Enhanced anti-Diastereo- and Enantioselectivity in Alcohol-Mediated Carbonyl Crotylation Using an Isolable Single Component Iridium Catalyst

Abstract

The cyclometallated iridium complex (S)-I derived from [Ir(cod)Cl]2, 4-cyano-3-nitrobenzoic acid, allyl acetate and (S)-SEGPHOS is conveniently isolated by precipitation or through conventional silica gel flash chromatography. This single component precatalyst allows alcohol mediated carbonyl crotylations to be performed at significantly lower temperature, resulting in enhanced levels of anti-diastereo- and enantioselectivity. Most significantly, the chromatographically isolated precatalyst (S)-I enables carbonyl crotylations that are not possible under previously reported conditions involving in situ generation of (S)-I.

Unlocking Hydrogenation for C–C Bond Formation: A Brief Overview of Enantioselective Methods

“…28a However, although in situ assembly of the catalyst is convenient and excellent enantioselectivities typically were observed (>95% ee), only modest levels of anti -diastereoselectivity were evident (5:1 – 11:1 dr). Use of the chromatographically purified catalyst allows the reaction to be performed at lower temperature (60 °C), resulting in enhanced levels of anti -diastereo- and enantioselectivity (Scheme 11).…”

“…Use of the chromatographically purified catalyst allows the reaction to be performed at lower temperature (60 °C), resulting in enhanced levels of anti -diastereo- and enantioselectivity (Scheme 11). 28b …”

A new and more powerfully activating diamine for practical and scalable enantioselective aldehyde crotylsilylation reactions

“…1,2 Despite several important conceptual and/or practical advances 3–10 since the development of Brown’s crotylboranes 11 and Roush’s crotylboronates, 12 it remains an unmet but eminently worthy goal to devise an asymmetric aldehyde crotylation method that is characterized by 1) wide scope and generality with respect to the aldehyde substrate, 2) access to either product diastereomer with uniformly very high levels of both diastereoselectivity and enantioselectivity, and 3) sustainable, safe, inexpensive, and otherwise practical and scalable procedures such that the crotylation of a low MW aldehyde on a tens-of-grams or larger scale is a simple undertaking that may be carried out in less than a day by a single chemist. There are only two methods that meet most of these conditions, the Brown protocol 11 and our recently reported EZ-CrotylMix methodology.…”

Total Synthesis of (+)-SCH 351448: Efficiency via Chemoselectivity and Redox-Economy Powered by Metal Catalysis

“…The symmetric macrodiolide is assembled from Fragments A and B via esterification and cross-metathesis/RCM reactions. 16 For the synthesis of Fragment A , 4 consecutive metal catalyzed reactions are employed: cross-metathesis to form alcohol 2 , 16,19 tandem nucleophilic 17a,b and electrophilic 18 allylations to convert alcohol 2 to pyran 4 19 and the Suzuki cross-coupling of pyran 4 with aryl triflate 5 . 20 Fragment B is prepared in 8 steps from 5-hexen-1-ol 1 .…”

“…20 Fragment B is prepared in 8 steps from 5-hexen-1-ol 1 . Key transformations include Kiyooka’s variant of the enantioselective Mukaiyama aldol reaction (applied to aldehyde 6 ) 21 followed by Fuwa’s cascading cross-metathesis- oxa -Michael cyclization 22,23 to form pyran 8 , which upon sequential asymmetric transfer hydrogenative allylation 17a,b and crotylation 17c,d delivers Fragment B . The proposed synthesis of (+)-SCH 351448 exploits several chemoselective and redox-economic transformations.…”