A new stereoselective route to trisubstituted bromo olefins utilizing .alpha.-bromoalkylides produced by halogen-metal exchange

Abstract

The development of general methods for the stereospecific synthesis of functionalized trisubstituted olefins has become of major importance in synthetic organic chemistry. As a new approach to the problem, the readily available triphenylphosphonium dibromomethylide has been alkylated with methyl and ethyl bromides to yield the corresponding salts 4, which react smoothly with butyllithium at low temperature to give a-bromoalkylides 5, formally the products of halogen-metal exchange. These ylides react with a variety of aldehydes in Wittig fashion, furnishing the corresponding trisubstituted bromo olefins 3 in yields of 30-55%. Reactions involving the ylide 5b are usefully stereoselective, and it has been shown that in all cases it is the thermodynamically more stable isomer which predominates. In striking contrast, reactions involving the homologue 5c are completely nonstereoselective, and this disparity appears unprecedented. Work directed toward the elucidation of the mechanisms of these processes has revealed that the detailed pathway of these reactions is determined by a number of finely balanced factors, which even a small perturbation is liable to upset. Equilibrium processes, solvent effects, and the relative thermodynamic stabilities of the resultant bromo olefins 3 all appear to exert an influence in determining reaction stereochemistry.

Total syntheses of the strobilurins G, M, and N

“…The combined organic solutions were evaporated, and the residue was purified by column chromatography (hexanes -EtOAc 6, 25.0, 25.9, 68.1, 68.9, 74.3, 79.9, 117.1, 117.6, 120.6, 122.5, 127.0, 128.0, 137.8, 142.6, 145.5, 152.9, 193.7 (14). To a suspension of (1,1-dibromoethyl)triphenylphosphonium bromide 9 (1.90 g, 3.60 mmol) in THF (15 mL), maintained at 240 8C, was added a solution of n-butyl lithium (2.5 M in hexane, 1.44 mL, 3.60 mmol). After 1 h of stirring, a solution of 13 (0.58 g, 1.83 mmol) in THF (15 mL) was added and the reaction mixture warmed to rt.…”

“…Formation of the dienyl halides 5 (X¼Br) should be realised with high (Z)-stereoselectivity via the Wittig reaction of an appropriate cinnamaldehyde 6 with the phosphorus ylide 8 derived from (1,1-dibromoethyl)triphenylphosphonium bromide. 9 …”

Natural Product Synthesis Featuring Intramolecular Diels–Alder Approaches – Total Syntheses of Tubelactomicins and Spiculoic Acid A

“…The diastereomeric ratio of two anti products in this crotylboration was approximately 3:1 in favor of the formation of 123. A two-step oxidative carbon-carbon bond cleavage of 123 provided the aldehyde 124, which was subjected to Wittig olefination with (1,1-dibromopropyl)triphenylphosphonium bromide [55] in the presence of a base (nBuLi). As a result, the (E)-trisubstituted alkene 125 was obtained stereoselectively [(E)/(Z) Ͼ 20:1].…”

Synthesis of Halomethylvinylcyclopropanecarboxylic Acids and Their Esters

“…Alternatively, a trisubstituted bromo olefin synthesis, utilizing o:-bromoalkylylides according to the method of Smithers,12) was applied to the 2-bromo-Ipropenyl derivatives. The Wittig reaction of o:-bromoethylidenetriphenylphosphorane with methyl cis-3-formyl-2,2-dimethylcyclopropanecarboxylate (12c) in THF at -45°C afforded a mixture of methyl (E)-and (Z)-cis-3-(2-bromo-I-propenyl)-2,2-dimethylcyclopropanecarboxylates (13c and 14c) in 75% yields, which was then sUbjected to transesterification with m-phenoxybenzyl alcohol in the presence of lithium amide in toluene to give the corresponding benzyl esters of 13d and 14d in the ratio of about 3: I after separation by Lobar column chromatography.…”