Bicyclo hexane synthesis

Fig. 6. Synthesis of prostaglandins via a bicyclo[3.1.0]hexane intermediate where MCPBA = m — chloroperbenzoic acid.

As described in Section 1.7.1, the utility of the Wenker reaction is limited to substrates without labile functionalities because of the involvement of strong acid and then strong base. The Fanta group prepared a variety of aziridines by taking advantage of the Wenker reaction.For example, 6-aza-bicyclo[3.1.0]hexane (14) was produced from the ring-closure of ( )-rra s-2-aminocyclopentanol hydrochloride (13). In a similar fashion, sulfate ester 16 was prepared from A-methyl dl-trans- >-ssmnoA-hydroxytetrahydrofuran (15). Subsequent treatment of sulfate ester 16 with NaOH then delivered aziridine I . " Additional examples of Wenker aziridine synthesis may also be found in references 15-17. 

Based on his previous work on the catalytic double addition of diazo compounds to alkynes173 using Cp RuCl(COD),174 Dixneuf has developed an efficient one-step synthesis of alkenyl bicyclo[3.1.0]-hexane derivatives of type 163 from enyne precursors 162 (Scheme 43). The catalytic cycle starts with the formation of an Ru=CHR species. It then adds to an alkyne to form ruthenacyclobutene 166, which evolves into vinylcarbene 167. [2 + 2]-Cycloaddition of 167 gives ruthenacyclobutane 168. The novelty in this transformation is the subsequent reductive elimination to give 170 without leading to the formation of diene 169. This can be attributed to the steric hindrance of the CsMes-Ru group. 

Special interest has been paid to the synthesis of bridged four-membered rings. The smallest system of this type, the bicyclo[1. l.l]pentane skeleton 6, could be prepared by photolysis of 3-diazobicyclo[2.1.1]hexan-2-one in methanol,43 however, the yield was very low ( 2%). 

The application of this reaction to other ring systems has shown that the yield of the bicyclic hydrocarbon decreases as the strain involved in the product increases. For example, the mercury sensitized decomposition of bicyclo [3.2.0] heptanone-3 (XXIII) leads to very little of bicyclo [2.2.0] hexane and gives more of bicyclo [2.1.1] hexane than of bicyclo [2.2.0] hexane. The reaction has been successfully applied to the synthesis of a substituted bicyclo [2.1.0] pentane (XXVIII) from a sub-... 

Synthesis of 2-azabicyclo[2.2.0]hex-5-enes and 2-azabicyclo[2.2.0]hexanes has been reviewed <2004H(64)577> as has the photochemical conversion of 2-pyridones to bicyclo[2.2.0]hexane lactams . 

Table 1 Synthesis of 1 -phenyl-2-thia-6-aza-bicyclo[2.2.0]hexane derivatives...

As shown in Equation (42), the cycloadditions of alkylidene malonates and their derivatives enable selective synthesis of both [2 + 2]- and [2 + 3]-adducts by a proper choice of reaction temperature.167,168 Methyl propiolate undergoes [2 + 2]-cycloaddition predominantly. Use of excess allyltriisopropylsilane induces double [2 + 21-cycloaddition to methyl propiolate, forming a bicyclo[2.2.0]hexane.1 7 The [2 + 2]-cycloadditions of (E)- and (Z)-crotylsilanes proceed stereospecifically. 

Based on his previous work describing the catalytic double addition of di-azo compounds to alkynes [59], Dixneuf used Cp RuCl(cod) and worked out a simple synthesis of alkenyl bicyclo[3.1.0]hexane derivatives 75 from enyne precursors 74 (Scheme 33). The catalytic cycle starts with the formation of... 

Diazabicyclo[2.2.2]oct-2-enes have been shown to undergo photoelimination of nitrogen in a similar fashion via singlet 1,4-biradicals.In a separate investigation, the azoalkane (32) was converted into the bicyclo[2.2.0]hexane (33) in 72% yield on irradiation, and an analogous transformation has been employed in the synthesis of compounds with a pentaprismane carbon skeleton. ... 

Bicyclo[3,l,0]hexanes.—Sabinene is the starting material for a synthesis of nootkatone (see Chapter 2, p. 109). It is first converted to sabinaketone (193), which is methylated to the isomer (194) of thujono. Doering has given a very... 

The intramolecular cyclopropanations of a-diazocarbonyl compounds have been extensively studied and recently reviewed . The reaction is satisfactorily accomplished when the diazo carbon atom is proximal to the double bond in the substrate. Thus, the construction of bicyclo[3.1.0]hexane and bicyclo[4.1.0]heptane skeletons has been achieved by this method, whereas the synthesis of bicyclo[5.1.0]octane or the larger bicyclic systems has usually been difficult (equation 73). Bicyclo[2.1.0]pentan-2-ones expected in the reaction of j8,y-unsaturated diazoketones are generally labile and readily undergo the ring cleavage to give jS,y-unsaturated ketenes. ... 

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