Catalytic (Asymmetric) Methylene Transfer to Aldehydes

Abstract

Over the past 15 years the Corey-Chaykovsky (CC) epoxidation process 1 involving the reaction between sulfonium ylides and aldehydes has evolved into a highly synthetically useful, catalytic asymmetric methodology. 2The use of semistabilized ylides such as those derived from the reaction of either benzyl halides or α-haloesters/amides with chiral sulfides at catalytic loadings can result in excellent levels of product enantiomeric excess.3 In stark contrast however, the asymmetric synthesis of terminal epoxides via methylene transfer is characterized by moderate yields and a requirement for (super)stoichiometric loadings of chiral sulfide catalysts. 4,5 For example, the benchmark literature procedures (Scheme 1) for the asymmetric sulfonium ylide-mediated formation of styrene oxide (2) from the archetypal substrate benzaldehyde (1) developed independently by Aggarwal 6a,b and Goodman 6c involve the use of 100-200 mol% of the chiral sulfides 3-4 and produce 2 in ca. 50-60% yield and <60% ee. 7 Hiyama et al. (ref. 7a) claimed that 2 could be synthesized in 97% ee in the presence of a chiral phase transfer catalyst. However our group (ref. 7b) recently demonstrated that Hiyama was in error and has actually observed the decomposition of the catalyst to a related epoxide (with a relatively large specific rotation) during the formation of 2 as a racemate: (a) Hiyama, T.; Mishima, T.; Sawada, H.; Nozaki, H. J. Am.

Organokatalytische asymmetrische Epoxidierungen – Reaktionen, Mechanismen und Anwendungen

“…[116] Unter Verwendung des Katalysators 135 und der Phosphazen-Base 136 wurde das terminale Epoxid 137 in 70 % Ausbeute und mit 43 % ee erhalten (Schema 44). In der Literatur gibt es gegenwärtig nur ein einziges Verfahren mit Sulfidkatalysatoren.…”

“…In der Literatur gibt es gegenwärtig nur ein einziges Verfahren mit Sulfidkatalysatoren. [116] Unter Verwendung des Katalysators 135 und der Phosphazen-Base 136 wurde das terminale Epoxid 137 in 70 % Ausbeute und mit 43 % ee erhalten (Schema 44). [117] Obwohl sich sulfidkatalysierte Epoxidierungen, die über den Weg der Alkylierung/Deprotonierung ablaufen, als einfache und wirksame Methode zur Herstellung der trans-Epoxide 124 erwiesen haben, ist der Anwendungsbereich dieser Reaktionen eher begrenzt.…”

Rieche formylation of carbon nanotubes – one-step and versatile functionalization route

“…In the quest for alternative routes, we have turned to a synthetic precursor of the carboxyl group, i.e., the aldehyde group, which might emerge as even more powerfulindeed, the high and multi-target reactivity of aldehydes (RCHO) locates them among the most important organic compounds. Denitely, the formyl group (-CHO) appears as a powerful surface modier, as it constitutes a convenient starting point for the synthesis of alcohols, 22,23 amines, 24,25 acids, 26 oximes, 27,28 alkenes, 29,30 alkynes, 31 epoxides, 32,33 etc. Therefore, formylation of CNTs is a natural synthetic route to practically countless post-modications of formylated CNTs that are susceptible to many readily available nucleophiles.…”

Efficient Catalytic Corey–Chaykovsky Reactions Involving Ketone Substrates

“…[7] The key realisation which led to the development of a catalytic protocol was that alkylation of the sulfide (i.e., 6!7, Scheme 2) by alkyl electrophiles is rate-determining. Thus, turnover is facilitated by the use of a powerful alkylating agent such as methyl triflate, which leads to the formation of the sulfonium salt 7 in a catalytically feasible time frame, which is cleanly deprotonated by a phosphazene base to form ylide 8.…”

“…While it was thus obvious that ketones represent a challenge from an electrophilicity standpoint, [7] the key question now was whether or not ketones would be unreactive enough towards ylide 8 under our optimised conditions (Scheme 1) to render C À C bond formation (as opposed to sulfide alkylation) the rate-determining step. If this were the case, it would be unlikely that a practical catalytic procedure would be possible.…”