Forming five-membered

A completely different, important type of synthesis, which was developed more recently, takes advantage of the electrophilicity of nitrogen-containing 1,3-dipolar compounds rather than the nucleophilicity of amines or enamines. Such compounds add to multiple bonds, e.g. C—C, C C, C—O, in a [2 + 3 -cycioaddition to form five-membered heterocycles. 

The evidence obtained clearly indicates that the above photorearrangements proceed by a mechanism involving a nitrile ylide intermediate since cycloadducts could be isolated when the irradiations were carried out in the presence of trapping agents. Intramolecular cycloaddition of the nitrile ylide followed by a 1,3-sigmatropic hydrogen shift of the initially formed five-membered ring readily accounts for the formation of the final product. 

Aldehydes, ketones and cumulated double bonds react with oxiranes to form five-membered heterocycles (e.g. Schemes 31 and 32) (64HC(19-1)453). 

There are essentially three methods which have been used for incorporation of the glycerol unit in macrobicyclic species. In all of these the pervasive problem is the tendency of glycerol to form five-membered acetals involving the primary and secondary hydroxyls rather than the two primary hydroxyls and the tendency of the glycerol equivalent 1,3-dichloro-2-propanol to form epichlorohydrin. 

Although cyclizations of fluonnated substrates to form five-membered rings were only rarely encountered in the literature prior to 1972, there has been an explosion of activity in this area recently, particularly with regard to 1,3-dipolar cycloadditions... 

An analogous cyclization to eventually form five-membered rings has also been observed for l-metalla-l,3,5-hexatrienes with an additional heteroatom within the chain, such as in the complexes 157. These are obtained by Michael additions of imines to alkynylcarbene complexes in good to excellent yields (reaction type F in Scheme 4), and their configurations were determined to be Z (>91%) in all cases. Upon warming in THF solution, complexes 157 underwent cyclization with reductive elimination to furnish 2Ff-pyrroles 158 in up to 97% yield (Scheme 34). With two cyclopropyl substituents at the terminus in... 

The overall reaction between CO2 and GMA to form five-membered cyclic carbonate is presented as follows [2] ... 

The overall reaction between CO2 and GMA was assumed to consist of two elementary reactions such as a reversible reaction of GMA and catalyst to form an intermediate and an irreversible reaction of this intermediate and carbon dioxide to form five-membered cyclic carbonate. Absorption data for CO2 in the solution at 101.3 N/m were interpreted to obtain pseudo-first-order reaction rate constant, which was used to obtain the elementary reaction rate constants. The effects of the solubility parameter of solvent on lc2/k and IC3 were explained using the solvent polarity. 

Figure 32 The first P,N-ligand shown in Figure 32 can form five-membered ring chelates, in allylic alkylation with Pd the second is a chelating (phosphinomethyl)oxazoline P,N-type ligand, that catalyzes...

When 1,2-bis(chlorodimethylsilyl)carborane 2 was treated with ammonia, an amminolysis reaction occurred to give the cyclic tetramethyldisilaazane 3. The ease with which this reaction occurs to form five-membered ring bears notice. Hydrolysis of 2 gives cyclic siloxane compound 4. Utilization of the same general... 

A general method for the synthesis of highly substituted styrenes as 6/4-91, vinyl-cyclohexadienes and related compounds was developed by Xi, Takahashi and coworkers [301] by reacting an intermediately formed five-membered zirconacycle 6/4-89 with propargyl derivatives 6/4-90 or allyl bishalides in the presence of CuCl (Scheme 6/4.21). 

Five-membered rings. Most five-membered rings arise from the 1,3-dipolar-ophile behaviour of thioketones and studies in this field have been carried out mainly by Huisgen, Mloston, Heimgartner, and their co-workers. An exemplified thioketone reactivity to form five-membered rings with several classes of compounds is shown in Table 2. 

Table 2 Exemplified thioketone reactivity to form five-membered rings... 

The process shown in Scheme 3.16 is rather interesting. It should be noted that in most cases this reaction is very stereoselective with respect to the arrangement of the substituents at C-4 and C-5 atoms. In light of recent data on the possible isomerization of nitrocyclopropanes (13) to form five-membered cyclic nitronates (5) (for more details, see Section 3.2.2.1.2), low chemoselectivity of many reactions involving sulfur ylides does not seem to be so fatal. 

The very first example of the catalytic reductive cyclization of an acetylenic aldehyde involves the use of a late transition metal catalyst. Exposure of alkynal 78a to a catalytic amount of Rh2Co2(CO)12 in the presence of Et3SiH induces highly stereoselective hydrosilylation-cyclization to provide the allylic alcohol 78b.1 8 This rhodium-based catalytic system is applicable to the cyclization of terminal alkynes to form five-membered rings, thus complementing the scope of the titanocene-catalyzed reaction (Scheme 54). 

The irradiation of 2//-aryl azirines yields nitrile ylides which can be trapped by various dipolarophiles to form five-membered ring heterocycles116,140-142 (equations 80-82). 

Preparation of cyclodextrin derivatives substitution at a secondary hydroxyl group of the cyclodextrin annulus. Murakami and cowor-kers described a new and convenient method for the regioselective tosylation of the 2-hydroxyl groups of alpha, beta, and gamma cyclodextrin by means of a cyclic tin intermediate. The method is based on the reaction of dibutyltin oxide with 1,2-diols to form five-membered dibutyl-stannylidene derivatives. Useful yields of the 2-6>-tosyl derivatives of the cyclodextrins were obtained. 

Both six-membered pyranose and five-membered furanose structures are encountered, a particular ring size usually being characteristic for any one sugar. Thus, although glucose has the potential to form both six-membered and five-membered rings, an aqueous solution consists almost completely of the six-membered hemiacetal form five-membered rings... 

Aliphatic substrates also perform well, forming five membered rings in good yield and high enantioselectivity Eq. 6a. Typical Michael acceptors, however, are not sufficiently electrophilic to induce cyclization to form six-membered aliphatic rings. In order to effect this cyclization, use of a more electrophilic Michael acceptor, such as alkylidene malonate 83, was required Eq. 6b [70]. The difference in reactivity is presumably due to the extra conformational freedom of the aliphatic linker compared to the fused aromatic linker of substrate 79 coupled with potential competing non-productive pathways. 

Substrates possessing an allene that participate in the Alder-ene reaction are less common, but a few examples are known. Malacria [11] and Livinghouse [12] have independently used cobalt to effect intramolecular allenic Alder-ene reactions but the scope of these reactions was not investigated. Sato has performed an allenic Alder-ene reaction to form five-membered rings, using stoichiometric amounts of titanium [13], and Trost has shown that 1,3-dienes can be prepared via an intermolecular Alder-ene reaction between allenes and enones using a ruthenium(II) catalyst [14]. 

Intramolecular carbon-hydrogen insertion reactions have well known to be elTectively promoted by dirhodium(ll) catalysts [19-23]. Insertion into the y-position to form five-membered ring compounds is virtually exclusive, and in competitive experiments the expected reactivity for electrophilic carbene insertion (3°>2° 1°) is observed [49], as is heteroatom activation [50]. A recent theoretical treatment [51] confirmed the mechanistic proposal (Scheme 15.4) that C-C and C-H bond formation with the carbene carbon proceeds in a concerted fashion as the ligated metal dissociates [52]. Chemoselectivity is dependent on the catalyst ligands [53]. 

The synthetic compounds of para. VII contain multiple groups which form five-membered chelate rings. Although the metal-oxygen distances, Tables 4 and 5, vary by amounts large compared with the standard deviations, it is clear that sodium-water distances are shorter than sodium-ether oxygen distances, even for the most flexible ligand, (XVIII). 

It is conceivable that, starting from a pre-formed, five-membered heterocycle of the tetrahydrofuranol type, or even a furanosyl derivative, a contraction or extension of a side chain, according to the situation, would permit synthesis of a 2,5-anhydride of a sugar. This method has been used effectively on several occasions. 

---