Five-membered rings lactones

Saturated y-lactones (five-membered ring) absorb at shorter wavelengths than esters or 5-lactones 1795-1760 cm-1 5-valerolactone absorbs at 1770 cm-1. Unsaturation in the y-lactone molecule affects the carbonyl absorption in the same manner as unsaturation in 5 lactones. 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

In the case of y,6-unsaturated acids, five-membered rings (y-lactones) are predominantly formed (as shown above note that Markovnikov s rale is followed), but six-membered and even four-membered lactones have also been made by this procedure. There is a gem- dimethyl effect that favors formation of 7-11 membered ring lactones by this procedure. ... 

Since five-membered rings are formed faster than four or six-membered rings, an otherwise electronically Symmetrical double bond (35) or (36) will be captured intramolecularly to give a y-lactone (37) in acid. 

Intramolecular insertion reactions show a strong preference for formation of five-membered rings.219 This was seen in a series of a-diazomethyl ketones of increasing chain length. With only one exception, all of the products were five-membered lactones.220 In the case of n = 3, the cyclization occurs in the side chain, again forming a five-membered ring. 

The preparation of five-membered rings in solid-phase organic chemistry has been reported in several publications. Versatile syntheses of these heterocycles with different numbers and kinds of heteroatoms have been described. The synthesis of five-membered rings containing one nitrogen atom (Fig. 3.6) as pyrrolidines (231) [311-316] pyrroles (232) [317-320] pyrrolidinones (233) [321-323] pyr-rolinones (234) [324—326] 2,5-pyrrolidinediones (235) [327-329] 2,4-pyrrolidine-diones (236) [330-332] 2,5-pyrrolinediones (237) [333] or heterocycles with one oxygen or one sulfur atom like tetrahydrofurans (238) [334—336] 2,5-dihydrofurans (239) [337], furans (240) [338, 339], yS-lactones (241) [340-343], 2,5-dihydrofura-nones (242) [344] (Scheme 3.35) and thiophenes (243) [345, 346] can be accomplished on solid supports. 

Lactonization, like esterification, is an equilibrium process. y-Lactones and 8-lactones are so readily formed that the carboxylic acid itself can provide the required acidic catalyst, and substantial amounts of the lactone are typically present in solutions of 4- or 5-hydroxy acids respectively (Table 7.3). Interestingly, the proportion of lactone is usually higher for five-membered rings than for six-membered rings. 

Lactones are cyclic esters derived from lactic acid (CsHeOs). They are constituents of many essential oils and plant volatiles. They contain a heterocyclic oxygen next to a carbonyl function in a five or more membered ring that is saturated or unsaturated. Those with a five-membered ring are called y-lactones, e.g. y-angel-ica lactone 148, whereas compounds containing a six-membered ring are called (5-lactones, e.g. (5-valerolactone 149 (Structure 4.45) [1-4, 6, 9, 22, 23,29, 62]. 

The molecular ion peak of five-membered ring lactones is distinct but is weaker when an alkyl substitutent is present at C4. Facile cleavage of the side chain at C4 (rules 3 and 8, Section 2.7) gives a strong peak at M -alkyl. 

These methods parallel the synthesis just described for the five-membered rings. As indicated in structures (42)—(49), standard reactions of aliphatic chemistry can be extended to the preparation of piperidines, tetrahydropyrans and pentamethylene sulfides (44 Z = N, O, S) glutarimides, glutaric anhydrides and glutaric thioanhydrides (46 Z = N, O, S) and 8-lactams, 8-lactones and 8-thiolactones (49 Z = N, O, S). 

Various alioyolio epoxides have been subjected to the action oJ oarbanionoid reagents. Cyclopentene oxide (Eq. 887) is unique thus far, in that it gives no lactone.870 Lactone formation is prevented b the high activation energy required to establish irwwt-fusion between two five-membered rings.870... 

The introduction of a second, five-membered ring has already been discussed in reference to the ready formation of furanosides from d-glucurono-M, 3-lactone.14 The rate constant, given in Table VIII for methyl 2, fwli-O-mcthyl-a-D-glucofuranosidurorio-G,3-lactone is much smaller than that for ethyl /3-D-glucofuranoside. The effect is also shown in the ready... 

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