Saucy–Marbet rearrangements of alkynyl halides in the synthesis of highly enantiomerically enriched allenyl halides

Abstract

A stereospecific Saucy-Marbet rearrangement of alkynyl halides is described here. These rearrangements provide an entry to highly enantiomerically enriched allenyl bromides and chlorides through excellent chirality transfer and the reservation of optical integrity of alkynyl halides.Allenes are among the most powerful building blocks in organic synthesis. 1,2 Recently, both Trost 3 and we 4 communicated copper(I)-catalyzed amidations of allenyl halides 2 en route to an atom-economical synthesis of allenamides 4 [Scheme 1], a class of heteroatom-substituted allenes that have attracted much attention from the synthetic community. 1,2,5-8 Specifically in our work, 4 the cross-coupling is completely stereospecific when employing enantiomerically enriched allenyl halides 2-P and 2-M [Scheme 1].However, we were met with the challenge of preparing optically pure allenyl halides. With the exception of diastereosel ective examples, 9,10 for axially chiral allenyl halides such as 2, the level of enantiomeric enrichment was at best modest even when employing known conditions starting from mesylation of optically pure propargyl alcohols (R)-1 and (S)-1. 1,2,11,12 Our interest 13 in both the Saucy-Marbet rearrangement for the synthesis of chiral allenes 9,14-16 and reactivities of alkynyl halides such as 5 17,18 prompted us to explore the synthesis of en antiomerically pure allenyl halides 7 by uniting the two concepts. 19 We communicate here the concept of employing a stereospecific Saucy-Marbet rearrangement of alkynyl halides in the synthesis of highly enantiomerically enriched allenyl halides.Conditions for the proposed rearrangement could be readily established using racemic alkynyl halides as shown in Table 1 Alkynyl iodide 8 was not as effective as alkynyl bromide 9 [entry 1 versus 2], and an acid catalyst such as AcOH was critical [entries 3-6] and so was the optimal temperature of 100 °C [entry 5 versus 6]. With these conditions in hand, enantiomerically pure alkynyl bromides (R)-and (S)-9 20 were prepared from their respective chiral propargyl alcohol (R)-and (S)-12 using AgNO 3 and NBS [Scheme 2]. Subsequent Saucy-Marbet rearrangements led to the respective allenyl bromides 11-P and 11-M in good yields over two steps. Given the ability of [3,3]-sigmatropic rearrangements to conserve and transfer chirality, these reactions should be highly stereoselective through intermediates (R)-and (S)-13, leading to 11-P and 11-M with high levels of enantiomeric purity. Representative examples of these © 2008 Elsevier Ltd. All rights reserved. *Corresponding author. Tel.: 1-608-890-1063; fax: 1-608-262-5345; e-mail: rhsung@wisc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be d...

Hochselektive Mangan(I)/Lewis‐Säure‐cokatalysierte direkte C‐H‐Propargylierung unter Verwendung von Bromallenen

“…Anschließende Umwandlungen ergaben 76 % Ausbeute an chiralem Bromallen (S)-2e mit 97 % ee im 5-Gramm-Maßstab. [19]…”

“…[19] Mehr als 30 Naturstoffe wurden entdeckt, die dieses Strukturmotiv tragen, während die Chemie der Bromallene kaum entwickelt ist. [19] Mehr als 30 Naturstoffe wurden entdeckt, die dieses Strukturmotiv tragen, während die Chemie der Bromallene kaum entwickelt ist.…”

“…[18d] Der Bromsubstituent am Allen dient nicht nur als Abgangsgruppe,s ondern auch als entscheidendes Element zur Steuerung der Elektronenverteilung in der Allen-Einheit. [19] Die Verwendung von chiralem Bromallen ((S)-2e,97% ee)lieferte in diesem Ansatz 81 %Ausbeute von 3k mit 91 % ee. Dieser induktive Effekt hat wichtige mechanistische Konsequenzen fürd ie Reaktion des Thiophen-oder Benzothiophensystems (Schema 3).…”

“…Bromallene sind eine Klasse leicht zugänglicher,m eist stabiler Verbindungen. [19] Mehr als 30 Naturstoffe wurden entdeckt, die dieses Strukturmotiv tragen, während die Chemie der Bromallene kaum entwickelt ist. [20] Die Verwendung von Bromallenen als Kupplungspartner bei der direkten C-H-Propargylierung zeigt ihren einzigartigen Charakter als potenzielle Bausteine in der organischen Synthese.…”

Highly Selective Manganese(I)/Lewis Acid Cocatalyzed Direct C−H Propargylation Using Bromoallenes

“…Bromoallenes are aclass of easily accessible,mostly stable compounds. [19] More than 30 natural products have been discovered bearing this structural motif,w hile the chemistry of bromoallenes is highly undeveloped. [20] Theu tility of bromoallenes as the coupling partner in the direct CÀH propargylation shows their unique character as potential building blocks in organic synthesis.H owever,t wo big challenges still exist:1 )The selective C = Ci nsertion [C(1) = C(2) vs.C (3) = C(2)] into the C-Mn bond would lead to ap ropargylic compound (Scheme 1d)o ra na llene product (Scheme 1e).…”