Felkin-Anh Rule

The Felkin-Anh rule is a rule for the selective addition to aldehydes and ketones with a stereocenter in the α-position to the carbonyl group. It was named after Hugh Felkin and Nguyen T. Anh .

Cram rule

In 1952 Donald J. Cram developed the theory ( Cram's rule ) that in the case of an addition to an aldehyde or ketone with a stereocenter in the α-position, a certain transition state is responsible for the resulting product. The largest remainder is antiperiplanar to the carbonyl oxygen and the nucleophile attacks at the Bürgi-Dunitz angle , which is close to 107 °, on the side with the smallest remainder.

Further development by Felkin and Anh

Since Cram's rule did not always correctly predict the preferred product, it was further developed by Felkin and later by Anh.

In their opinion, the remainder with the lowest σ * _CR aligns itself at right angles to the double bond. So the orbital overlaps with the π * _CO and forms a new LUMO . That radical is either the sterically most demanding radical or an electron-withdrawing group (e.g. Cl, methoxy group ). The nucleophile attacks in the Bürgi-Dunitz angle on the side with the lower steric demand.

General reaction using the example of a hydride addition using the Felkin-Anh transition state

Competition from the cram chelate

The Cram-chelate transition state competes with the Felkin-Anh transition state. In this the carbonyl oxygen and the electron-withdrawing group (OR, NR ₂ ) are coordinated by a metal ion. Since the nucleophile again attacks in the Bürgi-Dunitz angle on the side with the lower steric demand, exactly the anti-Felkin-Anh product results.

Which of the two products is formed depends on which residue is attached to the electron-withdrawing group and which metal ion should coordinate.

With hard, strongly coordinating metal ions (e.g. Mg ²⁺ , Zn ²⁺ ), the Cram chelate product is more likely to be formed, with softer, less strongly coordinating metal ions (e.g. K ⁺ ), the Felkin-Anh- Product.
With a sterically less demanding residue (e.g. a benzyl residue) the cram chelate product is formed, with a sterically demanding residue (e.g. TBDMS ) no chelate ring can be formed and the Felkin-Anh product is formed.

Further literature

P. Wyatt, S. Warren: Organic Synthesis (Strategy and Control). Wiley, Wiltshire et al. 2007, ISBN 978-0-471-92963-5 , pp. 429-431.

J. Clayden, N. Greeves, S. Warren, P. Wothers: Organic Chemistry. Oxford University Press, Oxford 2009, ISBN 978-0-19-850346-0 .

S. Guillarme, K. Plé, A. Banchet, A. Liard, A. Haudrechy: Alkynylation of Chiral Aldehydes: Alkoxy-, Amino- and Thioaldehydes. In: Chem. Reviews. 2006, 106 , pp. 2355-2403.

Individual evidence

↑ Reinhard Brückner: reaction mechanisms: organic reactions, stereochemistry, modern synthesis methods . Spektrum Akademischer Verlag ;, 2007, ISBN 3-8274-1579-9 .
↑ Reinhard Brückner : reaction mechanisms . Spektrum Akademischer Verlag, Heidelberg 2009, ISBN 978-3-8274-1579-0 , pp. 412 .
↑ Reinhard Brückner: reaction mechanisms . Spektrum Akademischer Verlag, Heidelberg 2009, ISBN 978-3-8274-1579-0 , pp. 418 f .

[1] Reinhard Brückner: reaction mechanisms: organic reactions, stereochemistry, modern synthesis methods . Spektrum Akademischer Verlag ;, 2007, ISBN 3-8274-1579-9 .

[2] Reinhard Brückner : reaction mechanisms . Spektrum Akademischer Verlag, Heidelberg 2009, ISBN 978-3-8274-1579-0 , pp. 412 .

[3] Reinhard Brückner: reaction mechanisms . Spektrum Akademischer Verlag, Heidelberg 2009, ISBN 978-3-8274-1579-0 , pp. 418 f .