The unique reactivity of "super silyl" in organic synthesis: A theoretical study

Akakura, Matsujiro; Boxer, Matthew B.; Yamamoto, Hisashi

doi:10.3998/ark.5550190.0008.a22

Cited by 7 publications

(3 citation statements)

References 3 publications

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“…Undoubtedly, the asymmetric aldol reaction provides a straightforward route for the stereoselective construction of these required polyol subunits. We recently introduced a cascade Mukaiyama aldol reaction based on super silyl and super Brønsted acid chemistry that gave the required polyol−carbonyls stereoselectively in a single step (Scheme A,B). , To upgrade the cascade process for even broader utility, such as rapid construction of polyketide frameworks, we here focused on 1,5-stereoselective aldol reactions that use our cascade products directly; these reactions represent a series of two consecutive aldol reactions of a central ketone with two polyol−aldehydes (Scheme C). , …”

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Super Silyl Stereo-Directing Groups for Complete 1,5-Syn and -Anti Stereoselectivities in the Aldol Reactions of β-Siloxy Methyl Ketones with Aldehydes

Yamaoka

Yamamoto

2010

J. Am. Chem. Soc.

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In this communication, we report that substrate-controlled 1,5-syn and -anti stereoinduction in the aldol reaction of beta-tris(trialkylsilyl)siloxy methyl ketones can be achieved with high diastereoselectivities. Tris(trialkylsilyl)silyl groups are easily prepared and play an important role in the selectivities of these reactions. Furthermore, all of the 1,3,5-triol stereoisomers can easily be prepared from beta-siloxy methyl ketones in no more than three steps.

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confidence: 99%

Super Silyl Stereo-Directing Groups for Complete 1,5-Syn and -Anti Stereoselectivities in the Aldol Reactions of β-Siloxy Methyl Ketones with Aldehydes

Yamaoka

Yamamoto

2010

J. Am. Chem. Soc.

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“…With the use of as little as 0.05 mol % loading of triflimide, the reaction succeeded in generating β,δ-dihydroxy aldehydes in a good yield and with perfect control of the diastereoselectivity (Scheme ). The high syn -selectivity obtained through this double AR could be attributed to the steric size of the extraordinarily bulky super silyl group. ,, In fact, the steric encumberment of this group not only slowed the rate of the addition of the second SEE to induce a high diastereoselctivity but also governed the intermediate in such a way that it avoids unfavorable steric interaction between the Lewis acid-coordinated oxygen and the R group that is present in conformation B, thus fostering the conformation A that would exclusively give the syn -adduct (Scheme ).…”

Section: Sequential Aldol–aldol Reactions (Aars)mentioning

confidence: 99%

“…Interestingly, silyl groups that contain Si–Si bonds are UV active, allowing for straightforward TLC analysis. Recently, as the tris(trialkylsilyl)silyl group has been remarkably successful when employed in radical reactions, it has subsequently been incorporated into ARs after experimental and theoretical calculations, demonstrating that a bulky super silyl group could stabilize the SEE and increase its reactivity …”

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confidence: 99%

Second Generation of Aldol Reaction

Gati

Yamamoto

2016

Acc. Chem. Res.

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Since the discovery of the Mukaiyama aldol reaction more than 40 years ago, several landmark publications have inspired researchers in the field. The Mukaiyama AR is one of the most significant named reactions in organic synthesis. In the past few decades, development of the modern AR has been at the forefront in addressing the challenges of regio-, chemo-, diastereo-, and enantioselectivity in organic synthesis. All of these selectivity challenges maybe present in a single pair of reactants, thus controlling the outcome of such a process has great practical value. More than 10 years ago, our group became involved in this iconic carbon-carbon bond-forming process and attempted to very closely investigate all possible features of the AR to solve several issues still encountered by chemists, most notably the selectivity challenges mentioned above. In this context, our group initiated the second generation of the AR based on a Lewis or Brønsted acid-catalyzed process in conjunction with the use of a "super silyl" (tris(trimethylsilyl)silyl) directing group, which has demonstrated unrivalled properties in controlling the outcome of the AR. Using the extraordinary power of the super silyl group, we were able to develop new methods and concepts that broadly impacted the ability to control the selectivity attributes and thus allowed for a highly stereoselective construction of polyketide, halogenated polyketide, polypropionate, and polyol scaffolds through inter- and/or intramolecular aldolization protocols. Our diastereoselective ARs of super silyl enol ethers and aldehydes have shown great efficiency and modularity in producing exclusively and preferentially syn- or anti-adducts, creating up to four new adjacent stereocenters in a one-pot sequential manner and under mild reaction conditions. The super silyl-directed AR does not only provide a solution to stereochemistry control challenges, but also offers an efficient, modular and high yielding technique toward nontrivial construction of complex architectures with unprecedented ease. We believe that the new Lewis- or Brønsted-acid-catalyzed super-silyl-directed AR processes chronicled in our laboratories have come to maturity and now offer a "road map" for strategic stereoselective synthesis of polyketide-like units. Herein we report our recent achievements in the diastereoselective C-C bond formation, through the super-silyl-directed AR, toward the synthesis of complex and sophisticated hydroxy aldehydes. We would like to note that due to the extremely broad range of work reported in this field, only stereoselective AR involving aldehyde-derived super SEEs will be discussed in this Account.

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