Spirocyclopropane opening

The two articles in this current volume describe recent developments with small ring compounds which have not teen compiled in such a context before. T. Hirao discusses selective transformations initiated by transition derivatives in the construction of functionally substituted five-, six- and seven-membered rings as well as open-chair compounds. Cycloadditions onto methylene- and alkylidene-cyclopropane derivatives, described by A. Goti, F. M. Cordero and A. Brandi, not only yield products with spirocyclopropane moieties which can be desirable as such or as potential mimics of gem-dimethyl groupings, but also intermediates which can undergo further transformations with ring-opening of the cyclopropane units. 

Sulfuryl chloride isocyanate with 1 gave the expected )5-lactam 177 only as a minor product, the principal product being the y-lactam derivative 178. It is reasonable to assume that the 1,4-zwitterionic intermediate 176 is responsible for the formation of 177 and 178 (Scheme 39) [104,130]. Sulfonation of 1 with SO3 also proceeds with ring opening of one of the cyclopropyl groups to give quantitatively the spirocyclopropane-y-sultone 179 (Scheme 39) [76,132]. 

Neighboring group participation effects appear to play a crucial role in the nucleophilic substitution of chlorine in Michael adducts of 1-R, 2-R, 3-X. Thus, this substitution proceeds very easily in any of the adducts formed with an electron rich nitrogen, sulfur and oxygen Michael donor. For the adducts of nitrogen nucleophiles, the facile substitution of the chlorine has been suggested to occur via formation of intermediate aziridinium ions 103 [8] (Scheme 32), and this postulate was later supported by isolation of azaspiropentane derivatives under appropriate conditions in several reactions (see Sect. 3.2.2) [11b, 53,56]. It is most likely that alkylthio substituents in adducts of type 85 participate in the same way to first form spirocyclopropane-annelated thiiranium ion intermediates which are subsequently opened by attack of the incoming nucleophile. 

Sulfur ylides are among the most interesting carbon nucleophiles and their synthetic importance has been recently reviewed.One especially interesting use of these ylides is their application to the synthesis of cyclopropane derivatives using unsaturated oxazolones. For example, stabilized sulfur yhdes react with unsaturated oxazolones 629 via a Michael reaction to give oxazolone spirocyclopropanes 630 as shown in Scheme 7.202 and Table 7.46 (Fig. 7.57), whereas the less stabilized sulfur ylides give ring-opened products 631 as the major compounds (Scheme 7.202). ... 

Recently, the cyclopropanation of (Z)-4-benzyIidene-2-phenyl-5(4//)-oxazolone 621 with phenyldiazomethane was reported to give the spirocyclopropane, rac- 21 in very high yield. Subsequent ring opening and hydrolysis of rac- 21 generated frani-l-amino-2,3-diphenyl-l-cyclopropanecarboxylic acid, rac-828 (cadiPhe) (Scheme 7.256). This new, constrained phenylalanine analogue induces a y-tum in the sohd state when incorporated into model dipeptides. The enantiomers of the Al-Boc (Boc = tert-butyloxycarbonyl) methyl ester of 828 have been resolved by HPLC. 

As mentioned earlier, alkylation of sugar enolates is a method of choice to introduce two different carbon chains in a defined sequence to construct a quaternary chiral center with the desired configuration [11] (see Scheme 39). Several other methods have been proposed, such as the ring opening of spirocyclopropanes [182] or the 1,4-addition of dimethylcuprate on a p-methyl-substituted enone [183]. 

Thermolysis of an allyl-cyclopropyl carbyne complex under the mild conditions used for the acyl carbynes did not result in an oxymetallacycle or a cyclopentenone. Instead, 2-cyclohexenone-5-spirocyclopropane was obtained in low yields (5%) together with moderate yields (43%) of the open-chain (3-allyl V-pentadienal) molybdenum complex (equation 104)163. 

In an alternative two-step transformation of 5-spirocyclopropane isoxazolidines to tetrahydropyridones, for example, 7-amino cyclopropanol 214, prepared by chemoselective N-O reduction of isoxazolidine 213, was converted into 215 by treatment with Cu(OAc)2 and LiOAc in the presence of catalytic amounts of Pd(OAc)2. Interestingly, 7-amino cyclopropanols can also undergo a Pd-catalyzed domino ring-opening/cyclization/oxidation process to afford dihy-dropyridones such as 216 when the reaction is carried out in the presence of air or O2 (Scheme 49) <2005JOC5636>. 

Finally, addition of thiourea to the spirocyclopropane (470) results in ring-opening with formation of 535 (equation 186) . In contrast to the 2-methoxy-substituted cyclopropanes, the thio-substituted products do not show any ring-opening on treatment with... 

Treatment of the spirocyclopropane 470 with halides results in ring-opening followed by intramolecular ring-closure, yielding mainly 672 together with small amounts of 673 (equation 237). ... 

Change of solvent to benzene also yields these dimers which are accompanied by the adducts (78) and the furan (79). The adducts (78) are formed via a hydrogen abstraction pathway. The photochemical isomerization of the spirocyclopropane derivatives (80) affords the carbazole derivatives (81). This reaction involves ring-opening of a cyclopropyl bond followed by cyclization of the resultant biradical. An oxidative step must also be operative. 

Four different complexes containing cyclopropane subunits, are obtained from (2,2 -bi-pyridine)(cycloocta-l,5-diene)nickel and methylenecyclopropane in varying amounts. All products (partly with ring opening) on further conversion give spirocyclopropane products in good yield. (See also Section I.B.2.2.2.). 

In the absence of water, the ester function was retained and a oxo carbonyl group was formed at the original alkoxy-substituted tertiary cyclopropane carbon atom, as demonstrated by the ring opening of bicyclic cyclopropane, e.g. 11 ° and 13, and spirocyclopropane, e.g. 

For a more recent application of this sequence of 1,3-dipolar addition to bicyclopropylidene and subsequent rearrangement with ring opening of one of the two spirocyclopropane groups see Goti, A. Anichini, B. Brandi, A. Kozhush-kov, S. I. Gratkowski, C. de Meijere, A. J. Org. Chem. 1996, 61, 1665, and refs cited therein. 

Under analogous reaction conditions, tricyclic isoxazolidines 85c afforded the p-homoprolines 87, probably by ring opening and A-acylation of the primary carbapenam intermediates 86c <04EJ02205>. The chemistry of spirocyclopropane isoxazolidines 85 as versatile precursors of different azaheterocycles has been reviewed <04M649>. 

Figure 8. Radical ring-opening polymerization of lO-methylene-9,10-dihydroanthryl-9-spirocyclopropane (MDSC).

---