User:Benjah-bmm27/degree/4/CLW

=Stereoselective synthesis, CLW=

=Revision of previously encountered selective reactions=

Chemoselectivity

 * As an example of chemoselectivity (selectivity between different functional groups), consider reduction of carbonyl compounds with metal hydrides
 * NaBH4 is very mild and reduces ketones in the presence of esters
 * LiAlH4 reduces both ketones and esters
 * In a keto-ester: (i) protect the ketone with ethylene glycol and H+, (ii) reduce the ester with LiAlH4, then (iii) deprotect with H+/H2O
 * It's preferable to avoid protecting groups wherever possible

Regioselectivity

 * As an example of regioselectivity (selectivity between parts of the same functional group), consider addition of carbon nucleophiles to enones
 * Hard nucleophiles like MeLi undergo direct addition (1,2-addition) to the carbonyl carbon, forming an alcohol
 * Soft nucleophiles like Me2CuLi undergo conjugate addition (1,4-addition, Michael reaction) to the &beta; carbon, forming ketone

Stereoselectivity

 * As an example of stereoselectivity (control over stereochemistry), consider epoxidation of a chiral cyclic allylic alcohol with mCPBA
 * Option 1: Don't protect the OH group
 * the OH group forms a hydrogen bond to mCPBA – chelation control
 * mCPBA delivers an oxygen atom to the top (hydroxy) face of the unprotected allylic alcohol
 * Option 2: Protect the OH group with Ac2O/py to get a chiral allylic acetate
 * mCPBA delivers an oxygen atom to the bottom (unblocked) face of the allylic acetate

=Selective reductions with boron and aluminium reagents=

Selective reduction of esters to aldehydes

 * Diisobutylaluminium hydride (DIBALH) is less flammable and easier to use than LiAlH4
 * It selectively reduces esters to aldehydes, if the reaction is conducted at −70 °C
 * An ester oxygen coordinates to Al, then hydride migrates from Al to C
 * The tetrahedral intermediate is stable at low temperature, and can be worked up with H+/H2O to the aldehyde
 * Yields well over 90% when done properly

Reduction of nitriles to aldehydes

 * Same conditions as above, proceeds via the imine which is then hydrolysed

Borane

 * Used in Et2O or THF solution or as the Me2S complex

Asymmetric (CBS) reduction

 * Corey-Bakshi-Shibata reduction (see APD Level 3 Asymmetric synthesis)
 * Uses the CBS catalyst
 * Hydride attack from the Si face
 * E.e. around 97%
 * Chair transition state, large group occupying an equatorial position determines the stereoselectivity
 * E. J. Corey, R. K. Bakshi, S. Shibata, J. Am. Chem. Soc. (1987) 109, 5551–5553

L-selectride

 * Stereoselective reduction of cyclohexanones with the bulky reagent L-selectride, Li[HB(sBu)3]
 * Small nucleophiles like LiAlH4 prefer axial attack (OH group ends up equatorial rather than axial – the thermodynamic product)
 * Bulky nucleophiles likes Li[HB(sBu)3] prefer equatorial attack to avoid steric clash with 1,3-hydrogens (OH group ends up axial – the kinetic product)

=Rearrangements=

Pericyclic rearrangements

 * Claisen rearrangement: forms aldehydes
 * Johnson-Claisen rearrangement:forms esters
 * Ireland-Claisen rearrangement: forms acids
 * Eschenmoser-Claisen rearrangement: forms amides

=To be added=
 * Evans–Saksena reduction
 * Yamaguchi esterification
 * Still-Gennari reaction
 * Pinnick oxidation
 * Dess-Martin periodinane