CHAPTER FOURTEEN Organometallic Compounds RLi+C=0→>R-C-OLi R-C-OH Alkyllithium Aldehyde Lithium alkoxide Alcohol the product variously CH,=CHLi+ -chI diethyl -CHCH=CH and an allylic alcohol Can identify the structural Vinvllithium reason for each classifica- Benzaldehyde 1-Phenyl-2-propen-1-ol (76%0) 14. 8 SYNTHESIS OF ACETYLENIC ALCOHOLS RC=CNa obtained by treatment of terminal alkynes with sodium amide in lin pe The first organometallic compounds we encountered were compounds of the type ammonia(Section 9.6) RC=CH+N△NH2 RC≡CNa+NH Terminal Sodium Ammonia alkyne amide alkylide These compounds are sources of the nucleophilic anion RC=C, and their reaction with primary alkyl halides provides an effective synthesis of alkynes(Section 9.6). The nucleophilicity of acetylide anions is also evident in their reactions with aldehydes and ketones, which are entirely analogous to those of Grignard and organolithium reagents. These reactions are normally R ried out in liquid ammo- RC≡CNa+RCR RC≡C-C—ONa>RC≡CCOH which the sodium salt Aldehyde Sodium salt of an alkylide or ketone alkynyl alcohol alcohol HOC≡CH HC≡CNa+ Sodium acetylide Cyclohexanon 1-Ethynylcyclohexanol (65-75%) Acetylenic Grignard reagents of the type RCECMgBr are prepared, not from an acetylenic halide, but by an acid-base reaction in which a Grignard reagent abstracts a proton from a terminal alkyne CH3(CH2)3C=CH+ CH3 CH, MgBr CH3(CH2)3C=CMg Br CH3CH 1-Hexyne Ethylmagnesium I-Hexynylmagnesium Ethane Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
14.8 SYNTHESIS OF ACETYLENIC ALCOHOLS The first organometallic compounds we encountered were compounds of the type RCPCNa obtained by treatment of terminal alkynes with sodium amide in liquid ammonia (Section 9.6): These compounds are sources of the nucleophilic anion RCPC: , and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9.6). The nucleophilicity of acetylide anions is also evident in their reactions with aldehydes and ketones, which are entirely analogous to those of Grignard and organolithium reagents. Acetylenic Grignard reagents of the type RCPCMgBr are prepared, not from an acetylenic halide, but by an acid–base reaction in which a Grignard reagent abstracts a proton from a terminal alkyne. CH3CH2MgBr Ethylmagnesium bromide CH3CH3 Ethane diethyl ether CH3(CH2)3C CH 1-Hexyne CH3(CH2)3C CMgBr 1-Hexynylmagnesium bromide HC CNa Sodium acetylide O Cyclohexanone 1. NH3 2. H3O 1-Ethynylcyclohexanol (65–75%) HO C CH RCR O Aldehyde or ketone H3O NH3 RC CNa Sodium alkynide Sodium salt of an alkynyl alcohol C ONa R R RC C Alkynyl alcohol CCOH R R RC NaNH2 Sodium amide RCPCH Terminal alkyne NH3 Ammonia RCPCNa Sodium alkynide NH3 33°C RLi Alkyllithium compound C O Aldehyde or ketone R C OLi Lithium alkoxide H3O R C OH Alcohol CH2 CHLi Vinyllithium CH O Benzaldehyde CHCH OH CH2 1-Phenyl-2-propen-1-ol (76%) 1. diethyl ether 2. H3O 556 CHAPTER FOURTEEN Organometallic Compounds In this particular example, the product can be variously described as a secondary alcohol, a benzylic alcohol, and an allylic alcohol. Can you identify the structural reason for each classification? These reactions are normally carried out in liquid ammonia because that is the solvent in which the sodium salt of the alkyne is prepared. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
14.9 Retrosynthetic Analysis CH3CH2)3C≡ CMgBr+HCH 时中CH3CH2)C≡CCH2OH 1-Hexynylmagnesium Formaldehyd 2-Heptyn-1-ol(82%) PROBLEM 14.6 Write the equation for the reaction of 1-hexyne with ethyl- agnesium bromide as if it involved ethyl anion (CH3 CH2 )instead of CHaCH MgBr and use curved arrows to represent the flow of electrons. 149 RETROSYNTHETIC ANALYSIS In our earlier discussions of synthesis, we stressed the value of reasoning backward from the target molecule to suitable starting materials. A name for this process is retrosyn thetic analysis. Organic chemists have employed this approach for many years, but the term was invented and a formal statement of its principles was set forth only relatively recently by E J. Corey at Harvard University. Beginning in the 1960s, Corey began stud- Corey was honored with the ies aimed at making the strategy of organic synthesis sufficiently systematic so that the 1990 Nobel Prize for his power of electronic computers could be applied to assist synthetic planning achievements in synthetic A symbol used to indicate a retrosynthetic step is an open arrow written from pi ganic chemistry. ct to suitable precursors or fragments of those precursors Target molecule precursor Often the precursor is not defined completely, but rather its chemical nature is empha sized by writing it as a species to which it is equivalent for synthetic purposes. Thus, a Problem 14 6 at the end of Grignard reagent or an organolithium reagent might be considered synthetically equiva- the preceding section intro- lent to a carbanion: duced this idea with the su RMgX or rli is synthetically equivalent to R: bromide be represented Figure 14.2 illustrates how retrosynthetic analysis can guide you in planning the synthesis of alcohols by identifying suitable Grignard reagent and carbonyl-containing precursors In the first step, locate the carbon of the target alcohol that bears the hydroxyl group, remembering that this carbon originated in the C-o group. Next, as shown in Figure 14.2, step 2, mentally disconnect a bond between that carbon and one of its other than hydrogen) at is to be trans ferred from the Grignard reagent. Once you recognize these two structural fragi the carbonyl partner and the carbanion that attacks it(Figure 14.2, step 3), you can ily determine the synthetic mode wherein a Grignard reagent is used as the synt quivalent of a carbanion( Figure 14.2, step 4). Primary alcohols, by this analysis, are seen to be the products of Grignard addi- tion to formaldehyde Disconnect this bond H R+C-OH R: C=0 H Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
PROBLEM 14.6 Write the equation for the reaction of 1-hexyne with ethylmagnesium bromide as if it involved ethyl anion instead of CH3CH2MgBr and use curved arrows to represent the flow of electrons. 14.9 RETROSYNTHETIC ANALYSIS In our earlier discussions of synthesis, we stressed the value of reasoning backward from the target molecule to suitable starting materials. A name for this process is retrosynthetic analysis. Organic chemists have employed this approach for many years, but the term was invented and a formal statement of its principles was set forth only relatively recently by E. J. Corey at Harvard University. Beginning in the 1960s, Corey began studies aimed at making the strategy of organic synthesis sufficiently systematic so that the power of electronic computers could be applied to assist synthetic planning. A symbol used to indicate a retrosynthetic step is an open arrow written from product to suitable precursors or fragments of those precursors. Often the precursor is not defined completely, but rather its chemical nature is emphasized by writing it as a species to which it is equivalent for synthetic purposes. Thus, a Grignard reagent or an organolithium reagent might be considered synthetically equivalent to a carbanion: Figure 14.2 illustrates how retrosynthetic analysis can guide you in planning the synthesis of alcohols by identifying suitable Grignard reagent and carbonyl-containing precursors. In the first step, locate the carbon of the target alcohol that bears the hydroxyl group, remembering that this carbon originated in the CœO group. Next, as shown in Figure 14.2, step 2, mentally disconnect a bond between that carbon and one of its attached groups (other than hydrogen). The attached group is the group that is to be transferred from the Grignard reagent. Once you recognize these two structural fragments, the carbonyl partner and the carbanion that attacks it (Figure 14.2, step 3), you can readily determine the synthetic mode wherein a Grignard reagent is used as the synthetic equivalent of a carbanion (Figure 14.2, step 4). Primary alcohols, by this analysis, are seen to be the products of Grignard addition to formaldehyde: Disconnect this bond R C H H OH R O H H C RMgX or RLi is synthetically equivalent to R Target molecule precursors (CH3CH2 ) CH3(CH2)3C CMgBr 1-Hexynylmagnesium bromide CH3(CH2)3C CCH2OH 2-Heptyn-1-ol (82%) HCH O Formaldehyde 1. diethyl ether 2. H3O 14.9 Retrosynthetic Analysis 557 Corey was honored with the 1990 Nobel Prize for his achievements in synthetic organic chemistry. Problem 14.6 at the end of the preceding section introduced this idea with the suggestion that ethylmagnesium bromide be represented as ethyl anion. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website