1955-45-9Relevant academic research and scientific papers
Lactonization as a general route to β-C(sp 3)–H functionalization
Zhuang, Zhe,Yu, Jin-Quan
, p. 656 - 659 (2020)
Functionalization of the β-C–H bonds of aliphatic acids is emerging as a valuable synthetic disconnection that complements a wide range of conjugate addition reactions1–5. Despite efforts for β-C–H functionalization in carbon–carbon and carbon–heteroatom bond-forming reactions, these have numerous crucial limitations, especially for industrial-scale applications, including lack of mono-selectivity, use of expensive oxidants and limited scope6–13. Notably, the majority of these reactions are incompatible with free aliphatic acids without exogenous directing groups. Considering the challenge of developing C–H activation reactions, it is not surprising that achieving different transformations requires independent catalyst design and directing group optimizations in each case. Here we report a Pd-catalysed β-C(sp3)–H lactonization of aliphatic acids enabled by a mono-N-protected β-amino acid ligand. The highly strained and reactive β-lactone products are versatile linchpins for the mono-selective installation of diverse alkyl, alkenyl, aryl, alkynyl, fluoro, hydroxyl and amino groups at the β position of the parent acid, thus providing a route to many carboxylic acids. The use of inexpensive tert-butyl hydrogen peroxide as the oxidant to promote the desired selective reductive elimination from the Pd(iv) centre, as well as the ease of product purification without column chromatography, render this reaction amenable to tonne-scale manufacturing.
SYSTEMS AND METHODS FOR REGIOSELECTIVE CARBONYLATION OF 2,2-DISUBSTITUTED EPOXIDES FOR THE PRODUCTION OF ALPHA,ALPHA-DISUBSTITUTED BETA-LACTONES
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Paragraph 0077; 0082; 0121-0123, (2021/01/29)
Provided are methods of producing carbonyl compounds (e.g., carbonyl containing compounds) and catalysts for producing carbonyl compounds. Also provided are methods of making polymers from carbonyl compounds and polymers formed from carbonyl compounds. A method may produce carbonyl compounds, such as, for example α,α-disubstituted carbonyl compounds (e.g., α,α-disubstituted β-lactones). The polymers may be produced from α,α-disubstituted β-lactones, which may be produced by a method described herein.
SYSTEMS AND METHODS FOR REGIOSELECTIVE CARBONYLATION OF 2,2-DISUBSTITUTED EPOXIDES
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Paragraph 0085, (2020/06/05)
Provided are methods of carbonylating cyclic substrates to produce carbonyl ated cyclic products. The cyclic substrates may be 2, 2-di substituted epoxides and the cyclic products may be β,β-di substituted lactones. The method may be carried out by forming and pressurizing a reaction mixture of the cyclic substrate, a solvent, carbon monoxide, and a [LA+][CO(CO)4-] catalyst, where [LA+] is a Lewis acid capable of coordinating to the cyclic substrate. The method may proceed with a regioselectivity of 90:10 or greater. The resulting carbonylated cyclic products may be converted to ketone aldol products that retain the stereochemistry and enantiomeric ratio of the carbonyl ated cyclic products.
Catalyst-controlled regioselective carbonylation of isobutylene oxide to pivalolactone
Hubbell, Aran K.,Lamb, Jessica R.,Klimovica, Kristine,Mulzer, Michael,Shaffer, Timothy D.,MacMillan, Samantha N.,Coates, Geoffrey W.
, p. 12537 - 12543 (2020/11/10)
Poly(pivalolactone) (PPVL) is a crystalline polyester with attractive physical and mechanical properties; however, prohibitively expensive syntheses of pivalolactone have thwarted efforts to produce PPVL on an industrial scale. Therefore, we developed a class of highly regioselective sandwich-type catalysts for the carbonylation of isobutylene oxide. These sterically encumbered complexes install carbon monoxide at the substituted epoxide carbon, generating a high level of contrasteric selectivity (up to >99:1). Further catalyst development improved catalyst solubility and reproducibility while maintaining high regioselectivity. In addition, a dibasic ester solvent extended catalyst lifetimes and suppressed side product formation. This contrasteric carbonylation of isobutylene oxide offers a route to sought-after pivalolactone and, therefore, PPVL.
LIGAND-ENABLED ?-C(sp3)–H LACTONIZATION FOR ?-C–H FUNCTIONALIZATIONS
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Paragraph 0047-0048; 0050-0051, (2020/12/11)
Provided herein is a method of forming a beta-lactone from a carboxylic acid having a beta-carbon with a hydrogen atom disposed thereon. The method comprises contacting a carboxylic acid of formula (1) as described herein with an effective amount of a pal
Regioselective Carbonylation of 2,2-Disubstituted Epoxides: An Alternative Route to Ketone-Based Aldol Products
Hubbell, Aran K.,Lapointe, Anne M.,Lamb, Jessica R.,Coates, Geoffrey W.
supporting information, p. 2474 - 2480 (2019/02/14)
We report the regioselective carbonylation of 2,2-disubstituted epoxides to β,β-disubstituted β-lactones. Mechanistic studies revealed epoxide ring-opening as the turnover limiting step, an insight that facilitated the development of improved reaction conditions using weakly donating, ethereal solvents. A wide range of epoxides can be carbonylated to β-lactones, which are subsequently ring-opened to produce ketone-based aldol adducts, providing an alternative to the Mukaiyama aldol reaction. Enantiopure epoxides were demonstrated to undergo the carbonylation/ring-opening process with retention of stereochemistry to form enantiopure β-hydroxy esters.
Orally Absorbed Derivatives of the β-Lactamase Inhibitor Avibactam. Design of Novel Prodrugs of Sulfate Containing Drugs
Gordon, Eric M.,Duncton, Matthew A. J.,Gallop, Mark A.
supporting information, p. 10340 - 10344 (2018/11/23)
Only one FDA-approved β-lactamase inhibitor has ever been orally available: clavulanic acid, approved in 1984. Avibactam, approved by FDA in 2015, is the first of a new class of BLIs called diazabicyclooctanes, or "DBOs". This class has much broader coverage than clavulanic acid but can only be administered by intravenous injection. Herein, we describe the synthesis and testing of the first approved BLI to be rendered orally bioavailable since clavulanic acid (1984).
Efficient oxidation of ethers with pyridine N-oxide catalyzed by ruthenium porphyrins
Kato, Nobuki,Hamaguchi, Yu,Umezawa, Naoki,Higuchi, Tsunehiko
, p. 411 - 416 (2015/05/13)
We found that oxidation of cyclic ethers with the Ru porphyrin-heteroaromatic N-oxide system gave lactones or/and ring-opened oxidized products with regioselectivity. A relatively high kinetic isotope effect was observed in the ether oxidation, suggesting that the rate-determining step is the first hydrogen abstraction.
Synthesis of β-lactones: A highly active and selective catalyst for epoxide carbonylation
Getzler, Yutan D. Y. L.,Mahadevan, Viswanath,Lobkovsky, Emil B.,Coates, Geoffrey W.
, p. 1174 - 1175 (2007/10/03)
A new highly active and selective catalyst for the synthesis of β-lactones from CO and epoxides is reported. The catalyst, [(N,N′-bis(3,5-di-tert-butylsalicylidene) phenylenediamino)Al(THF)2][Co(CO)4] ([(salph)Al(THF)2][Co(CO)4]) is easily prepared from the corresponding (salph)AlCl and NaCo(CO)4. At 50 °C and 880 psi of CO, the catalyst (1 mol %) carbonylates epoxides such as propylene oxide, 1-butene oxide, epichlorohydrin, and isobutylene oxide to the lactones β-butyrolactone, β-valerolactone, γ-chloro-β-butyrolactone, and β-methyl-β-butyrolactone in high yield. (R)-Propylene oxide was carbonylated to (R)-β-butyrolactone with retention of stereochemistry. Copyright
[Lewis acid]+[Co(CO)4]- complexes: A versatile class of catalysts for carbonylative ring expansion of epoxides and aziridines
Mahadevan, Viswanath,Getzler, Yutan D. Y. L.,Coates, Geoffrey W.
, p. 2781 - 2784 (2007/10/03)
Efficient carbonyl insertion into C-O and C-N bonds using [Lewis acid]+[Co(CO)4]- complexes 1 and 2 gives regio- and stereoselective carbonylation of a variety of epoxides and aziridines to yield β-lactones and β-lactams, respectively. Both transformations are proposed to occur by the same mechanism, yielding products with inversion of configuration at the site of CO insertion.
