Allylic alcohols Directed Simmons-Smith cyclopropanation

A combination of resolution and diastereofacial cyclopropanation has been used to prepare a variety of cyclopropyl ketones with high optical purity77. Optically active lithiated (S)-N,S-dimethyl-S-phenylsulfoximine (17) is added to prostereogenic enones such as 16, and the resulting diastereomeric allylic alcohols 18 are separated by column chromatography. Hydroxyl-directed Simmons-Smith cyclopropanation (see Section 1.6.1.5.1.2.) provides intermediates which are thermally decomposed to release the optically pure cyclopropyl ketones 20 and the sulfoximine 19. 

The landmark report by Winstein et al. (Scheme 3.6) on the powerful accelerating and directing effect of a proximal hydroxyl group would become one of the most critical in the development of the Simmons-Smith cyclopropanation reactions [11]. A clear syw directing effect is observed, implying coordination of the reagent to the alcohol before methylene transfer. This characteristic served as the basis of subsequent developments for stereocontrolled reactions with many classes of chiral allylic cycloalkenols and indirectly for chiral auxiliaries and catalysts. A full understanding of this phenomenon would not only be informative, but it would have practical applications in the rationalization of asymmetric catalytic reactions. 

Stereoselective samarium-based Simmons-Smith cyclopropanation of cyclopentyl allylic alcohols is the key step in the synthesis of the precursor of 1,25-dihydroxy vitamin D3.128 The desired chirality was generated in one case under the influence of the two stereogenic centers on the (R,/ )-butane-2,3-diol acetal 121 and in the other case was directed entirely by the allylic hydroxy group of 122. 

The addition of a-lithiovinyltrimethylsilane 151 83), generated from a-bromovinyl-trimethylsilane84,) with r-BuLi (1.5 equivalents) at —78 °C in ether, to ketones and aldehydes was also investigated. The allylic alcohols 152 thus obtained underwent smooth cyclopropanation when the modified Simmons-Smith procedure utilizing EtZnI85) was applied. The cyclopropylcarbinols 153 were directly dehydrated without rearrangement upon exposure to catalytic amounts of p-TsOH in benzene at 20 °C to give 149 in yields of 52-75%, Eq. (48) 79,8L). 

The zinc-based Simmons-Smith type procedures frequently require rather harsh conditions in order to provide acceptable cyclopropane yields. Also, the discrimination between allylic alcohols, homoallylic alcohols and olefins without a hydroxyl group is often not very pronounced. These drawbacks are avoided by a new method which substitutes samarium metal (or samarium amalgam) for zinc (Table 4)43. This cnahlcs only allylic alcohols to be cyclo-propanated under very mild conditions, even for highly crowded substrates. The hydroxy-directed diastereofacial selectivity is good to excellent for cyclic olefins. Due to this property, the method has been applied to the stereoselective synthesis of 1,25-dihydroxycholecalciferol44. 

Wolfgang Oppolzer s muscone synthesis is the first enantioselective macrocycli-sation. [195] It starts with pentadec-14-ynal, which is converted by hydro-boration and transmetaUation into the corresponding organozinc compound. The ring closure takes place in the presence of catalytic amounts of a diethylzinc/ (-)ejco-3-(diethylamino)bomeol adduct. After work-up, the cyclic allyl alcohol is obtained in 75 % yield and with an ee of 92 %. The hydroxy-group directs the diastereoselective cyclopropanation (Simmons-Smith reaction). The final steps are a Swern oxidation and selective ring-opening of the cyclopropane under Birch conditions. 

A number of enantioselective Simmons-Smith-type cyclopropanations have been disclosed, of which three classic examples are discussed in this section [19]. In the first, Charette described the use of a dioxaborolane (111, Scheme 15.13) as an effective chiral controller group [68]. The presence of the basic amide C=0 was found to be critical for directing the cyclopropanation reagent to a single olefin diastereoface. Treatment of allylic alcohols such as 110 with 111 and Zn(CH2l)2 led to the formation of intermediate boronates that subsequently underwent cyclopropanation with excellent yields and enantioselectivities. An impressive iterative application of this method was showcased by Charette in a total synthesis of the natural product U-1065305 (113), a cholesterol transferase inhibitor [69]. 

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