Dihydrofuran hydroboration

The 1,3-dipolar cycloaddition of nitrile oxides and 2-methylfuran provides suitable precursors for a-amino acids such as L-furanomycin 448 that contains a dihydrofuran ring (495). By using a chiral nitrile oxide derived from mannitol bis(acetonide), the enantiomerically pure furoisoxazoline 449 has been obtained. Hydroboration-oxidation of the latter leads to the hydroxy-substituted annulated THF derivative 450, which is converted via dihydrofuran 451 to furanomycin 448 in enantiomerically pure form (Scheme 1.55). 

Dialkyl and alkyl aryl ethers are cleaved by Si2I2887, by SiCl/Nal888 or by Me3SiCl/NaI889. The latter afford the functionalized erythro- 1,2-diols via hydroboration of 2-alkyl-4,5-dihydrofurans (equation 129)890. 

Asymmetric hydroborations of heterocyclic alkenes are highly regio- and enantioselective. For example, hydroboration of 2,3-dihydrofuran with Ipc2BH followed by oxidation provides 3-hydroxyfuran in 83% ee, which can be upgraded to essentially the enantiomerically pure form (>99% ee) (Figure 2). ... 

The hydroboration of alkenes is known to be activated either by pressure or catalysis. Consequently, the combination of these techniques might open the way for the hydroboration of particularly unreactive substrates. Maddaluno el al. recently investigated the hydroboration of some functionalized alkenes, comparing different reagents (catecholborane (CBH) versus pinacolborane (PBH)), and activation by Wilkinson catalyst (RhCl[PPh3]3) and pressure [24]. While bromoalkenes and al-lylamines were found to give the best results with CBH at ambient pressure, 2,3-dihydrofuran (52a, Scheme 7.17) was hydroborated most effectively by PBH in the... 

Erythro-l,2-diols. Hydroboration of 2-substituted 4,5-dihydrofurans followed by regioselective ring cleavage affords the diols in useful yields. 

Asymmetric induction has been observed in the hydroboration of heterocyclic rings such as dihydrofuran, dihydropyrrole, dihydropyran, and dihydrothiophenes.Table 5.6 ° shows the hydroboration-oxidation sequence that gives heterocyclic alcohols in good yield and with excellent % ee from heteroatom containing... 

A concise enantioselective synthesis of (-l-)-muscarine from (R)-benzyloxymethyloxirane was recently reported by Takano et al. (36) (Scheme 10). The starting oxirane was coupled with lithium acetylide-ethylenediamine, forming the hydroxyalkyne, which was converted to the acid-sensitive 2,3-dihydrofuran by methylation and subsequent treatment with base. The dihydrofuran derivative was hydroborated and oxidized in... 

The hydroboration of heterocyclic olefins having oxygen [50-56], sulfur [57], and nitrogen [58-68] are reported. Brown and coworkers [69] have conducted detailed hydroboration studies of many heterocyclics with an endocyclic double bond with borane-methylsulfide BMS, 9-BBN, CtuqBH, and SiajBH and have established the optimum conditions for clean and quantitative hydroboration. The hydroboration of 2,3- and 2,5-dihydrofuran with BMS (3 1 molar ratio) at 25 °C for 1 h afibrds trialkylborane, readily oxidized to 3-hydroxytetrahydro-furan, in excellent yield. But the synthesis of dialkylboranes from these olefins using olefins, BMS in 2 1 ratio is not possible at 0 °C. However, hydroboration of 2,3-dihydrofuran proceeds cleanly with 9-BBN in 1 1 ratio and oxidation affords the desired 3-hydroxytetrahydrofuran, in excellent yield. Similar results are obtained with dicyclohexylborane and disiamylborane (Table 5.14). 

At higher temperatures, the ring ruptures to afford 3-buten-l-ol or diol. At 25 °C 2,5-dihydrofuran has also been hydroborated, and comparative results are summarized [69] in Table 5.14. 

Table 5.15 Hydroboration of 2-methyl-4,5-dihydrofuran, 2,3-dihydrothiophene and N-(benzyloxycarbonyl)-3-pyrroline [69]... 

In 2-methyl-4,5-dihydrofuran both mesomeric and inductive effects operate in the same direction, and a significant acceleration in the rate of hydroboration is observed (Chart 5.12) [72]. 

In the case of 1,2-dihydrofuran, the hydroboration with 9-BBN is complete in 1 h, the oxidation of which afforded the corresponding alcohol in quantitative yield. However, the alkylborane, is not very stable at 25 °C in THF and gradually rearranges to the open-chain imsaturated alcohol. The hydroboration of the intermediate with 9-BBN affords the corresponding diol (Scheme 6.26). 

An enantioselective total synthesis of (+)-phomactin A (181) has been recently reported by Halcomb using intramolecular Suzuki coupling of a B-alkyl-9-BBN derivative to prepare the macrocycle in the final step [162,163], Thus, a regioselective hydroboration of the terminal olefin in the precursor 182 gave an internal alkyl-borane that was cyclized using modification of Johnson s conditions [164], The reaction illustrates the mildness of the Suzuki reaction since the coupling was carried out in the presence of the sensitive dihydrofuran ring (Scheme 3.95). 

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