Left: A manganese-oxo porphyrin system in two electron oxidation of olefins. Right: A homoscorpionate-copper family complexin atom transfer radical addition reactions.



catalytic carbon radical and its application in organic synthesis

1 Introduction

Carbon radical with high chemical reactivity, which is a typical example of the alkyl radicals. In recent years, a variety of methods to generate carbon radicals being actively studied and widely used in organic synthesis. A typical method of generating a radical by an alkyl radical initiator such as AIBN in the presence of an alkyl halide initiator and Bu 3 SnH or (Me 3 Si) 3 SiH reaction; pyrolysis Barton esters or diacyl peroxides; or a metal ion-electron oxidation reaction a) . However, these chemical reactions are measured, for small-scale laboratory use, but difficult to apply to large-scale industrial synthesis. There are some methods industrially produce alkyl radicals, for example, or a radical photo-initiator to initiate the reaction under the irradiation of alkanes, oxidation of these methods are used for self-paraffins. However, since the oxidation reaction process requires strict reaction conditions, especially at high temperatures should be completed. At such high temperatures, paraffin only homolytic CH bond occurs, and there are crack CC bond, which can be lower than the CC bond energy of CH bond. Therefore, the low selectivity of the reaction and reaction efficiency of such insufficient 2) . So far, no conventional method can be satisfactory under mild conditions, so that the CH bond paraffins are selectively cracked to produce carbon radicals. To achieve this goal, a new method to produce carbon radicals under mild conditions. The method of organic synthesis will become an indispensable tool.

Recently, we found that generated by N-hydroxy phthalimide N-phthalimide group (PINO) hydrocarbon radical can be substituted with multiple (e.g., under mild conditions: alkanes, alcohols, ethers, acetals and aldehydes) CH hydrogen atoms to form the corresponding key on the carbon free radicals which have a high selectivity and high catalytic efficiency 3) . NHPI is named “carbon radical generating catalyst” (abbreviated as CRPC). CRPC oxygenates can be synthesized using, for example, a ketone and an alkane to the corresponding carboxylic acid synthesis. CRPC also stimulated the same functional group under mild conditions to generate an addition to the alkanes with high selectivity nitroalkanes, alkyl sulfonic acids and oxidation of alkanes, wherein the reactions are difficult to achieve in the past. Also made ​​possible the synthesis of dicarboxylic acids, such as adipic acid, nitric oxide is often prepared now by-step reaction using molecular oxygen oxidation of cyclohexane can generate a high yield of adipic acid. N 2O is a compound of the greenhouse gases, it generates a greenhouse CO. 2 300-fold or even higher, and a method using nitric oxide inevitable greenhouse gas N 2 O.Manufacture of adipic acid from green to find a chemical point of view and does not produce N 2 O by-product is particularly important new synthetic methods. The reaction of alkyl radicals with CRPC catalytic alkane is an innovative approach and will have a significant impact on the chemical industry. Some reactions catalyzed by CRPC has achieved industrialization.

2 catalytic carbon radical generating new discovery methods

Grochowski and his colleagues first reported in 1977 NHPI catalytic applications, the addition to the reaction catalyzed ether diethyl azodicarboxylate (DEAD) on 4) . No detailed description of the time this reaction has not proved by the generation of PINO.However, the presence of a radical scavenger that no progress of the reaction, the reaction process as recognized ( Synthesis Scheme 1 ) below. The hydrogen atom of the hydroxyl NHPI imide groups on the turn added DEAD, thereafter the resulting product with an equilibrium N-phthalimide group, and a new radical. This step of generating the hydrogen PINO carbon atom α to the ether oxygen separation, generating new radicals A, A was added to generate a new addition of the radical B DEAD, a hydrogen atom of the ether-substituted radical B is generated on adducts C and radicals A.

Further, Masui et al reported in 1983 NHPI as one generated by electrolytic oxidation of secondary alcohols intermediate 5) . We believe PINO generated on the anode so that hydrogen atoms on the carbon α separating the alcohol, and then catalyze the oxidation products formed one ( synthesis scheme 2 ).

In the oxidation reaction of oxygen with molybdenum vanadium phosphate (NPMoV) catalyze the process of alcohol molecules can form an average composition expressed as (NH 4 ) 5 H 6 PV 8 Mo 4 O 40 , we think that alone does not lead to the use of catalysts for this reaction NPMoV But if it will enhance the binding reaction and NHPI (synthesis scheme 3 ). Found that the same reaction (path a) with the expected envisaged, but also unexpectedly found that in the presence of NHPI without NPMoV alcohol oxidation catalytic reaction (path b). The oxidation reaction is a reaction by the NHPI and molecular oxygen (a triplet radical molecules) caused and generate PINO, then replace the hydrogen atoms in the alcohol PINO generated on the corresponding ketone. In order to confirm NHPI generate PINO, in benzonitrile NHPI and oxygen molecules in the system contacts, using ESR spectrometer observed PINO generated a triplet spectrum as shown in Figure (( Figure 1 ).

CRPC has now been found PINO same function, it is possible under mild conditions to selectively replace hydrogen atoms on the CH bond of the organic matrix to generate carbon radical, itself back to NHPI. Due to the carbon radical is the active chemical substance, so the use of different types of molecules (e.g., molecular oxygen) which capture different functional groups can be introduced. The following detailed description of various catalytic reactions catalyzed NHPI, further comprising a new concept in the conventional organic synthesis and the like did not appear, therefore, NHPI will also be a major breakthrough in catalytic chemical synthesis.

3. Molecular oxygen oxidation of alkanes

Currently, the use of self-oxidation of cyclohexane to synthesize nylon-66 requires at least 2,000,000 tons of adipic acid feedstock annually. Now also widely used as a two-step reaction: the presence of a Co salt, is first converted by the air oxidation of cyclohexane to cyclohexanone / cyclohexanol (K / A oil) and then with nitric acid K / A oil synthesized adipoyl acid 6a) . The synthesis method developed in 1940 by DuPont, in principle, has been extended to still used today. The first step involves reaction of CH bond cleavage (CH bond dissociation energy: 99.5 kcal Mol -1 ), CH key must (pressure, 150 ~ 170 ℃) to break under severe reaction conditions. To avoid side reactions, cyclohexane forwarding rate must be controlled at 3% to 5%, such that the reaction efficiency is not satisfactory. The second step reaction using a large amount of nitric oxide by-product N 2 O. Because N 2 O is a matter for global warming, it is imperative that nitric oxide is not seeking a new method of adipic acid can be synthesized on the industry. Development along these lines, there have been reports on the use of hydrogen peroxide as the oxidant oxidation of cyclohexane production of adipic acid, the synthetic scheme as a green synthetic route cause of many people’s attention 6B) .

We have found using a small amount of Mn and NHPI catalyzed O 2 oxidation of cyclohexane to adipic acid ((1 atm) Eq.1 ) 7) , but it is difficult to make using only the NHPI oxidation reaction. However, after adding a small amount of Mn complexes (0.5mol%) production of adipic acid with a high selectivity, conversion rate reached about 70%. In recent years, do not use any solvents can successfully cyclohexane oxidation 8) . Since NHPI difficult to dissolve nonpolar solvent (e.g., cyclohexane), so in the absence of solvent, it is difficult to effectively catalyze the air oxidation of cyclohexane. The results showed that the preparation of a lipophilic derivative and carries the NHPI catalyst, in the absence of a solvent can efficiently catalyze the air oxidation of cyclohexane (( Figure 2 ).

Adamantane has a unique structure, and function of adamantane is an important raw material for the production of high-performance materials. Although there are many chemists experimented with molecular oxygen to oxidize adamantane, but there is no one person has access to sufficient yield and selectivity of the real purpose. In NHPI / Co catalyst system in the presence of acetic acid, molecular oxygen is generated in a yield of 85% alcohol and a small amount of adamantyl adamantanone (adamantane at 75 ℃ oxidesynthesis scheme 4 ) 9) . Allow the reaction to generate a high reaction selectivity condition mono or dihydric alcohol choice. The synthesis of this diol or triol synthetic acrylic and methacrylic resins is an important synthesis photoresist.

T-butanol used as an additive to increase the octane number of gasoline and high-purity organic solvent, the hydrated isobutylene industrially prepared tert-butanol.Isobutane oxidation to synthesize isobutanol directly is a more reasonable approach, while using the traditional auto-oxidation process is to synthesize tert-butyl hydroperoxide, the traditional synthetic methods under high pressure (10 atm), high temperature of about 200 ℃ to produce peroxide, t-butanol (yield about 75%), t-butanol (yield 21%) of 8% and the conversion rate of acetone (about 2%) 10) . In benzonitrile system generates a yield under high pressure conditions with NHPI catalyzed oxidation of isobutane 80% of tert-butyl alcohol ( Eq. 2 ) 11) .

Oxidation of alkylbenzenes 4

Molecular oxygen oxidation of benzene carboxylic acid is an important industrial organic synthesis reactions. Co catalyst 130到160 ℃ catalytic oxidation of toluene to generate the corresponding acid under high pressure, the conversion was 50% and the selectivity was about 80% benzoic acid 12) . However, the use of small amounts of NHPI and Co. (OAc) 2 as catalyst catalytic molecular oxygen oxidation of toluene can generate acid in high yield at room temperature under 1 atm (yield 81%) and traces of impure benzaldehyde ( Eq. 3 ) 13) . Under these reaction conditions, with Co (Ⅲ) Co substitution can not lead to the reaction (Ⅱ), experiments show that Co (Ⅱ) salt and oxygen reaction of Co (Ⅲ) complexes of oxygen to cause this reaction ( synthesis scheme 5 ); while using Co (Ⅲ) but not necessary to initiate the reaction to produce Co (Ⅲ) oxygen complexes, so the reaction does not occur at room temperature. When the temperature rises Co (Ⅲ) substrate is reduced to Co (Ⅱ) in turn generated Co (Ⅱ) react with oxygen molecules to form Co (Ⅲ) complexes of oxygen to initiate the reaction.Therefore, when using Co (Ⅲ) can be observed induction period. Facts have proved that the use of molecular oxygen under normal temperature and pressure catalytic oxidation of hydrocarbons such as toluene and other chemicals for oxidation is of great significance.

Terephthalate, PET resin is synthesized so that a large amount of its production, and the demand will increase in the near future. Today, with the Co / Mn / Br catalyst at high temperature by the auto-oxidation of p-xylene to terephthalic acid synthesis, the synthesis method developed by British Amoco, which is a disadvantage to discharge the gas phase system bromine, corrosion reaction device, so people eager to develop a catalyst halogen-free catalyst system.

NHPI catalyst we use a halogen-developed catalytic oxidation, the oxidation reaction with molecular oxygen to generate paraxylene terephthalic acid (Synthesis Scheme 6).Furthermore, the NHPI to generate an additional N-acetyl-acetyl phthalimide (NAPI) having high catalytic activity similar NHPI. It was found that if we use as a catalyst in a catalytic amount NAPI catalyst required to generate the same amount of terephthalic acid is a catalytic amount of NHPI half 14). In addition, we recently discovered three hydroxyimino cyanurate (THICA) having high catalytic activity. NHPI by-step catalytic oxidation of p-xylene was synthesized in a yield of 80% terephthalic acid requires NHPI catalyst 20mol%, and 3mol% THICA oxidation catalyst using the same effects can be obtained.

Oxidation of alkyl carboxylic acids synthesized heterocyclic compounds are widely used as pharmaceutical drug synthesis intermediates, such as the oxidation of nicotinic acid methyl pyridine synthesis is an important raw material synthetic vitamins.Currently, nitric oxide at high temperature and pressure 5 – ethyl-2 – methyl-pyridin-nicotinic acid, however, the key issue is also produced large amounts of nitrogen oxides. At the same time there are reports with Co / Mn / Br catalyzed oxidation of methyl pyridine synthesis from nicotinic acid, but the reaction conditions are harsh and very low selectivity 15) .

In a catalytic amount of NHPI and measurable Co. (OAc) 2 and Mn (OAc) 2 in the presence of acetic acid environment conditions, we use atmospheric oxygen were β-methyl pyridine oxidation experiments, the results obtained higher yields of niacin, And the yield can reach 77% ( Eq. 4 ) 16a) . NHPI / Co / Mn catalyst is a catalytic reaction does not produce polluting nitrogen oxides, can be very useful in the industrial synthesis. Further 3 – oxidation product methylquinoline 3 – quinolinecarboxylic acid widely found in nature, there are many reports on related pharmacological activity.However, in the past, many heavy metal salts such as KMnO 4 , CrO 3 is often used as the oxidant found to NHPI / Co / Mn catalyst system was added a small amount of NO 2oxidation of molecular oxygen issue with three – methylquinoline higher reaction yield quinoline carboxylic acid (yield 75%) ( Eq. 5 ) 16b) . Also found that even without the presence of transition metal salts can still use the NHPI / NO 2 catalyzed oxidation of quinoline molecular oxygen. Yet found using molecular oxygen oxidation of quinoline example, the reaction is so far the only successful with the oxidation reaction of molecular oxygen oxidation of quinoline.

Industrial synthesis of phenol using the two-step synthesis, the synthesis of the following steps: compressed air (5-7 atm) at 90到120 ℃ weakly alkaline systems in the cumene from the oxidation of cumene hydroperoxide (yield 20 ~ 30%), and then separating the unreacted cumene from the reaction solution was concentrated, and then treatment of the concentrated sulfuric acid to produce phenol and acetone products. While this method as early as the 1940s had established applications, but it is still the main method of industrial synthesis of phenol. However, the relatively low efficiency of the first step reaction. If the conversion of cumene to improve the yield of cumene hydrogen peroxide, the reaction will have greater usefulness. Was added to the reaction solution was found in the absence of a heavy metal salt in a small amount of acetonitrile system, indium chloride, the NHPI catalyst together with a radical initiator, AIBN can be obtained under the action of the phenol in 77% yield ( Eq. 6 ) 17) .

5. Molecular oxygen oxidation of alkenes and alkynes

Over 5.1 Synthesis of hydrogen peroxide in the olefin epoxidation

Epoxidation of olefins, especially molecular oxygen as the oxidant has a certain propylene oxide on an industrial scale. The most common method is to Halcon method (indirect oxidation method), the synthetic method has two steps: the first step is oxidized to ethylbenzene hydroperoxide from ethylbenzene, in the second stage catalytic ethylbenzene hydroperoxide as Mo completion of the epoxidation reaction oxidant epoxidation of olefins.

Previously, we found NHPI catalyst for oxidation of the secondary alcohol of molecular oxygen to form hydrogen peroxide and a ketone 19) , the reaction of hydrogen peroxide produced for the epoxidation of olefins. And a catalytic amount of hexafluoroacetone NHPI presence of 1 – phenylethanol and cis -2 – octene-oxidizing atmosphere under normal pressure, to form the corresponding hydroperoxide and then generated by the addition of hydrogen peroxide to a hexafluoroacetone mixture, and then do the real hydroperoxide oxidant reaction yield of 87% of cis – epoxide ( 7 Eq. ) 20) .Advances of the aldehyde radical intermediates generated by molecular oxygen oxidation of cis – epoxidation of the olefin to form the corresponding cis or trans – mixture of epoxide 21) . Thus, the molecular oxygen oxidation of cis – stereoselective olefin epoxidation reaction is difficult in reality.

Epoxidation process comprising two: (i) NHPI through catalytic reaction of oxygen alcohol intermediate α-hydroxy hydroperoxide ( A ) to form hydrogen peroxide, the reaction of this step is a free radical reaction; (ii) the hydrogen peroxide reaction with hexafluoroacetone in the α-hydroxy hydroperoxide ( B ) oxidizing the olefin epoxidation reaction ( Synthesis Scheme 7 ). NHPI catalyst for catalytic oxidation of secondary alcohols can also be used as an excellent synthetic method for the synthesis of hydrogen peroxide 22) .

5.2 propargyl alkyne to introduce oxygen bits

Alkyne propargyl position in CH bond dissociation energy is about 85 kcal Mol -1 , roughly equal to the allyl position olefins CH bond dissociation energy (~ 87 kcal Mol -1) 23) . Therefore, it is expected that if a catalytic NHPI O 2 oxidation to alkynes, propargyl bit can be selectively oxidized to form the corresponding α-acetylenic ketone.As we know the amount of Co, and the catalyst system comprising a complex of acetonitrile NHPI (10mol%) of 4 – octyne with O 2 molecules can be reacted at room temperature to give 4 – oct-yn-3-one, and the yield up to 75% (Eq.8) 24) . Acetylenic ketone is usually made ​​of a metal acetylide coupling reaction with an acylating agent synthesis. Propargyl oxygen into position very little literature, there is an example of SeO 2 oxidation catalyzed reaction of t-butyl peroxy alcohols 25) . The paper reported the first successful response to oxygen molecules of oxygen introduced into the reactor.

6 oxygen molecules oxidized K / A oil

K / A oil is a mixture of cyclohexanone and cyclohexanol consisting of chemical raw materials in the oil industry is an important intermediate for the production of adipic acid. Bayer – Villiger oxidation reaction can be cyclic ketones into lactones. So far, no catalysis using molecular oxygen as oxidant on Bayer – literature Villiger oxidation reaction, ε-caprolactone is cyclohexanone with peracetic acid by Bayer – Villiger Oxidation from. If the synthesis of ε-caprolactone using peracetic acid is not achieved, but the use of molecular oxygen as the oxidant K / A oil was catalytically Bayer – Villiger oxidation reaction of the synthesis, then the reaction to avoid the use of hazardous due to their peracetic acid becomes particularly important.

We NHPI has been proposed as an efficient catalyst for aerobic oxidation of secondary alcohols. NHPI oxidation of secondary alcohols to produce hydrogen peroxide, ketone and hydroxy peroxide intermediate is formed by 19) . At this point, we use exists in K / A oil oxidation of secondary alcohols of molecular oxygen to form hydrogen peroxide, which is used to generate hydrogen peroxide Bayer – oxidant Villiger reactions. The reaction of ε-caprolactone by the aerobic oxidation of the first K / A oil system cyclohexanol into hydrogen peroxide and cyclohexanone. Then the hydrogen peroxide and InCl 3 (synthesis scheme 8) 26) Villiger Oxidation – Bayer catalytically cyclohexanone. Indium trichloride is a Lewis acid which is stable in water, if the recovery reaction can also be reused.

NHPI in the presence of a catalytic amount of ethyl acetate to K / A oil first by aerobic oxidation reaction is preferably selective, then after processing for generating ammonia peroxide dicyclohexylamine (Eq. 9). Known, PDHA easily converted into a high yield of ε-caprolactam. This reaction is carried using a new synthetic method for the molecular oxygen ε-caprolactam precursors, because it does not generate a reaction byproduct ammonium sulfate is even more interesting.

7 functional groups using NHPI catalyst is added to the alkane molecules

7.1 CO is introduced into the adamantane

In CO. / O 2 using NHPI catalyst thoroughly adamantane carboxylate having a relatively high selectivity, and the environment. At 60 ℃, NHPI (10%) and CO / Air (15/1 atm) the presence of the reaction adamantyl adamantane carboxylic acid and a small amount of oxidation products having a selectivity of 56% under the conditions of (conversion rate of 75%) ( Eq. 10 ) 27) . Saturated hydrocarbons difficult CO via the hydroformylation reaction. Thus, to date, little information on the alkane radical catalyzed hydroformylation reactions reported in the literature. Can be found in some of the literature reports the use of a photoinitiator and a persulfate reaction 28) .

7.2 alkanes catalyzed nitration and sulfoxidation

Sulfoxidation nitration reaction of the aromatic compound and the reaction has been confirmed. However, there has not been a good general-purpose method for nitrification and sulfoxidation reactions. Nitration of alkanes in the industry is an important reaction, the nitric acid or NO 2 as a nitrating agent at temperatures up to 250 ~ 400 ℃ before reaction. However, under such a high temperature, CC bond cleavage is also prone, therefore, resulting in selective nitration reaction is quite poor. For example, cyclohexane, and NO at 240 ℃, 2 generates NITROCYCLOHEXANE nitration reaction, which has a yield of only 16% of 29) . NHPI and a catalytic amount of O 2 in the presence of conditions, we now cyclohexane NO 2 reactions can be found at 70 ℃ smoothly and the yield of the reaction of the nitro group can reach 70% of cyclohexane (( Scheme 9 Synthesis ). Furthermore, after the reaction by simple filtration of the catalyst may collect a certain amount of 30) . We have also achieved success with nitrate instead of NO 2 as a nitrating agent for such nitration 31) .

Only a few reports on the study of the oxidation of alkanes sulfonation. One example is the SO 2 / O 2 in the presence of an alkane by the reaction of the photoinitiator.However, the efficiency of the reaction is so low that no follow-up research reports. We found that a very small amount of adamantane with VO (acac) 2 , the SO 2 / O 2environment using the catalytic reaction of NHPI higher yield of adamantane sulfonic acid ( synthesis scheme 10 ). In addition, we also found that the reaction only by the VO (acac) 2 catalysis. Furthermore, lower alkanes such as propane can be used at room temperature, this method is effective sulfoxidation 32) .

Alkane oximation 7.3

Cyclohexanone oxime is one of the main raw material for the production of nylon-6, and its preparation method is first oxidized cyclohexane, cyclohexanone, and then reacted with hydroxylamine salt. However, because this method generates a large amount of reaction byproducts in the ammonium sulfate has many defects. We found that under argon as protective gas of cyclohexane and t-butyl nitrite and acetic acid at 80 ℃ by-step reaction of cyclohexanone oxime ( synthesis scheme 11 ). The new method has the advantage that the reaction is not oxime synthesis byproducts ammonium sulfate. In addition, one-step reaction of cyclohexanone oxime synthesis is possible, and is expected to be a breakthrough synthetic method. Furthermore since the t-butanol with NO2 is easily synthesized t-butyl nitrite, and t-butanol can be regenerated after the reaction was repeated using the reaction with high atom efficiency.

7.4 NHPI catalyst for alkane alkyl cations generated

NO is a diatomic molecule normally exists in the form of free radicals. If the removal of a hydrogen atom from NHPI generate PINO, so they can also take off the oxygen molecules, so that it can be applied as a new and NO synthesis. We try NHPI catalyst, adamantane benzonitrile reaction with NO and containing a small amount of acetic acid is obtained in a yield of 65% of N-1-adamantyl-benzamide ( synthesis scheme 12 ) 33a) .In addition, we also found that 1,3 – dihydro-isobenzofuran with acetonitrile NO reaction phthalaldehyde ( synthesis scheme 13 ) 33b) . Phthalaldehyde also be hydrolyzed by tetrabromo-o-xylene from o-xylene to get 34) . We all know that has not yet been directly from 1,3 – dihydro-isobenzofuran synthesis phthalaldehyde example. In this reaction, the resulting intermediate with a carbenium ion as the reaction of a nucleophilic reagent water hemiacetal, a hemiacetal and then the process is similar to the oxidation reaction of o-phthalaldehyde.

We found that using NHPI catalyzed with ammonium cerium nitrate (CAN) and then reaction of the alkyl radicals generated by the one-electron oxidation can generate alkyl cationic (( synthesis scheme 14 ) it is clear that this reaction process is PINO CAN NHPI and the reaction generates Under these conditions, the Ritter reaction is difficult in the past occurred in the benzyl position, now with the present synthesis method Ritter reaction becomes particularly simple 35) .

7.5 NHPI as a catalyst for reversing the polarity

Under argon atmosphere, a catalytic amount of NHPI, toluene as a solvent, BPO initiator with an aldehyde to generate a high yield of the olefin corresponding ketone.If ( Synthetic Scheme 15 ) is similar to the reaction process shows radical reactions, NHPI do polarity reversal catalyst 36) . Group by free radical addition to the addition of the olefin to generate a radical, and the addition of a nucleophilic radical having aldehyde that is easy on the H atom on the ratio of the substituent substituted NHPI, so that the chain reaction will be more stable .

8 catalyzed carbon-based radicals generated CC bond forming reactions

In organic synthesis radical coupling reaction is very useful method for forming CC bond. We have found that the possibility of using NHPI / O 2 system generates the corresponding alkanes catalyzed alkyl radicals. Therefore, we use the olefin to capture free radicals generated, we tested NHPI / O 2 catalytic alkane α, β-unsaturated ester is reacted with. In an air atmosphere, NHPI / Co. (acac) 3 as a catalyst for the reaction of methyl acrylate with adamantane. Found that the coupling product obtained in high yield with the ternary molecular oxygen, then the adamantyl radical addition to the double bond of methyl acrylate ( synthesis scheme 16 ) 37) . This reaction is considered to be the alkoxylation reaction of alkanes and a new radical coupling reaction, introduction of oxygen atoms and the CC bond formation reaction simultaneously.

NHPI / O 2 catalyzed 1,3 – dioxolane reacted with methyl acrylate, the reaction can be carried out smoothly and generate the corresponding β-hydroxy acetal (at room temperature synthesis scheme 17 ). Coupling acetal product after the acid treatment of easily converted to the corresponding ketone. This reaction is similar to the addition of the olefin group radical addition reaction, or oxidation of an olefin alkylation vital 38) .

As shown above, NHPI / O 2 can also generate α-hydroxy alcohols catalyzed carbon radicals. Thus, attempts to use α, β-unsaturated ester of α-generated capture hydroxyl radicals and the carbon found in the synthesis of α-hydroxy can-γ-lactone, α-hydroxy in the past-γ-lactone with other synthetic methods are difficult to get. Catalytic amount of Co salt and the presence of NHPI, isopropyl alcohol and methyl acrylate reaction α-hydroxy-γ, γ-dimethyl-γ-butyrolactone ( synthesis scheme 18 ). In this reaction, (i) by NHPI / Co (Ⅱ) catalysis in the presence of oxygen, the hydrogen atom on the alcohol, α-hydroxy-substituted carbon radical generator (A), (ii) A to the addition of methyl methacrylate generated on B, (iii) and then the generated oxygen atoms into the diol C, (iv) C intramolecular cyclization of the lactone.


. 1 (a) Curran, DP Comprehensive Organic Synthesis; Trost, B.; Fleming, IM, Eds;. Pergamon, 1991;. Vol 4, Chapters 4.1 and 4.2 (b) Ryu, I.; Sonoda, N.; Curran ., DP Chem Rev 1996, 96, 172 (c) Renaud, P.;.. Sibi, MP Radicals in Organic Synthesis; Wiley-VCH, 2001;. Vol 1, Basic principles, and Vol 2, Applications..

2 (a) Sheldon, RA;. Kochi, JK Metal-Catalyzed Oxidations of Organic Compounds;. Academic Press, 1981 (b) Hill, CL Activation and Functionalization of Alkanes;. Academic Press, 1989 (c) The Activation of Dioxygen and Homogeneous Catalytic Oxidation; Barton, DHR; Martell, AE; Sawyer, DT, Eds;. Plenum Press, 1993.

. 3 (a) Ishii, Y.; Sakaguchi, S.;….. Iwahama, T. Adv Synth Catal 2001, 343, 393 (b) Ishii, Y. Yuki Gosei Kagaku Kyokaishi (J. Synth Org Chem. .. Jpn) 2000, 59, 1 (c) Ishii, Y.; Sakaguchi, S.;… Iwahama, T. Yuki Gosei Kagaku Kyokaishi (J. Synth Org Chem Jpn) 1999, 57, 24.

. 4 Grochowski, E.; Boleslawska, T.; Jurczak, J. Synthesis 1977, 718.

. 5 Masui, M.; Ueshima, T.;.. Ozaki, S. Chem Commun 1983, 479.

6 (a) Davis, DD Ullman’s Encyclopedia of Industrial Chemistry, 5th ed; Gerhartz, W., Ed; John Wiley and Sons:… New York, 1985; Vol A1, pp 270-272 (b) Sato,.. K.; Aoki, M.; Noyori, R. Science 1998, 281, 1646.

. 7 (a) Ishii, Y.; Iwahama, T.; Sakaguchi, S.; Nakayama, K.;… Nishiyama, YJ Org Chem 1996, 61, 4520 (b) Iwahama, T.; Shoujo, K. ; Sakaguchi, S.;.. Ishii, Y. Org Process Res Dev 1998, 2, 255..

. 8 Sawatari, N.; Yokota, T.; Sakaguchi, S.;. Ishii, YJ Org Chem 2001, 66, 7889..

. 9 Ishii, Y.; Kato, S.; Iwahama, T.;. Sakaguchi, S. Tetrahedron Lett 1996, 37, 4993.

. 10 Winlker, DE;.. Hearne, GW Ind Eng Chem 1961, 53, 655..

. 11 Sakaguchi, S.; Kato, S.; Iwahama, T.; Ishii, Y. Bull Chem Soc Jpn 1998, 71, 1237…..

. 12 Parshall, GW; Ittel, SD Homogeous Catalysis, 2nd ed; John Wiley and Sons:. New York, 1992; pp 255-261.

. 13 Yoshino, Y.; Hayashi, Y.; Iwahama, T.; Sakaguchi, S.;. Ishii, YJ Org Chem 1997, 62, 6810..

. 14 Tashiro, Y.; Iwahama, T.; Sakaguchi, S.;… Ishii, Y. Adv Synth Catal 2001, 343, 220.

15 (a) Davis, DD Ullman’s Encyclopedia of Industrial Chemistry, 5th ed; Gerhartz, W., Ed; John Wiley and Sons:… New York, 1985; Vol A27, p 587 (b) Mukhopadhyay, S… ;.. Chandalia, SB Org Process Res Dev 1999, 3, 455..

. 16 (a) Shibamoto, A.; Sakaguchi, S.; Ishii, Y. Org Process Res Dev 2000, 4, 505 (b) Sakaguchi, S.;…. Shibamoto, A.; Ishii, Y. Chem . Commun. 2002, 180.

. 17 Fukuda, O.; Sakaguchi, S.;… Ishii, Y. Adv Synth Catal 2001, 343, 809.

. 18 Kitabatake, M.; Ishioka, R. Yuki Kasankabutsu: Sono kagaku to kogyoteki riyou (Organic peroxide: chemistry and industrial application); Kagaku Kogyo Sya: Tokyo, 1972.

19 (a) Iwahama, T.;. Sakaguchi, S.; Nishiyama, Y.; Ishii, Y. Tetrahedron Lett 1995, 36, 6923 (b) Iwahama, T.;.. Yoshino, Y.; Keitoku, T. ; Sakaguchi, S.;. Ishii, YJ Org Chem 2000, 65, 6502..

. 20 Iwahama, T.; Sakaguchi, S.;. Ishii, Y. Chem Commun 1999, 727..

. 21 Mukaiyama, T.; Takai, T.; Yamada, T.;. Rhode, O. Chem Lett 1990, 1661..

. 22 Iwahama, T.; Sakaguchi, S.;… Ishii, Y. Org Process Res Dev 2000, 4, 94.

23. Golden, DM Ann. Rev. Phys. Chem. 1982, 33, 493.

. 24 Sakaguchi, S.; Takase, T.; Iwahama, T.;. Ishii, Y. Chem Commun 1998, 2037..

. 25 Chabaud, B.;. Sharpless, KBJ Org Chem 1979, 44, 4202..

. 26 Fukuda, O.; Iwahama, T.; Sakaguchi, S.;. Ishii, Y. Tetrahedron Lett 2001, 42, 3479.

. 27 Kato, S.; Iwahama, T.; Sakaguchi, S.;. Ishii, YJ Org Chem 1998, 63, 222..

28 (a) Barton, DHR;… Doller, D. Acc Chem Res 1992, 25, 504 (b) Arndtsen, BA;.. Bergman, RG; Mobley, TA;.. Peterson, TH Acc Chem Res 1995. , 28, 154.

. 29 Markofsky, SB Ullmann’s Encyclopedia Industrial Organic Chemicals; Wiley-VCH: Weinheim, 1999; Vol 6, p 3487..

. 30 Sakaguchi, S.; Nishiwaki, Y.; Kitamura, T.; Ishii, Y. Angew Chem Int Ed Engl 2001, 40, 222……

. 31 Isozaki, S.; Nishiwaki, Y.; Sakaguchi, S.;. Ishii, Y. Chem Commun 2001, 1352..

. 32 Ishii, Y.; Matsunaka, K.;.. Sakaguchi, SJ Am Chem Soc 2000, 122, 7390..

. 33 (a) Sakaguchi, S; Eikawa, M.; Ishii, Y. Tetrahedron Lett 1997, 38, 7075 (b) Eikawa, M.;.. Sakaguchi, S.; Ishii, YJ Org Chem 1999, 64.. , 4676.

34 Bill, JC;… Tarbell, DS Organic Syntheses, Collect Vol IV; Wiley, 1963; p 807.

. 35 Sakaguchi, S.; Hirabayashi, T.;. Ishii, Y. Chem Commun 2002, 516..

36 Tsujimoto, S.;. Iwahama, T.; Sakaguchi, S.;. Ishii, Y. Chem Commun 2001, 2352..

. 37 Hara, T.; Iwahama, T.; Sakaguchi, S.;. Ishii, YJ Org Chem 2001, 66, 6425..

. 38 Hirano, K.; Iwahama, T.; Sakaguchi, S.;. Ishii, Y. Chem Commun 2000, 2457..

39 Iwahama, T.;. Sakaguchi, S.;. Ishii, Y. Chem Commun 2000, 613..

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