Michael Mellor

Direct Alkylation of Dianions of Cyclic β-Diketones. A General Synthesis of 4-Substituted Cyclopentane-1,3-diones

Abstract Intramolecular photochemical [2+2] cyclo-additions between enolised cyclopentane-1,3-diones and alkenes, provide a novel entry to tricyclic ring systems (viz 1) suitably functionalised for Grob fragmentation to the bicyclo [3,2,1] octane ring system (2) found in several important natural terpenoids.1

Synthetic photochemistry. Elaboration of the tricyclo[6.3.0.0]-undecane (‘hirsutane’) carbon skeleton by intramolecular photocyclisations of dicyclopent-1-enylmethanes

Irradiation of the dicylopent-1-enylmethane (5) in methanol is shown to lead to intramolecular [2 + 2] cycloaddition, followed by in situ addition of methanol to the presumed intermediate bicyclo[2.1.0]pentane (11), producing the cis,syn,cis-tricyclo[6.3.0.0]undecane (12) in >90% yield. The general method is applied in a synthesis of the hirsutane carbon skeleton [viz. (19)→(20)] found in hirsutic acid (7) and related natural sesquiterpenes.Attempts to expand the scope of the photoprocess to other fused polycyclic systems met with mixed success. Thus, although irradiation of the cyclopentenone (24) in methanol led to the bicyclo[3.3.0]octenone (25), the cyclopentenone (29) instead produced the isomeric alkene (30) resulting from a 1,3-H shift, and irradiation of (31) led only to decomposition.

Divergent photoreactivity in intramolecular cycloadditions amongst prop-2-enylcyclopentenones

Abstract Irradiation of the 1,4-diene(8) gave the corresponding geometrical isomer(10) whereas (5) produced the vinylcyclopropane(6), and (11a) and (11b) (in MeOH) led to the tricyclic adduct(14) and the isomeric cyclopentenone (15) respectively.

New synthetic approaches to fused-ring carbocycles based on intramolecular photocycloadditions of 1,3-dione enol esters

Irradiation of 3-acetoxy-2-pent-4-enylcyclohex-2-enone (12) leads to the tricyclic adduct (18), in high yield (>95%), which on hydrolytic cleavage in ethanolic potassium hydroxide gives rise to bicyclo[6.3.0]-undecane-2,6-dione (20).In contrast, irradiation of the isomeric enol acetate, 3-acetoxy-4-pent-4-enylcyclohex-2-enone (17) led to the two photoadducts (25) and (26) resulting from intramolecular photocycloaddition, and to the trione (24) produced via photo-Fries rearrangement of (17); the formation of (25) and (26) followed from the structures (29) and (27) produced after saponification-retroaldolisation of mixtures containing (25) and (26). Irradiation of the 6-pentenyl substituted enol ester (16) gave rise to only the photo-Fries rearrangement product (24).Irradiation of 1-acetoxy-2-pent-4-enoylcyclopentene(39) led (93%) to a 2:3 mixture of the photoadducts (41) and (42) whose structures followed from X-ray measurements. The corresponding cyclohexene (45), instead produced the product (46) of photo-Fries rearrangement on irradiation. Hydrolytic cleavage of (41) in KOH–EtOH leads to the bicyclo[5.3.0]decanone (47), whereas similar treatment of (42) instead gave directly the aldol (49) by way of the transient retro-aldol intermediate (48).

A new approach to fused carbocycles. Intramolecular photocyclisations of 1,3-dione enol acetates

Irradiation of the enol acetate (1) gave the tricyclic adduct (2) regioselectively and in quantitative yield, whereas (12) led (93%) to a mixture (3:2) of adducts (13) and (14), and the enol acetates (9) and (10) produced mainly the photo-Fries rearrangement products (8) and (11), respectively; hydrolytic cleavage of the tricyclic adducts (2) and (14) gave rise to the bicyclo[6.3.0]undecane (3) and bicyclo[5.3.0]decane (15) ring systems.

Some epoxy-olefin cyclisations

It is shown that certain alk-2-enyl-2,3-epoxy-3-methylcyclohexanones can be cyclised in good yield with some Lewis acids to decalone derivatives, but use of weak Lewis acids and/or nonpolar solvents leads to ring contraction.

A new synthetic approach to the bicyclo[3.2.1]octane ring system, based on intramolecular photocycloaddition involving cyclopentane-1,3-dione enol esters

Irradiation of 1:1 mixtures of enol acetates derived from 4-prop-2-enylcyclopentane-1,3-diones [i.e.(9), (23), (27), (32a), (32b)], leads to 6-acetoxytricyclo[3.2.1.03,6]octan-2-ones [i.e.(12), (24), (28), (33a), (33b)] in high yield (>70%). The adducts result from regioselective intramolecular [2 + 2] cycloaddition in the 5-prop-2-enyl enol acetate isomers [e.g.(10)], suggesting that equilibration between the isomeric enol acetates [e.g.(10) and (11)] is rapid during the irradiations. Fragmentation of the 6-acetoxytricyclo[3.2.1.03,6]octan-2-ones, either directly [e.g.(12)→(16); KOH–EtOH] or via the corresponding acetoxy-mesylates [e.g.(24)→(25)→(26)] provides a facile route to a range of substituted bicyclo[3.2.1]octane ring systems.Irradiation of the isomerically pure enol acetates (39), containing a methyl substituent at C-2, by contrast produce largely (ratio 3:2) 3-acetoxytricyclo[3.2.1.03,6]octan-7-one adducts (43) resulting from the alternative mode of intramolecular cycloaddition in the enol acetate (see Scheme 1); these adducts are also elaborated to bicyclo[3.2.1]octenones [e.g.(45)].

3-Methylcyclohex-2-enone derivatives as initiators of cyclisation. Part 2. Monocyclisations to six-membered rings

Cyclisation of 3-methylcyclohex-2-enones and the derived epoxides containing alkene, alkyne, and aryl side-chains yields bicyclo[4.4.0]decane derivatives when the alkene or alkyne is electronically biased towards six-membered ring formation and when the alkene is electronically unbiased.

3-Methylcyclohex-2-enone derivatives as initiators of cyclisation. Part 1. Introduction and synthesis of 2-substituted 3-methylcyclohex-2-enones

A series of C-2 substituted 3-methylcyclohex-2-enones has been prepared using the Hagemann ester route. A new synthesis of these compounds has been developed which involves the alkylation of the N,N-diethylaminoethyl ether of 1-hydroxy-5-methylcyclohexa-1,5-diene. The cyclohexenones have been converted into the corresponding α,β-epoxyketones using alkaline hydrogen peroxide.

Some epoxy-acetylene cyclisations

Two epoxy-acetylenes have been cyclised, one containing a terminal acetylene to a decalin derivative, the other to an hydrindane derivative.