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Stereoselective Transformations Starting with Chiral (Aikoxy)Methyl-Substituted Organosilicon Compounds

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Stereoselective Transformations Starting with Chiral (Aikoxy)Methyl-Substituted Organosilicon Compounds AWARDS 1996 (NSCS) . PREISTRAGER 1996 (NSCG) 133 CHIMIA 5/ (1997) Nr. 4lApriIJ A a 1996 ( rager•• Chimia 51 (/997) 133-139 © Neue Schweizerische Chemische Gesellschaft ISSN 0009-4293 Stereoselective Transformations Starting with Chiral (AIkoxy)methyl-Substituted Organosilicon Compounds Stefan Bienz* Stefan Bienz was born on Januar 17, 1958, in (Werner Prize 1996 of the NSCS) Lucerne (CH). He is citizen ofWolhusen (LU) and Lucerne, Switzerland. Academic Background: 1977-1983: Studies Abstract. The following short review summarizes the results we achieved with the in Chemistry at the Phi losophical Faculty II of investigation of chiral silicon groups as auxiliaries for the enantioselective synthesis. the University of Zurich, Switzerland. Gradu- (Alkoxy)methyl-substituted silicon compounds with 'Si-centered chirality', which ate research under the supervision of Prof. Dr. were prepared in optically active form by application of a bioreduction, have been M. Hesse at the Institute of Organic Chemistry towards the diploma (May 5, 1983; thesis: efficiently used as starting materials for a number of stereoselective reactions. Acylsi- 'Contribution to the Transformation of Car- lanes of this type upon treatment with organometallic reagents gave rise to 1,2-addition bocycIes to Lactams by Ring Enlargement products with high degrees of stereoselectivities. The respective a-hydroxysilanes Reaction') and 1983-1987 towards the Ph.D. could be stereospecifically desilylated to chiral secondary alcohols, or, depending on (December 18, 1987; thesis: 'Synthesis of the substitution pattern, further used as starting compounds for stereocontrolled Macrocyc\ic Natural Products by Ring En- oxidation, Cope- or Claisen-type rearrangement reactions. Chiral a-metallated vinyl- largement Reactions', distinguished for its silanes were converted to a-silyl-substituted allylic alcohols and to a-silyl-substituted excellence). 1988-1989: Postdoctoral studies at the Colo- a,j3-unsaturated ketones. The prior led to chiral allenes in a Peterson-type reaction - rado State University, Fort Collins, Colorado however, without stereoselectivity - the latter delivered stereoselectively j3-chiral (USA) with Prof. Dr. A. I. Meyers in the field silicon-free ketones upon stereocontrolled conjugate cuprate addition followed by of enantioselective synthesis. removal of the silicon auxiliary. Since 1990 at the Institute of Organic Chem- istry, University of ZUrich, Switzerland: Head assistant and lecturer; Summer 1995: Venia legendi (habilitation treatise: 'Enantioselec- 1. Introduction silanes 1that gave in highly enantioselec- tive Synthesis Using Amino Acid or Silicon tive allylation reactions rise to a variety of Based Chiral Auxiliaries and Synthesis of Organosilicon chemistry has undergone a compounds [5][6]. The chiral allylsilanes Polyamine Toxins from Spiders and Wasps'). tremendous development over the last two 1,however, do not possess a 'chiral silicon Research interests: stereoselective synthesis or three decades. It is fair to state that moiety' which delivers stereochemical in- with organosilicon compounds, synthetic rel- nowadays, the majority of multistep or- formation onto a carbon framework; the evant mass spectrometric methods and frag- ganic syntheses makes use of organosili- stereochemical information is already mentations, unusual substrates for bio- transformations, physiologically interesting con compounds in one way or another: as stored on the reactive group, which itself polyamine conjugates. reagents for C,C-bond formations, forfunc- is attached to an 'achiral silicon group' tional-group transformations, or for func- (silanes of the type A with 'proximate C- tional-group protections. With the advanc- centered chirality' [4]). Transfer of chiral- attained in several transformations with ing interest in the preparation of enantio- ity from a chiral silicon auxiliary to a proline-derivedchiral silanes 2 (that are of merically pure compounds, it is not sur- neighboring prostereogenic group, how- the type B) [2]. The scope of reactions prising that also attention has been in- ever, has been realized with silanes ofthe with this type of substrates, however, is creasingly directed towards stereoselec- type Band C. These compounds have limited, since no common chiral silicon tiveprocesses involvingchiral silicon com- located the chirality either on an inert side precursor (like, e.g., a chlorosilane) is pounds [1-6]. Some rather impressive re- chain (compounds of the type B with 're- employed. So far, only little use of chiral sults were obtained, e.g., with chiral allyl- mote C-centered chirality') or- in form of silicon compounds of the type C has been a stereogenic center - on silicon itself made for the enantioselective synthesis (compounds of the type C with 'Si-cen- [1-5]. This is probably due to the low *Correspondence: PO Dr. S. Bienz tered chirality' [4]). It is just astonishing, stereoselectivities that were obtained in Organisch-chemisches Institut Universitiit ZUrich though, how little work has been per- several reactions where almost exclusi ve- Winterthurerstrasse J 90 formed with such substrates. Some re- Iy derivatives of 3 have been used as the CH-8057 ZUrich markable stereoselectivities were lately chiral starting compounds. AWARDS 1996 (NSCS) . PREISTRAGER 1996 (NSCG) 134 CHIMIA 5/ (1997) Nr. 4 (April) Enhanced stereoselectivities were ex- external prostereogenic electrophiles, re- alents, followed by the respective func- pected to be attained, if (alkoxy)methyl- spectively, leading to novel chiral com- tional-group interconversion. They were substituted chiral silanes 4 were used in- pounds amenable to further transforma- alternatively transferred into (a-iodovi- stead of derivatives of3. These compounds tions. nyl)silanes 10 (the ultimate precursors of should be enabled to form cyclic chelate a-metallated vinylsilanes 6) by treatment intermediates or transition states with cat- with a suitable lithium acetylide, reduc- ionic additives (metals, M). As a conse- 2. Preparation of Chiral tion of the obtained alkynylsilanes 9 with quence of the rigid intermediary structure, (Alkoxy)methyl-Substituted Silanes diisobutylaluminum hydride (OIBAR), they should effect an improved discrimi- and quenching of the resultant vinylalane nation of the different spatial approaches Racemic chiral (alkoxy)methyl-substi- with iodine [8]. The stereochemistry of the reacting species. This is in fact tuted silanes were prepared straightfor- around the C=C bond of 10 can be control- observed, as will be shown in this short wardly from commercial (chloromethyl)- led by the proper choice of the reduction review: below, we describe the prepara- dichloro(methyl)silane (7) [7]: Stepwise conditions; for (E)-configurated silanes tion of chiral (benzyloxy)methyl-substi- substitution of the Cl-atoms (via bis(ben- 10, the C=C bond geometry can also be tuted silanes and some subsequent stereo- zyloxy)silane intermediates) - first at the inverted in the course of the subsequent selective transformations. Focus will be chloromethyl group with the benzyloxy metallation step. directed on the primary and subsequent residue, then at the silicon center with the Optically active acylsilanes 5 are ac- reactions of two types of chiral organosil- tert-butyl group - provided the racemic cessible by using a biotransformation step: icon compounds, namely acylsilanes 5 chlorosilane 8 (Scheme 1), which could be e.g., (±)-5a is recognized by several mi- and a-metallated vinylsilanes 6. These used as the common precursor for the croorganisms as a substrate and is reduced substrates should stereoselectively react synthesis of a variety of silanes. Com- stereospecifically to the corresponding a- either as electrophiles at the prostereogen- pound 8 was thus converted into acylsi- hydroxysilanes (+)-(SiR,R)-lla and (+)- ic carbonyl group or as nucleophiles with lanes 5 by reaction with acyl-anion equiv- (SiS,R)-lla' (Scheme 2) [9][10]. These diastereomeric alcohols were separated by chromatography and reoxidized to (-)- R (R)-5a and (+)-(S)-5a, respectively. Alter- I natively, the two alcohols can be convert- R-Si~R" MeI - Type A I e.g. r=<,R' 1 ed to the hydrosilanes (+)-(S)-12a and R Me-~i"" Rz Chiral Reactive Group Me R (-)-(R)-12a by treatment with KH (Brook rearrangement [11][12]) and reduction of ('Proximate C-Centered Chirality') the thus obtained silyl ethers with LiAlH4 [13]. Best results in the biotransformation R* r step were obtained with immobilized rest- R-Si-Reeae ing cells of Trigonopsis variabilis (DSM Type B I e.g. ("'={OMe 2 R 70714), which provided the desired prod- Me-SI-Reeae Chirallnert Substituent I ucts not only in high chemical yields and Me with enantiomeric excesses > 96%, but ('Remote C-Centered Chirality') also allowed to develop a handy workup procedure. R1 I . Ph 2 R -ShReeae 1.* Type C e.g. a.-Npht- SI-Rreae 3 R3 I 3. Stereoselective Reactions Starting Chiral Silicon Center Me with Chiral Acylsilanes ('Si-Centered Chirality') 3.1. 1,2-Addition to the Carbonyl Group The 1,2-addition of organometallic re- Bn I agents to the carbonyl group of acylsilanes 0, 5 afforded the respective addition prod- ( '¥ .. ucts 13 with varying degrees of diastereo- Me""Si 6 selectivity [7][14] (Scheme 3, shown ex- Mej( r: emplary for the conversion of (-)-(R)-5a R Me R''---. I Me \ to (+)-(SiR,R)-13a). Particularly high se- 0, lectivities were attained, when the reac- ( 'M 5 prostereogenic tions were carried out in nonbasic sol- Me....:./Me""Si "R " vents, like, e.g., hexane
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