Convergent Enantioselective Synthesis of Vinigrol, an Architecturally Novel Diterpenoid with Potent Platelet Aggregation Inhibitory and Antihypertensive Properties. 1. Application of Anionic Sigmatropy to Construction of the Octalin Substructure

Abstract

The coupling of building blocks 15 and 36e in the presence of MgBr(2).OEt(2) at 0 degrees C proceeds with an exo stereoselectivity (3.2:1) considerably more advantageous for the acquisition of carbinol 37e than in the absence of the additive (exo/endo = 1:5.7). The pivotal transformation that sets all of the relevant stereocenters of the cis-octalin 55 is the oxyanionic-accelerated [3,3]-sigmatropic rearrangement of 37e. A salient feature is the structurally enforced adoption of a boatlike transition state that serves to properly set four vicinal methine hydrogens in an all-cis arrangement. The ensuing conversion of 55 into iodo sulfone 62 has permitted X-ray crystallographic confirmation of all absolute stereochemical assignments since the isopropyl substituent was initially installed enantioselectively via the Evans oxazolidinone protocol. No intramolecular anionic cyclization of 62 to generate the tricyclic framework was seen. This absence of reactivity is attributed to conformational factors that inhibit attainment of the proper S(N)2 reaction trajectory.

Copper mediated defluorinative allylic alkylation of difluorohomoallyl alcohol derivatives directed to an efficient synthetic method for (Z)-fluoroalkene dipeptide isosteres

“…The organic extracts were washed with brine, dried over MgSO 4 , concentrated under reduced pressure to leave the residue, which was purified by silica gel column chromatography (hexane/ EtOAc = 7:1) to give 16 in 89% yield (8.8 g, 27 mmol). 1 H NMR data was identical to those reported in the literature [20]. Optical purity analyzed by HPLC using chiral column (CHIRALPAK AD-H, 25 cm  0.46 cm i.d.…”

“…In the case of a-methylated chiral aldehyde 10a [20] derived from the commercially available ester 15 (purity: 99% ee) allylation reaction proceeded smoothly to give a diastereomer mixture (11a, 85% yield, syn/anti = 1.6:1), which was easily separated by column chromatography on silica gel. Optical purity of the each isomer was found to be 99% ee keeping that of the starting material when the intermediate aldehyde 10a was used without purification by column chromatography after oxidation of the monoprotected diol 16 with Dess-Martin periodinane [21].…”

“…Medium pressure liquid chromatography (MPLC) was performed using prepacked column (silica gel, 50 mm) with RI detector. (diphenyl)silyl]oxy}-2-methyl-1-propanol 16 [20] Under argon atmosphere to a solution of (S)-3-{[tert-butyl(diphenyl)silyl]oxy}-2-methylpropanoate (11.0 g, 30 mmol) in toluene (150 ml) was added diisobutylaluminium hydride (0.9 M solution in hexane, 64 ml, 60 mmol) dropwise at À78 8C and then the whole was stirred for 5 h at the same temperature. The reaction mixture was quenched by addition of 1 M HCl (30 ml) and extracted with EtOAc.…”

Geometry-selective synthesis of the unsaturated side chains of the isodomoic acids

“…11 However, as with the Wittig olefination, only moderate yields and incomplete selectivities were obtained (Table 1, entries 6 and 7).…”

Functionalized organolithium compounds in total synthesis

“…Further synthetic transformations on this enone gave rise to (K)-brunsvigine (153). 70 Examples of the use of other vinyllithiums b-functionalized with other atoms can be found in the total synthesis of the antifungal agent papulacandin D, where (E)-b-trimethylsilylvinyllithium (155), generated by tin/lithium transmetalation from (E)-1-(tri-n-butylstannyl)-2-(trimethylsilyl)ethene (154) (Scheme 28), has been used as an acetaldehyde enolate equivalent. Thus, trimethylsilyllithium 155 was added to aldehyde 156 affording alcohol 157 which was converted into enal 158 on sequential reaction with phenylsulfenyl chloride and silver nitrate.…”