Spirocyclic compound

These rings meet at an atom alone. This means that the two rings are orthogonal about the tetrahe-i0 dral atom that is common to both. Even symmetrical-looking versions are unexpectedly chiral. The compound in the margin, for example, is not superimposable on its mirror image, and its chirality is rather similar to that of an allene. 

These sorts of compounds may look rather difficult to come by, but some simple ones are simply made. Cyclization of this keto-acid with polyphosphoric acid leads to a spirocyclic diketone. 

The spiro compound is formed because the more substituted cnol is preferred in acid solution, In a different case, with an enamine, a bridged product is preferred. 

After the first alkylation, the enamine prefers to re-form on the less substituted side so that the second alkylation occurs on the other side of the ketone from the first. The spirocyclic compound is further disfavoured as it would have a four-membered ring in this case. 

It is much more difficult to pass stereochemical information from one ring to the other in spirocyclic compounds because each ring is orthogonal to the other. Nonetheless, some reactions are surprisingly stereoselective—one such is the reduction of the spirocyclic diketone that we made a moment ago. Treatm( t with LiAlli4 gives one diastereoisomer of the spirocyclic diol. 

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The alkylpalladium intermediate 198 cyclizes on to an aromatic ring, rather than forming a three-membered ring by alkene insertion[161], Spirocyclic compounds are easily prepared[l62]. Various spiroindolines such as 200 were prepared. In this synthesis, the second ring formation involves attack of an alkylpalladium species 199 on an aromatic ring, including electron-rich or -poor heteroaromatic rings[l6.5]. 

Organic molecules m which one carbon atom is common to two rings are called spirocyclic compounds The simplest spirocyclic hydrocarbon is spiropentane a product... 

Stereocontrolled synthesis of spirocyclic compounds with heterocyclic fragments 99T9007. 

A series of interesting pyrazolo[3,4-(f pyrimidine derivatives was obtained by a thermal denitrocyclization reaction of hydrazones, e.g. 164 or 166, easily formed from the corresponding aldehyde or ketone hydrazones with halo-nitrouracil derivatives, e.g. 163 (71CC1442, 72CC298). Intermediates 164 or 166 can be isolated and their cyclization in suitable solvents (methanol, DMF, DMSO) provided high yields of the products. Aldehyde hydrazones yielded the corresponding l,7-dihydropyrazolo[3,4-J]pyrimidines, e.g. 165, whereas ketone hydrazones gave l,5-dihydropyrazolo[3,4-pyrimidine derivatives, e.g. spirocyclic compound 167 (Scheme 26). 

The Simmons-Smith reaction is well suited for the synthesis of spirocyclic compounds. It has for example been applied for the construction of the fifth cyclopropane ring in the last step of a synthesis of the rotane 8 ... 

An enantioselective variant of the diene cydization reaction has been developed by application of chiral zirconocene derivatives, such as Brintzinger s catalyst (12) [10]. Mori and co-workers demonstrated that substituted dial-lylbenzylamine 25 could be cyclized to pyrrolidines 26 and 27 in a 2 1 ratio using chiral complex 12 in up to 79% yield with up to 95% ee (Eq. 4) [ 17,18]. This reaction was similarly applied to 2-substituted 1,6-dienes, which provided the analogous cyclopentane derivatives in up to 99% ee with similar diastereoselectivities [19]. When cyclic, internal olefins were used, spirocyclic compounds were isolated. The enantioselection in these reactions is thought to derive from either the ate or the transmetallation step. The stereoselectivity of this reaction has been extended to the selective reaction of enantiotopic olefin compounds to form bicyclic products such as 28, in 24% yield and 59% ee after deprotection (Eq. 5) [20]. 

Deprotonation of 1,3,4-thiadiazolium salts affords carbenes that can be trapped with aromatic isocyanates to yield spirocyclic compounds. These reactions have been reviewed in CHEC(1984) <1984CHEC(6)545> and CHEC-11(1996) <1996CHEC-II(4)379>. 

FIGURE 23. Preparation of 8-M-4 spirocyclic compounds of Si and Ge(M = Si, Ge). Reprinted with permission from Reference 111. Copyright (1990) American Chemical Society... 

The addition of methanol or hydrazoic acid to ethenylidenecydopentadiene 3 demonstrates that 3 behaves like an acceptor-substituted allene (Scheme 7.27) [226, 227]. More examples of nudeophilic additions to alkyl-substituted derivatives of 3 were reported by Hafner [228]. Photoelectron spectroscopy of the spirocyclic compound 165b, easily accessible from azide 164b, shows that the lone-pair orbital n(N) of the 2H-azirine nitrogen atom interacts strongly with the Jt1-orbital of the cyclo-pentadiene ring [227]. 

Similarly, tandem hydroformylation/aldol sequences can be applied to the formation of bicyclic and spirocyclic compounds. Thus silyl enol ethers of 3-vinyl and 3-allyl cycloalkanones give ring anellated products (Scheme 33) [86,87]. 

Chlorocyclophosphazenes are not particularly reactive towards silicon-nitrogen compounds, but the spirocyclic compounds (47) have been prepared.112... 

Figure 8. ORTEP drawing of spirocyclic compound formed by thermal decomposition of (PhiPNjiNSX, where X = Cl or I.

Fig. 12. Molecular structure of a novel spirocyclic compound, (from Ref. 357)...

FIGURE 74. Solid state structure of metaUa-spirocyclic compound 141... 

The use of propargyl vinyl ethers prompted Toste et al. to develop a stereoselective preparation of 2-hydroxy-3,6-dihydropyrans, suitable for the synthesis of spirocyclic compounds. The reaction was catalyzed by a small amount (1 mol%) of [0(AuPPh3)3]... 

A second form of optical isomerism analogous to that shown by organic spirocyclic compounds has been demonstrated. Any molecule will be optically active if it is not superimposable on its mirror image. The two enantiomers of bisfben-zoylacetonato)beryllium are illustrated in Fig. 12.3. In order for the complex to be chiral, the chelating ligand must be unsymmetric (no/ necessarily asymmetric or chiral, itself) [Be cac ] is not chiral. 

For example, in the presence of norbornadiene the spirocyclic compound 661 is formed. According to the authors this provides evidence for the intermediate formation... 

In addition, there are many important nonantibiotic uses of 2-azetidinones in fields ranging from enzyme inhibition [15-21] to gene activation [22], Systems containing one carbon atom common to two rings, spirocyclic compounds, represent an important structural organization. Spirocyclic p-lactams (Fig. 3) behave as p-tum mimetics [23-26] as well as enzyme inhibitors [27, 28], they are precursors of a,a-disubstituted p-amino acids [29-32], and the spiranic p-lactam moiety is present in chartellines and chartelamides [33-38], a family of marine natural products. Synthetic studies and biosynthetic speculation inspired by an unexpected reaction on the marine alkaloid chartelline C have been described [38],... 

In continuation to this, they used ot,(3-unsaturated (3-lactams 79 for the construction of spirocyclic compounds 80-82 (Scheme 21) by the addition of a methylene... 

In the presence of molecular oxygen, oxygenation of the Al-C(O) bond is obtained, whereas the reaction with alcohols affords spirocyclic compounds <20070M1308>. 

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