Whilst searching for reaction mechanisms for Nitroaldol reactions, I stumbled upon this and thought other newbees could also benefit. The rest of the link is filled with information that is way over my head but could maybe provide handy info for more knowledgable bees.
http://dspace.library.drexel.edu/retrieve/1448/ch2.pdf
Aliphatic nitro compounds, in particular the lower homologues, play a central role in carbon-carbon bond forming reactions. Deprotonation of nitroalkanes yields nitro-stabilized carbanions (nitronates) that react with such C-electrophiles as aldehydes and ketones, to yield a new carbon-carbon bond with concomitant introduction of vicinally situated nitro and hydroxyl groups (Equation 2.14).
Since its discovery in 1895 by Henry, this reaction, now known as the Henry or nitroaldol reaction, has evolved into a significant reaction in organic synthesis. Several excellent reviews are available on the application of the nitroaldol reaction and are given in the references. Emphasis here will be on those aspects of the nitroaldol reaction that are relevant to the current investigation. Some general aspects of the nitroaldol reaction will be given to familiarize the reader with the reaction, its advantages as well as its shortcomings.
Treatment of primary and secondary nitroalkanes and carbonyl compounds (in particular aldehydes) with a base typically yields a diastereomeric mixture of 2-nitroalcohols. It is evident that this reaction is indeed an aldol type process, in which deprotonation of the nitroalkane, to yield the nitronate monoanion, is the first step. The powerful electron withdrawing capability of the nitro group imparts increased acidity to the protons at the ?-carbon, facilitating their removal by a base. Simple nitroalkanes have pKa values of 9-1042 while their aci-nitro tautomers (Scheme 2.1) have pKa values of 2-6.43
A consequence of these pKa values is relatively easy deprotonation to form the nitronate salts. Upon examination of Scheme 2.2, it can be seen that the intermediate nitronate anion is a resonance-stabilized ambident anion. These anions can undergo both C- alkylation and O-alkylation. For success in the nitroaldol reaction, C-alkylation is the required route. Consequently, base plays a pivotal role in the nitroaldol reaction, in that the nitronate is an essential intermediate.
Because the anion is planar, stereoselectivity in nitroaldol reactions is often low. The lack of stereoselectivity can also be attributed to the reversibility of the reaction and the ease of epimerization at the nitro-substituted carbon of the product 2-nitroalcohol. Another significant problem, leading to a lack of stereoselectivity, is the difficulty in achieving a stereoselective protonation on the nitronate bearing C-atom of the initial product. This last point will be discussed in more detail later. Aldehydes are preferentially used as the carbonyl component in the nitroaldol reaction. With aliphatic aldehydes, the corresponding 2-nitroalcohols are readily obtained, while with aryl aldehydes, the corresponding arylnitroalkenes are typically the major products.
From the following discussion it will be seen that a key to achieving synthetically useful nitroaldol reactions is proper choice of reaction conditions, in order to protect the initially formed 2-nitroalcohols from dehydration. One extensively studied aspect of the nitroaldol reaction is the choice of base. Table 2.3 provides examples of nitroaldol reactions employing various bases. The most commonly employed inorganic bases include alkali metal hydroxides, carbonates, bicarbonates, and alkoxides.
Common organic nitrogen bases (e.g., triethylamine, piperidine, and Huning’s base) are typically employed to deprotonate lower nitroalkanes. For higher nitroalkanes, nonionic organic nitrogen bases such as tetramethylguanidine (TMG), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (Table 2.3, Entries 1,2, and 6), and 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), in THF or acetonitrile have been employed. In general, the choice of reaction conditions is not crucial for reactions involving simple nitroalkanes and carbonyl compounds, but as the substrates become more complex, and in particular as they become more sterically hindered, carbonyl self-condensation becomes a serious side reaction.
One operational problem with the nitroaldol reaction is related to the work-up. Care must be taken during acidification at the end of the reaction to remove remaining base. Rapid acidification with strong acid can lead to the Nef reaction (Equation 2.15) resulting in the conversion of the nitronate to the aci-nitro compound and hence to an aldehyde or ketone. This problem can be avoided by the use of heterogeneous catalysts such as Al2O3 or Al2O3 supported KF (See Table 2.3, Entry 9). At room temperature Al2O3 yields the 2-nitroalcohol in high yield. Simply warming the reaction to 40°C facilitates dehydration. Another related modification involves the use of resin-bound bases such as Amberlyst?A-21, Amberlite?IRA-420, or DOWEX?1.
This document has been slightly altered because I could not copy the equations and tables. Refer to the link for a full version.
