Diastereoselective synthesis of highly substituted polycyclic scaffolds via a one-pot four-step tandem catalytic process

Synthesis of 5-Amino-2,5-dihydro-1H-benzo[b]azepines Using a One-Pot Multibond Forming Process

“…Having prepared a small library of ( E )-(2-allylamino)­cinnamyl alcohols, 6a was used for optimization of the one-pot process (Table ). Based on previous work, , the thermally mediated Overman rearrangement was performed at 140 °C and the RCM step was done using Grubbs’ second generation catalyst (10 mol %) (entry 1) . While this gave a yield of 69% over the three steps, both the rearrangement and metathesis stages required reaction times of 48 h. Increasing the temperature of the Overman rearrangement to 160 °C allowed a shorter reaction time (24 h) with a similar overall yield (entry 2).…”

A one-pot, three-step process for the diastereoselective synthesis of aminobicyclo[4.3.0]nonanes using consecutive palladium(ii)- and ruthenium(ii)-catalysis

“…Having identified the structural requirements and optimal conditions for an efficient Overman rearrangement, these were incorporated into a one-pot multi-reaction process including a Ru(II)-catalysed RCEYM step 23 and a Diels-Alder reaction for the preparation of novel aminobicyclo[4.3.0] nonanes (Scheme 3). Preliminary attempts at the one-pot preparation of 25 from phenyl substituted allylic alcohol 17 using Grubbs 2 nd generation catalyst (7 mol%) 24 for the RCEYM step and N-phenyl maleimide as a dienophile for the Diels-Alder step, under previously developed conditions for these reactions 14,15 gave low yields of 25 (∼25%). Analysis of the 1 H NMR spectrum of the reaction mixture showed the presence of the 1,6-enyne 22, indicating that the RCEYM step had not gone to completion.…”

“…Mp 151-153°C; spectroscopic data was consistent with the literature. 15 Methyl (1R*,7S*,7aS*)-2,3,5,6,7,7a-hexahydro-4-(4″-methoxyphenyl)-1-(2′,2′,2′-trichloromethylcarbonylamino)indene-7-carboxylate (37) Methyl (1R*,7S*,7aS*)-2,3,5,6,7,7a-hexahydro-4-(4″-methoxyphenyl)-1-(2′,2′,2′-trichloromethylcarbonylamino)indene-7-carboxylate (37) was synthesised as described for compound 34 using 7-(4″-methoxyphenyl)-3-(2′,2′,2′-trichloromethylcarbonylamino)hept-1-en-6-yne (24) (0.04 g, 0.11 mmol) and methyl acrylate (0.03 mL, 0.33 mmol). The Diels-Alder reaction was stirred for 5 days at 111°C.…”

“…15 While this approach permitted the facile preparation of a range of amino substituted bicyclo[4.3.0]nonanes, we found that some of the one-pot processes required particularly long reaction times and this was in part due to using thermal conditions to implement the Overman rearrangement (36 h). 14,15 In previous studies, we found that alkene and alkyne derived allylic trichloroacetimidates would not undergo effective palladium(II)-catalysed rearrangements due to binding of the catalyst to the unsaturated side-chains. 13,16 We were interested in exploring the structural requirements of alkyne derived allylic alcohols that could block catalyst side-chain binding and perform a Pd(II)-catalysed Overman rearrangement as part of a more rapid one-pot process leading to new C-5 substituted aminobicyclo[4.3.0]nonanes.…”

Recent Advances in One-Pot Enyne Metathesis Processes for the Preparation of Biologically and Medicinally Relevant Compounds

“…35 Conversely, starting from terminal alkynes (R = H), a further cross-metathesis step before the final DA reaction resulted in the installation of a substituent at C5 through a one-pot, four-step process. 36 In more recent work, alkynylsilyl-derived allylic trichloroacetimidates 32 were used as substrates for the preparation of aminobicyclo[4.3.0]nonanes 35 bearing a vinylsilane functional handle. 37 Interestingly, in the reported examples, the use of 1,7octadiene as an in situ source of ethylene resulted in accelerated RCEYM reactions.…”