The Scope of Catalytic Enantioselective Tandem Carbonyl Ylide Formation−Intramolecular [3 + 2] Cycloadditions

Abstract

Catalytic enantioselective tandem carbonyl ylide formation-intramolecular 1,3-dipolar cycloaddition reactions of 2-diazo-3,6-diketoesters show promising scope in terms of asymmetric induction as the tethered alkene/alkyne dipolarophile component is varied. Cycloadditions were found to occur in moderate to very good yields, with a difference in ee exhibited by the electronically different 2-diazo-3,6-diketoesters 1, 25 and 33, 34. Values for ee of up to 90% for alkene dipolarophiles and up to 86% for alkyne dipolarophiles were obtained.

Multi-Bond Forming Processes in Efficient Synthesis

“…[67] Wender and Howbert's metaphotocycloaddition route to hirsutene, [68] the more recent syntheses of hirsutellone B by Nicolaou et al [69] and Sorensen and coworkers, [70] the double Diels-Alder approaches to FR182877 by Sorenson and coworkers, [71] Evans and Starr, [72] and most recently Nakada and coworkers, [73] and Denmark et al's [4þ2]/[3þ2] domino approach towards daphnilactone B are also outstanding examples. [74] Generation of a reactive ylide from a carbenoid, a strategy pioneered by Padwa from the 1980s, with enantioselective methods emerging from the laboratory of Hodgson, [75] has also proven an effective strategy in the generation of several bonds and significant structural complexity in one step. [76,77] The research group of Boger has championed a complementary method of ylide formation to that of Padwa's in an uncatalysed, pericyclic intramolecular sequence featuring a hetero-Diels-Alder, retro-Diels-Alder, and dipolar cycloaddition.…”

Catalytic enantioselective intermolecular cycloadditions of 2-diazo-3,6-diketoester-derived carbonyl ylides with alkene dipolarophiles

“…Using the phenyl ketone 10c allowed an examination of the presence of a conjugated substituent on the ylide, which might be anticipated to exert a more significant effect than alkyl substitution. In that event, cycloaddition using 10c proceeded in slightly lower yields, compared with 10a-10b, to give cycloadduct 11c [53% using Rh 2 (OAc) 4 ], the structure of which was confirmed by crystallography. Comparing the effectiveness of the chiral catalysts in the syntheses of bicyclic ketones 11a-11c, a noticeable rise in ee to 77% was seen with phenyl ketone 10c using Rh 2 [(S)-DOSP] 4 4, whereas Rh 2 [(R)-DDBNP] 4 5 was less effective with 10c at ambient temperature (51% ee) but showed a steep rise in ee after lowering the reaction temperature to 0°C (80% ee); in parallel with earlier observations in intramolecular cycloadditions (25), with 10c there was no marked effect on ee with respect to temperature variation when using Rh 2 [(S)-DOSP] 4 …”

“…Moving from methyl ketone 10a to n-hexyl ketone 10b did not significantly affect the yield of cycloadduct 11b with Rh 2 (OAc) 4 (76%) or the ee with either of the chiral catalysts (Scheme 4). Using the phenyl ketone 10c allowed an examination of the presence of a conjugated substituent on the ylide, which might be anticipated to exert a more significant effect than alkyl substitution.…”

“…For example, no cycloadduct was observed from the reaction of ester 10a with vinylcyclohexane (10 eq) as dipolarophile under Rh 2 (OAc) 4 catalysis in CH 2 Cl 2 at 25°C. Cyclopentene, however, under similar conditions, allowed isolation of a 14% yield of cycloadduct after 4 h (see Supporting Text), although no cycloadduct was observed when using Rh 2 [(R)-DDBNP] 4 5.…”

“…4 and references therein). This chemistry builds on pioneering research by Ibata and especially Padwa, who established that transition metal-catalyzed decomposition of diazo compounds in the presence of carbonyl functionality generates transient carbonyl ylides that subsequently undergo cycloaddition in the presence of suitable dipolarophiles (5,6).…”