This account examines double asymmetric induction from theoretical and practical viewpoints. In the context of four major organic reactions-the aldol, Diels-Alder, catalytic hydrogenation, and epoxidation-it is shown that a double asymmetric induction can be analyzed in terms of the single asymmetric reactions of each of the two chiral reactants. A rule which qualitatively relates the results of these single asymmetric reactions with the outcome of the double asymmetric reaction is proposed. A powerful new strategy based on this rule for the predictable creation of new chiral centers is discussed and the use of this strategy for the synthesis of sugars and macrolides is presented.

Double Asymmetric Synthesis and a New Strategy for Stereochemical Control in Organic Synthesis

Preparation of polymer-supported ligands and metal complexes for use in catalysis.

2. Essential Components: Earlier Developments 5449 2.1. Activated alkenes/alkynes 5450 2.1.1. Acyclic activated alkenes/ alkynes 5450 2.1.2. Cyclic activated alkenes 5451 2.2. Electrophiles 5451 2.3. Catalysts 5452 3. Essential Components: Recent Developments 5452 3.1. Activated Alkenes/Alkynes 5452 3.2. Electrophiles 5460 3.3. Catalysts 5477 4. Asymmetric Baylis-Hillman Reaction: Earlier Developments 5495

Recent contributions from the Baylis-Hillman reaction to organic chemistry.

Allenes are the simplest class of cumulenes, with two contiguous CC bonds, and show unique physical and chemical properties. These features make allenes particularly attractive in modern organic chemistry. In this Review, attention is paid to the advances made in catalytic asymmetric synthesis and natural product syntheses based on well-established reactions of allenes, such as propargylation, addition, cycloaddition, cycloisomerization, cyclization, etc., with or without catalysts. Their versatile reactivity, substituent-loading ability, axial to center chirality transfer, and controllable selectivity allow access to target molecules by unique and efficient approaches. The main topics in this Review are presented with selected examples from 2003 to 2011.

Allenes in Catalytic Asymmetric Synthesis and Natural Product Syntheses

Recoverable Catalysts for Asymmetric Organic Synthesis

Starting from (+)-camphor-10-sulfonyl chloride (5), the crystalline sultam 8 was easily prepared. Lewis-acid-promoted Diels-Alder additions of the crystalline N-acry-loyl and N-crotonoyl derivatives 9 and 10, respectively, to cyclopentadiene and 1,3-butadiene at −130 to −78° furnished adducts 11, 12 and 17 with high chiral efficiency. Crystallization of the adducts and nondestructive removal of 8 gave either alcohols 13, 14 and 18 ir acid 19 in 99% enantiomeric purity. The sense of induction was reversed on using the enantiomer of 8 as the auxiliary. The structure of 10 was established by X-ray diffraction analysis.

Camphor‐Derived N‐Acryloyl and N‐Crotonoyl Sultams: Practical Activated Dienophiles in Asymmetric Diels‐alder Reactions. Preliminary Communication

Starting from the enantiomerically pure monoterpenes (+)-pulegone (3), (+)-limonene (7), (−)-β-pinene (9), (+)- and (−)-camphor (13) or (+)-cholestenone (11) the chiral alcohols 4, 5, 6, 8, 10, 12, 14, 15, 16, 17 et 18 were prepared; their acrylates II underwent a TiCl4-promoted Diels-Alder addition to cyclopentadiene (Scheme 3, Table) giving in a predictable manner either the (2R)- or the (2S)-adducts III with 63 to 88% asymmetric induction.

Asymmetric induction in Diels‐Alder reactions to acrylates derived from chiral sec‐alcohols. Preliminary communication

Asymmetric Diels-Alder reactions: facile preparation and structure of sulfonamido-isobornyl acrylates

For the asymmetric isomerization of geranyl- or neryldiethylamine ((E)- or (Z)-1, resp.) and allyl alcohols geraniol or nerol ((E)- or (Z)-2, resp.) to citronellal (4) in the presence of a [RhI(ligand)cycloocta-1,5-diene)]+ catalyst, the atropic ligands 5 – 11 are compared under homogeneous and polymer-supported conditions with the non-C2-symmetrical diphosphino ferrocene ligands 12 – 16. The tBu-josiphos ligand 13 or daniphos ligand 19, available in both antipodal series, already catalyse the reaction of (E)-1 at 20° (97% e.e.) and favourably compare with the binap ligand 5 (see Table 1). Silica-gel- or polymer-supported diphosphino ligands usually afford similar selectivity as compared to the corresponding ligands applied under homogeneous conditions, but are generally less reactive. In this context, a polymer-supported ligand of interest is the polymer-anchored binap (R)-6, in terms of reactivity, selectivity, and recoverability, with a turnover of more than 14400.

Synthesis of Citronellal by RhI-Catalysed Asymmetric Isomerization ofN,N-Diethyl-Substituted Geranyl- and Nerylamines or Geraniol and Nerol in the Presence of Chiral Diphosphino Ligands, under Homogeneous and Supported Conditions

Starting from (+)- or (−)-camphor, the antipodal alcohols 14 and 18, respectively, have been prepared; the corresponding acrylates 15 and 19 underwent TiCl2(i-PrO)2-mediated Diels-Alder additions to cyclopentadiene to give adducts 20a and 22a respectively, with 95 % endo- and 99.2% πpH-face selectivities. Adduct 22a was converted to enantiomerically pure norbornenone 26. Addition of 1,3-butadiene to acrylate 15 in the presence of TiCl4 afforded 3-cyclohexenyl carboxylate 29 with > 95.6 % stereodifferentiation. The TiCl2(i-PrO)2-promoted [4 + 2] cycloaddition of cyclopentadiene to allenic ester 43 proceeding with 99 % face differentiation served as the key step for an efficient enantioselective synthesis of (−)-β-santalene ((−)-41) with concomitant recovery of the chiral control alcohol 14.

Christian Chapuis

Papers

Camphor‐Derived N‐Acryloyl and N‐Crotonoyl Sultams: Practical Activated Dienophiles in Asymmetric Diels‐alder Reactions. Preliminary Communication

Asymmetric induction in Diels‐Alder reactions to acrylates derived from chiral sec‐alcohols. Preliminary communication

Asymmetric Diels-Alder reactions: facile preparation and structure of sulfonamido-isobornyl acrylates

Synthesis of Citronellal by RhI-Catalysed Asymmetric Isomerization ofN,N-Diethyl-Substituted Geranyl- and Nerylamines or Geraniol and Nerol in the Presence of Chiral Diphosphino Ligands, under Homogeneous and Supported Conditions

Asymmetric Diels‐Alder Reactions of Neopentyl‐Ether‐Shielded Acrylates and Allenic Esters: Syntheses of (−)‐Norbornenone and (−)‐β‐Santalene