Nucleophilic Oxirane Ring-Opening

The reaction of oxiranes with base can follow several paths, giving products of type (34-38 Scheme 27). (a) Formation of an oxiranyl anion (34) is rare (Section 5.05.3.5). (b) Nucleophilic ring opening to give (35) is common with unhindered bases (Section 5.05.3.4). (c) a-Elimination to give a carbene or carbenoid (36) is favored by alkyllithium bases and... 

The strict geometrical requirements for elimination can be put to further use, as illustrated by elegant procedures for the geometrical isomerization of alkenes. Trimethylsilyl potassium (10) and phenyldimethylsilyl lithium (11) both effect smooth conversion of oxiranes into alkenes, nucleophilic ring opening being followed by bond rotation and spontaneous syn fi-elimination ... 

Key steps, as shown in Scheme 4-15, involve the formation of a urethane intermediate 37 by treating epoxide 36 with methyl isocyanate in the presence of sodium hydride. Intramolecular A-nucleophilic ring opening of oxirane affords oxazolidine 38. Subsequent treatment furnishes product 34. 

Isopropenyl)oxirane (10.113, Fig. 10.26) and 2-methyl-2-vinyloxirane (10.114) were hydrolyzed by EH to the corresponding diols (10.116 and 10.117, respectively). Nucleophilic ring opening took place at the less-hindered, unsubstituted C-atom, with retention of configuration at C(2). (2R)-2-(Isopropenyl)oxirane was a better substrate than the (25)-enantiomer. Substrate enantioselectivity was more modest in the hydration of 2-methyl-2-vin-yloxirane (10.114), since this compound is chemically more reactive and undergoes partly nonenzymatic hydrolysis. 

Other examples include conversion of ketones to a-hydroxydimethylace-tals 1 (Scheme la), which result from a nucleophilic ring opening of the intermediate oxiranes 18 by methoxide ions, as shown in Scheme 10. Interestingly, it is possible to isolate such oxirane derivatives in a few cases such as that shown in Eq. (7) (85S326). 

Few solid-phase syntheses of oxazoles have been reported (Table 15.17). The most general strategy is the dehydration of a-(acylamino) ketones (Entry 2, Table 15.17) or 2-(acylamino)phenols (Entry 1, Table 15.17). Oxazolidin-2-ones have been prepared by intramolecular nucleophilic cleavage of carbamates from insoluble supports (Entries 5 and 6, Table 15.17). Resin-bound 2-aminoethanols, which are accessible by nucleophilic ring-opening of oxiranes with amines, undergo cyclocondensation with aldehydes to yield oxazolidines [220,221]. These compounds are unstable towards acids, and can be released from the support only under neutral or basic reaction conditions. 

Nucleophilic ring opening of oxiranes gives intermediates of the type 22, which readily ring-closed (Scheme 8) <2004JOC8780>. A similar reaction can be carried out in one step <2003GC436>. 

Boron trifluoride has been used in combination with organolithium-Lewis base complexes for the enantioselective nucleophilic ring opening of various oxiranes with excellent yields and high ee values 86,87 g)... 

Epoxides undergo a repertoire of fairly well-characterized reactions, perhaps the most typical being the nucleophilic ring opening process. Since the epoxide in question is usually found in a compound with multiple functionality, many new methodologies seek to optimize chemo- and regioselectivity. Fortunately, the oxirane lone pair provides a convenient handle to effect activation of the heterocycle toward C-0 bond cleavage thus, efficient catalysts are of particular interest. 

In addition to being highly efficient catalysts for the preparation of asymmetric oxiranes (see Section 1.04.2.6.1), chiral metal-salen complexes can mediate the enantioselective nucleophilic ring opening of epoxides Jacobsen reviewed this area in 2000 <2000ACR421>. 

On the action of BF3, a steroid oxirane undergoes rearrangement to a tetrahydro-furan. 7-Lactones are formed from oxirane by nucleophilic ring-opening (Eqs. 192-194). ° ... 

Nucleophilic ring-opening of oxiranes by lithium dialkylcuprates occurs at the sterically less-hindered side and the corresponding alcohol is formed.The reaction can be carried out under mOd conditions and the side-reactions observed with other organometallic compounds can be avoided. The mechanism of the transformations has been treated in detail. With MejCuLi the reaction proceeds stereoselectively and the new C-C bond is formed on the side opposite the C-0 bond of the oxirane (Eq. 

Lactones are common subunits in natural products and are therefore of high biological relevance. An approach to 7- and 5-lactones starts from Merrifield resin-bound to-alkenoic acids 99 (Scheme 26). Epoxidation and nucleophilic ring-opening of the oxiranes 100 produced the hydroxy acids 101, which cyclized upon treatment with trifluoroacetic acid to give five- and six-membered lactones 102. Treatment of the epoxides 100 with trifluoroacetic acid provided the lactone 102 (Nuc = OH) [41],... 

Reaction with oxiranes (epoxides).2 Dimethylcopperlithium and diphenyl-copperlithium1 are more useful than other organometallic reagents for the nucleophilic ring opening of epoxides. Thus dimethylcopperlithium reacts with propylene oxide (equation 1) and 1,2-epoxybutane (equation 2) to give the expected secondary alcohols as the predominant products. 

Pyridazines have been prepared from a variety of other heterocyclic systems and in most cases these transformations were specific. The 3(S), 4(5) 36, a constituent of the antibiotic antitumor luzopeptin A, was prepared in a multistep synthesis from malonaldehyde dimethyl acetal in 32% overall yield. In the last step a highly regiospecific nucleophilic ring opening of the glycidic acid (oxirane derivative) took place (89JOC3260). In another example, c75,frani-l,3-cycloundecadiene was transformed in five steps in low yield into 59. In the last step the epoxide 58 was treated with excess of LDA (89TL4649). 

Nucleophiles, e.g. ammonia or amines, cause oxiranes to ring-open to give amino alcohols ... 

In this reaction, an acid-base equilibrium precedes the nucleophilic ring-opening of the oxirane ring. 

Nucleophilic Ring-opening Reactions of Oxirans.—Reactions with Oxygen and Nitrogen Nucleophiles. A series of papers have appeared that deal with the reactions of lower aliphatic alcohols (R OH) with (120 = Me) to yield (121 ... 

In contrast to HFPO, 2,2-bis(trifluoromethyl)oxirane (2) ring opens with oxygen, nitrogen, sulfur, and carbon nucleophiles at the less hindered carbon, yielding tertiary alcoholsWith diethylamine, for example, 2 affords an aminoalcohol in 83% yield. Oxirane 2 played an important role in the development of monomers from which to build highly transparent, yet readily alkali-soluble photoresist copolymers... 

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