78,79] during a remarkable total synthesis of chiral carbocyclic nucleosides from D-glucose. Here, a diastereoselective intramolecular nitrone cycloaddition reaction was the decisive move to install the carbaseptanose ring system (Scheme 56). 

Borthwick, A.D. etal. An Efficient Synthesis of a Chiral Carbocyclic 2 -Deoxyribonucleoside Synthon by Directed Reduction. 2.1 1994 [108]... 

Hsiao, C.-N. et al. Efficient Syntheses of Protected (2S,3S)-2,3-Bis(hydroxy-methyl)cyclobutanone, Key Intermediates for the Synthesis of Chiral Carbocyclic Analogues of Oxetanocin. 4.1 1990 [127]... 

Synthesis of chiral carbocyclic nucleotides, nucleoside analogs with fragments of 5-membered carbocyclic polyols instead of the glycosyl group 92T571. 

Machado AS, Oleskta- A, Castillon S, Lukacs G (1985) Hydroxy group directed hydrogenation with rhodium and iridium catalysts. Synthesis of protected chiral carbocyclic analog of daunosamine. J Chem Soc Chem Commim 530-532... 

Two members of the Glaxo team have produced a comprehensive review on the synthesis of chiral carbocyclic nucleosides.198... 

An improved synthesis of chiral carbocyclic 2 -deoxyadenosine proceeds along similar lines to the carbocyclic thymidine synthesis described by the same group in Vol 21 (p.212).H3... 

C.-N. Hsiao and S.M. Hannick, Efficient synthesis of protected (25,3S)-2,3-bis(hydroxymethyl)cyclobutanone, key intermediates for the synthesis of chiral carbocyclic analogues of oxetanocin, Tetrahedron Lett. 31 6609 (1990) reports the synthesis of the (+)-enantiomer of 26 in a rather lengthy process. 

The asymmetric Michael addition of chiral nonracemic ketone enolates has most frequently been used as part of the Robinson annulation methodology in the synthesis of natural products171-172. The enolates are then derived from carbocyclic chiral ketones such as (+)-nopinone, (-)-dihydrocarvone, or (-)-3-methylsabinaketone. 

Casas R., Chen Z., Diaz M., Hanafi N., Ibarzo J., Jimenez J. M., Ortuno R. M. Some Versatile and Useful Strategies for the Asymmetric Synthesis of Chiral Polyfunctional Carbocyclic Derivatives An. Quim. 1995 91 42-49... 

By the radical pathway l, -diesters, -diketones, -dienes or -dihalides, chiral intermediates for synthesis, pheromones and unusual hydrocarbons or fatty acids are accessible in one to few steps. The addition of the intermediate radicals to double bonds affords additive dimers, whereby four units can be coupled in one step. By way of intramolecular addition unsaturated carboxyhc acids can be converted into five raembered hetero- or carbocyclic compounds. These radical reactions are attractive for synthesis because they can tolerate polar functional groups without protection. 

Hydrosilylation of dienes accompanied by cyclization is emerging as a potential route to the synthesis of functionalized carbocycles. However, the utility of cycliza-tion/hydrosilylation has been Umited because of the absence of an asymmetric protocol. One example of asymmetric cycUzation/hydrosilylation has been reported very recently using a chiral pyridine-oxazoUne ligand instead of 1,10-phenanthroline of the cationic palladium complex (53) [60]. As shown in Scheme 3-21, the pyridine-oxazoUne Ugand is more effective than the bisoxazoUne ligand in this asymmetric cyclization/hydrosilylation of a 1,6-diene. 

The tandem-Knoevenagel-ene reaction is a powerful tool to synthesize five-and six-membered carbocycles.2 5 The process is exemplified by the diastereoselective synthesis of 4a. Compound 4a has been obtained In both enantiomeric forms and as a racemate according to the procedure described here. The sequence includes the Knoevenagel reaction of citronellal, 1, and dimethyl malonate, 2, followed by the intramolecular ene cyclization of the chiral 1,7-diene 3 to yield the trans 1,2-disubstituted products 4a and 4b. Whereas the thermal cyclization of 3 at 160°C provides 4a and 4 b in a ratio of only 89.7 10.3, the Lewis acid... 

Hydrosilylation of 1,6-dienes accompanied by cyclization giving a five-membered ring system is emerging as a potential route to the synthesis of functionalized carbocycles.81,81a,81b 82 As its asymmetric version, diallylmalonates 86 were treated with trialkylsilane in the presence of a cationic palladium catalyst 88, which is coordinated with a chiral pyridine-oxazoline ligand. As the cyclization-hydrosilylation products, //ww-disubstituted cyclopentanes 87 were obtained with high diastereoselectivity (>95%), whose enantioselectivity ranged between 87% and 90% (Scheme 25).83 83a... 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

Borchardt and coworkers (265) have employed the chiral cyclopenten-ones derived from aldonolactones for the synthesis of the analogue 302a of neplanocin A. Neplanocin A (302b) and aristeromycin (303), carbocyclic analogs of adenosine having antiviral and antitumor activities, have also been synthesized (277,278). 

Chiral cyclobutanes can be prepared by cycloaddition of alkenes substituted with one or more chiral auxiliary groups. A diastereofacial selectivity of 95% was observed in the diethylalu-minum chloride catalyzed cycloaddition of 1,1-dimethoxyethene (36) with ( — )-dimenlhyl-3-yl fumarate (37).16 The chiral cyclobutane 38 has been used as an intermediate in the synthesis of carbocyclic oxetanocin analogs. 

Rhodium-catalysed asymmetric cyclization/hydroboration followed either by Pd-catalysed arylation or by oxidation was applied to the synthesis of a number of chiral, non-racemic carbocycles and heterocycles. Thus, reaction of enyne (28) with catecholborane, catalysed by a 1 1 mixture of [Rh(COD)2]+ Sbly,- and (S)-BINAP (5 mol%), followed by Pd-catalysed arylation with /7-IC6H4CF3, afforded benzyli-denecyclopentane (29) in 65% yield with 88% ee.46... 

---