Pinacol rearrangement applications

Antithetic conversion of a TGT by molecular rearrangement into a symmetrical precursor with the possibility for disconnection into two identical molecules. This case can be illustrated by the application of the Wittig rearrangement transform which converts 139 to 140 or the pinacol rearrangement transform which changes spiro ketone 141 into diol 142. 

A recent application of the metal mediated [6 + 4] cycloaddition reaction is the synthesis of nine-membered carbocycles by a sequential [6 + 4] cycloaddition-pinacol rearrangement, as employed by Rigby and Fales310. 

The base-catalysed reaction sequence (formulated in Expt 8.17) is thought to proceed via an intermediate heterocyclic pinacol which on acidification yields the required hydantoin as a result of a pinacolic rearrangement. The procedure is applicable in general to diaryl-1,2-diketones. 

An efficient pinacol rearrangement mediated by trialkyl orthoformate has been developed [83]. The reactions of various types of 1,2-diol with a catalytic amount of SnCU in the presence of trimethyl orthoformate afford the rearranged product in good yields via a cyclic ortho ester intermediate (Eq. 50). This combined system is applicable not only to cyclic and acyclic tri- and tetrasubstituted diols but also to diols forming acid-sensitive acetals. 

Other unsymmetrical diols, prepared (inefficiently) by the coupling of mixtures of ketones, have been studied. The preferred cation argument is also found to be applicable to mixed medium-ring analogs, i.e. the kinetically favored pinacol rearrangement product is that predicted by consideration of the relative stabilities of the two possible, initially formed, carbocations. ° Earlier work with these compounds may have given misleading results due to product instability. To illustrate, Mundy observed that (24) is converted to (25) as the temperature is increased. 

The rearranged olefin 50 may be used in a variety of synthetic applications. For instance it can be converted into the novel di-bis-tetrahydrofuran-acetal 95 in a one-pot operation using trimethylsilyl iodide in dichloromethane at 22 °C (Scheme 16) (12). The mechanism involves the formation of an oxonium intermediate 96 which undergoes a Prins cyclization to form the cation 97. Subsequent pinacol rearrangement generates 98 which cyclizes to 99. This acetal dimerizes under elimination of trimethylsilylbenzyl ether and benzyliodide. The structure of 95 has been elucidated by X-ray analysis (Fig. 3) which nicely shows the C2-symmetry of the dimeric structure. 

The Overman laboratoiy has developed a reaction which has been denominated a pinacol-terminated Prins cyclization or more simply a Prins-pinacol rearrangement [84]. An application to the synthesis of shahamin is shown in... 

Scheme 1.6 Development of an asymmenic pinacol rearrangement by Antilla and coworkers— and related application to a total synthesis of hopeanol I37L—...

Liang et al. demonstrated that the phosphoric acid catalysis was also applicable to pinacol rearrangement reaction. In the presence of 2.5 mol% phosphoric acid 6e, indolyl diols 85 dehydrated to form iminium intermediate XIO, which then underwent a [l,2]-aryl shift to furnish chiral a-indolyl ketone products 86 with high levels of stereoselectivity (up to 96% ee, Scheme 2.25) [36]. 

In 1994, the total syntheses of magellanine (98) and magellaninone were accomplished independently by Overman via a Prins pinacol rearrangement (55) and by Paquette via a tandem Michael-Michael addition (84,85). In 1999, Sha et al. developed an efficient a-carbonyl radical-initiated tandem cyclization reaction for the synthesis of angularly fused tricyclic ketones. Application of this methodology to the first total synthesis of (+)-paniculatine (146) has been achieved (Scheme 18) (93). 

Although zwitterions are mainly considered for their novel ion conductive matrix in this chapter, they are being used as not only as solvents and catalysts for organic reactions [42] but also as organogelators [43]. Zwitterions have been screened as solvent/catalysts for several classical acid-promoted organic reactions such as the Fischer esterification, alcohol dehydrodimerization, and the pinacol/ benzopinacole rearrangement. The zwitterion containing an equimolar trifluoro-methane sulfonic acid is liquid at room temperature. Because they can work as solvent/catalysts, as shown in the reactions discussed in this chapter, zwitterionic liquids should open the door to a whole new area of applications. 

A different outcome in the presence of an additional vinylic oxygen was observed by Overman s group (Scheme 52). The formation of the five-membered cyclic ether (108) is rationalized in terms of an SnCU-mediated acetal ring opening of (105), subsequent cyclization of (106) to (107), followed by a ring contraction to (108) by a pinacol-type rearrangement. This stereocontrolled reaction proved to be applicable to the synthesis of related natural products. ... 

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