Spirocyclic systems

In the synthesis of spirocyclic systems via an intramolecular Sakurai reaction, allylsilanes with an allyl moiety attached to the 3-position of the 2-cyclohexenone are required as starting materials. 

P nuclear magnetic resonance (NMR) spectroscopy has been of great use in determining the coordination state and stereochemistry of the phosphorus atom at the spiro position in spirophosphonia compounds, spirophosphoranes and spiroperphosporanides. The 31P chemical shift is also sensitive to the nature of the atoms directly bonded to the spiro phosphorus center and the size of rings of the spirocyclic system. 

Hexacoordinate spirocyclic phosphorus compounds have been prepared in which the spirocyclic system involves dative bonds from the dimethylamino-l-naphthyl ligand <1996JOM173, 1997PS181, 1999IC1336> for example 113 (Equation 29). Spirophosphoranide 122 was synthesized by deprotonation of the acid precursor 121 with triethyl-amine (Equation 30) <2001IC6229, 2002IC1645>. 

The new spiroannelation method gives, by use of both the tin and silicon chemistry, ready access to [4.4], [4.5], [5.5], [4.6], and [5.6] spirocyclic systems as well as five-, six-, and seven-membered rings possessing a quaternary center. An in situ oxidation, or protection of an initially formed crude secondary alcohol increases the ease of isolation of the product and leads to improved overall yields. Furthermore, for symmetrical substrates, this chemodifferentiates two oxygen functionalities at... 

Two additional synthetic routes to ( )-j8-vetivone (350) have been developed. In one of these a suitably substituted spirocyclic system [cf. (349)] is constructed by addition of Me2CuLi to the fulvene derivative (348)/ Subsequent functional group modification (cf. Scheme 32) provides ( )-j8 -vetivone (350). In the other total synthesis d the well-known intramolecular alkylation of para-substituted phenols has been used to produce a spirocyclic intermediate (353) which can be converted into ( )-/3-vetivone (350) (cf. Scheme 33). 

Such oligocyclizations have also been carried out on prochiral substrates such as 132 with asymmetric induction by chiral ligands on palladium. With (enantiomeric excess (ee) of 45% (Scheme 35). ... 

Specific deuterium labeling at C(3) was applied as well in the chiral spirocyclic system 7 all three possible one-center epimerization events are kinetically competitive at 198.9 °C161. 

If attack was at the point of attachment of the side chain (45), the spirocyclic system will open again (Equation 9.110), and a 1,4-migration of phenyl will have... 

This protocol was also applied to diazepam derivatives 6 [49]. When these compounds were treated with /V- be n z v I o x vc ar bon vI -1.- pro line acid chloride and tetrahydrofuroyl chloride, the expected spirocyclic systems 7 (Scheme 2) were obtained in good yields. In the case of the /V-benzyloxycarbonyl-i.-praline acid chloride, the reaction was carried out at room temperature, while the process involving the tetrahydrofuroyl chloride needed to be performed in refluxing toluene. This higher temperature was the likely cause of the loss of selectivity observed in the latter case, in which a 10 1 mixture of diastereoisomers was obtained. 

Also, while there are some more recent examples of synthetic approaches to spirocyclic systems incorporating azepine or benzazepine structural moieties, the scope to devise new and versatile approaches is still significant. Spirocyclic systems continue to hold considerable promise as scaffolds for the design of new pharmaceutical agents and new synthetic strategies would be of benefit in this area. 

Bridged and spirocyclic bicycloalkenones. The conversion of silyl enol ethers to a,/J-enones by Pd(OAc)2 (8, 378) can result in cyclization to bicyclic systems when applied to silyl enol ethers of cyclohexanones bearing an alkenyl side chain a or y to the carbonyl group. Although the factors favoring cyclization are not fully defined, this cyclization offers a route to a variety of bridged and spirocyclic systems.1... 

C2 X D2, 21> and the group of rearrangements of the A ZX compounds and the corresponding group for the spirocyclic systems are abstractly equal. 

These reaction conditions using fluorinated solvents have also been applied to the construction of other spirocyclic systems. 

Spirocycles.1 In the presence of trimethylsilyl triflate, the silyl enol ether of an aldehyde reacts selectively with the acetal function of 1 to form an intermediate with a carbonyl group that can then react with the initially inert allylsilane group of 1 to form a spirocyclic system. This methodology permits synthesis of spirocyclic sys-... 

An interesting spirocyclic system was created by the reaction of SnCU with 1,2-bis(2/-lithiumphenyl)ethane by Kuivila and Beumel682 in 1958. Spirocyclic compounds were also obtained in the reaction of SnCU with 1,4-dilithium-1,2,3,4-tetraphenylbutadiene683,684 or with ethyl bis(2-lithiumphenyl)amine685. 

The action of SOCI2 on the bridged diphosphorane 57aw yields a novel spirocyclic system (60au). The structure has been determined by X-ray analysis 247). All axial positions are shown to be occupied by oxygen atoms. 

For intramolecular exchange processes in spirocyclic systems this mechanism prevails but it is energetically less favorable than the previous one. 

Unfortunately, experimental data on spirocyclic systems are insufficient so far and the number of examples is thus restricted (Table 1). 

There are several ways to combine rings into polycychc and cage structures (e.g. spirocyclic systems and fused rings). These will not be discussed here. Theoretical speculations have been made about the possible existence of purely inorganic (carbon-free) fullerene-like polycychc cages, for example, boron-nitrogen molecules or sihcon analogs. ... 

All the above cascade alkene metathesis reactions are based on the ROM of a cycloalkene moiety. Harrity and co-workers have described the synthesis of functionalized spirocyclic systems by cascade selective olefin ringclosing metathesis reactions from an acyclic tetraalkene. The selectivity for five-membered ring closure over seven-membered ring closure would be the result of a kinetically favored cyclization process [42] (Scheme 20). The syn-... 

It was recently discovered that Rieke magnesium reacts with 1,2-dimethylenecyclo-alkanes in THF at ambient temperature to afford the corresponding magnesium complexes in high yields. Significantly, treatment of these diene-magnesium reagents with bis-electrophiles provides a unique approach to commonly encountered spirocyclic systems [13]. 

In comparison with previous methods, the use of 1,2-dimethylenecycloalkane-magnesium reagents provides a simple approach for spiroannulation as well as access to a wide variety of spirocyclic systems. Furthermore, spirocarbocycles prepared by this method contain functional groups, such as the exocyclic double bond or a keto group in one of the rings which may be used for further elaboration of these molecules. 

Inorganic Chemistry of the Main-group Elements Evidence for five-co-ordinate phosphorus (v) species with essentially square-pyramidal structures has been observed in a number of spirocyclic systems, such as (79)470 and (80).471,472 Complete structural data are available... 

Attempts have also been made to influence the position of the equilibrium by incorporation of the norcaradiene into a spirocyclic system, e.g. as in 5 and 6. For a review dealing with the NMR data of the norcaradienes, see ref 15. 

A related structure 15 with the lactone ring across one side of the cyclopropane was converted to a spirocyclic system 16 upon treatment with lithium dimethylcuprate. ... 

With a large R group (such as 8-quinolinyl or 9-anthryl), release of the steric strain favours a ligand coupling process between one unit of the spirocyclic system and the fifth ligand to afford a 2,2 -biphenyldiyl system. 

The tricyclic /3-aminocyclohexenone 234 was obtained via intramolecular photoarylation of the bromo arene derivative 233 (Scheme 40). Enamide 234 was treated with sodium hydride, followed by the mesylate derivative of [(trimethylsilyl)methyl]allyl alcohol, to give the allylated compound 235, which was converted to two allyliminium salts 236 and 237. However, attempts to photocyclize these compounds to tetracyclic derivatives were not successful, in contrast to the results of the earlier studies (Scheme 35) in which the spirocyclic system was easily generated in intermediates not rigidly tethered to the aromatic ring. 

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