Y-Lactones carbonylation

Rea.ctlons, Butyrolactone undergoes the reactions typical of y-lactones. Particularly characteristic are ring openings and reactions in which ring oxygen is replaced by another heteroatom. There is also marked reactivity of the hydrogen atoms alpha to the carbonyl group. 

When y-lactone 14 is treated with methylmagnesium bromide in THF at -78 °C, a carbonyl addition reaction takes place and gives, after aqueous workup, a hemiketal that is subsequently converted to... 

The addition of the dianion of /j-sulfmylcarboxylic acids to carbonyl compounds leads to the formation of the corresponding hydroxy derivatives which undergo spontaneous eyclization to give y-lactones. It was found that when optically active ( + )-(/ )-3-(4-methylphenylsulfinyl)pro-panoic acid is used for the reaction, the corresponding diastereomeric /i-sulfinyl-y-lactones are formed in a ratio which is dependent on the substituents of the carbonyl component. However, the diastereoselectivity was always moderate. 

The palladium-catalyzed carbonylation of 4-amino-2-alkynyl carbonates 40 or 5-hydroxy-2-alkynyl carbonates 41 afforded a-vinylidene-/i-lactams 42 [60] or a-vinyl-idene-y-lactones 43 [61] in good yields (Scheme 3.25). The initially formed (allenyl-carbonyl)palladium(II) intermediates were trapped by the intramolecular amino- or hydroxy-nucleophiles to give 42 or 43. 

Another interesting cyclization employing 2-hydroxy-substituted methoxyallenes 101 was reported by Takahashi et al. (Scheme 8.29) [85]. Their novel Ru3(CO)12-cata-lyzed carbonylation reaction of allenyl alcohols 101 furnished y-lactones 108 in almost quantitative yields. 

Cyclic alkynyl carbonates undergo carbonylation in the presence of a palladium catalyst and carbon monoxide (5 MPa) in MeOH to give allenic carboxylates (Eq. 9.118) [92], Bu3P proved superior to Ph3P as the catalyst ligand. An enynyl cyclic carbonate underwent double vicinal carbonylation at 80 °C to produce a five-membered lactone product in 52% yield (Eq. 9.119). When the reaction was performed at 50 °C, the bicyclic enone lactone was produced in 75% yield along with 10% of the y-lactone. 

Aldehydes and ketones can be hy-drodimerized to pinacols (Eq. 2) [34-37]. With aromatic carbonyl compounds, the yields and selectivities are mostly higher than with aliphatic ones. The reaction has been extended to imines (Eq. 2, X = NAr, N-Bn) [38-41] and to heterohydrodimerizations affording, for example, y-lactones (Eq. 3) [42-44]. 

Several related reations are summarized in Scheme 4.13. When a nucleophilic OH or NH2 group exists at the proper position of the olefinic substrate, cyclohy-drocarbonylation provides a lactone or a lactam. Allyl alcohols" " and homoallyl amines are converted into y-lactones and 8-lactams in high enantiomeric excesses. Thiol is employable as a nucleophile for hydrocarbonylation of a C—C double bond. A successful catalytic carbonylation is reported for hydrothiocarbonylation. ... 

Compound 58 was isolated as a yellow crystalline, optically active compound. HREIMS data for 58 gave a molecular formula of C15H16O4 with an inherent eight degrees of unsaturation. The IR spectrum was consistent with the presence of conjugated carbonyl functionalities including a y-lactone (1779 cm ) and a conjugated ketone (1665 cm ). The... 

Lithium homoenolates derived from carboxylic acids were generated from the corresponding /3-chloro acids by means of an arene-catalyzed lithiation. Chloro acids 186 were deprotonated with n-butyllithium and lithiated in situ with lithium and a catalytic amount of DTBB (5%) in the presence of different carbonyl compounds to yield, after hydrolysis, the expected hydroxy acids (187). Since the purification of these products is difficult, they were cyclized without isolation upon treatment with p-toluenesulfonic acid (PTSA) under benzene reflux, into substituted y-lactones 188 (Scheme 64) . 

When employing enantioenriched l-titano-2-alkenyl carbamates 334 in carbonyl addition, the selectivity depends on the enantiomeric purity that was achieved in its preparation (see Section IV.C.l). The (ii)-crotyl derivative (R)-334a has been employed several times (equation 92)224,252,253 optically active homoaldol products 346 are easily converted into y-lactones 347 by four different pathways, which require an oxidation step (see Section IV.C.6). Appfications in target synthesis include the natural products (-b)-quercus... 

Homopropargylic alcohols, 210, 212, and 214 in Table 12 are carbonylated to form a-silylmethylene-y-lactones, 211, 213, and 215, respectively, under similar reaction conditions." ... 

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]. 

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. 

De Groot et al. synthesized ( )-3(3-hydroxynagilactone F (54) [85] from compound 172 [86] with an overall yield of 0.2% (13 stages). The key steps in this synthesis were the formation of the 5-lactone by nuclelophilic addition to carbonyl and subsequent treatment with p-toluensulfonic acid, the introduction of the isopropyl in an a equatorial disposition following a procedure similar to that described by Hayashi et al. and finally the formation of the y-lactone via bromolactonization. 

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