Functionalized carbocycles

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. 

Scheme 8.27 presents a highly stereoselective one-pot tandem 1,4-addition-ISOC for the construction of functionalized carbocycles. Addition of Grignard reagents to nitroalkenes and subsequent ISOC are carried out in one pot. The advantages of ISOC over INOC, namely, greater stereoselectivity and adaptability to one-pot conditions, have been demonstrated in Scheme 8.27.138... 

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... 

Scheme 14.20. Transformation of titanacyclobutanes into functionalized carbocycles.

Singlet oxygen reacts with many carbocyclic 1,3-dienes to form the corresponding bridged endoperoxides, which can be further transformed into miscellaneous polyoxy functionalized carbocycles . The rate of photooxygenation of n-cyclic 1,3-dienes is gradually decreasing in the order n = 5) >6>7 8 While the rate... 

Silylative Cyclization to Form Bis(functionalized) Carbocycles 11.11.8.1 Cyclization/Disilylation... 

Bis(functionalized) carbocycles via cyclization-borylsilylation, 11, 405 via cyclization-disilylation, 11, 401 via cyclization-stannylsilylation, 11, 402 Bis(guanidate) titanium(II) complexes, preparation and reactivity, 4, 268... 

Cyclization—borylstannylation, diynes, 11, 407—40S Cyclization—disilylation, bis(functionalized) carbocycle formation, 11, 401... 

Several other important compounds found in the common aromatic amino acid pathway whose overproduction has been studied are shikimic acid (61) and, to a lesser extent, quinic acid (62) (Scheme 19.41).323 Both 61 and 62 are naturally occurring, highly functionalized carbocyclic rings with asymmetric centers, which can be used as starting material for the synthesis of GS4104 (63), a neuraminidase inhibitor discovered by Gilead Sciences and developed by Roche Pharmaceuticals under the trade name of Tamiflu .324 325 Manipulation of the aromatic amino acid pathway in E. coli has allowed for numerous strains to be assembled that produce both 61 and 62 as well as other intermediates.326 327 As reported by Chandran and co-workers, an E. coli strain has been constructed that synthesized 87 g/L (0.5m) of 61 in 36% (mol/mol) yield with a maximum productivity of 5.2 gL- lr1.328... 

Stereoselective synthesis of functionalized carbocyclic and heterocyclic compounds via tandem ester enolate Claisen rearrangement/RCM has been reported (Eq.79) [131,132],... 

The intramolecular carbolithiation of carbon—carbon double bonds is an interesting route to functionalized carbocyclic and heterocyclic systems that has been developed in the past years and widely used in organic synthesis. In this context, aryllithiums have been described to carbometalate double bonds allowing the preparation of indanes,... 

The predictable construction of heterocycles and highly functionalized carbocycles with or without intracycle asymmetry is paramount to synthesis of biologically important compounds and other areas of organic synthesis. " A number of methodological advances have been reported utilizing RCM for the construction of previously inaccessible rings. ... 

Intramolecular carbon-carbon bond formation is an effective means of creating a variety of functionalized carbocyclic and heterocyclic ring systems. Apparently, proper choice of Lewis acid promoters and conditions enables stereoselective ring construction by use of la and other Lewis acids. 

In connection with a program on developing free radical methodology, Praser-Reid described several approaches to densely functionalized carbocycles. This led to the construction of the carbocyclic core of tetrodotoxin [326]. The synthesis of cyclophellitol 414 and its epi derivative, described here, illustrates the principles of this strategy [327]. 

Alonso, R A, Burgey, C S, Rao, B V, Vite, G D, Vollerthun, R, Zottola, M A, Fraser-Reid, B, Carbohydrates to carbocycles — synthesis of the densely functionalized carbocyclic core of tetrodotoxin by radical cyclization of an anhydro sugar precursor, J. Am. Chem. Soc., 115, 6666-6672, 1993. 

Barton deoxygenation, 548, 549 [Functionalized carbocycles] bicyclic compounds, 551 caiba-D-fructofuranose, 547 Corey lactone, 549 Cp2TiCl catalyst, 553, 563 cyclic transition state, 548, 549 cyclohexanes, 554 cyclopentanes, 546 1,2-dialkylcyclopentanes, 548 electron spin resonance, 552 eneynes, 556... 

Related to the intramolecular pinacolic coupling reactions in some respects is a ketone-nitrile reductive coupling process. This process also permits the construction of highly functionalized carbocycles, although the yields are sranewhat reduced owing to the reluctance of nitriles to undergo such radical addition reactions (equation 75). Presumably, simple reduction of the ketone to the alcohol c< npetes with the desired process. 

The Dieckmann condensation in tandem with the Claisen condensation or Michael reaction can be used to assemble highly functionalized carbocycles, including the 1,2-, 1,3", and 1,4-dione species depicted belowd ... 

Carbohydrates have been starting materials for the synthesis of functionalized carbocycles for a long time [47 9]. More recently, ring-closing metathesis... 

This high diastereofacial selectivity also operates with similarly substituted, but more complex, silyl enol ethers41 42. These examples also demonstrate a remarkable degree of chemoselectiv-ity and prove the suitability of this approach for the stereoselective construction of functionalized carbocyclic systems. 

Synthesis of Functionalized Carbocycles by Cyclization of Acyclic Sugar Derivatives... 

T. V. RajanBabu, Functionalized Carbocyclic Derivatives from Carbohydrates Free Radical and Organometallic Methods, in Preparative Carbohydrate Chemistry (Ed. S. Hanessian), Marcel Dekker, 1997, Chap 25. 

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