A-Methyl-8-valerolactone

Node and coworkers have used this aromatization strategy for the synthesis of (-) aphanor-phine.27 The Diels-Alder reaction of chiral nitroalkene, prepared by the asymmetric nitroolefi-nation reaction of a-methyl-8-valerolactone, with the Danishefsky s diene followed by aromatization is used as a key step for this total synthesis, as shown in Scheme 8.6. 

Node and Fuji have developed a new chiral synthesis of various alkaloids using chiral nitroalkene, (S)-(-)-2-methyl-2-(2 -nitrovinyl)-S-valerolactone. Scheme 8.11 shows a total synthesis of (-)-physostigmine, a principal alkaloid of the Calabar bean.53 The key nitroalkene is prepared by asymmetric nitroolefination of a-methyl-8-lactone using a chiral enamine (see... 

A procedure for preparation of /8-methyl-8-valerolactone from 3-methylpentane-1,5-dioP shows that copper chromite is an effective catalyst for dehydrogenation. Presumably the reaction proceeds through the aldehyde and hemiacetal. The evolution of hydrogen is nearly quantitative and the yield of lactone high. 

Various substituted lactones were used for enzymatic polyester synthesis via ROP ( )-a-methyl- 3-propiolactone [101], P-methyl-P-propiolactone [78], a-decenyl-P-propiolactone [27], a-dodecenyl-P-propiolactone [46],benzyl-P-D,L-malonolactonate [104], a-methyl-e-caprolactone [96], oc-methyl-8-valerolactone [96], l,4-dioxane-2-one [91], and others (see also Table 4.2). 

The first natural product synthesized using the bis-heteroannulation strategy was evodone, a structurally simple member of the naturally occurring furanoterpenes. The synthesis began with commercially available 4-methyl-8-valerolactone 170, which was converted to the cycloaddition precursor 171 in fom steps (Fig. 3.52). 

HL 8-Membered lactone 8-OL 8-Octanolide HDL 16-Hexadecanolide MVL a-Methyl-5-valerolactone UDL 11-Undecanolide aMCL a-Methyl-e-caprolactone 8-DL 5-Decalactone y-BL y-Butyrolactone y-CL y-Caprolactone y-VL y-Valerolactone 5-VL 6-Valerolactone ... 

Five membered, unsubstituted, lactone 7-butyrolactone (y-BL) was polymerised by PPL or PCL [16, 73] into small oligomers with a degree of polymerisation (DP) of 8-11. In the Pseudomonas sp, lipase catalysed polymerisation of y-VL and y-CL, less than 10% conversion was observed at 60 °C for 480 hours [75]. Unsubstituted and substituted six membered lactone 6-valerolactone (6-VL) [26, 69, 79-80] and a-methyl-6-valerolactone (MVL) [81] were polymerised using Rhizopus japonicus lipase, CCL, PFL, PPL and CAL enzymes. For unsubstituted 5-VL, the reactions were run for 5-10 days and the highest molecular weights obtained were in the range of 2,000 Da. CAL catalysed polymerisation of a-methyl-6-valerolactone yielded polyester with a M of up to 11,400 at 60 °C in 24 hours. 

Ethyl-/3-methylglutaric acid has been prepared by the acid hydrolysis of a,a -dicyano- S-ethyl-fl-methylglutarimide, 3-cy-ano-4-ethyl-6-imino-2-keto-4-methylpiperidine-5-carboxamide or the diimide of 8-ethyl- 9-methylpropane-a,a,a, a -tetracarboxylic acid by the oxidation of jS-ethyl-fl-methyl-5-valerolactone with chromic acid and by the reaction of sodium hypobromite on l,4-dimethyl-l-ethyl-3,S-cyclohexanedione. ... 

This case study highlights the formidable challenge posed by epimerization en route to the synthesis of nonpeptidic fragments of cyclic peptide natural products. (3S,4R,7S)-HTMMD was prepared from (R)-4-methyl-5-valerolactone 74 in nine steps (Scheme 8.6a). After convenient synthesis of aldehyde 77 and its asymmetric aldol condensation with the ketene acetal 79, HTMMD skeleton 80 was isolated as a single isomer. After installation of allyl ester, the alcohol was coupled with Fmoc-Ala-Cl in the presence of DMAP/DIPEA (4-dimethylaminopyridine/diisopropylethylamine) followed by fluorenylmethyloxy-carbonyl (Fmoc) deprotection to afford the ester segment 81b in excellent yield. The amount of DMAP and temperature (—15 °C) were critical to avoid racemiza-tion. Modified Tsunoda s diastereoselective aza-Claisen rearrangement [145] was used as the key step in the 13-step synthesis of N-methylhydroxyisoleucine 86b... 

The effect of the substituent posihon and ring size of the methyl-substituted lactones was studied in detail by Kobayashi and coworkers [5, 6]. Only CALB induced the polymerization of a-methyl substituted 8-valerolactone and CL (a-MeVL and a-MeCL Scheme 15.1). Both monomers were reactive, but no enanti-oselection occurred under the reaction conditions employed [55]. Moving the methyl substituent to the co-position resulted in a low polymerizabihty of the... 

Good yields of aldehydes from esters as well as hydroxyaldehydes from lactones can be obtained by reduction with NaAlH4 at low temp.— E NaAlH4 in tetra-hydrofuran added gradually at —45 to —60° to a soln. of methyl hydro-cinnamate in the same solvent, and the product isolated after 3 hrs. stirring -> hydrocinnamaldehyde. Y 80%.—Similarly d-Valerolactone 8-hydroxy-valeraldehyde. Y 75%. F. e. s. L. I. Zakharkin et al., Tetrah. Let. 1963, 2087. 

Despite the increased activity towards the ROP of lactide of the thiourea/ sparteine system, a stronger base was required to facilitate the ROP of 5-valerolactone and e-caprolactone [38]. Both l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or 7-methyl-l,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (Figure 14.1), in conjunction with the thiourea, were shown to be highly efficient catalyst systems for the ROP of less-strained monomers, in particular 5-valerolactone. The ROP of this monomer under the conditions applied was shown to proceed rapidly, with... 

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