Tertiary from ketones

Besides the initiation with the vinyl ether adducts, trimethylsilyl halides in conjunction with oxolane [135] or a carbonyl compound [136-141] also provide an interesting method of end-functionalization. As discussed in Chapter 4, Section V.E.2 (also Figure 9 therein), the a-end group is (CH3)3SiO—, derived from the silyl compound, to be converted into the hydroxyl group [140,141], Depending on the structure of the carbonyl compounds, it is either secondary (from aldehyde) [136-139] or tertiary (from ketone) [137,138,140,141], both of which are difficult to obtain from the vinyl ether adducts (note that the adduct of AcOVE leads to a primary alcohol [30,31]). 

SECONDARY AND TERTIARY ALKYL KETONES FROM CARBOXYLIC ACID CHLORIDES AND LITHIUM PHENYLTHIO(ALKYL)CUPRATE REAGENTS tert-BUTYL PHENYL KETONE... 

Titanium enolates can be prepared from lithium enolates by reaction withatrialkoxy-titanium(IV)chloride,suchasfra-(isopropoxy)titaniumchloride.21 Titanium enolates are usually prepared directly from ketones by reaction with TiCl4 and a tertiary amine.22 Under these conditions, the Z-enolate is formed and the aldol adducts have syn stereochemistry. The addition step proceeds through a cyclic TS assembled around titanium. 

Tin enolates are also used in aldol reactions.27 Both the Sn(II) and Sn(IV) oxidation states are reactive. Tin(II) enolates can be generated from ketones and Sn(II)(03SCF3)2 in the presence of tertiary amines.28 The subsequent aldol addition is syn selective and independent of enolate configuration.29 This preference arises from avoidance of gauche interaction of the aldehyde group and the enolate P-substituent. The syn stereoselectivity indicates that reaction occurs through an open TS. 

E. Tertiary alcohols from ketones, esters, and lactones... 

None of the trifluoromethyl dibenzoheterocyclic salts synthesized above successfully trifluoromethylated enolate anions derived in situ from ketones with a base, with the exception of an enolate anion derived from 2-methyl-1-indanone, which has a tertiary a-carbon. The reactivity of the enolate anions may have been too great for these dibenzoheterocyclic salts. There-... 

Trimethylsilyl enol ethers can be prepared directly from ketones. One procedure involves reaction with trimethylsilyl chloride and a tertiary amine.20 This procedure gives the regioisomers in a ratio favoring the thermodynamically more stable enol ether. Use of... 

Lutz, R. E., J. A. Freek, and R. S. Miirphey Secondary and tertiary amino ketones and alcohols derived from desoxybenzoin and 1,2-di-phenylethanol. Ring-chain tautomerism of the a-(p-hydroxyethyl-amino)-ketones. J. Amer. chem. Soc. 70, 2015 (1948). 

The potential substrates for the Strecker reaction fall into two categories ald-imines (derived from aldehydes, for which cyanide addition results in formation of a tertiary stereocenter) and ketoimines (derived from ketones, for which addition results in a quaternary stereocenter). As in the case of carbonyl cyanation, significant differences are observed between the substrate subclasses. To date, while a few catalyst systems have been found to display broad substrate scope with respect to aldimine substrates, successful Strecker reactions of ketoimines have been reported in only two cases. As is the case for all asymmetric catalytic methodologies, the breadth of the substrate scope constitutes a crucial criterion for the application of the Strecker reaction to a previously unexplored substrate. 

The metal lias to a great extent replaced zinc, which was used in 1849 by Frankland in the preparation of paraffin hydrocarbons and the zinc alkyls, and subsequently by Wagner for preparing secondary alcohol from aldehydes, by Saytzeff in preparing tertiary alcohols from ketones, and by Butlerow iu the preparation of both ketones and tertiary alcohols from acid chlorides. 

In chapter 24 we saw that carbonyl compounds dimerise by a radical reaction when electrons are transferred to them from metals. The typical pinacol 37 formed from acetone 36 is important because it rearranges6 in acid to give a tertiary alkyl ketone 38 known as pinacolone . The key step is a methyl migration as one of the OH groups is lost 39. 

The reaction of aldehydes and ketones with Grignard reagents is a useful method of synthesising primary, secondary, and tertiary alcohols (Following fig.). Primary alcohols can be obtained from formaldehydes, secondary alcohols can be obtained from aldehydes, and tertiary alcohols can be obtained from ketones. The reaction involves the formation of a carbon-carbon bond and so this is an important way of building up complex organic structures from simple starting materials. 

Fig. 5.42. Electrophilic functionalization of phenyllithium. Tertiary alcohols can be synthesized from ketones.

Another interesting reaction type detected from the photoreaction of tertiary amine-ketone system which have found use in alkaloids chemistry [172] involves sequential electron transfer and proton transfer followed by back electron transfer to yield iminium cations (Eq. 35) leading to dealkylation products upon aqueous workup. The regiocontrol in these dealkylations is dictated by preferential deprotonation at the less branched amine cation radical a-carbon. 

The hydroxy acids obtained from aldehydes will contain the group,. —CH(OH) —COOH, and are thus secondary alcohols while those obtained from ketones will contain the group, =C(OH) —COOH, and are tertiary alcohols. These reactions are of especial importance in connection with the poly-hydroxy aldehydes and ketones, which, as we shall find, are the sugars. The cyan hydrines, or hydroxy acid nitriles, which are the intermediate products in these reactions, are not isolated as such, the reaction being completed without interruption. 

P-Enamino esters. Tertiary imines derived from ketones undergo C-acylation with InijCO to give A(-(P-aminoacryloyI)imidazoles which on alcoholysis generates the esters. Thio esters are obtained when thiols are involved in the last step. 

Kobayashi et al. have found that dimethyltrifloxysilyl enolates, prepared in situ from ketones and dimethylsilyl ditriflate in the presence of a tertiary amine, react smoothly with electrophiles such as aldehydes and acetals without catalyst at -78 °C to afford the corresponding aldol adducts in high yields [94]. The use of ethyl ketones as the substrates achieves high levels of syn selectivity (Scheme 10.29). 

Chiral N acylhydrazone derivatives may also be prepared from various ketones by condensation with N aminooxazolidinone 7a (Table 2.2) [22]. Mixtures of E/Z isomers were usually obtained, although ketone N acylhydrazones 14d and 15d, with highly branched tertiary butyl (tBu) substituents, were formed as single isomers. Others have recently used the amination and condensation procedures to prepare very similar chiral N acylhydrazones from ketones with excellent results [23]. 

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