A-Alkylation of ketones

IrCl(cod)]2, in the presence of PPh3 and KOH, catalyzed the a-alkylation of ketones with alcohols [41]. As an example, the reaction of 2-octanone 87 with 1-butanol 88 was catalyzed by the iridium complex to give 6-dodecanone 89 in 80% yield (Equa-hon 10.19). The alkylation proceeded with complete regioselectivity at the less-hindered side of 2-octanone, and the reaction was promoted by a catalytic quantity of KOH (10mol%) in the absence of both a hydrogen acceptor and a solvent. 

A related process, from this conceptual point of view (Eq. 16), the use of the aldehyde generated in situ for further reactions, has allowed the a-alkylation of ketones with primary alcohols [62], Several ketones have been condensed with 1-butanol or benzyl alcohol affording the corresponding a-alkylated ketones in good yields (up to 96%) in the presence of [ lr(/z-Cl)(cod) 2] andKOH. 

Exercise 17-28 a. Alkylation of ketones is much less successful with ethyl and higher primary halides than for methyl halides. Explain why competing reactions may be particularly important for such cases. 

Stereoselective a-alkylation of ketones. This reaction can be effected by reaction of silyl enol ethers with benzyl acetates complexed with Cr(CO), in the presence of ZnCh (I equiv.). This methodology is particularly useful because only the adduct anti to the metal is obtained. Use of an optically active chromium complex such as 1 results in 100% stereoselective alkylation. 

A, A -Dialkylhydrazones are often converted into the carbonyl form by a variety of oxidative methods. The respective compounds (like 100) shown in Scheme 93, derived from proline-based systems (RAMP and SAMP), are widely used as potent chiral auxiliaries and have provided a very versatile method for the diastereoselective a-alkylation of ketones. SAMP and RAMP hydrazones can be cleaved with O3, by reductive techniques and by hydrolysis with strong acids. 

Enamines are employed in the majority of cases as a means of activating the a-carbon as a nucleophile for reaction with an electrophilic carbon partner (Scheme 13). In the historical picture of the development of methods for a-alkylation of ketones and aldehydes, they represented a significant advance over... 

Whitesell, J. K., Whitesell, M. A. Alkylation of ketones and aldehydes via their nitrogen derivatives. Synthesis 1983, 517-536. 

Alkylation of carbonyl compounds and derivatives. The 02/Co(OAc)2-Mn(OAc)2 system is useful to accomplish a-alkylation of ketones with 1-alkenes. Acetals also add to acrylic esters under O2 in the presence of catalytic amounts of Co(OAc)2 and A-hydroxyphthalimide to afford a-hydroxy-y-oxo ester acetals. The adducts of methyl vinyl ketone suffer oxidative degradation in situ. 

Potassium tert-butoxide Syntheses with boranes a-Alkylation of ketones via a-balogenation and reaction with boranes... 

The Mannich reaction is very closely related to the Knoevenagel condensation reaction in that it involves iminium intermediates. The reaction, which is carried out in mildly acidic solution, effects a-alkylation of ketones and aldehydes with dial-kylaminomethyl groups. The electrophilic species is the iminium ion derived from... 

English-Zimmerman fragmentation, vinylogons 31,147 Enimines s. Ketenimines Enisocyclics s. a. Enecyclo... Enolate anions, a-alkylation of ketones via - 31, 890 Enolates s. a. Ammonium enolates, Metal -kinetic, trapping with formaldehyde 29,894s31 Enol carbonates... 

In 2011, inspired by Cozzi and Cheng, Tian and co-workers [130] developed asymmetric Sjvl a-alkylation of ketones and aldehydes with V-benzylic sulfonamides... 

SCHEME 8.28. Enantioselective a-alkylation of ketones reported by Tian and co-workers... 

SCHEME 8.42. Brpnsted acid-catalyzed direct a-alkylation of ketones. 

An umpolung reaction at the a-carbon of carbonyl compounds has been reported, in which nucleophilic o -arylation and a-alkylation of ketones is effected by polarity inversion of V-alkoxyenamines, without isolation of enamines or imines being necessary. The mild conditions for a-arylation do not require transition-metal species. ... 

G-Formylation with l,3>dioxolane ring opening a-Alkylation of ketones... 

Some of the most commonly reported C-alkylation methods involving the transition-metal-catalyzed transfer hydrogenation of alcohols can be described as follows (1) the a-alkylation of ketones and carbonyl compounds (2) alcohol-alcohol coupling reactions to afford ketones and (3) P-alkylation by alcohol dimerization, which is also referred to as a Guerbet reaction. 

The first of these reactions, the a-alkylation of ketones and carbonyl compounds, involves the following process (as shown in Schemes 1, 2) [46-57] (1) the initial oxidation of the alcohol substrate, through a hydrogen transfer process to give the corresponding aldehyde and metal-hydride intermediate (2) the aldol condensation of the enol (generated by the tautomerization of the ketone substrate) with the... 

Scheme 2 Representative reaction pathway for the a-alkylation of ketones...

In a recent example of this type of reaction, Seayad and co-workers reported the use of an effective silica-supported palladium catalyst, which showed high catalytic activity towards the a-alkylation of ketones. In a representative example of this transformation, acetophenone (2.0 mmol) was reacted with benzyl alcohol (6.0 mmol) in the presence of the silica-supported heterogenized palladiiun catalyst (as shown in Scheme 40) combined with LiOH (20 mol%) at 140 °C to give the corresponding a-alkylated product, 1,3-diphenylpropan-l-one, in 83 % yield. Using this heterogenized Pd catalyst system, it is possible to recycle the catalyst by a... 

In addition, transition-metal-free dehydrogenative a-alkylation of ketones with primary alcohols involving the Meerwein-Ponndorf-Verley-Oppenauer redox cycle has recently been developed by using LiOrBu or NaOH as base [237, 238]. 

Yamada YM, Uozumi Y (2006) A solid-phase self-organized catalyst of nanopalladium with main-chain viologen polymers a-alkylation of ketones with primary alcohols. Org Lett 8(7) 1375-1378 Yamada YM, Uozumi Y (2007) Development of a convoluted polymeric nanopalladium catalyst oi-alkylation of ketones and ring-opening alkylation of cyclic 1, 3-diketones with primary alcohols. Tetrahedron 63(35) 8492-8498... 

Xu Q, Chen J, Tian H et al (2014) Catalyst-free dehydrative a-alkylation of ketones with alcohols green and selective autocatalyzed synthesis of alcohols and ketones. Angew Chem Int Ed 53(l) 225-229... 

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