Dehydration aldols

The reaction conditions needed for aldol dehydration are often only a bit more vigorous (slightly higher temperature, for instance) than the conditions needed for the aldol formation itself. As a result, conjugated enones are usually obtained directly from aldol reactions without isolating the intermediate jS-hydroxy carbonyl compounds. 

The real value of aldol dehydration is that removal of water from the reaction mixture can be used to drive the aldol equilibrium tow ard product. Even though the initial aldol step itself may be unfavorable, as it usually is for ketones, the subsequent dehydration step nevertheless allows many aldol condensations to be... 

The final two stages are very straightforward. Oxidative scission of the C3-C5 double bond in 6 with ozone provides triketone 5 which, without purification, is subjected to a base-induced intramolecular aldol/dehydration reaction. The crystalline product obtained from this two-step sequence (45 % overall yield) was actually an 85 15 mixture of ( )-progesterone and a diastereomeric substance, epimeric at C-17. Two recrystallizations afforded racemic progesterone [( )-(1)] in diastereomerically pure form. 

The irreversible elimination drives the reversible aldol reaction and gives a favourable conjugated ketone in a favourable six-membered ring. On paper, one could also draw an acceptable mechanism in which the order of events was reversed. This is not so neat, and would require generating an enolate anion y to the a,P-unsaturated ketone formed by the first aldol-dehydration sequence. 

Base-catalyzed aldol dehydration Preliminary examination ... 

The silyl enol ether is not isolated but reacted immediately with the aldehyde to give an excellent yield of the aldol. Dehydration in acid solution with toluene sulfonic acid (TsOH) gives the enone. You can see by the high yield in the aldol reaction that there is no significant self-condensation of either partner in the aldol reaction. 

H2 and CO co-reactants and H20 co-product not shown). Since aldol dehydration and hydrogenation is fast, the portion from aldehyde to heavy alcohol can be treated without much detriment as a single, simple portion, at least if heavy-alcohol formation is a minor side reaction. The two pathways from olefin to aldehyde and paraffin cannot be separated because they must be expected to go through a common intermediate. 

Many aldols dehydrate spontaneously at room temperature or upon acidification by acetic acid. Thus, the condensation of benzaldehyde with propionaldehyde or butyraldehyde gives the a-alkylcinnamaldehydes directly (58-67%). ... 

Two new toxic sesquiterpenoids, myodesmone (36) and isomyodesmone (37), have been isolated from the essential oils of certain Myoporum species. It has been suggested that these two compounds may be derived from myoporone (38), also found in some specimens of Myoporum deserti, by an in vivo aldolization-dehydration process via the ketol (39). In addition to ipomeamarone (40 R = H), it is reportedthat a new sesquiterpenoid, ipomeamaronol (40 R = OH) also occurs in diseased sweet potato root tissue. 

One of the most important reactions for the construction of six-member rings (the Diels-Alder reaction is another) is based on a tandem reaction sequence a Michael addition reaction followed by an intramolecular aldol-dehydration reaction. This sequence is called the Robinson annulation (Sir Robert Robinson, Nobel Prize, 1947). " ... 

Semiplenamides A 359 to G 365, a series of new anandamide-like fatty acid amides, were isolated from a 1997 Papua New Guinea collection of the marine cyanobacterium Lyngbya semiplena, and all these new metabolites displayed toxicity in the brine shrimp model system. Only semiplenamides A 359, B 360, and G 365 showed weak affinity for the rat cannabinoid CBl receptor. Semiplenamide A 364 was also a moderate inhibitor (IC50 = 18.1 pM) of the anandamide membrane transporter (AMT). Novel 5y -aldol/dehydration methodology was developed for the stereoselective synthesis of the core ( )-a, P-unsaturated amide functionality of this class of natural product, and employed for the efficient synthesis of semiplenamide... 

The Robinson annulation consists of a Michael addition followed by aldol cyclization with dehydration. In the retrosynthetic direction, disconnect the alkene formed in the aldol/dehydration, then disconnect the Michael addition to discover the reactants. 

To achieve type c aldolization, the monoprotected heptaketone (148) was prepared as shown in Scheme 6. ° Condensation of the dianion of 2,4-pentanedione with the ethylene ketal of diethyl 3-oxo-glutarate presumably affords (148). However, the substance eludes isolation or even spectral identification. Instead, naphthalene derivative (149) is obtained in 39% yield. Further aldolization, dehydration, and removal of the ethylene glycol moiety provides the naturally occurring anthrone (150). 

The products of aldol/dehydration reactions of active methylene compounds with unsaturated aldehydes undergo in situ hetero-IMDA reaction. Reaction of 2-phenyl-5-methyl-2.4-di-hydro-3//-pyrazol-3-one with 2-(3-methyl-2-butenyloxy)benzaldehyde in acetonitrile containing catalytic 1,2-ethanediammonium diacetate gave the products of a highly stereoselective IMDA reaction82. 

Pyridinium tosylate. IS, 276 16, 287-281 Dehydration of aldols. Dehydration < (PPTS) and MsCI-EtjN give very different tive and stereoselective, affording mainU tl... 

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