For more than a half of a century, Barry Trost has been a highly influential scientist in almost every aspect of organic synthesis, including methodology and total synthesis. He started his career at a remarkably young age. After obtaining his B.Sc. degree in chemistry from the University of Pennsylvania (1962), he moved to MIT where he completed his Ph.D. with H. O. House, working on fundamental aspects of enolate chemistry. Remarkably, at the age of 24, immediately after obtaining his Ph.D. degree in 1965, he accepted an offer of an Assistant Professorship at the University of Wisconsin. Four years later, at the age of 28, he became a Full Professor. In 1987, he moved to Stanford University, where he was appointed Tamaki Professor of Humanities and Sciences.

Trost's remarkable impact on multiple areas of organic chemistry is documented in nearly 1000 research publications and patents. He is one of the world‘s leading organic chemists, a member of the National Academy of Sciences, and one of the most cited chemists worldwide. The scientific community has recognized him with numerous awards, including the Paul Janssen Prize, ASSU Graduate Teaching Award, Bing Teaching Award, ACS Roger Adams Award, Presidential Green Chemistry Challenge Award, Herbert C. Brown Award for Creative Research in Synthetic Methods, Belgian Organic Synthesis Symposium Elsevier Award, Nichols Medal, Yamada Prize, ACS Nobel Laureate Signature Award for Graduate Education in Chemistry, ACS Cope Award, Israel Chemical Society Barry Cohen Medicinal Chemistry Award, the Ryoji Noyori Prize, the August-Wilhelm-von-Hofmann Medal, the International Precious Metal Institute Junichiro Tanaka Distinguished Achievement Award, the Linus Pauling Medal Award, to name a few.

The nearly 600 former Trost group members, graduate students, and postdocs from all around the world, who take leadership positions in academia and industry, have amplified Barry Trost's extraordinary impact on science and organic synthesis in particular.

We are proud of being members of the Trost family. Keinan belonged to the University of Wisconsin era (Figure 1) and was working on Pd-catalyzed allylation reactions (1977–79), while Portnoy worked at Stanford on Ru-catalyzed enone-alkyne coupling reactions (1995–97). The Israeli aspect of Trost's group includes two additional postdocs, Genia Sklute and Elliad R. Silcoff. In 1997 Trost became Doctor Scientiarum Honoris Causa of the Technion-Israel Institute of Technology.

This special issue, titled “Organometallic Door to Synthesis,” highlights Trost's recognition of the enormous potential of transition metals in organic synthesis at a time when the two fields were very much separated. His high-impact program on palladium catalysis includes several pioneering milestones. His allylic alkylations demonstrated high chemo-, regio- and enantioselectivity. His palladium-catalyzed trimethylenemethane chemistry enabled many cycloaddition reactions that complement the Diels–Alder reaction. His palladium-hydride intermediates led to novel ene/yne-cyclization reactions to produce 1,4- or 1,3-dienes, allowing for synthesizing macrocyclic and medium-ring systems.

Trost's ruthenium-catalyzed organic synthesis demonstrated the first examples of catalytic processes involving vinylidene and allenylidene ruthenium intermediates. This chemistry enabled unprecedented reactions and products, such as 1,5-dicarbonyl compounds, [2+2+2] cycloaddition of alkynes to 1,5-cyclooctadiene, and a [5+2] cycloaddition to form seven-membered rings.

Application of new binuclear chiral zinc-catalysts allowed for asymmetric transformations, such as the aldol, Mannich, and Michael reactions, as well as the asymmetric alkinylation of carbonyls.

Trost's new tools of transition metal catalysis and main group element reagents have enabled the total synthesis of more than 200 molecular targets, many of which are biologically active.

Most of the manuscripts contributed to this Special Issue by Trost group alumni deal with metal-catalyzed synthesis. However, other contributions involve metal-free synthetic methodology, as well as total synthesis.

Bellow we provide brief summaries of these contributed articles.

Metal-Based Synthetic Methodology

F. Dean Toste and Christopher A. Kalnmals provide an extensive review of many synthetic methods less known than the celebrated allylic alkylations, metal-catalyzed cycloisomerizations, and trimethylenemethane cycloadditions. Yet, these highly useful methods have enjoyed widespread adoption by the community of organic synthesis. These “less famous” synthetic methods, which include metal-catalyzed alkyne-alkyne and alkyne-alkene couplings, as well as reduction/oxidation reactions, were used for the total synthesis of a variety of natural products, pharmaceuticals, and other complex bioactive molecules.

Adrien Quintard presents interesting multi-catalytic combinations of iron/copper metal- and organo-catalysis (mostly developed by his group) for overcoming the limitations of single-catalyst reaction mode. He screens different categories of such reactions and outlines the advantages with a particular emphasis on enantioselective catalysis.

Zachary T. Ball reviews the use of boronic acid reagents in bioconjugation. These reagents, combined with metal catalysts, offer unique selectivity patterns in modifying biopolymers. As a result, they provide access to novel biopolymer architectures for various uses in chemical biology.

Virginie Ratovelomanana-Vidal and Jean-Pierre Genet review the development of atropisomeric ligands and chiral transition metal complexes for asymmetric hydrogenation reactions. These transformations, which include reduction of alkenes, ketones, and heteroaromatics, were applied in industrial processes and total synthesis of biological targets.

Michael J. Krische describes in his communication two distinct catalytic methods of reductive biaryl cross-coupling. He employs these formate-mediated transformations for the coupling of pyridines and anisoles.

Phil Ho Lee describes a new method for preparing highly functionalized benzothiazines from readily available starting materials. The methodology uses Rh- and Ir-based catalytic systems that benefit from broad scope, high functional group tolerance, and good regioselectivity.

Joshua D. Sieber describes the exploration of a variant of Pd-catalyzed allylic alkylation, which employs allenamides as allyl electrophile-forming substrates. This regioselective reaction represents an addition of a carbon nucleophile to the terminal double bond of an allenic system, a complementary method to the more common Pd-catalyzed allylic substitution.

Metal-Free Synthetic Methodology

Oliver R. Thiel surveys the application of the green methodology in the development of processes leading to active pharmaceutical ingredients. He demonstrates how concepts such as atom economy, solvent minimization, reagent optimization, synthetic convergence, reduced energy use, real-time analysis, and strong safety focus have contributed to more environmentally benign processes.

Alison J. Frontier reviews methods for concurrent installation of multiple quaternary stereogenic centers in cyclic and polycyclic molecules, focusing on the cyclization steps. The review covers processes disclosed in the total synthesis of natural products and methodology studies during the past two decades.

Christian G. Bochet surveys the application of the photochemical methodology, which independently targets different photosensitive sites using light beams of different wavelengths. The review follows the extension of this synthetic methodology to various fields, including catalysis, chemical biology, and lithography.

John D. Chisholm describes a metal-free method for amino-oxidation of electron-rich olefins, utilizing anilines in combination with an inexpensive organic oxoammonium salt as a key reagent. He demonstrates that the solvent controls the stereochemical outcome of this addition to the olefin substrate.

Debayan Sarkar describes in his communication the oxidative cleavage of a hydroxybenzyl substituent of various naphthols with a concomitant dearomatization and introduction of bromo- and azido-functionalities onto the cyclic scaffold.

Synthesis of Natural Products and Analogs

Guillaume Mata and Christopher A. Kalnmals shed light on the total synthesis of numerous natural products, pharmaceuticals, and other biorelevant molecules, performed in the Trost laboratories during the past 20 years. Among more than a hundred compounds, prepared by Trost and coworkers during this period, many complex targets, such as bryostatins 3 and 16, callipeltoside A, ushikulide A, codeine, perophoramidine, and lasonolide A, are highlighted in this survey.

Georges Massiot shares in his essay insights from the field of natural products and the work of Prof. Trost in this research area. He includes a description of the cases from his own experience and outlines the difficulties and remaining problems in this field.

Uli Kazmaier focuses on the bottromycin class of natural products, emphasizing the synthetic approaches to bottromycin and its analogs, spanning half a century of research.

George A. O'Doherty describes the synthesis of a model compound of a proposed biosynthetic precursor of Gilvocarcin M and its regioisomeric analog, to elucidate the biosynthetic origin of this natural product. In both model molecules, a carbasugar unit mimics the original sugar portion of the natural product, while O-glycoside linkage replaces the C-glycoside connection.

Paul R. Hanson describes an iterative one-pot sequential synthetic route to the demethylated macrolactone fragment of (−)-lyngbouilloside, en route to the preparation of the complete unnatural analog of this natural product.

Seijiro Matsubara reveals in his paper that as little as three substituents are sufficient to convert cubane into a chiral molecule, which can serve as a chiral pharmacophore or a chiral ligand. The routes to various trisubstituted cubanes involve metal reagents and HPLC enantiomeric resolution.

Barry Trost has always been a highly gifted scientist blessed with imagination, creativity, scholarship, dedication, and enthusiasm for chemistry. He has served as a role model for many generations of young scientists, and even at the age of 80, he keeps producing excellent science. We celebrate his 80th birthday and wish him all the best for many years to come.

We wish to thank all those who took part in this endeavor, particularly the authors who shared with us their thoughts and perspectives, the reviewers and the highly professional team at Wiley-VCH.

Enjoy your reading!

中文翻译：

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庆祝 Barry M. Trost 教授诞辰 80 周年

半个多世纪以来，巴里·特罗斯特 (Barry Trost) 几乎在有机合成的各个方面都是一位极具影响力的科学家，包括方法论和全合成。他在非常年轻的时候就开始了他的职业生涯。在获得学士学位后。他在宾夕法尼亚大学获得化学学位（1962 年），之后搬到麻省理工学院完成了博士学位。与 HO House 一起研究烯醇化学的基本方面。值得注意的是，在 24 岁的时候，他获得了博士学位。1965 年获得博士学位后，他接受了威斯康星大学助理教授职位的邀请。四年后，28 岁的他成为一名正教授。1987 年，他搬到斯坦福大学，在那里他被任命为玉木人文科学教授。

近 1000 份研究出版物和专利记录了 Trost 对有机化学多个领域的显着影响。他是世界领先的有机化学家之一，美国国家科学院院士，也是全球被引用次数最多的化学家之一。科学界授予他无数奖项，包括 Paul Janssen 奖、ASSU 研究生教学奖、Bing 教学奖、ACS Roger Adams 奖、总统绿色化学挑战奖、Herbert C. Brown 合成方法创新研究奖、比利时有机Synthesis Symposium Elsevier 奖、Nichols 奖章、Yamada 奖、ACS 诺贝尔奖获得者化学研究生教育签名奖、ACS Cope 奖、以色列化学学会 Barry Cohen 药物化学奖、Ryoji Noyori 奖、August-Wilhelm-von-Hofmann 奖章、

来自世界各地的近 600 名前 Trost 小组成员、研究生和博士后，在学术界和工业界担任领导职务，放大了 Barry Trost 特别是在科学和有机合成方面的非凡影响。

我们为成为 Trost 家族的一员而感到自豪。Keinan 属于威斯康星大学时代（图 1），正在研究 Pd 催化的烯丙基化反应（1977-79），而 Portnoy 在斯坦福大学研究 Ru 催化的烯酮-炔偶联反应（1995-97）。Trost 小组的以色列方面包括另外两名博士后，Genia Sklute 和 Elliad R. Silcoff。1997 年，Trost 成为以色列理工学院的 Scientiarum Honoris Causa 博士。

这期题为“有机金属合成之门”的特刊突出了 Trost 对过渡金属在有机合成中的巨大潜力的认识，当时这两个领域非常分离。他在钯催化方面的高影响计划包括几个开创性的里程碑。他的烯丙基烷基化显示出高化学选择性、区域选择性和对映选择性。他的钯催化的三亚甲基甲烷化学使许多环加成反应成为可能，以补充 Diels-Alder 反应。他的氢化钯中间体导致了新的烯/炔环化反应以产生 1,4- 或 1,3-二烯，从而合成大环和中环系统。

Trost 的钌催化有机合成展示了涉及亚乙烯基和亚烯基钌中间体的催化过程的第一个例子。这种化学反应实现了前所未有的反应和产物，例如 1,5-二羰基化合物、炔烃与 1,5-环辛二烯的 [2+2+2] 环加成，以及形成七元环的 [5+2] 环加成。

新的双核手性锌催化剂的应用允许不对称转化，例如羟醛、曼尼希和迈克尔反应，以及羰基的不对称炔化。

Trost 的过渡金属催化新工具和主族元素试剂已使 200 多个分子目标的全合成成为可能，其中许多具有生物活性。

Trost 集团校友为本期特刊撰写的大部分手稿都涉及金属催化合成。然而，其他贡献涉及无金属合成方法，以及全合成。

波纹管我们提供这些贡献的文章的简要总结。

金属基合成方法

F. Dean Toste和Christopher A. Kalnmals对许多比著名的烯丙基烷基化、金属催化的环异构化和三亚甲基甲烷环加成鲜为人知的合成方法进行了广泛的回顾。然而，这些非常有用的方法已被有机合成界广泛采用。这些“不太出名”的合成方法，包括金属催化的炔-炔和炔-烯烃偶联，以及还原/氧化反应，被用于各种天然产物、药物和其他复杂生物活性分子的全合成.

Adrien Quintard展示了铁/铜金属和有机催化（主要由他的团队开发）的有趣多催化组合，以克服单催化剂反应模式的局限性。他筛选了此类反应的不同类别，并概述了优势，特别强调了对映选择性催化。

Zachary T. Ball回顾了硼酸试剂在生物偶联中的应用。这些试剂与金属催化剂相结合，在改性生物聚合物方面提供了独特的选择性模式。因此，它们为化学生物学的各种用途提供了获得新型生物聚合物结构的途径。

Virginie Ratovelomanana-Vidal和Jean-Pierre Genet回顾了用于不对称氢化反应的阻转异构配体和手性过渡金属配合物的发展。这些转化，包括烯烃、酮和杂芳烃的还原，被应用于工业过程和生物目标的全合成。

Michael J. Krische在他的通讯中描述了两种不同的还原联芳基交叉偶联催化方法。他将这些甲酸盐介导的转化用于吡啶和苯甲醚的偶联。

Phil Ho Lee描述了一种从容易获得的起始材料制备高度官能化苯并噻嗪的新方法。该方法使用基于 Rh 和 Ir 的催化系统，这些系统受益于广泛的范围、高官能团耐受性和良好的区域选择性。

Joshua D. Sieber描述了对 Pd 催化的烯丙基烷基化变体的探索，该变体使用丙二烯酰胺作为形成烯丙基亲电试剂的底物。这种区域选择性反应代表将碳亲核试剂加成到丙二烯系统的末端双键上，这是对更常见的 Pd 催化烯丙基取代的补充方法。

无金属合成方法

Oliver R. Thiel调查了绿色方法在开发生产活性药物成分的过程中的应用。他展示了原子经济、溶剂最小化、试剂优化、合成收敛、减少能源使用、实时分析和强烈的安全性等概念如何促进更环保的过程。

Alison J. Frontier回顾了在环状和多环分子中同时安装多个四元立体中心的方法，重点是环化步骤。该审查涵盖了过去二十年中天然产物全合成和方法学研究中公开的过程。

Christian G. Bochet调查了光化学方法的应用，该方法使用不同波长的光束独立瞄准不同的光敏部位。该评论将这种合成方法扩展到各个领域，包括催化、化学生物学和光刻。

John D. Chisholm描述了一种用于富电子烯烃的氨基氧化的无金属方法，利用苯胺结合廉价的有机氧代铵盐作为关键试剂。他证明溶剂控制了这种添加到烯烃底物的立体化学结果。

Debayan Sarkar在他的通讯中描述了各种萘酚的羟基苄基取代基的氧化裂解，伴随着脱芳构化和溴和叠氮官能团在环状支架上的引入。

天然产物和类似物的合成

Guillaume Mata和Christopher A. Kalnmals阐明了过去 20 年在 Trost 实验室进行的众多天然产物、药物和其他生物相关分子的全合成。在此期间，Trost 及其同事制备的一百多种化合物中，有许多复杂的靶点，如苔藓抑素 3 和 16、callipeltoside A、ushikulide A、可待因、perophoramidine 和 lasonolide A，在本次调查中得到了重点关注。

Georges Massiot在他的论文中分享了他对天然产品领域的见解以及 Trost 教授在该研究领域的工作。他根据自己的经验对案例进行了描述，并概述了该领域的困难和遗留问题。

Uli Kazmaier专注于博曲霉素类天然产物，强调博曲霉素及其类似物的合成方法，跨越半个世纪的研究。

George A. O'Doherty描述了一种建议的 Gilvocarcin M 生物合成前体及其区域异构类似物的模型化合物的合成，以阐明这种天然产物的生物合成来源。在这两种模型分子中，碳糖单元模拟天然产物的原始糖部分，而 O-糖苷键取代了 C-糖苷连接。

Paul R. Hanson描述了 (-)-lyngbouilloside 的去甲基化大环内酯片段的迭代一锅顺序合成路线，在制备这种天然产物的完全非天然类似物的过程中。

Seijiro Matsubara在他的论文中透露，只需三个取代基就足以将立方烷转化为手性分子，该分子可以用作手性药效团或手性配体。各种三取代古巴烷的路线涉及金属试剂和 HPLC 对映体拆分。

巴里·特罗斯特 (Barry Trost) 一直是一位才华横溢的科学家，拥有想象力、创造力、奖学金、奉献精神和对化学的热情。他为几代青年科学家树立了榜样，即使到了80岁，他仍在不断创造出优秀的科学成果。我们庆祝他 80 岁生日，并祝愿他在未来的许多年里一切顺利。

我们要感谢所有参与这项工作的人，特别是与我们分享他们的想法和观点的作者、审稿人以及 Wiley-VCH 高度专业的团队。

享受你的阅读！