To form Five-Membered Rings

Cyclization of o-azidobiphenyls to carbazoles is one of the oldest and best studied arylnitrene reactions. Carbazole formation (67) has finally been shown to involve cyclization of a singlet nitrene (68), generated by photolysis or thermolysis of 2-azidobiphenyl, settling a controversy of some standing.  

The lack of pronounced substituent effects on this reaction by electron-withdrawing and -donating groups in the two aryl rings is neatly accommodated by this mechanism. The nitrene may behave as a or component, depending upon whether a full or empty orbital of the singlet nitrene is utilized. Presumably the tt process would be thermally allowed, the 7t photochemically allowed. 

By a skillful use of sensitizers, quenchers, filters, and choice of temperature used for photolysis, the decomposition of 2-azido-2 -methyl-biphenyl can be controlled to give a predominance of either carbazole (via singlet nitrene) or phenanthridine (via triplet)  

In the latter example the corresponding amine (25%) and azo compound (12.5%) were also obtained. 

Some recent synthetically useful examples of cyclizations that yield five-membered rings are illustrated below. They include cyclizations onto neighboring phenyl, pyrone, and indole rings  

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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... 

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... 

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 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). 

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]. 

Photochemically initiated electrocyclizations can be used to form five-membered rings (e.g. Section 4.5.1.1.2.i). 

Reactions in which the ring is cleaved or completely fragmented are fairly common in these systems. Ring contraction to form five-membered rings is also common especially where sulfur is extruded, and these reactions are considered separately, as are reactions which involve desulfurization or reduction. Reactions which lead to ring opening but are initiated by nucleophilic attack at ring carbons have already been discussed in Section 2.28.3.3.3. 

Most cyclizations to form five-membered rings involve the 5-exo mode of cyclization. An exception has been reported in the intramolecular sulfenoamination of 3-alkenylamines used in the synthesis of pyrrolidine alkaloids (equation 102).215 229 Other examples include the aminomercurations of Af-sub-stituted-l-amino-3-butenes162,23° and the methylsulfenilium ion-initiated cyclization of 0-(2-propenyl)-/V-tosylaniline 231... 

Organotin-zinc derivatives can be used as reagents in organic synthesis. Thus, the stannyl zincate complex Me3Sn(Et)2ZnLi reacts with alkoxy-unsaturated ketones to form five-membered ring heterocycles434. 

The compounds 135-137,139,141 and 145 listed under (60) react easily with Mg to form five-membered rings. In contrast to 147, the compound me2(CH2Br)Si-CH2-CH2-SiCl3 does not react with Li but only with Mg ... 

Photochemically initiated electrocyclizations can be used to form five-membered rings (e.g., Section 4.5.1.1.2.1). The formation or rupture of ring bridges often involves electrocyclic reactions (e.g., Sections 4.4.4.1, 4.4.8.3.4, and 4.6.1). 

The primary intermediates (dipolar 1 1 adducts 54) can add another molecule of HFA to form five-membered rings. l,3,4-A -Dioxaphospholanes 56 are the kinetically favored products from reactions of trivalent phosphorus compounds with HFA, but normally rearrange below ambient temperatures to yield the thermodynamically stable l,3,2-2 -dioxaphospholanes 57. 

Where halogen or acetate is the counterion, the cyclomet-alated products are halide- or acetate-bridged dimers. Particularly in the case of halides, these dimers are easily cleaved by various ligands, such as pyridine, phosphines, phosphites, and acetylacetone, to give more soluble, monomeric species. Cyclometalation, especially with nitrogen atom donors, inserts into C-H bonds to form five-membered rings. However, formation of six-membered rings can occur (equation 67). 

Cycloaddition reactions of 18-electron transition metal ti -allyl complexes with unsaturated electrophiles to form five-membered rings have been extensively investigated. These transformations constituted a family of metal-assisted cycloaddition reactions in which the metal functions as an electron-donor center. These are typically two-step processes that involve the initial formation of a dipolar metal r) -alkene intermediate (2) and subsequent internal cyclization (equation 2). The most extensively investigated application of this methodology has been with dicarbonyl-ii -cyclopentadienyliron (Fp) complexes from the laboratory of Rosenblum. These (ri -allyl)Fp complexes are available either by metallation of allyl halides or tosylates with a Fp anion, or by deprotonation of (alkene)Fp cations. ... 

Functionalized y-lactones are important synthetic intermediates for a number of biologically active natural products [102]. An interesting strategy based upon the AD reaction of unsatuxated esters or carbamates, combined with the spontaneous kinetic cycHzation to form five-membered ring lactones, has recently been established (Scheme 27). Thus, asymmetric dihydroxylation of p,y- and y,8-un-saturated esters 73 and 74 results in the hydroxyl-substituted lactones 75 or the side-chain functionaUzed system 76 respectively, in high optical purity. This strategy was appHed to the synthesis of numerous natural products. 

The expanded capabilities of this catalyst allowed the construction of additional ring systems [44]. A transannular olefin insertion formed a bicyc-lo[3.3.1]nonane structure (Eq. 69). Multiple insertion steps can selectively transform a monocyclic substrate into a propellane derivative (Eq. 70). The catalytic cycle begins at the monosubstituted olefin, followed by the insertion of the remaining double bonds to form five membered rings. 

Orthometallated complexes are intermediates in numerous cyclic carbonylation reactions involving aromatics with nitrogen donor groups in their side chains. For example, aromatic ketoximes and azobenzene are carbonylated at elevated temperatures and pressures with a cobalt carbonyl catalyst to form five-membered ring heterocycles in which a carbonyl group has replaced the metal in the presumed orthometallated intermediate ... 

The tendency to form five-membered rings is illustrated in the complex obtained with methyl-t-butyl-N,N-dimethylhydrazone[Pd—CHj—C(=NNMe2)Bu-t]20r-Cl)2, where t-Bu has not been metallated, which would have given rise to a six-membered ring d. 

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