Spiro-ring Annelations

A new approach to the 5-keto-aldehydes frequently employed as spiro-system precursors utilizes the known regiospecific hydration of acetylenic ketones. Thus the acetylenic aldehyde (167), produced by alkylating the t-butylimine (166) with trimethylsilylpropargyl bromide, underwent simultaneous regiospecific hydration and deprotection to (168) on treatment with mercuric sulphate in aqueous THF containing a trace of H2S04. °  

Lange and his co-workers have reported a short, convenient approach to the sesquiterpene (—)-acorenone (170) centred about the stereoselective Michael addition of l-methoxybut-3-en-2-one to the less hindered face of the enamine (169) followed by aldol cyclization, ° and Oppolzer etal. have synthesized acorenone and several other members of the same sesquiterpene family by further elaboration of the cis,trans mixture of esters (171) formed, with 100% cndo-selectivity, during the intramolecular thermal ene reaction of the 1,6-diene (172).  

Oppolzer, K. K. Mahalanabis, and K. Battig, Helv. Chim. Acta, 1977,60, 2388. 

The construction of spiro[n,5]dienones by base-catalysed intramolecular alkylation of suitably substituted phenols has now been applied to the synthesis of jS-vetivone (174), and a novel approach to spiro[4,5]deca-6,9-dien-8-one systems such as (173) and (176) has been found to lie in the copper(i)-halide-catalysed decomposition of phenolic a-diazo-ketones, e.g. (175).  

Wender and Eck have found the novel cuprate reagents (178 n = 4 or 5) to be useful spiro-annelating reagents, reacting with 3-halogeno-2-cycloalkenones, e.g. (177), to give spiro-systems directly in yields which compare favourably with the multistep routes currently employed.  

In a total synthesis of the natural sesquiterpene ( — )-acorenone B (186), White and his co-workers employed as a key stage the intramolecular cycloaddition of a 

Fischli, Q. Branca, and J. Daly, Helv. Chim. Acta, 1976, 59, 2443. 

The Lewis-acid-catalysed Diels-Alder reaction between cyclohexenone (188) and isoprene produces spiro-adduct (189) as the major product, and treatment of steroid 4,6-dien-3-ones with Trost s diphenylcyclopropylsulphonium ylide (190) has been shown to produce spiro[2,4]heptan-4-ones (191).  

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Ethoxyallylidenetriphenylphosphorane (94) has been shown to be a novel cyclohexanone annelating reagent, undergoing addition to a/8-unsaturated ketones to produce 2-alkoxycyclohexa-1,3-dienes (masked cyclohexenones and useful eno-philes) (Scheme 24)7 The method is highly versatile, permitting the construction of monocyclic, fused, bicyclic, and spiro-ring systems. 

Compounds with a variety of functional groups can be synthesized from arsine oxides by metalation and reaction with electrophilesS subsequent reduction and replacement of the arsenic group by nucleo-philes. Benzothiazoles have been used as versatile carbonyl equivalents, which react under very mild conditions one or two C-branches can be attached stereoselectively and annelation of fused and spiro rings has been described . 

The conformation and dimensions of the substituted spirocyclic chromans (160) have been ascertained. The heterocyclic ring adopts a C-2, C-3 half-chair form, whilst the spiro-annelated cyclohexadienone ring is a C-T envelope (80TL4973, 8lAX(B)1620, 82AX(B)1001>. 

Fourteen derivatives of spiro[(2/7-l-benzopyran)-2,2 -l, 3 -dithiolane] (118) were prepared (64-81% yield) and studied. They existed in solution as the spiro form, exhibiting observable photocoloration only at -100°C. The colored forms ( a.max usually in the 600-615-nm region) were readily decolorized upon heating or irradiating with visible light. Their spectra underwent hypsochromic shifts upon introduction of a donor (alkoxy) substituent in the 7-position, annellation of a benzene ring to the 5,6- positions, or replacement of the sulfur atoms with oxygen atoms.130... 

Both cyclic and acyclic enone systems participate in the (trimethylsilyl)cyclopentene annelation (Table 6). a-Methylene ketones react to form spiro-fiised systems and the intermediates derived from ace-tylcyclohexanone, cyclohexenone and cyclopentanone cyclize to yield S,S- and 6,3-fiised ring systems. ... 

Haloalkyl phenyl sulfides produce cycloalkyl phenyl sulfides on treatment with base. The synthesis of cyclopropyl phenyl sulfides has attracted particular interest since these compounds can be metal-lated - - by Bu"Li in THF and the resulting 1-phenylthiocyclopropyllithium has been used for spiro-annelation of various cycloalkanones. - Thus, 3-chloro-l-phenylthiopropane leads to phenylthiocyclopropane on reaction with potassium amide in liquid ammonia (Scheme 7, entry a), but attempts to prepare 2-methylcyclopropyl phenyl sulfide from 3-chloro-l-phenylthiobutane by an analogous route failed in the cyclization step. Neither 3-mesyloxy- and 3-tosyloxy-l-phenylthiododecanes " nor 3-tosyloxy-l-phenylthiobutane produce cyclopropane derivatives either on reaction with LDA in THF (Scheme 7, entry b). Failure in these ring closure reactions has been attributed to inadequate car-... 

A pinacol rearrangement, driven by the ring strain release of a cyclobutanone ring, has been exploited in formulating a novel, high-yield spiro-annelation technique (Scheme 35). ... 

Cyclopent-2-enone rings can be easily obtained under mild conditions from a,a-dibromoketones and enamines in the presence of iron carbonyls Spiro-annelation with S-cyclopropylids provides easy access to spiropentane derivatives and similar compounds . Ring expansion from 5- to 7-membered rings has been efficiently performed with cyclopropenes The transformation of nerolidol to the tricyclic a-cedrene has been achieved by a remarkable stepwise cyclization process... 

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