Highly substituted tetrahydrofuran

As for oxygen heterocycles, several reports involving the diastereoselective synthesis of highly substituted tetrahydrofuran derivatives have appeared. SnCLj-mediated [3 + 2] cycloaddition of allylsilane with optically active a-ketoesters affords 211 with excellent diastereoselectivity (equation 173)314-317. 

The synthesis of highly substituted tetrahydrofurans by means of a multicomponent reaction based on this palladium-mediated cyclization process was reported by Balme and co-workers [94]. In this reaction, formation of enolate 103 by the initial 1,4-addition of an allylic alcohol to the conjugate acceptor 102 is followed by a... 

The synthesis of polysubstituted tetrahydrofurans was also achieved in a stereoselective manner by a formal [3+2] cycloaddition of an allylsilane with a-triethylsiloxy aldehydes. An example showing the mechanism is illustrated <02JA3608>. In another approach, allylsilane was also allowed to react with a-keto esters in a [3+2] annulation reaction, providing highly substituted tetrahydrofurans in good yields as single diastereomers <02OL2945>. 

An electrochemical oxidation route to tetrahydrofuran and tetrahydropyran rings has been described, in which a silyl-substituted enol ether reacts with a regioselectivity that is reversed from the normal polarity of enol ethers (Scheme 61) <2000JA5636>. Aldol reactions of a-diazo-/ -ketoesters with aldehydes produce adducts which undergo Rh(ii)-catalyzed 0-H insertion reactions to yield highly substituted tetrahydrofurans <1997TL3837>. 

The addition of a carbonyl compound to methyl 2-siloxycyclopropanecarboxylate (113 equation 47) in the presence of a stoichiometric amount of TiCU affords a mixture of hyctoxyalkylation products (114) and (115), which are versatile starting materials for highly substituted tetrahydrofurans, dihydrofu-rans, and y-butyrolactones. ... 

A semipinacol rearrangement in tandem with a cyclization has been shown to be a powerful method for the construction of carbocyclic rings. Here the cyclization is initiated by an acetal function and terminated by a semipinacol rearrangement (Scheme 25). In some cases, the cyclization has been found to be stereospecific at the acetal center (equation 48), and up to four chiral centers can be generated in a single step (equation 49). Highly substituted tetrahydrofurans are obtained from cyclic acetals (Scheme 26), and stereoselective tetrahydrofuran annelations are possible using bicyclic acetals (Scheme 27). ... 

In Kozikowski s synthesis of showdomycin, treatment of the oxabicyclic 130 with bicarbonate induced a retro-Dieckmann reaction to reveal the highly substituted tetrahydrofuran intermediate 131, Eq. 93 [142]. 

A new PRCC reaction catalyzed by an organic photoredox system to synthesize highly substituted tetrahydrofurans from readily available allylic alcohols and oxidizable alkenes was demonstrated. This is a simple synthetic disconnection that provides valuable cyclic ether scaffolds. The method demonstrates a broad range of functional group compatibility and could find unique applications in complex molecule synthesis (13AGE3967). 

SCHEME 13.93 Tributylphosphine-catalyzed synthesis of highly substituted tetrahydrofuran derivatives 445. 

Related rearrangements that form more highly substituted tetrahydrofurans 8 and 9 are summarized in Figure 4. In these cases, as well as other related ones we have reported, the rearrangements are highly stereoselective a single tetrahydrofuran stereoisomer is formed, even when acetals derived from mixtures of stereoisomeric allylic diols are employed as rearrangement substrates. [9] The... 

Grandjean, J.-M., Nicewicz. D. A. (2013). Synthesis of highly substituted tetrahydrofurans by catalytic polar radical-crossover cycloadditions of alkenes and alkenols. Angewandte Chemie International Edition, 52, 3967-3971. 

In a unique twist on the use of oxocarbenium reduction to generate tetrahydrofurans, Romo and Mitchell reported the generation of 2,5-cis- and 2,5-trani-tetra-hydrofurans from the reductive cyclization of ketones having a pendant p-lactone (Scheme 5) [8]. This reaction builds upon previously reported results from Mead et al. and leads to the stereospecific synthesis of highly substituted tetrahydrofurans [9]. For example, when a fi-p-lactone 13 was subjected to TESOTf and excess Et3SiH, they isolated 2,5-trans-tetrahydrofuran 14 in 82 % yield as a 14 1 mixture of dia-stereomers, while the corresponding yn-p-lactone 16 gave 2,5-cfr-tetrahydrofuran 17 in 78 % yield as a >19 1 mixture of diastereomers. The stereochemical outcome of these reactions is consistent with the Woerpel et al. model as depicted for the reduction of 15 and 18. 

Yang and coworkers have also examined cyclopropane [3+2]-cycloadditions to give highly substituted tetrahydrofurans (Scheme 19) [19]. Interestingly, the AICI3-mediated cycloaddition of trans-cyclopropane 65 with electronically neutral or electron-deficient aryl aldehydes led to a predominance of cfr-tetrahydrofuran 64, while the use of electron-rich aryl aldehydes resulted in the generation of the corresponding trans-tetrahydrofurans 67. The authors demonstrated that the reaction was reversible and that the trans isomer resulted from the equilibration of the cis isomer. 

The Overman group has studied and utilized Prins-pinacol cascades to generate highly substituted tetrahydrofuran rings over the past 20 years [63]. An example from the Overman group is given in Scheme 56 where acetal 209 (from the... 

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