The O‐Directed Free Radical Hydrostannation of Propargyloxy Dialkyl Acetylenes with Ph₃SnH/cat. Et₃B. A Refutal of the Stannylvinyl Cation Mechanism

Abstract

In this Personal Account, we will give an overview of the room temperature O‐directed free radical hydrostannation reaction of propargylically‐oxygenated dialkyl acetylenes with Ph3SnH and catalytic Et3B/O2 in PhMe. We will show how this excellent reaction evolved, and how it has since been used to stereoselectively construct the complex trisubstituted olefin regions of three synthetically challenging natural product targets: (+)‐pumiliotoxin B, (−)‐(3R)‐inthomycin C, and (+)‐acutiphycin. Throughout this Account, we will pay special attention to highlighting important facets of the I−SnPh3 exchange processes that have so far been used in the various different steric settings that we have addressed, and we will document the range of cross coupling protocols that have critically underpinned the first successful applications of this method in complex natural product total synthesis. Last, but not least, we will comment on various aspects of the O‐directed free radical hydrostannation mechanism that have been published by ourselves, and others, and we will discuss all of the factors that can contribute to the observed stereo‐and regio‐chemical outcomes. We will also challenge and refute the recent non‐directed stannylvinyl cation mechanism put forward by Organ, Oderinde and Froese for our reaction, and we will show how it cannot be operating in these exclusively free radical hydrostannations.

Radical Silyl‐ and Germylzincation of Propargylic Alcohols

“…By analogy with Hale ’s proposal for the hydrostannylation reactions with Ph 3 SnH, [37] we conjecture that formation of adduct VII by interaction between the oxygen and the germanium atoms facilitates H‐atom transfer from Ph 3 GeH and provides radical VIII poised for addition across the C≡C triple bond at the proximal (α) carbon. The lower reactivity observed with O ‐silylated substrate 24 is consistent with this hypothesis, as in that case, the less favorable O−Ge interaction should prevent facilitation of the H‐atom transfer step and therefore the radical chain should be less efficient.…”

“…Opposite regioselectivity with respect to terminal propargylic alcohols was observed, as the α regioisomers ( 8α and 9α ) were formed predominantly. In the absence of a strong steric bias to orient the radical addition step, this general behavior can be ascribed to an O‐directing effect similar to the one observed for the better‐established hydrostannylation reactions with Ph 3 SnH, wherein interaction between the oxygen and the tin atoms directs the addition at the carbon of the alkyne proximal to the O‐atom [37] . Note that in the case of 5 , the vinyl radical arising from the addition of the triphenylgermyl radical at the α carbon beneficiates from stabilization by the adjacent phenyl group, and this explains the higher levels of regioselectivity (compare Entries 2 and 3 with 4 and 5 ).…”

Twofold π-Extension of Polyarenes via Double and Triple Radical Alkyne peri-Annulations: Radical Cascades Converging on the Same Aromatic Core

“…The importance of the directing interaction between the OMe group and Sn-centered radicals, a process that briefly became controversial before being convincingly addressed by Hale and coworkers, [54][55][56][57][58][59][60] was confirmed by testing various radical sources. Sn-centered radicals (Ph3SnH or Bu3SnH) substantially outperformed other radical sources (Si-centered radicals, Togni II, and RB(OH)2/Mn III ).…”

Hydroelementation of diynes

“…Over the last few decades, several reviews have been published focusing on this subject. 14,17,18,22,25,30,[48][49][50][51][52][53][54][55][56][57][58][59][60][61] Particularly useful are hydroboration, hydrosilylation, hydroamination, hydrophosphination, and hydrostannation processes, which lead to important building blocks in organic and materials chemistry. Although many different terminal and internal alkynes have been used in these transformations, literature focused on the hydroelementation of conjugated or separated diynes is much rarer and has never been collated in a review before.…”