Proc. Indian Acad. Sci. (Chem. Sci.), Vol. 100, Nos 2 & 3, April 1988, pp. 143-185. t~ Printed in India. Synthetic methods and reactions* G K SURYA PRAKASH and GEORGE A OLAH* Donald P and Katherine B Loker Hydrocarbon Research Institute, and Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA Abstract. This review deals with the development of a series of reagents and reactions for organic synthesis using simple starting materials. A wide array of carbocationic and onium ion reagents, haiogenating agents, FriedeI-Crafts catalysts, metal-induced oxidation- reductions and silicon reagents were utilized in basic (unit) reactions, which serve as building blocks for general synthetic transformations. Keywords. Carbocations; onium ions; halogenating agents; Friedel-Crafts reactions; oxidizing agents; reducing agents; silicon reagents. Introduction Synthetic chemistry in general is directed either towards the preparation of specific molecules or towards the development of new reactions and reagents as well as improvement of existing methods. Over the years our group has been involved in developing selective reagents and methods for organic synthetic transformations using simple and inexpensive starting materials. The development of basic (unit) reactions are important as they serve as building blocks for all syntheses including those of complex target molecules such as natural products. In this review we give an account of our synthetic studies of recent years. In a short review it is not possible to give sufficient background for such a diverse and broad field or comparison with other existing methods and reactions. The reader should be aware of the large diversity of existing synthetic methods to which we hope to have made some useful contributions. Nitronium and nitrosonium salts and related reagents as nitrating agents Conventional electrophilic nitration of aromatic compounds (Hoggett et al 1971) using mixtures of sulfuric and nitric acids has several inherent difficulties. In particular, the water produced in the reaction dilutes the acid and therefore reduces its strength. Furthermore, the strong oxidizing ability of the mineral acids makes them unsuitable for nitrating many acid-sensitive compounds. Disposal of the spent acid also poses a significant environmental problem. In order to circumvent these difficulties we developed nitronium salts (such as NO~ BF~- and NO~-PF6) and related reagents as effective and efficient nitrating agents. * For correspondence *Considered synthetic methods and reactions. Part 131. For part 130 see: M B Sassaman, K D Kotian, G K S Prakash and G A Olah. 1987 J. Org. Chem. 52 4314. 143 144 G K Surya Prakash and George A Olah Nitronium ion salts are readily prepared from the reaction of nitric acid (or organic and inorgarric nitrates) with HF and BF3 (Olah and Kuhn 1973) and other Lewis acids such as PFs, SbF~, etc. When nitric acid is used in the preparation NO+BF4 is formed as by-product because of the presence of nitrous acid as an impurity. This can be avoided by purifying the nitric acid with urea. These nitronium ion salts nitrate aromatics in organic solvents in close-to-quantitative yields (Olah et a11961, 1962; Olah and Kuhn 1962). As HF and BF3(PFs) can be easily recovered and recycled, the method can be considered as a nitric acid nitration using a superacidic catalyst (Olah et al 1985a). HNO3 + HF + 2BF3, " NO~-BFs + BF3 : OH2 RONO2 + HF + 2BF3. : NO+BFz + BF3ORH Ar-H + NO~-BF4 ArNO2 + HF + BF3 (PFs (PF.s) Nitronium ion salts are such powerful nitrating agents that they can effect even trinitration of benzene to trinitrobenzene (Olah and Lin 1974a). Nitronium ion salts enable nitration of any conceivable aromatic substrate. It is, however, unfortunate that till recently controversial mechanistic studies of aromatic nitration (Eberson and Radner 1987) overshadowed the broad preparative utility of the nitronium salts. Nitronium salts have also been found to nitrate aliphatic hydrocarbons. In particular, adamantane gives moderate yield of 1-nitroadaman- tane (Olah and Lin 1971; Olah and Olah 1987). More recently desililative nitration of alkyl and allyi silanes has been achieved using nitronium salts (Olah and Rochin 1987). Nitronium ions salts have been found to react with bistrimethylsilylacetylene to produce nitrotrimethylsilyl acetylene (Schmitt and Bedford 1986). The reaction is catalyzed by external fluoride ion and in all probability proceeds through an addition elimination path. Electrophilic nitration of alkenes with nitronium salts has been carried out in pyridinium polyhydrogen fluoride medium (vide infra) to give nitrofluorinated alkanes. More selective nitronium ion salts, such as N-nitropyridinium salts, which are prepared from the corresponding pyridines, act as convenient transfer nitrating agents (Cupas and Pearson 1968; Olah et al 1980a). Transfer nitrations are applicable to both carbon and heteroatom nitrations. For example, they allow safe, acid-free preparation of alkyl nitrates and polynitrates from alcohols (polyols) in nearly quantitative yield (Olah et al 1978a). N-Nitroamines have also been used as convenient transfer nitrating agents using Lewis or Bronsted acid catalysis (Olah et al 1981a). With BF3 as catalyst, alkyl nitrates such as CH3ONO 2 and n-BuONO2 (Olah and Lin 1973, 1974b) or acetone cyanohydrin nitrate (Olah et al 1978b) or silver nitrate (Olah et al 1981b) were found to be efficient selective nitrating agents. Nitrations with alkyl nitrates were also carried out by using superacidic solid perfluorinated sulfonic acid catalyst (including Nation-H | to be discussed later) instead of liquid protic or Friedel-Crafts Lewis acid catalysts. Further the azeotropic nitration of aromatics with nitric acid was also developed over these superacid catalysts. Furthermore mercury(II)-promoted azeotropic nitration of aromatics with Nation- H (vide infra) works rather well (Olah et al 1982a). Synthetic methods and reactions 145 NO2 FSO3H 02N NO2 H CH3NO2 I Si --CH3 NO;BF; .~ ~i--F + CH3NO2 I I BF3 CH _ I 3 NO;BF4 I CH2"- CH~-CH2._.?t_CH 3 ~CH2"-- CH=CH2 NO2 I CH3 + BF3 i I .O;Bq 1 SI--~C--Si-- 02N--C,,=C--Si~ l I F- I \, / R 1.3,5- (CH3)3C6H 3 + N~ PF6-( BF4- ) NO2 R 1,3,5-(CH3)3C6HzNO z + PF 6 (BF4) I* H We have also found that nitrosonium salts (Cook 1963) in dimethylsulfoxide (Olah et al 1978c) can act as a good nitrating agent. The S-nitro to S-nitritoonium ion transformation was directly observed by 13C and 15N NMR spectroscopy (Olah et al 1979a). 146 G K Surya Prakash and George A Olah R CHz--CH--CH 2 Jr ~ ~(BF4-) ----- CH2--CH--CH 2 + OHI OHI OHI "I ONOI 2 L 0 z ONOI 2 NO;~ R 3 ~ (BF4-) R ~ .. ell,, (CH,),, (CH,), i" H I NOz R H BF3 ArH + H3CONO2 or BuONO2 or (H30)2C(ONO2)Cn ArNO2 or AgNO3 CnF2n+iSO3H CH3C6H5 + HNO3 CH3C6H4NO2 + H20 or Nafion-H R R R Hg(N03) 2 > or Hg-Nationate Hg(NO3) NO2 (or Hg-Nafionate) ] .o; H3C~;_O_ + H3C~+ + NO . S--ONO ArH ArNO2 + (CH3)2S J H3C H3C/ Synthetic methods and reactions 147 Oxidative reactions with NO + and NO~ salts Stable nitronium (NO~-) and related nitrosonium (NO +) salts (Cook 1963), particularly with PF6 and BFz counterions, can act as selective mild oxidizing agents. Nitrosonium tetrafluoroborate in CH2CI2 has been employed to oxidize secondary tributylstannyl and trimethylsilyl ethers to the corresponding ketones. Under similar conditions benzylic alcohols are oxidized to their respective carbonyls (Olah and Ho 1976a). Regioselective oxidation of alkyl(cycloalkyl)- methyl ethers has been achieved using nitronium tetrafluoroboratc (Ho and Olah 1977a). Both nitronium and nitrosonium ions oxidatively cleave oximes and N,N-dimethyl-hydrazones to their corresponding carbonyl compounds (Olah and Ho 1976b). Nitrosonium hexafluorophosphate has been used for the regioselective oxidative cleavage of benzylic esters (Ho and Oiah 1977b). Thiocarbonyls have been transformed to carbonyls using nitrosonium tetrafluoroborate (Olah et al 1984). Nitronium and nitrosonium ions also cleave thioketals (Olah et al 1979). 2 NO+BF4 R2 0 R\CH--O--MR3 > RI/ CH2CI2 Rl MR3=Sn(n-C4H9)3, Si(CH3)3 ~I CH2Cl2 R2 Nitronium ion, besides being a good nitrating agent (reacting at the nitrogen end as a polarizable electrophile), can also react at the oxygen end (by rearrangement). Dialkyl(aryl) sulfides and selenides as well as trialkyi-(aryi-)phosphines, triaryl arsines and triarylstibines react with nitronium salts to give the corresponding oxides (Olah et al 1979a). Furthermore, sulfoxides are oxidized to sulfones with nitronium ion (Olah and Gupta 1983). Both nitronium and nitrosonium ions are good hydride- and halide-abstracting agents. Fluorination of haloadamantanes and diamantane has been achieved with nitronium ion in pyridinium polyhydrogen fluoride medium (Oiah et al 1983a). The reaction has been extended to polyhaloadamantanes and diamantanes (Olah et al 1984b). Recently, under similar conditions, 1,4,9-tribromotriamantane unex- pectedly gave 1,4,7,9-tetrafluorodiamantane (Krishnamurthy et al 1986), a reaction which involves hydride abstraction. More recently, unusual /3-fluorination of secondary alkyl and cycioalkyl bromides in their reaction with NO_,+ ion in pyridinium polyhydrogen fluoride medium was observed. The reaction should involve a bromonium ion intermediate (Hashimoto et al 1987). Direct ionic fluorination of alkanes such as adamantane, diamantane and triphenylmethane has been achieved with NO § ion in pyridinium polyhydrogen fluoride (Olah et al 1983b). 148 G K Surya Prakash and George A Olah R2CHOCH3 > R2C-O CH2Cl2 1 NO+ + R1 R\C.N~oH/ or 1102 ) ~C----'O R2 CH2CI2 R2 / R1 "%fC~N.../CH3 C=O R2'' \CH 3 R2/ 1•2 NO+BF; RI"'.I/O--CHC6H5 CH2C12 , RL~-o. 0 ~ S 1) NO+BF; CH2C|2 2) H20 0 CH2CI2 + ~0 2 ONO 0 NO2 I II R~S~R 1, R~S~R + R~S R > R~S~R + NO+ + + NO2+ R~Se~R > R~Se~R + NO+ § NO2 R3X > R3P----O + NO+ X=P, As, or Sb, R=alkyl, aryl .0;% R~-S---R R~ S~R + NO+PF6- II 0 Synthetic methods and reactions " 149 X F No2 ~"~ (HF)nF- IU X=CI, Br.