Oxidation of aldehyde to acid or ester

1. Jones reagent
acidic condition, strong oxidant.

2. I2/MeOH/KOH
forms methylester. mild condition, alkene is untouched.
can't make t-buylester by this way.
tert-aldehyde is more reactive than sec-aldehyde.

3. KMnO4/PH buffer/t-BuOH/water
mild condition, benzyl ether untouched.

4. NaClO2, t-BuOH, PH buffer
mild condition, works for very hindered aldehydes.
t-amlyne used to prevent alkenes from oxidation.

Intermolecular Enolate Heterocoupling

ASAP J. Am. Chem. Soc., ASAP Article, 10.1021/ja804159y
Web Release Date: August 5, 2008
Michael P. DeMartino, Ke Chen, and Phil S. Baran

The direct, convergent synthesis of unsymmetrical 2,3-disubstituted-1,4-dicarbonyl compounds from two carbonyl subunits has proven extremely difficult, several methods for the synthesis of hypothetical succinate 1 are depicted in Figure 2.9,
Efficient, enantioselective syntheses of such entities have escaped synthetic grasp, in spite of their presence in countless natural products and innumerable medicinal remedies. All of the methods depicted suffer from one or more of the following limitations: multistep sequences, installation of requisite disposable functionality on one or both of the monomers, and stereoselectivity problems with prefunctionalization methods and/or during the union of the two monomers. No stereoselectivity was observed or necessary for the most efficient of these methods, the Stetter reaction, as the product was subjected to a pyrrole synthesis. This report is a full account of a research program initiated originally to eliminate the first two of these issues and having since evolved to address the third. By taking advantage of an underutilized and underappreciated reactivity of carbonyl enolates, the oxidative heterocoupling of two enolates joins two different sp3-hybridized carbon centers in a single step without requiring prefunctionalization of the corresponding monomers.

indicator of basicity

Triphenylmethane

The pKa of the hydrogen on the central carbon is around 31. The trityl anion absorbs strongly in the visible region, making it red. This colour can be used as an indicator when maintaining anhydrous conditions with calcium hydride; the hydride reagent reacts with water to form solid calcium hydroxide, while it is also a strong enough base to generate the trityl anion. If the hydride is used up then the solution will turn colourless. The sodium salt can be prepared also from the chloride.

Before the popularization of butyllithium and related strong bases, trityl sodium was often used as a strong, non-nucleophilic base.in the lab, in small scale reaction, triphenylmethane can be used to indicate excess n-Buli or LDA.

titration of n-BuLi

Titration of BuLi (http://www.pushingarrows.com/Lab/page12/page12.html)

- Equipments and reagents needed:
dry isobutyl alcoholanhydrous ether1,10-phenanthroline (indicator)2- or 3-necks 25 ml round bottom flask (with magnetic stirrer bar)dry syringes – 5.0 ml, 2.0 ml, 1.0mlice bath(hexane to wash out needle and syringe contaminated with BuLi)- Procedures:
To a dry* 2- or 3-necks 25 ml round bottom flask with magnetic stirrer bar was added 5.0 ml of anhydrous ether under an inert atmosphere.
A crystal of indicator 1,10-phenanthroline was added and after it dissolved completely, the mixture was cooled to 0°C for about 10 minutes.
The maximum amount of dry isobutyl alcohol that is needed to quench the BuLi could be calculated as follows:

For example, if the previous titration was determined to be 3.1M then 2.0ml of this BuLi solution should contain

3.1M x 2.0ml / 1000ml = 6.2x10-3 mol of BuLi.

Since it takes 1 equivalent of isobutyl alcohol (MW 74.12; density 0.803 g/ml) to quench the BuLi, therefore

6.2x10-3 mol x 72.14g/mol / 0.803 g/ml = 0.57 ml of isobutyl alcohol was potentially needed.

2.0ml of BuLi solution was then added under an inert atmosphere and it was titrated by slow addition of approx. 1.0ml of dry isobutyl alcohol.

The colour change should be very apparent.

n-BuLi : orange-brown to bright yellow
t-BuLi : purple to bright yellow
Using the amount of isobutyl alcohol added (initial volume – final volume), the molarity of the BuLi solution can be calculated as follows:

For example, if 0.41 ml of isobutyl alcohol was used,

0.41 ml x 0.803 g/ml / 74.12 g/mol = 4.44x10-3 mol of isobutyl alcohol was used = 4.44x10-3 mol of BuLi present

The strength of the BuLi solution is therefore

4.44x10-3 mol / (2.0 ml / 1000ml) = 2.22M
(2.22M vs 3.1M makes a big difference!)
* oven dried then cooled under a stream of inert gas, or flame dried under reduced pressure then cooled under a stream of inert gas.

Reductive Decyanation

1. naphthalene/Li
liminted to nitriles which have a adjacent electron-withdrawing group.

2. LiDBB/THF
more reactive than LN.
1. addition of nitrile into LiDBB THF solution at -78C. reverse addition gave side products.
2. when making lidbb, n-BuLi was used to remove trace of water, otherwise, the concentration of lidbb is low.

who is doing this ?
Professor Scott D. Rychnovsky

Ketone to ketal

Ketal is sensitive to acid but very stable to base or radical.

forming
1. 1,2 diol or 1,3 diol, DCM(or meoh), p-TsOH hydrate(or ppts), trimethyl(or triethyl) orthoformate, rt.

Note:
1. 2,2-dimethyl -1,3-diol is more reactive than ethylene glycol, because ketal so formed is more stable. On my congested aldehyde, ethylene glycol failed , but 2,2-dimethyl1,3-diol succeed.
2. you can premix p-TsOH, trimethylorthoformate and 2,2-dimethyl-1,3-diol to form a stable compound. Then isolate this compound and add your aldehyde or ketone. In this procedure, "only a small amount of acid is needed to complete the reaction". cited from a JOC paper. 1993, 5479.

2. diol, toluene or benzene, p-TsOH, Dean-Stark to remove water.
high temp.

removal
acid. equilibrium reaction.