Daryl S. Walter

Sequential radical macrocyclisation-transannulation approach to ring-fused bicycles

Abstract The scope for tandem radical mediated macrocyclisation-transannulation processes (Scheme 1) in the elaboration of polycycles is illustrated with the facile syntheses of linear 5,6-, 6,6- and 5,7-ring fused carbobicycles, viz 7, 8, 11, 13 from appropriate iododienone precursors, viz 1, 2, 12 on treatment with Bu 3 SnH-AIBN.

A cascade macrocyclisation-transannulation approach to polycycle constructions

Abstract Treatment of the iodotrienone 1 with Bu3SnH-AIBN results in the formation of the angular 5,7,5-ring fused tricycle 6, by way of a novel sequential 13-endo-trig macrocyclisation followed by two successive 5-exo-trig transannulation processes.

A Lewis Acid Promoted Oxidative Cyclization

Replacing trifluoroacetic acid with a catalytic amount of Lewis acid in the osmium mediated oxidative cyclization results in higher yielding reactions that can proceed nearly an order of magnitude faster. The osmium loading can also be reduced to as little as 0.2 mol %. Furthermore, these mildly acidic conditions are capable of tolerating a wide range of acid sensitive protecting groups that are incompatible with previous cyclization conditions.

Cascade radical mediated macrocyclisation-transannulation reactions leading to ring-fused bicycles

The scope for tandem radical mediated macrocyclisation–transannulation processes in the elaboration of ring-fused carbocycles has been examined. Thus, a range of E-iodo dienones viz. 21, 30b, 40, 42 and 44 were first prepared using synthetic sequences based on sound literature precedent. Treatment of the iodo dienone 21 with Bu3SnH–AIBN led to a 3 : 2 mixture of trans-and cis-isomers of 1-decalone, 35 and 36, respectively, in a combined yield of 72%, whereas the positional isomer 30b of 21 underwent 10-endo macrocyclisation and transannulation to a 1 : 1 mixture of trans-1-decalone 35 and cis-octahydroazulen-1-one 39 (combined yield 68%), resulting from competitive 6-exo/5-exo transannular cyclisation from the intermediate cyclodecenone radical 38.In further investigations of the scope for sequential radical macrocyclisation–transannulations in the synthesis of bicyclic systems, the iodo dienone 40 was found to undergo regioselective cyclisation to the cis-tetralone 41(50%), whereas the iodo dienone 42 produced only (Z)-cyclooct-3-enone 54 and none of the expected bicyclo[3.3.0] octanone 43 on treatment with Bu3SnH–AIBN. Only the 4-cyclo-pentylcyclohexanone 61, and none of the hoped for 7,6-bicyclic ketone 45, was produced from radical cyclisation of the iodo dienone 44.The differing reaction pathways followed by the iodo dienones 21, 30b, 40 and 42 have been rationalised in terms of the conformational preferences of the macrocyclic α-keto radical intermediates, e.g. 32, 38 and 52 involved in the various cyclisations supported by some preliminary MM2 studies and calculations.

A cascade radical macrocyclisation–transannulation approach towards the construction of ring-fused tricycles and polycycles

Treatment of the iodo trienone 6 with Bu3SnH–AIBN results in the formation of the angular 5,7,5-ring-fused tricyclic ketone 20 by way of a novel sequential 13-endo-trig macrocyclisation followed by two successive 5-exo-trig transannulation processes, viz 7→8→/18/19→20. The cis-anti-trans stereochemistry of 20 was established from an X-ray crystal structure determination of the corresponding 2,4-dinitrophenylhydrazone. By contrast, treatment of the iodo trienone 21 with Bu3SnH–AIBN, under the same conditions, led to the substituted cyclopropane 33 (instead of the hoped-for tricyclic ketone 22), and only the product 38 of macrocyclisation (without further transannulation to the triquinane 24) was produced when the iodo trienone 23 was treated similarly.

Synthesis and reactivity of a novel group of hydroxylamine-containing 2π- and 4π-components

The synthesis of hydroxylamine-based reagents, alkene 2, alkyne 3 and a butadienyl variant pyrone 4 are described. While the relative instability of alkyne 3 has limited further evaluation, alkene 2 and pyrone 4 successfully participate in 1,3-dipolar and Diels–Alder cycloaddition reactions respectively. Reaction of 4 with DMAD gives O-arylated hydroxylamine 13, the structure of which is confirmed by crystallographic analysis.

Alkylation of enol silyl ethers by Pummerer-generated vinylthionium ions: a novel masked Michael reaction

Reaction of the enol silyl ethers (3) and (4) with the allyl sulphoxides (2), (7), (10), and (14) under Pummerer conditions using trimethylsilyl trifluoromethanesulphonate (TMSOTf) and di-isopropylethylamine (Hunigs base) affords the E-masked Michael adducts (5), (6), (8), (9), (12), (13), and (15) in good yields. The vinylthionium ion intermediate is competitively intercepted by Hunigs base in the reaction to afford, for the allyl sulphoxide (7), the quaternary ammonium Inflate salt (18), which is the sole product in the absence of silyl ether. The amine interception occurs with other pyramidal amines (triethylamine, quinuclidine, and diethyltrimethylsilylamine). The adduct (18) can be alkylated in moderate yield by less reactive enolates, e.g. malonate, using palladium(0) as catalyst.