De Mayo reaction

A remarkable combination of a photochemical [2+2] cycloaddition with a retro-aldol reaction and cyclization is the so-called de Mayo reaction. Biichi and coworkers have used this method for the total synthesis of loganin (5-35). Thus, reac-... 

Irradiation of a 12 % solution of acetylacetone in cyclohexene afforded the diketone (2), which should go through the intermediate (7) following a retro-aldol reaction 5 6). This reaction is best known as the de Mayo reaction 7>, which enables the... 

The reaction itself is rather attractive and useful as a synthetic tool, because of its practical simplicity. Indeed, 1,5-dicarbonyl compounds can be readily prepared from olefin and 1,3-dicarbonyl compound in a one-pot reaction. Subsequent aldolization of the resulting 1,5-dicarbonyl compounds would furnish cyclohexenones. The reaction mechanism and stereochemistry of the de Mayo reaction has been comprehensively reviewed7), and the basic strategy of which has also been developed and extended. The following examples would demonstrate some applications and variations of the de Mayo reaction. 

Irradiation of the enol acetate (38) gave pure tricyclic acetoxyketone (39) in quantitative yield 17 -18). On alkaline hydrolysis, compound (39) was converted to the intramolecular de Mayo reaction product (40) in 78% yield 17,18). Epi-precapnella-diene (41) was obtained by further reactions of compound (40)19>. 

An ingenious new method for the preparation of Woodward s intermediate (97) by Pearlman70 constitutes another formal synthesis of reserpine. The essence of this new approach is an adaptation of the de Mayo reaction which allows the introduction of vicinal aldehyde and acetic ester functions on to a double-bond (Scheme 13). An internal [2tt + 27r] photocyclization of the diene (98) gave the tetracyclic cyclobutane derivative (99), which was converted into the ester (100) by standard procedures. Methanolysis of the acetate function with concomitant retro-aldol fission completed the introduction of the vicinal aldehyde and acetic ester functions obvious manipulation then gave the desired intermediate (97). 

From a preparative point of view the heteroatom in P-position has an influence because important latent cyclobutane cleavage pathways exist in the product. The prototypical reaction of this type is the [2 + 2]-photocycloaddition/retro-aldol reaction sequence (de Mayo reaction) [55-57], the course of which is illustrated for substrate A3 (Q = O, PG = protecting group) in the reaction with ethylene as a generic olefin. 

A very useful extension of the de Mayo reaction has been recently introduced by Blechert et al. (Scheme 6.26) [78]. The retro-aldol fragmentation was combined with an intramolecular enantioselective allylation (asymmetric ring-expanding allylation) catalyzed by a chiral Pd complex. Bicycloheptane 68, for example, was accessible by intermolecular [2 + 2]-photocycloaddition of cyclopentenone 67 with allene. Further transformation in the presence of Pd2(dba)3 (dba = dibenzylideneacetone) and the chiral oxazoline ligand 69 (tBu-phox) resulted in the enantioselective formation of cycloheptadione 70. 

Sato, M., Sunami, S., Kogawa, T., and Kaneko, C. (1994) An Efficient synthesis of cis-hydroindan-5-ones by novel modified de mayo reactions using... 

A modified de-Mayo reaction (shown in Scheme 21) also served as a tool in the first synthesis of a saturated taxane framework with a geminal dimethyl group (79,80). Photocycloaddition of cyclohexene (functioning as a ring C model) to a bicyclic 1,3-diketone derivative from 85 is the key step. In the course of the cyclobutane annealing, the C-8 a ring connection is established contrary to C-3,... 

The importance of the ethylene ketal described above with respect to stereocontrol of the de-Mayo reaction is emphasized by later published works of two other teams. Fetizon and co-workers obviously followed a similar concept and carried out photocycloaddition reactions with 96a in model studies (Scheme 23) (Si). As can be seen from retroaldol product 98, exclusive a attack of the cyclohexene has taken place. Thus, the relative stereochemistry of the BC ring connection is opposite to that of taxane. Totally comparable results were obtained by Berkowitz et al. in the course of cycloaddition reactions of cyclopentene, cyclohexene, or those of a cyclohexenone ketal to the camphor derivative 96b (.84). 

The 2 + 2 addition to olefins, or e.g., the double bond of the keto-enol form of BM-DBM can also occur, leading to intermediate cyclobutanols which then undergo ring opening (De Mayo reaction) to form structures such as those shown in Figure 9. (Bringhen A. Personal communication 1993). 

The photocycloaddition of alkenes to the enol acetate (30) affords the adducts (31) in an example of the well-established de Mayo reaction. ... 

De Mayo reaction, [2+2]-cycloaddition of olefins and a,f-unsaturated carbonyl compounds... 

The formation of cyclobutanes starting from a,P-unsaturated carbonyl compounds and olefins is referred to as the de Mayo reaction. The carbonyl component is excited upon irradiation by ti <—ti transition. The regioselectivity is determined by orbital coefficients and polarity effects that depend on the solvent, but the stereochemical information of the olefin is not preserved in intermolecular processes, indicating the non-concerted character of a triplet reaction. In this case 1,4-biradical intermediates are formed and the most stable one determines the stereochemistry of the main product. The cycloadducts of pentanones are most often cis-fused while hexanones preferentially give transcycloadducts. ... 

The product is formed via a [2+2]-cycloaddition de Mayo reaction) between cyclopentenone (2) and cyclobutene. The reaction is carried out under photochemical conditions, because the thermal process is symmetrically forbidden. A cw-cyclobutane is formed as is expected for de Mayo reactions with cyclopentanone (see Key Chemistry). 

This reaction is a diastereoselective de Mayo reaction. Its stereochemistry is controlled by the configuration of substrate 7. The P-face of cyclopentanone 7 is effectively shielded by the dimethylphenylsilyl moiety. Therefore, the triplet state of 7 attacks the cyclobutene 6 via the a-face, forming the fourth annulated cyclobutane ring of the ladderane core. Typically for cyclopentanone systems, the annulation proceeds syn-selectively and the product is obtained as a 7 1 mixture of diastereomers 8 and 20, which is separated by preparative TLC yielding pure 8. 

This highly selective variant of the de Mayo reaction is a novel approach for the solution of the long-standing problem of performing enantioselective photoreactions. ... 

The unusual pentacyclic system of (+)-pentacycloanammoxic acid (1) was created in 21 steps with an overall yield of 2%. The stereochemistry of the target was established relatively late in this convergent synthesis by a novel diastereoselective de Mayo reaction using the chiral cyclopentanone 7. Determination of the absolute configuration of (+)-l was accomplished in the course of the total synthesis by X-ray diffraction of the a,P-unsaturated ketone 25. Although many photochemical transformations occur in this total synthesis, the authors are in doubt about the involvement of photochemical processes in the biosynthesis of 1, as the natural environment of C. B. anammoxidans is dark and anaerobic. 

Sato, M., Takayama, K., Sekiguchi, K., Abe, Y., Furuya, T., inukai, N., Kaneko, C. Synthesis of opticaiiy active cyclopenta[c]pyran-4-carboxyiic acid derivatives, buiiding biocks for iridoids. An attractive aiternative to the asymmetric de Mayo reaction. Chem. Lett. 1989, 1925-1928. 

De Mayo reaction. Synthesis of 1,5-diketones by photoaddition of enol derivatives of 1,3-diketones to olefins, followed by a retro-aldol reaction. 

The de Mayo reaction with cyclohexa-l,3-diones is a method which still attracts interest as a synthetic approach to natural products. Typical of this is the short route to hirsutene (88). This involves photoaddition of the cyclohexanedione (89) to... 

The utility of ) -enaminones (vinylogous amides) and -enamidones (vinylogous imides) has been successfully demonstrated in both inter- and intramolecular [2 + 2] photocycloaddition reactions. The vinylogous amide, which reacts as a -heteroatom substituted enone, serves as the nitrogen analogue of the enol form of a j -diketone in the de Mayo reaction ". ... 

The photocycloadditions of alkenes with the enol form of 1,3-diketones (the de Mayo reaction-, e.g. Scheme 6.68) or electron transfer-mediated reaction (see below) can also be utilized for synthesis of large rings. 

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