Use of the Hosomi-Sakurai allylation in natural product total synthesis
Introduction
Introduction of an allyl group into a specific site or functionality in a given molecule, often accompanied by a functional group transformation, the allylation reaction is highly useful and versatile in organic synthesis [1]. Since a three-carbon chain homologation of a carbon-hydrogen or heteroatom-hydrogen bond (e.g., O–H, N–H, and S–H) is feasible, the allylation reaction has found broad and diverse applications for the extension of carbon chains. From a broader standpoint, moreover, the carbon-carbon double bond in an allyl group can serve as a further synthetic handle for functional group manipulations or a carbon chain elongation [2].
The Tsuji-Trost allylic substitution reaction is highly versatile for the controlled forging of carbon-carbon and carbon-heteroatom bonds in the fields of both natural product synthesis and medicinal chemistry (Scheme 1a) [[3], [4], [5], [6], [7], [8], [9], [10], [11], [12]]. In general, this reaction employs catalytically generated π-allylpalladium complexes as electrophilic allylation reagents. A diverse range of soft carbon nucleophiles, such as active methylene compounds with two electron-withdrawing groups (EWGs), enamines, enolates, and nitroalkanes, and various nitrogen-, oxygen-, and sulfur-based soft nucleophiles can react with symmetric or asymmetric π-allyl complexes to afford the corresponding allylation products under mild reaction conditions. Highly regio-, diastereo-, and enantioselective allylic substitution methodologies have intensively been developed over the past several decades [[13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24[, [25], [26], [27], [28]].
One of the most fundamental reactions in organic synthesis is arguably the carbon-carbon bond-forming reaction in which a new carbon-carbon bond is created. A radical allylation, namely the Keck radical allylation, is also a highly useful carbon-carbon bond-forming reaction (Scheme 1b) [29,30]. Such reactions involve the addition of a carbon-centered radical to an appropriate allyl transfer reagent and subsequent fragmentation for the reinstallation of the allyl group. The carbon-centered radicals can be generated in situ from various precursors, including alkyl bromides, chlorides, phenylselenides, and thioacylimidazole derivatives, in the presence of a radical initiator (e.g., AIBN, BPO, etc.) [31]. Allylstannanes, such as allyltributyltin and allyltriphenyltin, have been used as a source of the allyl radical in the Keck radical allylation. However, the inherent toxicity and continual purification problems frequently encountered with organotin compounds have restricted large-scale application of tin-based methodology [32].
The nucleophilic addition of an allylmetal reagent to carbonyl compounds, namely carbonyl allylation, is one of the most frequently used carbon-carbon bond-forming reactions in synthetic organic chemistry (Scheme 1c). Accordingly, a substantial amount of effort has been devoted to the development of useful allylmetal reagents since Mikhailov and Bubnov reported the first carbonyl allylation using triallylborane as an isolable allylmetal reagent in 1964 [33]. To date, a variety of useful allylmetal reagents, including Si, Sn, B, Cr, Li, Ma, Zn, Ti, Zr, and In-based reagents, have been reported in the literature [34]. Also developed is catalytic methods for the generation of allylmetal species under mild reaction conditions [35].
The Hosomi-Sakurai reaction is the Lewis acid-promoted allylation of carbonyl compounds and their derivatives with allyltrimethylsilane as an allylating reagent (Scheme 2a). Since Sakurai and Hosomi published their seminal paper on the allylation of a wide range of aromatic and aliphatic aldehydes and ketones in 1976 [36], we have called this transformation as the Hosomi-Sakurai allylation, Sakurai allylation, and Sakurai reaction, etc. It has become a powerful tool in modern organic synthesis, which allows access to homoallylic alcohols and their derivatives from various carbon electrophiles and allylsilanes. When compared to other allylating reagents, inexpensive allylsilanes have several advantages such as their high stability, low toxicity, high functional group compatibility, relative inertness to moisture, and long storage period without special precautions [[37], [38], [39], [40], [41], [42], [43], [44], [45]]. However, the reactivity of allylsilanes towards non-activated electrophiles is moderate. Therefore, Lewis acid activation is critical in the Hosomi-Sakurai allylation of carbonyl compounds. We commonly use strong Lewis acids such as TiCl4, BF3·OEt2, SnCl4, and EtAlCl2 for this purpose [46]. Regiospecific transposition of the allyl moiety is a notable feature of the reaction and can be rationalized by the selective formation of a highly stabilized β-silylcarbocation as an intermediate (the β-silicon effect) via the nucleophilic attack at the γ-carbon of the allylic system (Scheme 2b) [47]. In 1978, Hosomi and Sakurai reported that fluoride ion also could facilitate the carbonyl allylation in a completely different way to Lewis acids. They suggested that tetra-n-butylammonium fluoride (TBAF) readily activates allylsilanes to generate a nucleophilic allyl species, presumably due to the high stability of Si–F bond, which in turn can chemoselectively attack various aldehydes and ketones to produce the corresponding homoallyl silyl ethers [48].
Thanks to its carbon-carbon bond-forming nature and ability to generate a chiral carbon center under mild reaction conditions, the Hosomi-Sakurai reaction has continuously attracted a great deal of attention from the synthetic community over the past several decades. A wide range of carbon electrophiles, including acetals [49], aldimines [50,51], aldehydes, carboxylic acid chlorides [52], epoxides [53], ketals [50], ketoimines [54], ketones, and α,β-unsaturated carbonyl compounds [55], has participated in Lewis acid- or fluoride ion-promoted allylation with various allylsilanes. A diverse range of Lewis acids [49,[56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77]], Brønsted acids [[78], [79], [80], [81], [82], [83], [84], [85]], heterogeneous catalysts [[86], [87], [88], [89]], and other catalysts have been investigated. Numerous examples of useful catalytic versions of the Hosomi-Sakurai allylation have now been available [46].
Hosomi and Sakurai’s discovery has also provoked the studies of enantioselective carbonyl allylation with chiral allylmetal reagents. Since Hoffmann and Herold reported the first example of chiral allylating reagent derived from a chiral pool, (+)-camphor, in 1978 [90], a variety of asymmetric carbonyl allylation methods have been investigated using a wide assortment of chirally modified allylmetal reagents [[91], [92], [93], [94], [95], [96], [97], [98], [99], [100], [101], [102], [103]]. The development of catalytic enantioselective carbonyl allylation, which can avoid the stoichiometric use of expensive chiral auxiliaries, has been a more valuable and challenging research topic for gaining access to optically active homoallylic alcohols [38,42,[104], [105], [106], [107], [108], [109], [110], [111], [112], [113], [114], [115], [116], [117], [118], [119], [120], [121], [122], [123], [124], [125], [126], [127], [128], [129], [130], [131], [132]]. Many useful methods for the catalytic enantioselective Hosomi-Sakurai allylation of aldehydes have been developed. Most of these processes employ chiral Lewis aid catalysts [[133], [134], [135], [136], [137], [138], [139], [140]], chiral Lewis base catalysts [[141], [142], [143], [144], [145], [146], [147], [148], [149], [150], [151], [152], [153], [154], [155], [156], [157], [158], [159], [160], [161]], or chiral Brønsted acid catalysts [162,163] in combination with allyltrialkylsilanes, allyltrialkoxysilanes or allyltrichlorosilane as nucleophiles. More recently, the List group reported the design and synthesis of a series of highly acidic iminodiphosphorimidate (IDPi) Brønsted acids, which enable highly enantioselective Hosomi-Sakurai allylation of various aldehydes under the silylium Lewis acid organocatalysis [164,165]. Very recently, Ryu and co-workers disclosed an asymmetric Hosomi-Sakurai allylation of aldehydes by using a chiral oxazaborolidinium ion (COBI) catalyst. This useful protocol provides access to a range of chiral homoallylic alcohols in high yields with excellent asymmetric inductions [439]. In contrast, the development of the catalytic asymmetric allylations of ketones, highly useful synthetic methods for chiral tertiary homoallylic alcohols, is still challenging because ketones generally show lower reactivity than aldehydes. Up to now, few examples of the catalytic asymmetric Hosomi-Sakurai allylations of ketones have been developed [[166], [167], [168]].
Homoallylic alcohols are commonly occurring structural motifs and ubiquitous in a wide range of natural and unnatural compounds. Especially, chiral homoallylic alcohols are valuable building blocks in the synthesis of biologically active natural, agrochemical, and pharmaceutically relevant products. Moreover, the presence of two functional groups in homoallylic alcohols, namely the alcohol and olefin functionality that can separately participate in many classes of synthetic transformations to afford a diverse range of more advanced intermediates and target molecules, can increase their significance and versatility [2]. Consequently, a myriad of synthetic methods has been investigated and developed over the past several decades. Among these methods, the carbonyl allylation represents the most straightforward and versatile transformation to prepare these useful motifs [34].
Ever since its discovery in 1976 [36], the Hosomi-Sakurai allylation has found widespread applications in organic synthesis. Due to the ability to create a new carbon-carbon bond under mild reaction conditions, high functional group compatibility, and the possibility of substrate-controlled stereoselectivity, combined by advantages associated with allylsilanes, this allylation has found useful application in the total synthesis of complex natural products, especially biologically active polyketides [124]. This review covers only selected examples of natural product total syntheses, over the past two decades between 1999 and 2019, that employ the Hosomi-Sakural allylation or its related reactions as one of the pivotal transformations.
Section snippets
Total synthesis of (+)-halichlorine
(+)-Halichlorine (1) was isolated in 1996 from the Japanese marine sponge Halichondria okadai Kadota by Uemura and co-workers [169,170]. The gross structure and relative stereochemistry of this novel marine alkaloid were established by extensive NMR spectroscopic analysis. It was identified to act as a selective inhibitor of the induced expression of the cell surface protein, VCAM-1 (vascular cell adhesion molecule-1) [169].
In 1999, the Danishefsky group revised the relative and absolute
Conclusion and outlook
As described in this review, a diverse range of different structural motifs found in complex natural products can be efficiently constructed through the Hosomi-Sakurai allylation or related methodologies by the combination with other relevant transformations. Notably, a range of aza-, oxa-, and carbocycles can be conveniently prepared via intramolecular versions of the allylation as well as cascade processes coupled with it.
In general, the yield of this synthetically useful transformation is
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
We dedicate this paper to Professor Samuel J. Danishefsky, honoring his pioneering accomplishments in organic synthesis. We thank the National Research Foundation (NRF) of the Korea-Basic Science Research Program (Nos. NRF-2017R1D1A1B03029926 and NRF-2020R1F1A1076460) and the Dongguk University Research Fund of 2020 for financial support.
Jun Hee Lee obtained his B.S. (1995) degree in chemistry from Dongguk University and M.S. (1997) and Ph.D. (2001) degrees in chemistry from Sogang University under the guidance of the late Prof. Jahyo Kang. After completing mandatory military service, he moved abroad to work with Professors Dean Toste (UC Berkeley) and Samuel J. Danishefsky (Columbia University) as a postdoctoral fellow. In 2010, he returned to Korea and worked at Ewha Womans University with Prof. Sang-gi Lee and Ajou
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Jun Hee Lee obtained his B.S. (1995) degree in chemistry from Dongguk University and M.S. (1997) and Ph.D. (2001) degrees in chemistry from Sogang University under the guidance of the late Prof. Jahyo Kang. After completing mandatory military service, he moved abroad to work with Professors Dean Toste (UC Berkeley) and Samuel J. Danishefsky (Columbia University) as a postdoctoral fellow. In 2010, he returned to Korea and worked at Ewha Womans University with Prof. Sang-gi Lee and Ajou University as a Research Professor and the Institute of Basic Science (IBS) as a Principal Research Fellow. In 2016, he began his independent career at Dongguk University Gyeongju Campus as Assistant Professor of the Department of Advanced Materials Chemistry. He has a broad interest both in synthetic organic and organometallic chemistry. His current research interest focuses on the development of highly chemoselective reactions for the synthesis of biologically active compounds.