Paterson aldol

I. Paterson Aldol Condensations of Ketones Using Chiral Boron Reagents ... 

Clever combinations of both concepts were applied by Paterson and coworkers in a series of total syntheses of natural products [149]. The marine natural product swinholide A, a cytotoxic macrolide with an unusual 44-membered dilactone ring, demonstrates the potential of the methods for the construction and combination of carbon chains with multiple functionality and a high dense of stereogenic centers. The macrolide swinholide A featuringtwo identical seco-acid subunits is shown in Scheme 4.67, and the stereogenic centers created by the different Paterson aldol protocols using cis- and trans-boron enolates are marked by asterisks [150]. 

The so-generated ester serves at the same time as a protecting group and renders the Evans-Tishchenko reaction a transformation in natural product syntheses. Scheme 2.146 shows a typical combination of Paterson aldol reaction followed by anti-selective reduction. The DlPCl-mediated aldol reaction sets the configuration at the new secondary alcohol (102). This configuration is then used for the... 

SCHEME 8.16. The Paterson aldol reaction using a chiral Z-enolate. 

Bernard A, A M CapeUi, A Comotti, C Gannari, J M Goodman and I Paterson 1990. Transltion-St Modeling of the Aldol Reaction of Boron Enolates A Force Field Approach. Journal of Orga Chemistry 55 3576-3581. 

Paterson, I., Delgado, O., Florence, G.J., Lyothier, I., Scott, J.P., Sereinig, N. (2003) 1,6-Asymmetric Induction in Boron-Mediated Aldol Condensations Application to a Practical Total Synthesis of (-F)-Discodermolide. Organic Letters, 5, 35-38. 

Scheme 13.71 shows the most recent version of a synthesis of (-l-)-discodermolide developed by Ian Paterson s group at Cambridge University. The synthesis was based on three major subunits and used boron enolate aldol addition reactions to establish the stereochemistry. 

The synthesis of the BC-ring fragment 26 begins with the enantioselective aldol reaction of aldehyde 22 and chiral boron enolate 23 derived from (—)-DIP-Cl as described by Paterson and Brown [42]. The aldol adduct 24 is converted to the... 

Scheme 22 Vinylogous aldol reaction used in Paterson s synthesis of swinholide A...

The same natural product was synthesized by Paterson et al. [45] who assembled the carbon skeleton of the macrolide from three larger subunits as well. Instead of the Evans-Metternich variant they used their boron-mediated antz-selective aldol strategy which relies as the Evans-Metternich aldol on stereo-induction from the a-chiral center and translates the E-enolate geometry, established due to the use of Cy2BCl, to the anti aldol product (Scheme 33). 

In 2003, Paterson and co-workers reported a second-generation strategy for the synthesis of discodermolide, which aimed to eliminate the use of all chiral reagents and auxiliaries, and reduce the total number of synthetic steps (Scheme 24) [58, 59], These specific aims were achieved by employing an unprecedented aldol coupling at C5-C6 between C1-C5 aldehyde 118 and the advanced C6-C24 methyl ketone 119 and utilising diol 120 as a common precursor for the synthesis of the three subunits 118, 121 (C9-C16) and 98 (C17-C24). 

A. S. Franklin, I. Paterson, Recent Developments in Asymmetric Aldol Methodology, Contemporary Organic Synthesis 1994, 1, 317. 

C. J. Cowden, I. Paterson, Asymmetric Aldol Reactions Using Boron Enolates, Org. Prep. Proced. Int. 

I. Paterson C. J. Cowden, D. J. Wallace, Stereoselektive Aldol Reactions in the Synthesis of Polyketide Natural Products, in Modem Carbonyl Chemistry, Ed. J. Otera, Wiley-VCH, Weinheim, 2000, 249-297. 

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