25 with the reagent derived from 1,1-diiodoethane and diethylzinc (eq 12). 43,44 The level of induction was highly dependent on the nature of the nitrogen protecting group.An interesting cyclopropanation of an exocyclic olefin was reported by Ronald (eq 13). 45 The cyclopropanation of 2-methylenecyclohexanol using 13 Table 4. Cyclopropanation of (E)-3-Penten-2-ol 47 conditions ratio 31:32

Introduction 2643 2. Nucleophilic Addition of Organometallic Reagents to N-Acyl Pyridinium Salts 2644 2.1. Regioselective Additions to N-Acyl Pyridinium Species and Their Derivatives 2644 2.1.1. Influence of Pyridine Ring Substituents on Regioselectivity of Addition 2646 2.1.2. Control of Regio-and Diastereoselectivity by the Introduction of Removable Blocking Groups 2648 2.2. Synthesis of 4-Pyridones: 1,2-Addition to 4-Methoxypyridines 2649 2.2.1. Diastereoselective Addition to 3-Trialkylsilyl-4-methoxypyridines 2651 2.2.2. Application in the Synthesis of Natural Products Containing Chiral Piperidine Units 2652 2.3. Diastereoselective 1,2-Addition to N-Imidoyl Pyridinium Salts 2652 2.4. Enantioselective 1,2-Addition Controlled by a Chiral Catalyst 2657 2.5. Diastereoselective 1,4-Addition Controlled by Pyridine 3-Substituents 2657 3. Nucleophilic Addition to N-Alkyl Pyridinium Salts and Their Derivatives 2659 3.1. Regioselective Additions to N-Alkyl Pyridinium SaltsNature of the Nucleophile 2659 3.1.1. Organometallic Reagents as Nucleophiles 2659 3.1.2. Cyanide as Nucleophile 2663 3.2. Diastereoselective Additions of Organometallic Reagents to N-Alkyl Pyridinium Salts 2663 3.3. Regioselective Additions of Enolates to N-Alkyl Pyridinium Salts 2666 3.3.1. Wenkert Procedure: Seminal Work 2667 3.3.2. Wenkert Procedure: Addition of Nucleophiles Positioned at the Nitrogen of Indole Derivatives 2670 3.3.3. Wenkert Procedure: Addition of Enolates Located at the C-2/C-3 Position of Indoles 2671 3.3.4. Addition of Miscellaneous Nucleophiles to N-Alkyl Pyridinium Species 2674 4. Nucleophilic Additions to N-Heteroatom Pyridinium Species 2676 4.1. Nucleophilic Additions to Pyridine N-Oxides and N−O Salts 4.1.1. Properties, Synthesis, and Deprotection of Pyridine N-Oxides 4.1.2. Addition of Grignard Reagents to Pyridine N-Oxides 4.1.3. Addition of Cyanide Nucleophiles via Reissert-Type Reactions 4.1.4. Addition of Hetero Nucleophiles to Pyridine N-Oxides and N−O Salts 4.

Almost 30 years after Emschwiller prepared IZnCH 2 I, Simmons and Smith discovered that the reagent formed by mixing a zinc‐copper couple with CH 2 I 2 in ether could be used for the stereospecific conversion of alkenes to cyclopropanes. Nowadays, the Simmons‐Smith cyclopropanation reaction is one of the most widely used reactions in the organic chemist's arsenal for the conversion of olefins into cyclopropanes. This popularity is mainly due to the stereospecificity of the reaction with respect to the double bond geometry and its compatibility with a wide range of functional groups. The chemoselectivity of the reaction toward some olefins is excellent and very few side reactions are observed with functionalized substrates. The metal carbenoid is electrophilic in nature and electron‐rich alkenes usually react much faster than electron‐poor alkenes. Furthermore, the ability to use proximal hydroxy or ether groups to dictate the stereochemical outcome of the CC bond forming process was recognized early on, and this unique property has been successfully exploited on numerous occasions. It has been recognized that halomethylmetal reagents are powerful synthetic tools for the stereoselective addition of a methylene unit to chiral acyclic allylic alcohols and allylic ethers. In addition, the use of halomethylzinc reagents in the presence of chiral additives is one of the few ways to cyclopropanate allylic alcohols efficiently and with good enantiocontrol. Carbenoids can be divided into the following two classes: (1) those of general structure MCH 2 X and (2) those corresponding to M = CH 2 . This chapter is focussed exclusively on the first class in which M = Zn, Sm, or Al. Although other metal carbenoids of type MCH 2 X, such as those derived from Cu, Cd, Hg, and In, have been reported to be effective reagents for the cyclopropanation of some olefins, they have been used only sporadically, and this review does not highlight these reactions. This chapter covers cyclopropanation reactions involving haloalkylzinc, aluminum, and samarium reagents published since the comprehensive chapter in Organic Reactions by Simmons that surveyed the literature up to 1973.

A very effective chiral controller has been found for the conversion of allylic alcohols into the corresponding enantiomerically enriched cyclopropanes using bis(iodomethyl)zinc. A variety of chiral, nonracemic cyclopropylmethanols could be obtained according to this method. This methodology was extended with success to the cyclopropanation of unconjugated and conjugated polyenes and homoallylic alcohols. The cyclopropanation of allylic carbamates has also been investigated with this system, but it was found that enantioenriched cyclopropylmethylamines are best prepared from enantioenriched cyclopropylmethanols.

This communication describes a metal-free methodology involving an efficient and controlled reduction of secondary amides to imines, aldehydes, and amines in good to excellent yields under ambient pressure and temperature. The process includes a chemoselective activation of a secondary amide with triflic anhydride in the presence of 2-fluoropyridine. The electrophilic activated amide can then be reduced to the corresponding iminium using triethylsilane, a cheap, rather inert, and commercially available reagent. Imines can be isolated after a basic workup or readily transformed to the aldehydes following an acidic workup. The amine moiety can be accessed via a sequential reductive amination by the addition of silane and Hantzsch ester hydride in a one-pot reaction. Moreover, this reduction tolerates various functional groups that are usually reactive under reductive conditions and is very selective to secondary amides.