Carbocyclic spiro compounds

Review Syn 383 (1974) (Synthesis of Carbocyclic Spiro Compounds via Intramolecular Alkylation Routes)... 

It is observed that C-quinonylethylenaminones mainly give tricyclic heterocycles as products, which undergo ring opening to carbocyclic spiro compounds in solution148 (equation 96). 

The syntheses of carbocyclic spiro-compounds via cycloaddition have been reviewed and some steroid examples are included. The synthesis of the antimineralocorticoid (379) was reported along with the syntheses of the 6/3-... 

The preparation of carbocyclic spiro-compounds by intramolecular alkylation has been reviewed. ... 

Let us now turn to simpler systems in which there are two, not three, structural alternatives for the potential product. Buchta and his collaborators published many papers on the preparation of spiro-compounds 4). His work stemmed primarily from his greater interest in these 4) rather than in the propellane by-products obtained in certain cases 4d >. The case was reversed for our group. Propellanes were paramount but sometimes spiro-compounds were obtained 5 K First we shall discuss a number of carbocyclic examples. 

Polycyclic parent hydrides. These are classified as bridged polyalkanes (also known as von Baeyer bridged systems, from the nomenclature system developed to name them), spiro compounds, fused polycyclic systems and assemblies of identical rings. The four systems may be either carbocyclic or heterocyclic. In developing their names, the following principles are used. 

The photochromic compounds of potential interest, based on the 2//-chromene ring system, are the 2//-benzopyrans (1.18) or the three isomeric naphthopyrans (1.19-1.21). However, 2H-naphtho[2,3-( ]pyrans (1.21) show little or no useful photochromic behaviour and can be discounted from any further discussion. Although R and can be part of a carbocyclic spiro ring, they are more commonly unconnected substituents such as gem dialkyl or aryl groups. 

Several saturated parent systems shown in Scheme 1, especially (2), (4) and (7), have been incorporated into spiro compounds or have been fused with a variety of non-aromatic carbocyclic or heterocyclic rings. Unsaturated compounds with an endocyclic carbon-carbon double bond, formally possible in all systems with three adjacent heteroatoms, are only known in very few cases (e.g. cyclic sulfites and sulfates of enediols) or in the form of benzo or other condensed systems (mainly cyclic sulfites and sulfates of aromatic 1,2-dihydroxy compounds). For details concerning the various types of derivatives, see Section 4.33.4.2. 

Tri-, tetra- to polycyclic compounds (part B) appear in the structural formula index in order of ring size (carbocyclic before heterocyclic ring compounds) under appropriate compound headings. Part C contains spiro compounds with similar ordering followed by part D which contains assemblies of identical cyclic systems (c.g., bicyclopropyl). 

Condensed and other carbocyclic systems An interesting dimerization reaction was performed with cyclohexylidenemalononitrile 188. The reaction was performed in methanolic sodium methanolate and yielded the spiro compound 189. Acidic intramolecular cycloaddition of alkylidenemalononitrile 190 (with concentrated sulfuric acid) gave the naphthalene 191. 1 -Tetraloneanil 192 reacted with 179 to yield phenanthrene 193. ... 

Whereas alkylation of activated methylene systems by classical methods produces a mixture of mono- and dialkylated products, with the latter frequently predominating, phase-transfer catalytic procedures permit better control and it is possible to obtain only the monoalkylated derivatives. Extended reaction times or more vigorous conditions with an excess of the alkylating agent lead to dialkylated products or, with dihaloalkanes, carbocyclic compounds as the technique mimics dilute concentration conditions, e.g. the resonance stabilized cyclopentadienyl anion, generated under solidiliquid two-phase conditions, or under liquiddiquid conditions, reacts with 1,2-dihaloethanes to form spiro[2,4]hepta-4,6-diene (70-85%) [1-3]. Reaction with dichloromethane produces bis(cyclopenta-2,4-dien-l-yl)methane (60%) [4],... 

Spiropyrans refers in general to a (substituted) 27/-pyran having a second ring system, usually (but not necessarily) heterocyclic, attached to the 2-carbon atom of the pyran in a spiro manner as shown in structure 1 i.e., a carbon atom is common to both rings. Compounds in which the second ring system is merely a saturated carbocycle such as cyclohexyl or adamantyl are better considered simply as 2,2-dialkylpyrans, and are discussed in Chapter 3. 

Reductive dehalogenation is an efficient method of synthesis of cyclopropanes spiroannulated to five- and higher-membered carbocycles (i.e. compounds in which spiroannulation does not result in accumulation of extra strain) . The required gem-(dihalomethyl)cycloalkanes are usually prepared by halogenation of the precursor diols (equation 1). The cyclization is most efficiently accomplished in the Zn-alcohol-water system . For example, spiro[2.5]octane 7 was prepared in 91% yield using this procedure. This method is useful even for a one-step preparation of bis-spirocyclopropyl compounds as exemplified in equation 2. However, the application of the reductive dehalogenation method to the synthesis of more strained SPC (i.e. spirohexane or spiropentane) often leads to rearranged products. For example, methylenecyclopentane was the only product obtained from bis(bromomethyl)cyclobutane (equation 3) ... 

A large number of polycyclic heterocycles containing two or more six-membered rings that share two or more carbon atoms are known. For the majority of these systems, only one of the six-membered rings contains the heteroatoms and the other rings are fused carbocyclic rings such as cyclohexane, benzene, naphthalene, and in rare examples, anthracene. Systems in which more than one of the six-membered rings contain heteroatoms are also briefly discussed these include spiro-cyclic compounds and substituted naphthalenes. 

The success of the strategy is further applied for the synthesis of carbo-and spiro-aimulated aromatic compounds [146,147] by the intramolecular cyclization of silyl enolethers to PET-generated arene radical cations. Two types of carbocyclic compounds (170 and 173), varying in ring sizes, may be synthesized [146] starting from the same ketone (i.e., 169), as two types of silyl enol ethers can be produced using either thermodynamic or kinetic enolisation procedures. The core spiro structure (177) of the anticancer antibiotic ffed-ericamycin is also prepared [147] by the PET cyclization of 176 (Scheme 36). 

The enantioselective spiro ring construction is an important issue because many natural compounds have chiral spiro centers [103,104]. Pd catalyses of Spiro cyclizations have been reported by asymmetric intramolecular Mizoroki-Heck reactions [105,106]. In spite of a similar potential, transition metal-catalyzed ene-type carbocyclization has never been applied to asymmetric spiro cyclizations [107-110]. 

The asymmetric hydroacylation reaction of 1,5-enal was employed by Castillon and co-workers in the enantioselective synthesis of carbocyclic nucleosides (Scheme 8.14). When compound 31 was treated with a cationic rhodium catalyst, the cyclie ketone 32 could be obtained with up to 95% ee. Starting from an elegantly designed substrate 33, the group of Tanaka and Suemune realized the synthesis of enantioenriched spiro[4.4]nonanediones 36 and 37 via an iterative Rh-eatalyzed asymmetric intramolecular hydroacylation reaction (Scheme 8.15). ... 

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