Spiro cyclopropyl derivatives

Spiro-pyrazoline derivatives (18) are obtained smoothly from 16-methy-lene-17-ketones (17). ° The sole products formed from (18) by pyrolysis or cleavage in the presence of boron trifluoride etherate, are the 16-spiro-cyclopropyl steroids (19). ... 

In an analogous manner, treatment of 4-(2-haloethyl)-phenols and -l-naphthols " with bases produces spiro[2.5]octa-4,7-dien-6-ones and their benzo analogues, respectively. The basic treatments of jS-oxiranyl ketones , esters (equation 13) , nitriles , sulfones and alkynes affords 2-(hydroxymethyl) cyclopropyl derivatives, usually as the sole cyclization product. The cyclization occurs regiospecifically by the intramolecular attack of the anion on the y-carbon in the oxirane ring. Attack of the anion on the 5-carbon in the oxirane, which should lead to the formation of cyclobutanols, usually does not take... 

Very recently the synthesis of derivatives which incorporated a spiro-cyclopropyl group at N-1 by bridging to C-2 was reported [53]. The fused spiro-cyclopropane ring was obtained through an intramolecular addition of Grignard reagent, as shown in Fig. 20. 

While the unsubstituted TMM system has proved to be efficient in the synthesis of loganin and the approach of the spiro ring system of the Ginkgolides, the substituted system gave good results in the synthesis of brefeldin. The use of a cyclopropyl derivative culminated in the synthesis of ( )-ll-hydroxyjasionone. 11-Hydroxyjasionone is... 

The availability of cyclopentenones from butanolides allows the lactone annulation to facilitate the synthesis of cyclopentyl natural and unnatural products. An example that highlights the latter is dodecahedrane (178) for which 179 constitutes a critical synthetic intermediate 136,137). Lateral fusion of cyclopentenones as present in 179 can arise by acid induced reorganization and dehydration of 180. While a variety of routes can be envisioned to convert a ketone such as 182 into 180, none worked satisfactorily137 On the other hand, the cyclobutanone spiro-annulation approach via 181 proceeds in 64 % overall yield. Thus, the total carbon cource of dodecahedrane derives from two building blocks — cyclopentadiene and the cyclopropyl sulfonium ylide. 

As a consequence, the pyrrolidine derivative IV will be produced in as much as the nucleophilic attack of nitrogen is restricted to the carbon atom bearing the propylamino chain (spiro mode) since the analogous interaction with the other tertiary cyclopropyl carbon (fused mode, see dotted arrow) should afford the unrecorded piperidine derivative V. In actual fact, the spiro mode generally prevails over the latter. 

Table 1 lists the experimental conditions for the electrochemical formation of a cyclopropyl ring from a variety of 1,3-dihaloalkanes, mostly from dibromoalkyl derivatives. A free cyclopropyl ring as well as a spiro derivative (entry 6), bicyclobutanes (entries 8-10) and other fused and highly strained systems such as tricyclene (entry 11) and a propellane derivative (entries 12,13) were obtained. In addition, Carroll and Peters have found evidence for the intermediacy of [2.2.1 ]propellane upon reducing 1,4-dihalonorbor-nanes electrochemically at a low temperature, although attempts to isolate it were unsuccessful. The intramolecular electrochemical reduction of a dihalo-substituted tricyclic compound leads to cyclization with formation of a tetracyclic derivative in which... 

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-... 

Cyclopropyl-substituted 1,3-dienes react in the normal fashion in the Diels-Alder reaction. Most of the dienes have been incorporated in cyclic structures with additional strain added to the cyclopropane ring. Compounds of this type that have been studied rather extensively, include derivatives of 3,4-dimethylenetricyclo[3.1.0.0 "]hexane, " bicyclo[4.1.0]hexa-2,4-diene, ""- - """ spiro[2.4]hepta-4,6-diene, - -" - "-" - " - ° - " -... 

Lateral nuclear shifts have been found to contribute to the photochemistry of spiro[cycloalkyIphenalenes] (334) The cyclopropyl and cyclopentyl derivatives of (334), i.e. n=0 or 2, appear to react by cleavage to biradicals (335) which recombine to produce the isolated products (336) and (337). The cyclohexyl homologue (334), n=3, yields (338) which may be a di-m-methane rearrangement product. 

Hashimoto and coworkers [69] have recently begun to explore the use of chiral rhodium catalysts in the intramolecular dipolar cycloadditirai reactions of indoles, and have applied their methodology to the synthesis of the Aspidosperma ring system. Thus, the cycloaddition of the cyclopropyl carbonyl ylides derived from cyclopropyl diazo-5-imido-3-ketoesters 135 upon treatment with dirhodium (11) tetrakis[Af-tetrachlorophthaloyl-(5)-ferf-leucinate] gave cycloadducts 136 along with the spiro[2.3]hexanes 137 in only moderate yields (Scheme 34). Although the reaction proceeds with exclusive endo diastereoselectivity, only moderate enantioselectivities of up to 66% enantiomeric excess (ee) could be obtained. 

The synthesis of agarospirol (epihinesol) portrays an efficient stereoselective approach to spiro[4-5] decanes based on the intramolecular keto-carbene insertion reaction (A— B) and cleavage of the derived cyclopropyl alcohol (C) to give a spiroketone. 

A second common reaction of sulphonium ylides is Michael addition to ajS-unsaturated carbonyl compounds, giving cyclopropanes. This reaction forms the basis of a cyclopentene synthesis starting from sulphonium allylide (14). Other recent examples include the preparation of spiro[cyclopropane-l,4-A -pyrazolin]-5 -one derivatives (15) and cyclopropyl-ulose (16). Un-... 

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