Picosecond radical kinetics.: Fast ring openings of secondary and tertiary trans-2-phenylcyclopropylcarbinyl radicals
Picosecond radical kinetics.: Fast ring openings of secondary and tertiary trans-2-phenylcyclopropylcarbinyl radicals
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DOI：
10.1021/jo981020a
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发表时间：
1998-11-13
影响因子：
3.6
通讯作者：
Newcomb, M
中科院分区：
文献类型：
--
作者：
Choi, SY;Toy, PH;Newcomb, M
重排活性中间体的前体已被广泛应用于机械探针研究中，其中有人试图通过检测重排产物来确定活性中间体的存在。为了达到这种目的，重排反应必须比未重排中间体的竞争反应快，而且通常需要非常快的重排反应。如果所讨论的反应中间体是自由基，并且已知自由基重排的速率常数，则可以将该中间体称为“自由基时钟”，它可用于对相互竞争的自由基过程进行“计时”。1，2我们对自由基动力学和可能涉及自由基中间体的生化过程的探针研究的兴趣促使我们开发了一种间接动力学方法，PTOC-硫醇或PTOC-硒醇法，用于测量室温下寿命在皮秒范围内的自由基的动力学。3-6我们用这种方法校准了几个苯基取代的环丙基碳基的开环，1a-3a，74a和5a，8和6a-9a9(图1)，它们是校准最快的自由基反应之一。超快的2-芳基环丙基甲醇自由基时钟的校准使相应的碳氢前体能够定量地应用于酶催化的羟基化反应的研究，试图牵涉到自由基中间体并对这些过程中的“氧反弹”步骤进行计时。用1b探针研究了油酸假单胞菌细胞中非血红素单加氧酶的羟化反应、重组的甲氧基球囊菌(Bath)的重组可溶性甲烷单加氧酶(SMMO)羟基酶、丝状芽孢杆菌OB3b的10种重组可溶性甲烷单加氧酶(SMMO)、烟青霉(Caldarimyces Fumago)的11氯过氧化物酶(CPO)、12、13和各种细胞色素P450(P450)酶。14-16探针3b、14-5b、17和6b18也被用于研究P450催化的羟基化反应。探针1b-9b是伯基1a-9a的前体，伯烯重排时生成伯烯(方案1)。Zaks和Dodds12的一份报告中，1b被用于研究CPO催化的羟基化反应的机理，结合已知的伯烯与CPO19的不相容，促使我们设计出在重排时产生取代烯烃的探针，用于CPO机理研究。为了得到二烷基和三烷基取代的烯烃重排产物，需要烷基取代的环丙基甲醇自由基前驱体。因此，制备了探针10b和11b，它们被CPO13和P45020羟化，对于探针10b，在GIF氧化21(1)Griller，D.；InGold，KU Acc中。化学。(2)Newcomb，M.四面体1993，49,1151-1176。(3)Newcomb，M.；Park，S.-U.J.Am化学。SoC。1986、108、4132-4134。
Precursors to reactive intermediates that rearrange have been applied widely in mechanistic probe studies wherein one seeks to implicate a reactive intermediate by the detection of rearranged products. For such purposes, the rearrangement must be faster than competing reactions of the unrearranged intermediate, and very fast rearrangements often are desired. If the reactive intermediate in question is a radical and the rate constant for the radical rearrangement is known, the intermediate can be referred to as a “radical clock” which can be used to “time” competing radical processes. 1, 2 Our interest in radical kinetics and in probe studies of biochemical processes that might involve radical intermediates led us to develop an indirect kinetic method, the PTOC-thiol or PTOC-selenol method, for measuring the kinetics of radicals that have lifetimes in the picosecond range at room temperature. 3-6 We have used this method for the calibration of several ring openings of phenyl-substituted cyclopropylcarbinyl radicals, 1a-3a, 7 4a and 5a, 8 and 6a-9a9 (Figure 1), which are among the fastest calibrated radical reactions. The calibration of ultrafast 2-arylcyclopropylcarbinyl radical clocks has permitted quantitative applications of the corresponding hydrocarbon precursors in studies of enzyme-catalyzed hydroxylation reactions in an attempt to implicate radical intermediates and to time the “oxygen rebound” step in these processes. Probe 1b has been used to study hydroxylation by a non-heme monooxygenase in cells of Pseudomonas oleovorans, 10 reconstituted soluble methane monooxygenase (sMMO) hydroxylase from Methylococcus capsulatus (Bath) and Methylosinus trichosporium OB3b, 11 chloroperoxidase (CPO) from Caldariomyces fumago, 12, 13 and various cytochrome P450 (P450) enzymes. 14-16 Probes 3b, 14 5b, 17 and 6b18 have also been used to study P450-catalyzed hydroxylation reactions.Probes 1b-9b are precursors to primary radicals 1a-9a, which afford primary alkenes upon rearrangement (Scheme 1). A report by Zaks and Dodds12 in which 1b was used in a study of the mechanism of CPO-catalyzed hydroxylation reactions combined with the known incompatibility of primary alkenes with CPO19 prompted us to design probes that yield substituted alkenes upon rearrangement for use in CPO mechanistic studies. To obtain dialkyl-and trialkyl-substituted alkene rearrangement products, alkyl-substituted cyclopropylcarbinyl radical precursors were required. Hence, probes 10b and 11b were prepared, and their hydroxylations by CPO13 and P45020 and, for probe 10b, in Gif oxidations21 (1) Griller, D.; Ingold, KU Acc. Chem. Res. 1980, 13, 317-323.(2) Newcomb, M. Tetrahedron 1993, 49, 1151-1176.(3) Newcomb, M.; Park, S.-U. J. Am. Chem. Soc. 1986, 108, 4132-4134.