Cyclobutanes annulated

Contrary to the phosphine-catalyzed reaction of the allene buta-2,3-dienoate, which adds to CgQ in a ]3-i-2] cycloaddihon ]354], the allene amide 317 forms the cyclobutane annulated fuUerene derivahve in good yields (Scheme 4.63) [355]. The reaction was also performed with similar allene amides bearing a six- or seven-membered lactam. 

Another example above shows site-selectivity through hyper-conjugative activation in the presence of the Fe(PDP)-catalyst in case of terpenoid substrate comprising sensitive cyclopropane and cyclobutane annulated nine-membered ring. The cyclopropane component effectively overrides steric effects and activates the two adjacent methylene groups at C-6, thus favoring C-3 for oxidation for its remoteness from ketone (EWG). C-3 oxidation is thus a major product with other oxidation products formed in minor amounts, where the Fe(/ ,/ -PDP) enantiomeric version of the catalyst shows improved performance over the earlier Fe(5,5-PDP) due to a better match of the catalyst with substrate topology. 

Some years ago we began a program to explore the scope of the palladium-catalyzed annulation of alkenes, dienes and alkynes by functionally-substituted aryl and vinylic halides or triflates as a convenient approach to a wide variety of heterocycles and carbocycles. We subsequently reported annulations involving 1,2-, 1,3- and 1,4-dienes unsaturated cyclopropanes and cyclobutanes cyclic and bicyclic alkenes and alkynes, much of which was reviewed in 1999 (Scheme l).1 In recent days our work has concentrated on the annulation of alkynes. Recent developments in this area will be reviewed and some novel palladium migration processes that have been discovered during the course of this work will be discussed. 

The novel [6+2] annulation approach developed by the Takeda group has also been included in a threefold anionic/pericyclic process (Scheme 2.149) [340]. The reaction leads to functionalized eight-membered rings 2-659 in a highly stereoselective manner, starting from acylsilanes 2-656 and 3-(trimethylsilyl)vinyl-lithium (2-657). After 1,2-addition and 1,2-Brook rearrangement, the cyclobutane 2-... 

As mentioned previously, the Stille reaction can also be combined with an elec-trocyclization. Trauner and coworkers [99] used this approach for the synthesis of a part of SNF4435C (6/1-190) and its natural diastereomer. SNF4435C, which was isolated from the culture broth of an Okinawan strain of Streptomyces spectabilis, acts as an immunosuppressant and multidrug resistance reversal agent [100]. In order to form the annulated cyclobutane skeleton in 6/1-190, the vinyl iodide... 

Cyclobutanes, synthesis with phosphaal-kenes, 13 Cyclopentadienes annulation to enamines, 176-177 synthesis, 197-198 Cyclopenta[b]pyrans, synthesis, 199 Cyclopentenylidenes, synthesis, 192-193... 

This reaction is a diastereoselective de Mayo reaction. Its stereochemistry is controlled by the configuration of substrate 7. The P-face of cyclopentanone 7 is effectively shielded by the dimethylphenylsilyl moiety. Therefore, the triplet state of 7 attacks the cyclobutene 6 via the a-face, forming the fourth annulated cyclobutane ring of the ladderane core. Typically for cyclopentanone systems, the annulation proceeds syn-selectively and the product is obtained as a 7 1 mixture of diastereomers 8 and 20, which is separated by preparative TLC yielding pure 8. 

Annulation. Allyldimethyltritylsilane reacts with electron-deficient alkenes to afford silylcyclopentanes. However, the reaction with bicyclic conjugated y-lactams at low temperatures leads mainly to cyclobutane derivatives. 

If the [3-h 2]-cycloaddition reaction of a methylenecyclopropane is performed with a remote alkene or alkyne moiety within the same molecule, products 2 of the bicyclo[3.n.0]-type (n < 3) or the bicyclo-[n.3.0]-type (n > 3) can, in principle, be obtained. The former of these product types can be considered as unhkely, as an alkene or alkyne separated by only one or two atoms from the methylenecyclopropane would give rise to a strained annulated ring, i.e. a cyclopropane or a cyclobutane. It is known from investigations of photochemically initiated intramolecular [2 3-2] cycloadditions of alkenes that the minimum size required for a spacer between 7t-systems is three atoms in a reaction of a non-crossed type. There are actually a few examples of photoinduced intramolecular cycloadditions of the crossed type involving substrates with short spacers (n =... 

The majority of the intramolecular (2 + 2)-cycloreversions of hetero-bicyclic compounds proceed via ring opening of an annulated cyclobutene or azetine ring. Only in one instance has the same reaction of a cyclobutane ring been proposed as an intermediate step, viz., in the reaction of a thiirene 1,1-dioxide with enamines (Section II,B).33... 

An alternate approach to the iridoid core, again developed by Biichi, utilized the [2+2] cycloaddition of cyclopentene 28 and tricarbonyl 29 (Scheme 6). Following photochemical annulation, the resulting cyclobutane 30 underwent a retro-aldol reaction and hemiacetal formation to provide racemic cyclopenta[c]pyran 31. Elaboration of 31 to loganin (16) required 10 additional steps. ... 

Pyrolysis of bicyclopentanes usually leads to the cleavage of the central C—C bond to give a vibrationally excited diradical, which suffers a consecutive 1,2-H shift (Table 8 entries Ic, 4b, 6b) or subsequent C—C bond cleavage (Table 8 entries 5b, 6b, 9, 10a, b, 12b, 13a, 14, 16). In other cases syn/anti isomerizations of the substrates are observed (Table 8 entries 2e, 4a, 10c). The higher annulated syn/anti-pentacyclo[5.3.0.0 . 0 . 0 ]-decanes (Table 8 entry 18) react preferably by pyrolytic cleavage of the cyclobutane unit, whereas the cyclopropane ring is not affected. 

The total synthesis of cannabicyclol, clusiacyclol A and B, iso-erio-brucinol A and B and eriobrucinol involves an oxa-[3 + 3] annulation for the construction of the chroman nucleus and a stepwise cationic [2 + 2] cycloaddition for the cyclobutane formation (13OL3130).The synthesis of... 

While analogous products are obtained by the Pd-catalyzed annulation of 1,3-dienes, this procedure may have advantages when the unsaturated cyclopropanes or cyclobutanes are more readily prepared. However, a large excess of alkenes was required. In 2004, they succeeded to extend their methodology to functionalized alkenes. Under the same reaction conditions, the corresponding annulated products were produced in moderate to good yields (Scheme 2.82b). 

Peterson alkenation cyclobutane synthesis and cyclopentane annulation via l-lithio-l-(trunethylsilyl)cyclopropane)... 

In the early 1960s, Brannock et al. reported a thermal [2+2] cycloaddition of enamines. Enamines react with a variety of electron-deficient alkenes such as acrylates, nitro-olefines, acetonitriles, vinylsulfones, fumarates, and malei-mides to give aminocyclobutanes [4]. The reaction generally does not require the assistance of an acid catalyst. Narasaka et al. exploited asymmetric thermal [2+2] cycloaddition of vinyl and aUenyl sulfides with electron-deficient alkenes catalyzed by Lewis acid [5]. Yamazaki et al. have reported that a stoichiometric amount of Lewis acid activates [2+2] cycloaddition of vinylselenides with highly electron-deficient olefins [6]. These reactions proceed via a stepwise annulation to give mercapto- and seleno-cyclobutanes, respectively. However, cyclobutane formation from silyl enol ethers, which are one of the most easily prepared ketone... 

---